Since the first SARS-CoV-2 (COVID-19) outbreak in Wuhan, China, in December 2019, more than 6.6 million deaths have occurred. Management strategies for patients with COVID-19 pneumonia/ARDS have continued to evolve during the pandemic. One of the strategies for those cases refractory to traditional ARDS treatments has been the use of extracorporeal membrane oxygenation (ECMO).

Before the COVID-19 pandemic, a substantial amount of data regarding the use of ECMO in ARDS was gathered during the H1N1 influenza outbreak in 2009. Mortality ranged from 8% to 65% (Zangrillo, et al. Crit Care. 2013;17[1]:R30). From these data, we learned the importance of patient selection. Young patients with few co-morbidities and less than 7 days supported by mechanical ventilation did remarkably better than elderly patients or those who had prolonged positive-pressure ventilation prior to ECMO.  

To date, the mortality rate for COVID-19 patients with ARDS requiring ECMO is 48% based on data from ELSO. Interestingly though, using May 1, 2020, as a cutoff date, mortality rates for patients with COVID-19 receiving ECMO significantly increased from 37% to 52% (Barbaro, et al. Lancet. 2021;398[10307]:1230). This escalation in mortality engendered concern that ECMO may not be useful in treating patients with COVID-19 and ARDS.

Several factors can be cited for this increase in mortality. First, many new ECMO programs launched after May 1. These new programs had a higher mortality rate (59%) compared with established programs, suggesting that program and provider experience play a significant role in patient outcomes (Barbaro, et al. Lancet. 2021;398[10307]:1230). Second, patients in the latter part of 2020 experienced much longer intervals between the onset of symptoms and time of intubation. Clinicians had a tendency to delay intubation as long as possible. Subsequently, the number of days receiving high flow nasal oxygen or noninvasive ventilation (NIV) was significantly longer (Schmidt, et al. Crit Care. 2021;25[1]:355). These data suggest that prolonged NIV on high Fio2 may be a negative prognostic indicator and should be considered when assessing a patient’s candidacy for ECMO.

Early in the pandemic, clinicians realized that average ECMO run times for patients with COVID-19 and ARDS were significantly longer, 15 vs 9 days, respectively (Jacobs, et al. Ann Thorac Surg. 2022;113[5]:1452). With such long run times, beds were slow to turn over, and a shortage of ECMO beds resulted during the height of the pandemic. In a retrospective study, Gannon looked at 90 patients, all of whom were deemed medically appropriate for ECMO. Two groups were created: (1) no capacity for ECMO vs (2) ECMO provided. Mortality rates were staggering at 89% and 43%, respectively (P =.001) (Gannon, et al. Am J Respir Crit Care Med. 2022;205[11]:1354). This study demonstrated a profound point: during a pandemic, when demand overcomes supply, there is a unique opportunity to see the effect of lifesaving therapies, such as ECMO, on outcomes. This study was particularly poignant, as the average age of the patients was 40 years old.  

It is now widely accepted that prone positioning has survival benefit in ARDS. Prone positioning while receiving ECMO has generally been avoided due to concern for potential complications associated with the cannula(s). However, it has been shown that prone positioning while receiving veno-venous (VV) -ECMO reduces mortality rates, 37% proned vs 50% supine positioning (P =.02) (Giani, et al. Ann Am Thorac Soc. 2021;18[3]:495). In this study, no major complications occurred, and minor complications occurred in 6% of the proning events. Prone positioning improves ventilation-perfusion mismatch and reduces hypoxic vasoconstriction, which is thought to be right-sided heart-protective.  

Right-sided heart dysfunction (RHD) is common in ARDS, whether COVID-19-related or not. The pathogenesis includes hypoxic vasoconstriction, pulmonary fibrosis, and ventilator-induced lung injury. Pulmonary microthrombi and patient-specific characteristics, such as obesity, are additional factors leading to RHD in patients with COVID-19. During the pandemic, several articles described using right-sided heart protective cannulation strategies for patients with COVID-19 requiring ECMO with favorable results (Mustafa, et al. JAMA Surg. 2020;155[10]:990; Cain, et al. J Surg Res. 2021;264:81-89). This right-sided heart protective strategy involves inserting a single access dual lumen cannula into the right internal jugular vein, which is advanced into the pulmonary artery, effectively bypassing the right ventricle. This setup is more typical of right ventricle assist device (RVAD), rather than typical VV-ECMO, which returns blood to the right atrium. Unfortunately, these studies did not include echocardiographic information to evaluate the effects of this intervention on RVD, and this is an area for future research. However, this vein to pulmonary artery strategy was found to facilitate decreased sedation, earlier liberation from mechanical ventilation, reduced need for tracheostomy, improved mobilization out of bed, and ease in prone positioning (Mustafa, et al. JAMA Surg. 2020;155[10]:990).

In conclusion, there is evidence to support the use of ECMO in patients with COVID-19 patients and ARDS failing conventional mechanical ventilation. The success of ECMO therapy is highly dependent on patient selection. Prolonged use of NIV on high Fio2 may be a negative predictor of ECMO survival and should be considered when assessing a patient for ECMO candidacy. Prone positioning with ECMO has been shown to have survival benefit and should be considered in all patients receiving ECMO.
 

Dr. Gaillard, Dr. Staples, and Dr. Kapoor are with the Department of Anesthesiology, Section on Critical Care, at Wake Forest School of Medicine in Winston-Salem, N.C. Dr. Gaillard is also with the Department of Emergency Medicine and Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy, and Immunology at Wake Forest School of Medicine.

Since the first SARS-CoV-2 (COVID-19) outbreak in Wuhan, China, in December 2019, more than 6.6 million deaths have occurred. Management strategies for patients with COVID-19 pneumonia/ARDS have continued to evolve during the pandemic. One of the strategies for those cases refractory to traditional ARDS treatments has been the use of extracorporeal membrane oxygenation (ECMO).

Before the COVID-19 pandemic, a substantial amount of data regarding the use of ECMO in ARDS was gathered during the H1N1 influenza outbreak in 2009. Mortality ranged from 8% to 65% (Zangrillo, et al. Crit Care. 2013;17[1]:R30). From these data, we learned the importance of patient selection. Young patients with few co-morbidities and less than 7 days supported by mechanical ventilation did remarkably better than elderly patients or those who had prolonged positive-pressure ventilation prior to ECMO.  

To date, the mortality rate for COVID-19 patients with ARDS requiring ECMO is 48% based on data from ELSO. Interestingly though, using May 1, 2020, as a cutoff date, mortality rates for patients with COVID-19 receiving ECMO significantly increased from 37% to 52% (Barbaro, et al. Lancet. 2021;398[10307]:1230). This escalation in mortality engendered concern that ECMO may not be useful in treating patients with COVID-19 and ARDS.

Several factors can be cited for this increase in mortality. First, many new ECMO programs launched after May 1. These new programs had a higher mortality rate (59%) compared with established programs, suggesting that program and provider experience play a significant role in patient outcomes (Barbaro, et al. Lancet. 2021;398[10307]:1230). Second, patients in the latter part of 2020 experienced much longer intervals between the onset of symptoms and time of intubation. Clinicians had a tendency to delay intubation as long as possible. Subsequently, the number of days receiving high flow nasal oxygen or noninvasive ventilation (NIV) was significantly longer (Schmidt, et al. Crit Care. 2021;25[1]:355). These data suggest that prolonged NIV on high Fio2 may be a negative prognostic indicator and should be considered when assessing a patient’s candidacy for ECMO.

Early in the pandemic, clinicians realized that average ECMO run times for patients with COVID-19 and ARDS were significantly longer, 15 vs 9 days, respectively (Jacobs, et al. Ann Thorac Surg. 2022;113[5]:1452). With such long run times, beds were slow to turn over, and a shortage of ECMO beds resulted during the height of the pandemic. In a retrospective study, Gannon looked at 90 patients, all of whom were deemed medically appropriate for ECMO. Two groups were created: (1) no capacity for ECMO vs (2) ECMO provided. Mortality rates were staggering at 89% and 43%, respectively (P =.001) (Gannon, et al. Am J Respir Crit Care Med. 2022;205[11]:1354). This study demonstrated a profound point: during a pandemic, when demand overcomes supply, there is a unique opportunity to see the effect of lifesaving therapies, such as ECMO, on outcomes. This study was particularly poignant, as the average age of the patients was 40 years old.  

It is now widely accepted that prone positioning has survival benefit in ARDS. Prone positioning while receiving ECMO has generally been avoided due to concern for potential complications associated with the cannula(s). However, it has been shown that prone positioning while receiving veno-venous (VV) -ECMO reduces mortality rates, 37% proned vs 50% supine positioning (P =.02) (Giani, et al. Ann Am Thorac Soc. 2021;18[3]:495). In this study, no major complications occurred, and minor complications occurred in 6% of the proning events. Prone positioning improves ventilation-perfusion mismatch and reduces hypoxic vasoconstriction, which is thought to be right-sided heart-protective.  

Right-sided heart dysfunction (RHD) is common in ARDS, whether COVID-19-related or not. The pathogenesis includes hypoxic vasoconstriction, pulmonary fibrosis, and ventilator-induced lung injury. Pulmonary microthrombi and patient-specific characteristics, such as obesity, are additional factors leading to RHD in patients with COVID-19. During the pandemic, several articles described using right-sided heart protective cannulation strategies for patients with COVID-19 requiring ECMO with favorable results (Mustafa, et al. JAMA Surg. 2020;155[10]:990; Cain, et al. J Surg Res. 2021;264:81-89). This right-sided heart protective strategy involves inserting a single access dual lumen cannula into the right internal jugular vein, which is advanced into the pulmonary artery, effectively bypassing the right ventricle. This setup is more typical of right ventricle assist device (RVAD), rather than typical VV-ECMO, which returns blood to the right atrium. Unfortunately, these studies did not include echocardiographic information to evaluate the effects of this intervention on RVD, and this is an area for future research. However, this vein to pulmonary artery strategy was found to facilitate decreased sedation, earlier liberation from mechanical ventilation, reduced need for tracheostomy, improved mobilization out of bed, and ease in prone positioning (Mustafa, et al. JAMA Surg. 2020;155[10]:990).

In conclusion, there is evidence to support the use of ECMO in patients with COVID-19 patients and ARDS failing conventional mechanical ventilation. The success of ECMO therapy is highly dependent on patient selection. Prolonged use of NIV on high Fio2 may be a negative predictor of ECMO survival and should be considered when assessing a patient for ECMO candidacy. Prone positioning with ECMO has been shown to have survival benefit and should be considered in all patients receiving ECMO.
 

Dr. Gaillard, Dr. Staples, and Dr. Kapoor are with the Department of Anesthesiology, Section on Critical Care, at Wake Forest School of Medicine in Winston-Salem, N.C. Dr. Gaillard is also with the Department of Emergency Medicine and Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy, and Immunology at Wake Forest School of Medicine.

Since the first SARS-CoV-2 (COVID-19) outbreak in Wuhan, China, in December 2019, more than 6.6 million deaths have occurred. Management strategies for patients with COVID-19 pneumonia/ARDS have continued to evolve during the pandemic. One of the strategies for those cases refractory to traditional ARDS treatments has been the use of extracorporeal membrane oxygenation (ECMO).

Before the COVID-19 pandemic, a substantial amount of data regarding the use of ECMO in ARDS was gathered during the H1N1 influenza outbreak in 2009. Mortality ranged from 8% to 65% (Zangrillo, et al. Crit Care. 2013;17[1]:R30). From these data, we learned the importance of patient selection. Young patients with few co-morbidities and less than 7 days supported by mechanical ventilation did remarkably better than elderly patients or those who had prolonged positive-pressure ventilation prior to ECMO.  

To date, the mortality rate for COVID-19 patients with ARDS requiring ECMO is 48% based on data from ELSO. Interestingly though, using May 1, 2020, as a cutoff date, mortality rates for patients with COVID-19 receiving ECMO significantly increased from 37% to 52% (Barbaro, et al. Lancet. 2021;398[10307]:1230). This escalation in mortality engendered concern that ECMO may not be useful in treating patients with COVID-19 and ARDS.

Several factors can be cited for this increase in mortality. First, many new ECMO programs launched after May 1. These new programs had a higher mortality rate (59%) compared with established programs, suggesting that program and provider experience play a significant role in patient outcomes (Barbaro, et al. Lancet. 2021;398[10307]:1230). Second, patients in the latter part of 2020 experienced much longer intervals between the onset of symptoms and time of intubation. Clinicians had a tendency to delay intubation as long as possible. Subsequently, the number of days receiving high flow nasal oxygen or noninvasive ventilation (NIV) was significantly longer (Schmidt, et al. Crit Care. 2021;25[1]:355). These data suggest that prolonged NIV on high Fio2 may be a negative prognostic indicator and should be considered when assessing a patient’s candidacy for ECMO.

Early in the pandemic, clinicians realized that average ECMO run times for patients with COVID-19 and ARDS were significantly longer, 15 vs 9 days, respectively (Jacobs, et al. Ann Thorac Surg. 2022;113[5]:1452). With such long run times, beds were slow to turn over, and a shortage of ECMO beds resulted during the height of the pandemic. In a retrospective study, Gannon looked at 90 patients, all of whom were deemed medically appropriate for ECMO. Two groups were created: (1) no capacity for ECMO vs (2) ECMO provided. Mortality rates were staggering at 89% and 43%, respectively (P =.001) (Gannon, et al. Am J Respir Crit Care Med. 2022;205[11]:1354). This study demonstrated a profound point: during a pandemic, when demand overcomes supply, there is a unique opportunity to see the effect of lifesaving therapies, such as ECMO, on outcomes. This study was particularly poignant, as the average age of the patients was 40 years old.  

It is now widely accepted that prone positioning has survival benefit in ARDS. Prone positioning while receiving ECMO has generally been avoided due to concern for potential complications associated with the cannula(s). However, it has been shown that prone positioning while receiving veno-venous (VV) -ECMO reduces mortality rates, 37% proned vs 50% supine positioning (P =.02) (Giani, et al. Ann Am Thorac Soc. 2021;18[3]:495). In this study, no major complications occurred, and minor complications occurred in 6% of the proning events. Prone positioning improves ventilation-perfusion mismatch and reduces hypoxic vasoconstriction, which is thought to be right-sided heart-protective.  

Right-sided heart dysfunction (RHD) is common in ARDS, whether COVID-19-related or not. The pathogenesis includes hypoxic vasoconstriction, pulmonary fibrosis, and ventilator-induced lung injury. Pulmonary microthrombi and patient-specific characteristics, such as obesity, are additional factors leading to RHD in patients with COVID-19. During the pandemic, several articles described using right-sided heart protective cannulation strategies for patients with COVID-19 requiring ECMO with favorable results (Mustafa, et al. JAMA Surg. 2020;155[10]:990; Cain, et al. J Surg Res. 2021;264:81-89). This right-sided heart protective strategy involves inserting a single access dual lumen cannula into the right internal jugular vein, which is advanced into the pulmonary artery, effectively bypassing the right ventricle. This setup is more typical of right ventricle assist device (RVAD), rather than typical VV-ECMO, which returns blood to the right atrium. Unfortunately, these studies did not include echocardiographic information to evaluate the effects of this intervention on RVD, and this is an area for future research. However, this vein to pulmonary artery strategy was found to facilitate decreased sedation, earlier liberation from mechanical ventilation, reduced need for tracheostomy, improved mobilization out of bed, and ease in prone positioning (Mustafa, et al. JAMA Surg. 2020;155[10]:990).

In conclusion, there is evidence to support the use of ECMO in patients with COVID-19 patients and ARDS failing conventional mechanical ventilation. The success of ECMO therapy is highly dependent on patient selection. Prolonged use of NIV on high Fio2 may be a negative predictor of ECMO survival and should be considered when assessing a patient for ECMO candidacy. Prone positioning with ECMO has been shown to have survival benefit and should be considered in all patients receiving ECMO.
 

Dr. Gaillard, Dr. Staples, and Dr. Kapoor are with the Department of Anesthesiology, Section on Critical Care, at Wake Forest School of Medicine in Winston-Salem, N.C. Dr. Gaillard is also with the Department of Emergency Medicine and Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy, and Immunology at Wake Forest School of Medicine.

Diffuse Lung Disease & Transplant Network

Interstitial Lung Disease Section

Delay in diagnosis of IPF: How bad is the problem?

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with a poor prognosis. Antifibrotic therapies for IPF are only capable of slowing disease progression without reversing established fibrosis. As such, the therapeutic efficacy of antifibrotic therapy may be reduced in patients whose diagnosis is delayed.

Unfortunately, diagnostic delay is common in IPF. Studies demonstrate that IPF diagnosis is delayed by more than a year after symptom onset in 43% of subjects, and more than 3 years in 19% of subjects (Cosgrove GP et al. BMC Pulm Med. 2018;18[9]). Approximately one-third of patients with IPF have undergone chest CT imaging more than 3 years prior to diagnosis, and around the same proportion has seen a pulmonologist within the same time span (Mooney J, et al. Ann Am Thorac Soc. 2019;16[3]:393). A median delay to IPF diagnosis of 2.2 years was noted in patients presenting to a tertiary academic medical center and was associated with an increased risk of death independent of age, sex, and forced vital capacity (adjusted hazard ratio per doubling of delay was 1.3) (Lamas DJ et al. Am J Respir Crit Care Med. 2011;184:842).

Robust improvements are clearly required for identifying patients with IPF earlier in their disease course. The Bridging Specialties Initiative from CHEST and the Three Lakes Foundation is one resource designed to improve the timely diagnosis of ILD (ILD Clinician Toolkit available at https://www.chestnet.org/Guidelines-and-Topic-Collections/Bridging-Specialties/Timely-Diagnosis-for-ILD-Patients/Clinician-Toolkit). This, and other initiatives will hopefully reduce delays in diagnosing IPF, allowing for optimal patient care.

Adrian Shifren, MBBCh, FCCP, Member-at-Large

Saniya Khan, MD, MBBS, Member-at-Large

Robert Case Jr., MD, Pulmonary & Critical Care Fellow
 

Critical Care Network

Mechanical Ventilation and Airways Section

Noninvasive ventilation

Noninvasive ventilation (NIV) is a ventilation modality that supports breathing by using mechanically assisted breaths without the need for intubation or a surgical airway. NIV is divided into two main types, negative-pressure ventilation (NPV) and noninvasive positive-pressure ventilation (NIPPV).

NPV

NPV periodically generates a negative (subatmospheric) pressure on the thorax wall, reflecting the natural breathing mechanism. As this negative pressure is transmitted into the thorax, normal atmospheric pressure air outside the thorax is pulled in for inhalation. Initiated by the negative pressure generator switching off, exhalation is passive due to elastic recoil of the lung and chest wall. The iron lung was a neck-to-toe horizontal cylinder used for NPV during the polio epidemic. New NPV devices are designed to fit the thorax only, using a cuirass (a torso-covering body armor molded shell).

For years, NPV use declined as NIPPV use increased. However, during the shortage of NIPPV devices during COVID and a recent recall of certain CPAP devices, NPV use has increased. NPV is an excellent alternative for those who cannot tolerate a facial mask due to facial deformity, claustrophobia, or excessive airway secretion (Corrado A et al. European Resp J. 2002;20[1]:187).
 

NIPPV

NIPPV is divided into several subtypes, including continuous positive airway pressure (CPAP), bilevel positive airway pressure (BPAP or BiPAP), and average volume-assured pressure support (AVAPS or VAPS). CPAP is defined as a single pressure delivered in inhalation (Pi) and exhalation (Pe). The increased mean airway pressure provides improved oxygenation (O₂) but not ventilation (CO₂). BPAP uses dual pressures with Pi higher than Pe. The increased mean airway pressure provides improved O₂ while the difference between Pi minus Pe increases ventilation and decreases CO₂.

AVAPS is a form of BPAP where Pi varies in an automated range to achieve the ordered tidal volume. In AVAPS, the generator adjusts Pi based on the average delivered tidal volume. If the average delivered tidal volume is less than the set tidal volume, Pi gradually increases while not exceeding Pi Max. Patients notice improved comfort of AVAPS with a variable Pi vs. BPAP with a fixed Pi (Frank A et al. Chest. 2018;154[4]:1060A).

Samantha Tauscher, DO, Resident-in-Training

Herbert Patrick, MD, MSEE, FCCP , Member-at-Large
 

Pulmonary Vascular & Cardiovascular Disease Network

Pulmonary Vascular Disease Section

A RACE to the finish: Revisiting the role of BPA in the management of CTEPH

Pulmonary thromboendarterectomy (PTE) is the treatment of choice for patients with CTEPH (Kim NH et al. Eur Respir J. 2019;53:1801915). However, this leaves about 40% of CTEPH patients who are not operative candidates due to inaccessible distal clot burden or significant comorbidities (Pepke-Zaba J et al. Circulation 2011;124:1973). For these inoperable situations, riociguat is the only FDA-approved medical therapy (Delcroix M et al. Eur Respir J. 2021;57:2002828). Balloon pulmonary angioplasty (BPA) became a treatment option for these patients in the last 2 decades. As technique refined, BPA demonstrated improved safety data along with improved hemodynamics and increased exercise capacity (Kataoka M et al. Circ Cardiovasc Interv. 2012;5:756).

A recently published crossover study, the RACE trial, compared riociguat with BPA in treating inoperable CTEPH (Jaïs X et al. Lancet Respir Med. 2022;10[10]:961). Patients were randomly assigned to either riociguat or BPA for 26 weeks. At 26 weeks, patients with pulmonary vascular resistance (PVR) more than 4 Woods Units (WU) were crossed over to receive either BPA or riociguat therapy. At 26 weeks, the BPA arm showed a greater reduction in PVR but more complications, including lung injury and hemoptysis. After a 26-week crossover period, the reduction in PVR was similar in both arms. The complication rate in the BPA arm was lower when preceded by riociguat.

In patients with inoperable CTEPH, BPA has emerged as an attractive management option in addition to the medical therapy with riociguat. However, BPA should be performed at expert centers with experience. Further studies are needed to strengthen the role and optimal timing of BPA in management of post PTE patients with residual PH.

Samantha Pettigrew, MD, Fellow-in-Training

Janine Vintich, MD, FCCP, Member-at-Large

Diffuse Lung Disease & Transplant Network

Interstitial Lung Disease Section

Delay in diagnosis of IPF: How bad is the problem?

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with a poor prognosis. Antifibrotic therapies for IPF are only capable of slowing disease progression without reversing established fibrosis. As such, the therapeutic efficacy of antifibrotic therapy may be reduced in patients whose diagnosis is delayed.

Unfortunately, diagnostic delay is common in IPF. Studies demonstrate that IPF diagnosis is delayed by more than a year after symptom onset in 43% of subjects, and more than 3 years in 19% of subjects (Cosgrove GP et al. BMC Pulm Med. 2018;18[9]). Approximately one-third of patients with IPF have undergone chest CT imaging more than 3 years prior to diagnosis, and around the same proportion has seen a pulmonologist within the same time span (Mooney J, et al. Ann Am Thorac Soc. 2019;16[3]:393). A median delay to IPF diagnosis of 2.2 years was noted in patients presenting to a tertiary academic medical center and was associated with an increased risk of death independent of age, sex, and forced vital capacity (adjusted hazard ratio per doubling of delay was 1.3) (Lamas DJ et al. Am J Respir Crit Care Med. 2011;184:842).

Robust improvements are clearly required for identifying patients with IPF earlier in their disease course. The Bridging Specialties Initiative from CHEST and the Three Lakes Foundation is one resource designed to improve the timely diagnosis of ILD (ILD Clinician Toolkit available at https://www.chestnet.org/Guidelines-and-Topic-Collections/Bridging-Specialties/Timely-Diagnosis-for-ILD-Patients/Clinician-Toolkit). This, and other initiatives will hopefully reduce delays in diagnosing IPF, allowing for optimal patient care.

Adrian Shifren, MBBCh, FCCP, Member-at-Large

Saniya Khan, MD, MBBS, Member-at-Large

Robert Case Jr., MD, Pulmonary & Critical Care Fellow
 

Critical Care Network

Mechanical Ventilation and Airways Section

Noninvasive ventilation

Noninvasive ventilation (NIV) is a ventilation modality that supports breathing by using mechanically assisted breaths without the need for intubation or a surgical airway. NIV is divided into two main types, negative-pressure ventilation (NPV) and noninvasive positive-pressure ventilation (NIPPV).

NPV

NPV periodically generates a negative (subatmospheric) pressure on the thorax wall, reflecting the natural breathing mechanism. As this negative pressure is transmitted into the thorax, normal atmospheric pressure air outside the thorax is pulled in for inhalation. Initiated by the negative pressure generator switching off, exhalation is passive due to elastic recoil of the lung and chest wall. The iron lung was a neck-to-toe horizontal cylinder used for NPV during the polio epidemic. New NPV devices are designed to fit the thorax only, using a cuirass (a torso-covering body armor molded shell).

For years, NPV use declined as NIPPV use increased. However, during the shortage of NIPPV devices during COVID and a recent recall of certain CPAP devices, NPV use has increased. NPV is an excellent alternative for those who cannot tolerate a facial mask due to facial deformity, claustrophobia, or excessive airway secretion (Corrado A et al. European Resp J. 2002;20[1]:187).
 

NIPPV

NIPPV is divided into several subtypes, including continuous positive airway pressure (CPAP), bilevel positive airway pressure (BPAP or BiPAP), and average volume-assured pressure support (AVAPS or VAPS). CPAP is defined as a single pressure delivered in inhalation (Pi) and exhalation (Pe). The increased mean airway pressure provides improved oxygenation (O₂) but not ventilation (CO₂). BPAP uses dual pressures with Pi higher than Pe. The increased mean airway pressure provides improved O₂ while the difference between Pi minus Pe increases ventilation and decreases CO₂.

AVAPS is a form of BPAP where Pi varies in an automated range to achieve the ordered tidal volume. In AVAPS, the generator adjusts Pi based on the average delivered tidal volume. If the average delivered tidal volume is less than the set tidal volume, Pi gradually increases while not exceeding Pi Max. Patients notice improved comfort of AVAPS with a variable Pi vs. BPAP with a fixed Pi (Frank A et al. Chest. 2018;154[4]:1060A).

Samantha Tauscher, DO, Resident-in-Training

Herbert Patrick, MD, MSEE, FCCP , Member-at-Large
 

Pulmonary Vascular & Cardiovascular Disease Network

Pulmonary Vascular Disease Section

A RACE to the finish: Revisiting the role of BPA in the management of CTEPH

Pulmonary thromboendarterectomy (PTE) is the treatment of choice for patients with CTEPH (Kim NH et al. Eur Respir J. 2019;53:1801915). However, this leaves about 40% of CTEPH patients who are not operative candidates due to inaccessible distal clot burden or significant comorbidities (Pepke-Zaba J et al. Circulation 2011;124:1973). For these inoperable situations, riociguat is the only FDA-approved medical therapy (Delcroix M et al. Eur Respir J. 2021;57:2002828). Balloon pulmonary angioplasty (BPA) became a treatment option for these patients in the last 2 decades. As technique refined, BPA demonstrated improved safety data along with improved hemodynamics and increased exercise capacity (Kataoka M et al. Circ Cardiovasc Interv. 2012;5:756).

A recently published crossover study, the RACE trial, compared riociguat with BPA in treating inoperable CTEPH (Jaïs X et al. Lancet Respir Med. 2022;10[10]:961). Patients were randomly assigned to either riociguat or BPA for 26 weeks. At 26 weeks, patients with pulmonary vascular resistance (PVR) more than 4 Woods Units (WU) were crossed over to receive either BPA or riociguat therapy. At 26 weeks, the BPA arm showed a greater reduction in PVR but more complications, including lung injury and hemoptysis. After a 26-week crossover period, the reduction in PVR was similar in both arms. The complication rate in the BPA arm was lower when preceded by riociguat.

In patients with inoperable CTEPH, BPA has emerged as an attractive management option in addition to the medical therapy with riociguat. However, BPA should be performed at expert centers with experience. Further studies are needed to strengthen the role and optimal timing of BPA in management of post PTE patients with residual PH.

Samantha Pettigrew, MD, Fellow-in-Training

Janine Vintich, MD, FCCP, Member-at-Large

Diffuse Lung Disease & Transplant Network

Interstitial Lung Disease Section

Delay in diagnosis of IPF: How bad is the problem?

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with a poor prognosis. Antifibrotic therapies for IPF are only capable of slowing disease progression without reversing established fibrosis. As such, the therapeutic efficacy of antifibrotic therapy may be reduced in patients whose diagnosis is delayed.

Unfortunately, diagnostic delay is common in IPF. Studies demonstrate that IPF diagnosis is delayed by more than a year after symptom onset in 43% of subjects, and more than 3 years in 19% of subjects (Cosgrove GP et al. BMC Pulm Med. 2018;18[9]). Approximately one-third of patients with IPF have undergone chest CT imaging more than 3 years prior to diagnosis, and around the same proportion has seen a pulmonologist within the same time span (Mooney J, et al. Ann Am Thorac Soc. 2019;16[3]:393). A median delay to IPF diagnosis of 2.2 years was noted in patients presenting to a tertiary academic medical center and was associated with an increased risk of death independent of age, sex, and forced vital capacity (adjusted hazard ratio per doubling of delay was 1.3) (Lamas DJ et al. Am J Respir Crit Care Med. 2011;184:842).

Robust improvements are clearly required for identifying patients with IPF earlier in their disease course. The Bridging Specialties Initiative from CHEST and the Three Lakes Foundation is one resource designed to improve the timely diagnosis of ILD (ILD Clinician Toolkit available at https://www.chestnet.org/Guidelines-and-Topic-Collections/Bridging-Specialties/Timely-Diagnosis-for-ILD-Patients/Clinician-Toolkit). This, and other initiatives will hopefully reduce delays in diagnosing IPF, allowing for optimal patient care.

Adrian Shifren, MBBCh, FCCP, Member-at-Large

Saniya Khan, MD, MBBS, Member-at-Large

Robert Case Jr., MD, Pulmonary & Critical Care Fellow
 

Critical Care Network

Mechanical Ventilation and Airways Section

Noninvasive ventilation

Noninvasive ventilation (NIV) is a ventilation modality that supports breathing by using mechanically assisted breaths without the need for intubation or a surgical airway. NIV is divided into two main types, negative-pressure ventilation (NPV) and noninvasive positive-pressure ventilation (NIPPV).

NPV

NPV periodically generates a negative (subatmospheric) pressure on the thorax wall, reflecting the natural breathing mechanism. As this negative pressure is transmitted into the thorax, normal atmospheric pressure air outside the thorax is pulled in for inhalation. Initiated by the negative pressure generator switching off, exhalation is passive due to elastic recoil of the lung and chest wall. The iron lung was a neck-to-toe horizontal cylinder used for NPV during the polio epidemic. New NPV devices are designed to fit the thorax only, using a cuirass (a torso-covering body armor molded shell).

For years, NPV use declined as NIPPV use increased. However, during the shortage of NIPPV devices during COVID and a recent recall of certain CPAP devices, NPV use has increased. NPV is an excellent alternative for those who cannot tolerate a facial mask due to facial deformity, claustrophobia, or excessive airway secretion (Corrado A et al. European Resp J. 2002;20[1]:187).
 

NIPPV

NIPPV is divided into several subtypes, including continuous positive airway pressure (CPAP), bilevel positive airway pressure (BPAP or BiPAP), and average volume-assured pressure support (AVAPS or VAPS). CPAP is defined as a single pressure delivered in inhalation (Pi) and exhalation (Pe). The increased mean airway pressure provides improved oxygenation (O₂) but not ventilation (CO₂). BPAP uses dual pressures with Pi higher than Pe. The increased mean airway pressure provides improved O₂ while the difference between Pi minus Pe increases ventilation and decreases CO₂.

AVAPS is a form of BPAP where Pi varies in an automated range to achieve the ordered tidal volume. In AVAPS, the generator adjusts Pi based on the average delivered tidal volume. If the average delivered tidal volume is less than the set tidal volume, Pi gradually increases while not exceeding Pi Max. Patients notice improved comfort of AVAPS with a variable Pi vs. BPAP with a fixed Pi (Frank A et al. Chest. 2018;154[4]:1060A).

Samantha Tauscher, DO, Resident-in-Training

Herbert Patrick, MD, MSEE, FCCP , Member-at-Large
 

Pulmonary Vascular & Cardiovascular Disease Network

Pulmonary Vascular Disease Section

A RACE to the finish: Revisiting the role of BPA in the management of CTEPH

Pulmonary thromboendarterectomy (PTE) is the treatment of choice for patients with CTEPH (Kim NH et al. Eur Respir J. 2019;53:1801915). However, this leaves about 40% of CTEPH patients who are not operative candidates due to inaccessible distal clot burden or significant comorbidities (Pepke-Zaba J et al. Circulation 2011;124:1973). For these inoperable situations, riociguat is the only FDA-approved medical therapy (Delcroix M et al. Eur Respir J. 2021;57:2002828). Balloon pulmonary angioplasty (BPA) became a treatment option for these patients in the last 2 decades. As technique refined, BPA demonstrated improved safety data along with improved hemodynamics and increased exercise capacity (Kataoka M et al. Circ Cardiovasc Interv. 2012;5:756).

A recently published crossover study, the RACE trial, compared riociguat with BPA in treating inoperable CTEPH (Jaïs X et al. Lancet Respir Med. 2022;10[10]:961). Patients were randomly assigned to either riociguat or BPA for 26 weeks. At 26 weeks, patients with pulmonary vascular resistance (PVR) more than 4 Woods Units (WU) were crossed over to receive either BPA or riociguat therapy. At 26 weeks, the BPA arm showed a greater reduction in PVR but more complications, including lung injury and hemoptysis. After a 26-week crossover period, the reduction in PVR was similar in both arms. The complication rate in the BPA arm was lower when preceded by riociguat.

In patients with inoperable CTEPH, BPA has emerged as an attractive management option in addition to the medical therapy with riociguat. However, BPA should be performed at expert centers with experience. Further studies are needed to strengthen the role and optimal timing of BPA in management of post PTE patients with residual PH.

Samantha Pettigrew, MD, Fellow-in-Training

Janine Vintich, MD, FCCP, Member-at-Large

CHEST FOUNDATION GRANT AWARDS

CHEST Foundation Research Grant in Women’s Lung Health Disparities

Laura Sanapo, MD, The Miriam Hospital, Providence, R.I.

This grant is jointly supported by the CHEST Foundation and the Respiratory Health Association.



CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease

Benjamin Wu, MD, New York University

This grant is supported by AstraZeneca.



CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease

Richard Zou, MD, University of Pittsburgh Medical Center

This grant is supported by the CHEST Foundation.



CHEST Foundation and AASM Foundation Research Grant in Sleep Medicine

Gonzalo Labarca, MD, Universidad San Sebastian, Concepción, Chile

This grant is jointly supported by the CHEST Foundation and AASM Foundation.



CHEST Foundation and American Academy of Dental Sleep Medicine Research Grant in Sleep Apnea

Sherri Katz, MD, FCCP, Children’s Hospital of Eastern Ontario, Ottawa

This grant is supported by the CHEST Foundation and American Academy of Dental Sleep Medicine.



CHEST Foundation Research Grant in Sleep Medicine

Nancy Stewart, DO, University of Kansas Medical Center, Kansas City

This grant is supported by Jazz Pharmaceuticals.



CHEST Foundation Research Grant in Severe Asthma

Gareth Walters, MD, University Hospitals Birmingham (England)

This grant is supported by AstraZeneca.

CHEST Foundation Research Grant in Severe Asthma

Andréanne Côté, MD, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec

This grant is supported by AstraZeneca.



CHEST Foundation and APCCMPD Research Grant in Medical Education

Christopher Leba, MD, MPH, University of California, San Francisco

This grant is jointly supported by the CHEST Foundation and APCCMPD.



CHEST Foundation Research Grant in COVID-19

Clea Barnett, MD, New York University

This grant is supported by the CHEST Foundation.



CHEST Foundation Research Grant in Critical Care

Katherine Walker, MD, Brigham and Women’s Hospital, Harvard Medical School, Boston

This grant is supported by the CHEST Foundation.

CHEST Foundation Research Grant in Venous Thromboembolism

Daniel Lachant, DO, University of Rochester (N.Y.) Medical Center/Strong Memorial Hospital

This grant is supported by the CHEST Foundation.



CHEST Foundation Research Grant in Pulmonary Hypertension

Christina Thornton, MD, PhD, University of Calgary (Alta.)

This grant is supported by the CHEST Foundation.



CHEST Foundation Research Grant in Pulmonary Fibrosis

Christina Eckhardt, MD, Columbia University, New York

This grant is supported by an independent grant from Boehringer Ingelheim Pharmaceuticals and Genentech.



CHEST Foundation Research Grant in Pulmonary Fibrosis

John Kim, MD, University of Virginia, Charlottesville

This grant is supported by an independent grant from Boehringer Ingelheim Pharmaceuticals and Genentech.



John R. Addrizzo, MD, FCCP Research Grant in Sarcoidosis

Kerry Hena, MD, New York University

This grant is in honor of John R. Addrizzo, MD, FCCP and is jointly supported by the Addrizzo family and the CHEST Foundation.



CHEST Foundation Research Grant in Pediatric Lung Health

Adam Shapiro, MD, McGill University Health Centre, Montreal

This grant is supported by the CHEST Foundation.



CHEST Foundation Young Investigator Grant

Sameer Avasarala, MD, Case Western Reserve University, Cleveland

This grant is supported by the CHEST Foundation.



CHEST/ALA/ATS Respiratory Health Equity Research Award

Matthew Triplette, MD, Fred Hutchinson Cancer Research Center, Seattle

The Respiratory Health Equity Research Award is jointly supported by the American Lung Association, the American Thoracic Society, and the CHEST Foundation.



CHEST/ALA/ATS Respiratory Health Equity Research Award

Ayobami Akenroye, MD, MPH, Brigham and Women’s Hospital, Boston

The Respiratory Health Equity Research Award is jointly supported by the American Lung Association, the American Thoracic Society, and the CHEST Foundation.



CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP

Lorriane Odhiambo, PhD, Augusta (Ga.) University

This grant is supported by the CHEST Foundation.



CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP

Katie Stevens, Team Telomere, New York

This grant is supported by the CHEST Foundation.



CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP

Matthew Sharpe, MD, The University of Kansas Medical Center, Kansas City

This grant is supported by the CHEST Foundation.
 

SCIENTIFIC ABSTRACT AWARDS

Alfred Soffer Research Awards

Presented abstracts will be judged by session moderators, and award recipients will be selected for their outstanding original scientific research. Finalists will be evaluated on the basis of their written abstract and the quality of their oral presentation. This award is named in honor of Alfred Soffer, MD, Master FCCP, who was Editor in Chief of the journal CHEST® from 1968 to 1993, and Executive Director of CHEST from 1969 to 1992.



Young Investigator Awards

Investigators who are enrolled in a training or fellowship program or who have completed a fellowship program within 5 years prior to CHEST 2022 are eligible for Young Investigator Awards.

Presenters will be evaluated on the basis of their written abstract and presentation. Recipients will be selected by judges from the Scientific Presentations and Awards Committee for their outstanding original scientific research.

Top Rapid Fire Abstract Award

Awards are granted to two presenters from all the rapid fire sessions at the CHEST Annual Meeting for outstanding original scientific research and presentation



Top Case Report Award

Awards are granted to one presenter in each oral case report session at the CHEST Annual Meeting for outstanding original scientific research and presentation



Top Rapid Fire Case Report Award

Awards are granted to one presenter in each rapid fire oral case report session at the CHEST Annual Meeting for outstanding original scientific research and presentation

 

ALFRED SOFFER RESEARCH AWARD WINNERS

Palak Rath, MD

A Sense Of Urgency: Boarding Of Critical Care Medicine Patients In The ED

Syed Nazeer Mahmood, MD

Quantifying The Risk For Overtreatment And Undertreatment Of Severe Community Onset Pneumonia
 

YOUNG INVESTIGATOR AWARD WINNERS

Anusha Devarajan, MD, MBBS

Pneumomediastinum And Pneumothorax In COVID-19 Pneumonia: A Matched Case-Control Study

Marjan Islam, MD

Thoracic Ultrasound In COVID-19: Use Of Lung And Diaphragm Ultrasound In Evaluating Dyspnea In Survivors Of Critical Illness From COVID-19 Pneumonia In A Post-ICU Clinic

Aaron St Laurent, MD

Duchenne Muscular Dystrophy Respiratory Profiles From Real-World Registry Data: A Retrospective Longitudinal Study
 

ABSTRACT RAPID FIRE WINNERS

Andrew J.O. Davis, MD

Early Gas Exchange Parameters Not Associated With Survival In COVID-19-Associated ARDS Patients Requiring Prolonged Venovenous Extracorporeal Membrane Oxygenation

Benjamin Emmanuel

Clinical Outcomes In Patients With Severe Asthma Who Had Or Had Not Initiated Biologic Therapy: Results From The CLEAR Study
 

CASE REPORT SESSION WINNERS

Sathya Alekhya Bukkuri

Smarca4-Deficient Undifferentiated Tumor: A Rare Thoracic Malignancy

Zachary A. Banbury, MD

Fungal Aortitis In A Patient For Whom Blood Transfusion Is Not An Option: A Rare But Potentially Fatal Complication Of Aortic Valve Replacement

Harinivaas Shanmugavel Geetha, MD

Respiratory Distress After Potentially Fatal Aspirin Overdose: When To Intubate?

Lisa Hayes

Systemic Epstein-Barr Virus-Related T-Cell Lymphoproliferative Disorder: A Rare Cause Of Dyspnea And Pulmonary Infiltrates In An Immunocompetent Adult

Mohammed Alsaggaf, MBBS

Calcium Oxalate Deposition In Pulmonary Aspergillosis

Cheyenne Snavely

Traffic Jam In The Vasculature: A Case Of Pulmonary Leukostasis

Clarissa Smith, MD

Talcoma In Lung Cancer Screening: A Rare Benign Cause Of PET Scan Avidity

Nitin Gupta, MD

The Clue Is In The Blood Gas: A Rare Manifestation Of Lactic Acidosis

Moses Hayrabedian, MD

A Century-Old Infection Mimicking Malignancy: A Case Of Diffuse Histoplasmosis

Gabriel R. Schroeder, MD

A Case Of Wind-Instrument Associated Hypersensitivity Pneumonitis

Fizza Sajid, DO

Leaping From Lush Tropical Environments To The L-Train: A Case Of Severe Leptospirosis In New York City

Krista R. Dollar, MD

Looking Past The Ground Glass: It Was Only Skin Deep

Konstantin Golubykh, MD

Point-Of-Care Ultrasound In The Timely Diagnosis Of Colonic Necrosis

Arsal Tharwani

Abdominal Compression In End-Stage Fibrotic Interstitial Lung Disease (ILD) Improves Respiratory Compliance

Ryan Kozloski

When Asthma Isn’t: Multispecialty Approach To Fibrosing Mediastinitis

Zach S. Jarrett, DO

Vanishing Cancer: A Case Of Smoking-Related Organizing Pneumonia

Stephen Simeone

Intravascular Papillary Endothelial Hyperplasia Presenting As Thrombus In Transit With Acute Pulmonary Embolism

David Gruen, MD

Tackling Posterior Reversible Encephalopathy Syndrome (PRES): A Rare Case Of Subtherapeutic Tacrolimus Causing PRES In Steroid-Resistant Nephropathy

Nicholas Kunce, MD

An Unusual Case Of Subacute Bacterial Endocarditis Presenting With Catastrophic Subarachnoid Hemorrhage

Phillip J. Gary, MD

Sarcoid-Like Reaction After Treatment With Pembrolizumab

Shreya Podder, MD

Endobronchial Valves For Treatment Of Persistent Air Leak After Secondary Spontaneous Pneumothorax In Patients With Cystic Fibrosis

Alina Aw Wasim, MD, MBBS

Chest-Wall Castleman Disease Mimicking Thymoma Drop Metastasis

Ndausung Udongwo

The ‘Rat Bite Sign” On Cardiac MRI: Left Dominant Arrhythmogenic Cardiomyopathy As An Atypical Etiology Of Sudden Cardiac Arrest

Grant Senyei, MD

Management Of Ventriculopleural Shunt-Associated Pleural Effusion

Garima Singh, MD

COVID-19-Associated Thrombotic Thrombocytopenia Purpura (TTP)
 

CASE REPORT RAPID FIRE WINNERS

Sandeep Patri

Hyperammonemia Postlung Transplantation: An Uncommon But Life-Threatening Complication

Trung Nguyen

Dyspnea During Pregnancy Revealing Multiple Pulmonary Arteriovenous Malformations And A New Diagnosis Of Hereditary Hemorrhagic Telangiectasia

Pedro J. Baez, MD

Adenoid Cystic Adenocarcinoma: A Rare Esophageal Malignancy Misdiagnosed As COPD

Brette Guckian, DO

Management Of Pulmonary Cement Emboli After Kyphoplasty

Brinn Demars, DO

Tumor Emboli In The Pulmonary Artery Secondary To Chondrosarcoma: A Rare Presentation Mimicking Pulmonary Thromboembolism

Aakriti Arora

A Case Of Pulmonary Hypertension As A Possible Extracranial Manifestation Of Moyamoya Disease

Racine Elaine Reinoso

Clot In Transit: The Role Of Point-Of-Care Ultrasound In Early Diagnosis And Improved Outcomes

Qiraat Azeem, MD

A Case Of Autosomal-Dominant Hyper-IgE Syndrome Masquerading As Cystic Fibrosis

Jason R. Ballengee, DO

Third-Trimester Pregnancy Complicated By Non-Small Cell Lung Cancer Initially Presenting With Central Airway Obstruction And Stenosis

Sam Shafer

Caught In The Fray: Neurosarcoidosis Presenting As Chronic Respiratory Failure

Takkin Lo, MD, MPH

China White In Asthmatic Recreational Drug Users: Does It Contribute To Pneumatocele Development?

Sanjeev Shrestha, MD

Successful Treatment Of Microscopic Polyangiitis Using Novel Steroid-Sparing Agent Avacopan

Kristina Menchaca, MD

Cardiac Tamponade Without The Beck Triad: A Complication Of Severe Hypothyroidism

Olivia Millay, BS

Spontaneous Coronary Artery Dissection Of Left Anterior Descending Artery Complicated By Ventricular Septal Rupture

Akruti P. Prabhakar, DO

Delayed Lead Perforation Of The Right Atrium In The Presence Of Persistent Left Superior Vena Cava: A Rare Coincidence

Kevin Hsu, MD

A Modified Valsalva Maneuver For Ventilated And Sedated Patients With Unstable Supraventricular Tachycardia

Nang San Hti Lar Seng

Cardiovascular Manifestations Of Paraaortic Paragangliomas

Rocio Castillo-Larios

Membranous Dehiscence After Tracheal Resection And Reconstruction Healed Spontaneously With Conservative Treatment

Fizza Sajid, DO

A Young Broken Heart, Reversed

Janeen Grant-Sittol, MD

Inhaled Tranexamic Acid Use For Massive Hemoptysis In Vasculitis-Induced Bronchoalveolar Hemorrhage

Raman G. Kutty, Md, PhD

Progressive Lung Infiltrates In Patient With Acquired Immunodeficiency: A Rare Case Of GLILD

Tanwe Shende

Mycobacterium Shimoidei: A Rare Nontuberculous Infection In A U.S. Patient

Sarah M. Upson, MD

Not Your Typical Lactic Acidosis

Prachi Saluja, MD

Late-Onset Immune Thrombotic Thrombocytopenic Purpura (TTP) After Asymptomatic COVID-19 Infection

Steven S. Wu, MD

Type 1 Multiple Endocrine Neoplasia-Associated Tracheobronchial Tumors Managed By Rigid Bronchoscopy-Directed Multimodal Tumor Destruction

Konstantin Golubykh, MD

The Reversal That Helped: Role Of Bedside Echocardiography In Takotsubo Cardiomyopathy

Eric Salomon, MD

Obstructive Tracheobronchial Pulmonary Aspergillosis Managed With Local Bronchoscopic Intervention Alone

Daniel Hoesterey, MD

A Rare Case Of Critical Illness Due To Eczema Herpeticum With Disseminated Herpes Simplex Virus Infection

Awab U. Khan, DO

Severe Colchicine Toxicity In A Suicide Attempt Causing Multiorgan Failure: A Survival Story

Jacob Cebulko

Disseminated Strongyloidiasis In A Patient With Acute Lymphocytic Leukemia

Hasan Baher, MD

Hiding In Plain Sight: Disseminated Pulmonary TB

Navneet Ramesh

Multimodal Management Of Gastric Variceal Bleeding In Hemorrhagic Shock

Jason L. Peng, MD

Improving Compliance With Continuous Anterior Chest Compression In ARDS Caused By COVID-19: A Case Series

Sushan Gupta, MD

Complete Resolution Of Vasoreactive Pulmonary Artery Hypertension In Chronic Hypersensitive Pneumonitis

Mamta S. Chhabria, MD

A Fistulous Issue: Gastropleural Fistula As A Complication Of Gastrectomy

Anita Singh, DO, MBA

Identifying A Novel Surfactant Protein Mutation In A Family With Pulmonary Fibrosis

Rana Prathap Padappayil, MBBS

Delayed Cerebral Venous Sinus Thrombosis (CSVT) After An Invasive Meningioma Resection: An Uncommon Presentation Of A Common Complication

Rubabin Tooba, MD

The Morphing Cavity: An Image Series Of A Patient’s Pulmonary Infarction Over Time

Sally Ziatabar, DO

A Rare Case Of Disseminated Blastomycosis

Sumukh Arun Kumar

Incidental Pulmonary Cavitary Lesions As An Uncommon Presentation Of Lemierre Syndrome

Sophia Emetu

Pet Peeve: Dyspnea From Undiagnosed Pasteurella Multocida Empyema

Chidambaram Ramasamy, MD

A Case Of Diffuse Alveolar-Septal Pulmonary Amyloidosis And Cardiomyopathy

Rachel Swier

Acid-Fast Bacteria In Bronchiectasis: If The Glass Slipper Does Not Fit, Non-TB Mycobacteria, Consider Tsukamurella

Catherine Durant, MD

Idiopathic Multicentric Castleman Disease With Tafro Syndrome And Sjögren Syndrome

Ali Al-Hilli, MD, MSc

Sarcoidosis-Like Reaction During Treatment For Metastatic Breast Cancer With CDK 4/6 Inhibitors: Just An Epiphenomenon Or A Causal Relationship?

Scott Slusarenko, DO

Rapidly Progressive Perimyocarditis In SARS-CoV-2 Infection

Agatha M. Formoso, MD

Two Infants Presenting With Polymicrobial Pneumonia And Hypoxemic Respiratory Failure Associated With Heterozygous Variants In Carmil2 And Itk

Juan Adams-Chahin

The Silence Of “Lam”: A Case Of Tuberous Sclerosis Complex Associated With Lymphangioleiomyomatosis (Lam)

Kathleen Capaccione, MD

Lung Cancer Is Not Always The Answer: Exploring The Differential Diagnosis Of Thoracic Masses

Joann Wongvravit, DO

West Nile-Induced Myasthenia Gravis Crisis: An Unexpected Case Of Respiratory Failure

Ethan Karle, Do

A Rare Cause Of Community-Acquired Bacterial Pneumonia In A Patient With Poorly Controlled Diabetes

Taylor C. Becker, MD

Calcified Cavitary Conundrum: Delayed Diagnosis Of Histoplasmosis

Anneka Hutton, MD

Disseminated Listeriosis: A Deadly Triplicate

Omar Kandah, DO

COVID-19 Cardiac Tamponade With Cardiogenic Shock In A Previously Vaccinated Young Adult: A Case Report

Cihan Caglayan, MD

Partial Anomalous Pulmonary Venous Connection Diagnosed After Central Venous Catheter Placement

Michelle Jones, DO

Delayed Hemophagocytic Lymphohistiocytosis (HLH) Diagnosis In A Patient With Pulmonary Sarcoidosis And Newly Diagnosed T-Cell Lymphoma: A Case Report

Mariah Evarts, MD

A Normotensive Woman With Profound Lactic Acidosis And Stress-Induced Cardiomyopathy

Rachel V. Tan, MD

A Four-Boding Future: Polyviral Infection With SARS-CoV-2, Parainfluenza Virus Type 3, Influenza A, And Adenovirus

Thanh Hoang

Recurrent Syncope From Intermittent Torsades In Loperamide Abuse

Alissa Ali, MD

Ground Glass Opacities In A Patient Receiving Treatment With All-Trans Retinoic Acid And Arsenic Trioxide

Sean M. Masi, DO, MBA

Ferritin-Guided Therapeutic Plasma Exchange (TPE) Administration In COVID-19-Induced Cytokine Storm Syndrome: A Case Series

Anjali Sachdeva

Successful Biopsy Of Aortopulmonary Window Lymph Node With Robotic-Assisted Bronchoscopy

Rehan Saeed, MD

Multiple Sclerosis After COVID-19: A Sign Of Things To Come?

Harshitha Mergey Devender

Invasive Pulmonary Aspergillosis Associated With Nonspecific Interstitial Pneumonia Causing Recurrent Respiratory Failure



Be sure to check out the other award winners on page 20 in the January issue of CHEST Physician: https://tinyurl.com/2bcdcbj3 .

CHEST FOUNDATION GRANT AWARDS

CHEST Foundation Research Grant in Women’s Lung Health Disparities

Laura Sanapo, MD, The Miriam Hospital, Providence, R.I.

This grant is jointly supported by the CHEST Foundation and the Respiratory Health Association.



CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease

Benjamin Wu, MD, New York University

This grant is supported by AstraZeneca.



CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease

Richard Zou, MD, University of Pittsburgh Medical Center

This grant is supported by the CHEST Foundation.



CHEST Foundation and AASM Foundation Research Grant in Sleep Medicine

Gonzalo Labarca, MD, Universidad San Sebastian, Concepción, Chile

This grant is jointly supported by the CHEST Foundation and AASM Foundation.



CHEST Foundation and American Academy of Dental Sleep Medicine Research Grant in Sleep Apnea

Sherri Katz, MD, FCCP, Children’s Hospital of Eastern Ontario, Ottawa

This grant is supported by the CHEST Foundation and American Academy of Dental Sleep Medicine.



CHEST Foundation Research Grant in Sleep Medicine

Nancy Stewart, DO, University of Kansas Medical Center, Kansas City

This grant is supported by Jazz Pharmaceuticals.



CHEST Foundation Research Grant in Severe Asthma

Gareth Walters, MD, University Hospitals Birmingham (England)

This grant is supported by AstraZeneca.

CHEST Foundation Research Grant in Severe Asthma

Andréanne Côté, MD, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec

This grant is supported by AstraZeneca.



CHEST Foundation and APCCMPD Research Grant in Medical Education

Christopher Leba, MD, MPH, University of California, San Francisco

This grant is jointly supported by the CHEST Foundation and APCCMPD.



CHEST Foundation Research Grant in COVID-19

Clea Barnett, MD, New York University

This grant is supported by the CHEST Foundation.



CHEST Foundation Research Grant in Critical Care

Katherine Walker, MD, Brigham and Women’s Hospital, Harvard Medical School, Boston

This grant is supported by the CHEST Foundation.

CHEST Foundation Research Grant in Venous Thromboembolism

Daniel Lachant, DO, University of Rochester (N.Y.) Medical Center/Strong Memorial Hospital

This grant is supported by the CHEST Foundation.



CHEST Foundation Research Grant in Pulmonary Hypertension

Christina Thornton, MD, PhD, University of Calgary (Alta.)

This grant is supported by the CHEST Foundation.



CHEST Foundation Research Grant in Pulmonary Fibrosis

Christina Eckhardt, MD, Columbia University, New York

This grant is supported by an independent grant from Boehringer Ingelheim Pharmaceuticals and Genentech.



CHEST Foundation Research Grant in Pulmonary Fibrosis

John Kim, MD, University of Virginia, Charlottesville

This grant is supported by an independent grant from Boehringer Ingelheim Pharmaceuticals and Genentech.



John R. Addrizzo, MD, FCCP Research Grant in Sarcoidosis

Kerry Hena, MD, New York University

This grant is in honor of John R. Addrizzo, MD, FCCP and is jointly supported by the Addrizzo family and the CHEST Foundation.



CHEST Foundation Research Grant in Pediatric Lung Health

Adam Shapiro, MD, McGill University Health Centre, Montreal

This grant is supported by the CHEST Foundation.



CHEST Foundation Young Investigator Grant

Sameer Avasarala, MD, Case Western Reserve University, Cleveland

This grant is supported by the CHEST Foundation.



CHEST/ALA/ATS Respiratory Health Equity Research Award

Matthew Triplette, MD, Fred Hutchinson Cancer Research Center, Seattle

The Respiratory Health Equity Research Award is jointly supported by the American Lung Association, the American Thoracic Society, and the CHEST Foundation.



CHEST/ALA/ATS Respiratory Health Equity Research Award

Ayobami Akenroye, MD, MPH, Brigham and Women’s Hospital, Boston

The Respiratory Health Equity Research Award is jointly supported by the American Lung Association, the American Thoracic Society, and the CHEST Foundation.



CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP

Lorriane Odhiambo, PhD, Augusta (Ga.) University

This grant is supported by the CHEST Foundation.



CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP

Katie Stevens, Team Telomere, New York

This grant is supported by the CHEST Foundation.



CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP

Matthew Sharpe, MD, The University of Kansas Medical Center, Kansas City

This grant is supported by the CHEST Foundation.
 

SCIENTIFIC ABSTRACT AWARDS

Alfred Soffer Research Awards

Presented abstracts will be judged by session moderators, and award recipients will be selected for their outstanding original scientific research. Finalists will be evaluated on the basis of their written abstract and the quality of their oral presentation. This award is named in honor of Alfred Soffer, MD, Master FCCP, who was Editor in Chief of the journal CHEST® from 1968 to 1993, and Executive Director of CHEST from 1969 to 1992.



Young Investigator Awards

Investigators who are enrolled in a training or fellowship program or who have completed a fellowship program within 5 years prior to CHEST 2022 are eligible for Young Investigator Awards.

Presenters will be evaluated on the basis of their written abstract and presentation. Recipients will be selected by judges from the Scientific Presentations and Awards Committee for their outstanding original scientific research.

Top Rapid Fire Abstract Award

Awards are granted to two presenters from all the rapid fire sessions at the CHEST Annual Meeting for outstanding original scientific research and presentation



Top Case Report Award

Awards are granted to one presenter in each oral case report session at the CHEST Annual Meeting for outstanding original scientific research and presentation



Top Rapid Fire Case Report Award

Awards are granted to one presenter in each rapid fire oral case report session at the CHEST Annual Meeting for outstanding original scientific research and presentation

 

ALFRED SOFFER RESEARCH AWARD WINNERS

Palak Rath, MD

A Sense Of Urgency: Boarding Of Critical Care Medicine Patients In The ED

Syed Nazeer Mahmood, MD

Quantifying The Risk For Overtreatment And Undertreatment Of Severe Community Onset Pneumonia
 

YOUNG INVESTIGATOR AWARD WINNERS

Anusha Devarajan, MD, MBBS

Pneumomediastinum And Pneumothorax In COVID-19 Pneumonia: A Matched Case-Control Study

Marjan Islam, MD

Thoracic Ultrasound In COVID-19: Use Of Lung And Diaphragm Ultrasound In Evaluating Dyspnea In Survivors Of Critical Illness From COVID-19 Pneumonia In A Post-ICU Clinic

Aaron St Laurent, MD

Duchenne Muscular Dystrophy Respiratory Profiles From Real-World Registry Data: A Retrospective Longitudinal Study
 

ABSTRACT RAPID FIRE WINNERS

Andrew J.O. Davis, MD

Early Gas Exchange Parameters Not Associated With Survival In COVID-19-Associated ARDS Patients Requiring Prolonged Venovenous Extracorporeal Membrane Oxygenation

Benjamin Emmanuel

Clinical Outcomes In Patients With Severe Asthma Who Had Or Had Not Initiated Biologic Therapy: Results From The CLEAR Study
 

CASE REPORT SESSION WINNERS

Sathya Alekhya Bukkuri

Smarca4-Deficient Undifferentiated Tumor: A Rare Thoracic Malignancy

Zachary A. Banbury, MD

Fungal Aortitis In A Patient For Whom Blood Transfusion Is Not An Option: A Rare But Potentially Fatal Complication Of Aortic Valve Replacement

Harinivaas Shanmugavel Geetha, MD

Respiratory Distress After Potentially Fatal Aspirin Overdose: When To Intubate?

Lisa Hayes

Systemic Epstein-Barr Virus-Related T-Cell Lymphoproliferative Disorder: A Rare Cause Of Dyspnea And Pulmonary Infiltrates In An Immunocompetent Adult

Mohammed Alsaggaf, MBBS

Calcium Oxalate Deposition In Pulmonary Aspergillosis

Cheyenne Snavely

Traffic Jam In The Vasculature: A Case Of Pulmonary Leukostasis

Clarissa Smith, MD

Talcoma In Lung Cancer Screening: A Rare Benign Cause Of PET Scan Avidity

Nitin Gupta, MD

The Clue Is In The Blood Gas: A Rare Manifestation Of Lactic Acidosis

Moses Hayrabedian, MD

A Century-Old Infection Mimicking Malignancy: A Case Of Diffuse Histoplasmosis

Gabriel R. Schroeder, MD

A Case Of Wind-Instrument Associated Hypersensitivity Pneumonitis

Fizza Sajid, DO

Leaping From Lush Tropical Environments To The L-Train: A Case Of Severe Leptospirosis In New York City

Krista R. Dollar, MD

Looking Past The Ground Glass: It Was Only Skin Deep

Konstantin Golubykh, MD

Point-Of-Care Ultrasound In The Timely Diagnosis Of Colonic Necrosis

Arsal Tharwani

Abdominal Compression In End-Stage Fibrotic Interstitial Lung Disease (ILD) Improves Respiratory Compliance

Ryan Kozloski

When Asthma Isn’t: Multispecialty Approach To Fibrosing Mediastinitis

Zach S. Jarrett, DO

Vanishing Cancer: A Case Of Smoking-Related Organizing Pneumonia

Stephen Simeone

Intravascular Papillary Endothelial Hyperplasia Presenting As Thrombus In Transit With Acute Pulmonary Embolism

David Gruen, MD

Tackling Posterior Reversible Encephalopathy Syndrome (PRES): A Rare Case Of Subtherapeutic Tacrolimus Causing PRES In Steroid-Resistant Nephropathy

Nicholas Kunce, MD

An Unusual Case Of Subacute Bacterial Endocarditis Presenting With Catastrophic Subarachnoid Hemorrhage

Phillip J. Gary, MD

Sarcoid-Like Reaction After Treatment With Pembrolizumab

Shreya Podder, MD

Endobronchial Valves For Treatment Of Persistent Air Leak After Secondary Spontaneous Pneumothorax In Patients With Cystic Fibrosis

Alina Aw Wasim, MD, MBBS

Chest-Wall Castleman Disease Mimicking Thymoma Drop Metastasis

Ndausung Udongwo

The ‘Rat Bite Sign” On Cardiac MRI: Left Dominant Arrhythmogenic Cardiomyopathy As An Atypical Etiology Of Sudden Cardiac Arrest

Grant Senyei, MD

Management Of Ventriculopleural Shunt-Associated Pleural Effusion

Garima Singh, MD

COVID-19-Associated Thrombotic Thrombocytopenia Purpura (TTP)
 

CASE REPORT RAPID FIRE WINNERS

Sandeep Patri

Hyperammonemia Postlung Transplantation: An Uncommon But Life-Threatening Complication

Trung Nguyen

Dyspnea During Pregnancy Revealing Multiple Pulmonary Arteriovenous Malformations And A New Diagnosis Of Hereditary Hemorrhagic Telangiectasia

Pedro J. Baez, MD

Adenoid Cystic Adenocarcinoma: A Rare Esophageal Malignancy Misdiagnosed As COPD

Brette Guckian, DO

Management Of Pulmonary Cement Emboli After Kyphoplasty

Brinn Demars, DO

Tumor Emboli In The Pulmonary Artery Secondary To Chondrosarcoma: A Rare Presentation Mimicking Pulmonary Thromboembolism

Aakriti Arora

A Case Of Pulmonary Hypertension As A Possible Extracranial Manifestation Of Moyamoya Disease

Racine Elaine Reinoso

Clot In Transit: The Role Of Point-Of-Care Ultrasound In Early Diagnosis And Improved Outcomes

Qiraat Azeem, MD

A Case Of Autosomal-Dominant Hyper-IgE Syndrome Masquerading As Cystic Fibrosis

Jason R. Ballengee, DO

Third-Trimester Pregnancy Complicated By Non-Small Cell Lung Cancer Initially Presenting With Central Airway Obstruction And Stenosis

Sam Shafer

Caught In The Fray: Neurosarcoidosis Presenting As Chronic Respiratory Failure

Takkin Lo, MD, MPH

China White In Asthmatic Recreational Drug Users: Does It Contribute To Pneumatocele Development?

Sanjeev Shrestha, MD

Successful Treatment Of Microscopic Polyangiitis Using Novel Steroid-Sparing Agent Avacopan

Kristina Menchaca, MD

Cardiac Tamponade Without The Beck Triad: A Complication Of Severe Hypothyroidism

Olivia Millay, BS

Spontaneous Coronary Artery Dissection Of Left Anterior Descending Artery Complicated By Ventricular Septal Rupture

Akruti P. Prabhakar, DO

Delayed Lead Perforation Of The Right Atrium In The Presence Of Persistent Left Superior Vena Cava: A Rare Coincidence

Kevin Hsu, MD

A Modified Valsalva Maneuver For Ventilated And Sedated Patients With Unstable Supraventricular Tachycardia

Nang San Hti Lar Seng

Cardiovascular Manifestations Of Paraaortic Paragangliomas

Rocio Castillo-Larios

Membranous Dehiscence After Tracheal Resection And Reconstruction Healed Spontaneously With Conservative Treatment

Fizza Sajid, DO

A Young Broken Heart, Reversed

Janeen Grant-Sittol, MD

Inhaled Tranexamic Acid Use For Massive Hemoptysis In Vasculitis-Induced Bronchoalveolar Hemorrhage

Raman G. Kutty, Md, PhD

Progressive Lung Infiltrates In Patient With Acquired Immunodeficiency: A Rare Case Of GLILD

Tanwe Shende

Mycobacterium Shimoidei: A Rare Nontuberculous Infection In A U.S. Patient

Sarah M. Upson, MD

Not Your Typical Lactic Acidosis

Prachi Saluja, MD

Late-Onset Immune Thrombotic Thrombocytopenic Purpura (TTP) After Asymptomatic COVID-19 Infection

Steven S. Wu, MD

Type 1 Multiple Endocrine Neoplasia-Associated Tracheobronchial Tumors Managed By Rigid Bronchoscopy-Directed Multimodal Tumor Destruction

Konstantin Golubykh, MD

The Reversal That Helped: Role Of Bedside Echocardiography In Takotsubo Cardiomyopathy

Eric Salomon, MD

Obstructive Tracheobronchial Pulmonary Aspergillosis Managed With Local Bronchoscopic Intervention Alone

Daniel Hoesterey, MD

A Rare Case Of Critical Illness Due To Eczema Herpeticum With Disseminated Herpes Simplex Virus Infection

Awab U. Khan, DO

Severe Colchicine Toxicity In A Suicide Attempt Causing Multiorgan Failure: A Survival Story

Jacob Cebulko

Disseminated Strongyloidiasis In A Patient With Acute Lymphocytic Leukemia

Hasan Baher, MD

Hiding In Plain Sight: Disseminated Pulmonary TB

Navneet Ramesh

Multimodal Management Of Gastric Variceal Bleeding In Hemorrhagic Shock

Jason L. Peng, MD

Improving Compliance With Continuous Anterior Chest Compression In ARDS Caused By COVID-19: A Case Series

Sushan Gupta, MD

Complete Resolution Of Vasoreactive Pulmonary Artery Hypertension In Chronic Hypersensitive Pneumonitis

Mamta S. Chhabria, MD

A Fistulous Issue: Gastropleural Fistula As A Complication Of Gastrectomy

Anita Singh, DO, MBA

Identifying A Novel Surfactant Protein Mutation In A Family With Pulmonary Fibrosis

Rana Prathap Padappayil, MBBS

Delayed Cerebral Venous Sinus Thrombosis (CSVT) After An Invasive Meningioma Resection: An Uncommon Presentation Of A Common Complication

Rubabin Tooba, MD

The Morphing Cavity: An Image Series Of A Patient’s Pulmonary Infarction Over Time

Sally Ziatabar, DO

A Rare Case Of Disseminated Blastomycosis

Sumukh Arun Kumar

Incidental Pulmonary Cavitary Lesions As An Uncommon Presentation Of Lemierre Syndrome

Sophia Emetu

Pet Peeve: Dyspnea From Undiagnosed Pasteurella Multocida Empyema

Chidambaram Ramasamy, MD

A Case Of Diffuse Alveolar-Septal Pulmonary Amyloidosis And Cardiomyopathy

Rachel Swier

Acid-Fast Bacteria In Bronchiectasis: If The Glass Slipper Does Not Fit, Non-TB Mycobacteria, Consider Tsukamurella

Catherine Durant, MD

Idiopathic Multicentric Castleman Disease With Tafro Syndrome And Sjögren Syndrome

Ali Al-Hilli, MD, MSc

Sarcoidosis-Like Reaction During Treatment For Metastatic Breast Cancer With CDK 4/6 Inhibitors: Just An Epiphenomenon Or A Causal Relationship?

Scott Slusarenko, DO

Rapidly Progressive Perimyocarditis In SARS-CoV-2 Infection

Agatha M. Formoso, MD

Two Infants Presenting With Polymicrobial Pneumonia And Hypoxemic Respiratory Failure Associated With Heterozygous Variants In Carmil2 And Itk

Juan Adams-Chahin

The Silence Of “Lam”: A Case Of Tuberous Sclerosis Complex Associated With Lymphangioleiomyomatosis (Lam)

Kathleen Capaccione, MD

Lung Cancer Is Not Always The Answer: Exploring The Differential Diagnosis Of Thoracic Masses

Joann Wongvravit, DO

West Nile-Induced Myasthenia Gravis Crisis: An Unexpected Case Of Respiratory Failure

Ethan Karle, Do

A Rare Cause Of Community-Acquired Bacterial Pneumonia In A Patient With Poorly Controlled Diabetes

Taylor C. Becker, MD

Calcified Cavitary Conundrum: Delayed Diagnosis Of Histoplasmosis

Anneka Hutton, MD

Disseminated Listeriosis: A Deadly Triplicate

Omar Kandah, DO

COVID-19 Cardiac Tamponade With Cardiogenic Shock In A Previously Vaccinated Young Adult: A Case Report

Cihan Caglayan, MD

Partial Anomalous Pulmonary Venous Connection Diagnosed After Central Venous Catheter Placement

Michelle Jones, DO

Delayed Hemophagocytic Lymphohistiocytosis (HLH) Diagnosis In A Patient With Pulmonary Sarcoidosis And Newly Diagnosed T-Cell Lymphoma: A Case Report

Mariah Evarts, MD

A Normotensive Woman With Profound Lactic Acidosis And Stress-Induced Cardiomyopathy

Rachel V. Tan, MD

A Four-Boding Future: Polyviral Infection With SARS-CoV-2, Parainfluenza Virus Type 3, Influenza A, And Adenovirus

Thanh Hoang

Recurrent Syncope From Intermittent Torsades In Loperamide Abuse

Alissa Ali, MD

Ground Glass Opacities In A Patient Receiving Treatment With All-Trans Retinoic Acid And Arsenic Trioxide

Sean M. Masi, DO, MBA

Ferritin-Guided Therapeutic Plasma Exchange (TPE) Administration In COVID-19-Induced Cytokine Storm Syndrome: A Case Series

Anjali Sachdeva

Successful Biopsy Of Aortopulmonary Window Lymph Node With Robotic-Assisted Bronchoscopy

Rehan Saeed, MD

Multiple Sclerosis After COVID-19: A Sign Of Things To Come?

Harshitha Mergey Devender

Invasive Pulmonary Aspergillosis Associated With Nonspecific Interstitial Pneumonia Causing Recurrent Respiratory Failure



Be sure to check out the other award winners on page 20 in the January issue of CHEST Physician: https://tinyurl.com/2bcdcbj3 .

CHEST FOUNDATION GRANT AWARDS

CHEST Foundation Research Grant in Women’s Lung Health Disparities

Laura Sanapo, MD, The Miriam Hospital, Providence, R.I.

This grant is jointly supported by the CHEST Foundation and the Respiratory Health Association.



CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease

Benjamin Wu, MD, New York University

This grant is supported by AstraZeneca.



CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease

Richard Zou, MD, University of Pittsburgh Medical Center

This grant is supported by the CHEST Foundation.



CHEST Foundation and AASM Foundation Research Grant in Sleep Medicine

Gonzalo Labarca, MD, Universidad San Sebastian, Concepción, Chile

This grant is jointly supported by the CHEST Foundation and AASM Foundation.



CHEST Foundation and American Academy of Dental Sleep Medicine Research Grant in Sleep Apnea

Sherri Katz, MD, FCCP, Children’s Hospital of Eastern Ontario, Ottawa

This grant is supported by the CHEST Foundation and American Academy of Dental Sleep Medicine.



CHEST Foundation Research Grant in Sleep Medicine

Nancy Stewart, DO, University of Kansas Medical Center, Kansas City

This grant is supported by Jazz Pharmaceuticals.



CHEST Foundation Research Grant in Severe Asthma

Gareth Walters, MD, University Hospitals Birmingham (England)

This grant is supported by AstraZeneca.

CHEST Foundation Research Grant in Severe Asthma

Andréanne Côté, MD, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec

This grant is supported by AstraZeneca.



CHEST Foundation and APCCMPD Research Grant in Medical Education

Christopher Leba, MD, MPH, University of California, San Francisco

This grant is jointly supported by the CHEST Foundation and APCCMPD.



CHEST Foundation Research Grant in COVID-19

Clea Barnett, MD, New York University

This grant is supported by the CHEST Foundation.



CHEST Foundation Research Grant in Critical Care

Katherine Walker, MD, Brigham and Women’s Hospital, Harvard Medical School, Boston

This grant is supported by the CHEST Foundation.

CHEST Foundation Research Grant in Venous Thromboembolism

Daniel Lachant, DO, University of Rochester (N.Y.) Medical Center/Strong Memorial Hospital

This grant is supported by the CHEST Foundation.



CHEST Foundation Research Grant in Pulmonary Hypertension

Christina Thornton, MD, PhD, University of Calgary (Alta.)

This grant is supported by the CHEST Foundation.



CHEST Foundation Research Grant in Pulmonary Fibrosis

Christina Eckhardt, MD, Columbia University, New York

This grant is supported by an independent grant from Boehringer Ingelheim Pharmaceuticals and Genentech.



CHEST Foundation Research Grant in Pulmonary Fibrosis

John Kim, MD, University of Virginia, Charlottesville

This grant is supported by an independent grant from Boehringer Ingelheim Pharmaceuticals and Genentech.



John R. Addrizzo, MD, FCCP Research Grant in Sarcoidosis

Kerry Hena, MD, New York University

This grant is in honor of John R. Addrizzo, MD, FCCP and is jointly supported by the Addrizzo family and the CHEST Foundation.



CHEST Foundation Research Grant in Pediatric Lung Health

Adam Shapiro, MD, McGill University Health Centre, Montreal

This grant is supported by the CHEST Foundation.



CHEST Foundation Young Investigator Grant

Sameer Avasarala, MD, Case Western Reserve University, Cleveland

This grant is supported by the CHEST Foundation.



CHEST/ALA/ATS Respiratory Health Equity Research Award

Matthew Triplette, MD, Fred Hutchinson Cancer Research Center, Seattle

The Respiratory Health Equity Research Award is jointly supported by the American Lung Association, the American Thoracic Society, and the CHEST Foundation.



CHEST/ALA/ATS Respiratory Health Equity Research Award

Ayobami Akenroye, MD, MPH, Brigham and Women’s Hospital, Boston

The Respiratory Health Equity Research Award is jointly supported by the American Lung Association, the American Thoracic Society, and the CHEST Foundation.



CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP

Lorriane Odhiambo, PhD, Augusta (Ga.) University

This grant is supported by the CHEST Foundation.



CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP

Katie Stevens, Team Telomere, New York

This grant is supported by the CHEST Foundation.



CHEST Foundation Community Service Grant Honoring D. Robert McCaffree, MD, Master FCCP

Matthew Sharpe, MD, The University of Kansas Medical Center, Kansas City

This grant is supported by the CHEST Foundation.
 

SCIENTIFIC ABSTRACT AWARDS

Alfred Soffer Research Awards

Presented abstracts will be judged by session moderators, and award recipients will be selected for their outstanding original scientific research. Finalists will be evaluated on the basis of their written abstract and the quality of their oral presentation. This award is named in honor of Alfred Soffer, MD, Master FCCP, who was Editor in Chief of the journal CHEST® from 1968 to 1993, and Executive Director of CHEST from 1969 to 1992.



Young Investigator Awards

Investigators who are enrolled in a training or fellowship program or who have completed a fellowship program within 5 years prior to CHEST 2022 are eligible for Young Investigator Awards.

Presenters will be evaluated on the basis of their written abstract and presentation. Recipients will be selected by judges from the Scientific Presentations and Awards Committee for their outstanding original scientific research.

Top Rapid Fire Abstract Award

Awards are granted to two presenters from all the rapid fire sessions at the CHEST Annual Meeting for outstanding original scientific research and presentation



Top Case Report Award

Awards are granted to one presenter in each oral case report session at the CHEST Annual Meeting for outstanding original scientific research and presentation



Top Rapid Fire Case Report Award

Awards are granted to one presenter in each rapid fire oral case report session at the CHEST Annual Meeting for outstanding original scientific research and presentation

 

ALFRED SOFFER RESEARCH AWARD WINNERS

Palak Rath, MD

A Sense Of Urgency: Boarding Of Critical Care Medicine Patients In The ED

Syed Nazeer Mahmood, MD

Quantifying The Risk For Overtreatment And Undertreatment Of Severe Community Onset Pneumonia
 

YOUNG INVESTIGATOR AWARD WINNERS

Anusha Devarajan, MD, MBBS

Pneumomediastinum And Pneumothorax In COVID-19 Pneumonia: A Matched Case-Control Study

Marjan Islam, MD

Thoracic Ultrasound In COVID-19: Use Of Lung And Diaphragm Ultrasound In Evaluating Dyspnea In Survivors Of Critical Illness From COVID-19 Pneumonia In A Post-ICU Clinic

Aaron St Laurent, MD

Duchenne Muscular Dystrophy Respiratory Profiles From Real-World Registry Data: A Retrospective Longitudinal Study
 

ABSTRACT RAPID FIRE WINNERS

Andrew J.O. Davis, MD

Early Gas Exchange Parameters Not Associated With Survival In COVID-19-Associated ARDS Patients Requiring Prolonged Venovenous Extracorporeal Membrane Oxygenation

Benjamin Emmanuel

Clinical Outcomes In Patients With Severe Asthma Who Had Or Had Not Initiated Biologic Therapy: Results From The CLEAR Study
 

CASE REPORT SESSION WINNERS

Sathya Alekhya Bukkuri

Smarca4-Deficient Undifferentiated Tumor: A Rare Thoracic Malignancy

Zachary A. Banbury, MD

Fungal Aortitis In A Patient For Whom Blood Transfusion Is Not An Option: A Rare But Potentially Fatal Complication Of Aortic Valve Replacement

Harinivaas Shanmugavel Geetha, MD

Respiratory Distress After Potentially Fatal Aspirin Overdose: When To Intubate?

Lisa Hayes

Systemic Epstein-Barr Virus-Related T-Cell Lymphoproliferative Disorder: A Rare Cause Of Dyspnea And Pulmonary Infiltrates In An Immunocompetent Adult

Mohammed Alsaggaf, MBBS

Calcium Oxalate Deposition In Pulmonary Aspergillosis

Cheyenne Snavely

Traffic Jam In The Vasculature: A Case Of Pulmonary Leukostasis

Clarissa Smith, MD

Talcoma In Lung Cancer Screening: A Rare Benign Cause Of PET Scan Avidity

Nitin Gupta, MD

The Clue Is In The Blood Gas: A Rare Manifestation Of Lactic Acidosis

Moses Hayrabedian, MD

A Century-Old Infection Mimicking Malignancy: A Case Of Diffuse Histoplasmosis

Gabriel R. Schroeder, MD

A Case Of Wind-Instrument Associated Hypersensitivity Pneumonitis

Fizza Sajid, DO

Leaping From Lush Tropical Environments To The L-Train: A Case Of Severe Leptospirosis In New York City

Krista R. Dollar, MD

Looking Past The Ground Glass: It Was Only Skin Deep

Konstantin Golubykh, MD

Point-Of-Care Ultrasound In The Timely Diagnosis Of Colonic Necrosis

Arsal Tharwani

Abdominal Compression In End-Stage Fibrotic Interstitial Lung Disease (ILD) Improves Respiratory Compliance

Ryan Kozloski

When Asthma Isn’t: Multispecialty Approach To Fibrosing Mediastinitis

Zach S. Jarrett, DO

Vanishing Cancer: A Case Of Smoking-Related Organizing Pneumonia

Stephen Simeone

Intravascular Papillary Endothelial Hyperplasia Presenting As Thrombus In Transit With Acute Pulmonary Embolism

David Gruen, MD

Tackling Posterior Reversible Encephalopathy Syndrome (PRES): A Rare Case Of Subtherapeutic Tacrolimus Causing PRES In Steroid-Resistant Nephropathy

Nicholas Kunce, MD

An Unusual Case Of Subacute Bacterial Endocarditis Presenting With Catastrophic Subarachnoid Hemorrhage

Phillip J. Gary, MD

Sarcoid-Like Reaction After Treatment With Pembrolizumab

Shreya Podder, MD

Endobronchial Valves For Treatment Of Persistent Air Leak After Secondary Spontaneous Pneumothorax In Patients With Cystic Fibrosis

Alina Aw Wasim, MD, MBBS

Chest-Wall Castleman Disease Mimicking Thymoma Drop Metastasis

Ndausung Udongwo

The ‘Rat Bite Sign” On Cardiac MRI: Left Dominant Arrhythmogenic Cardiomyopathy As An Atypical Etiology Of Sudden Cardiac Arrest

Grant Senyei, MD

Management Of Ventriculopleural Shunt-Associated Pleural Effusion

Garima Singh, MD

COVID-19-Associated Thrombotic Thrombocytopenia Purpura (TTP)
 

CASE REPORT RAPID FIRE WINNERS

Sandeep Patri

Hyperammonemia Postlung Transplantation: An Uncommon But Life-Threatening Complication

Trung Nguyen

Dyspnea During Pregnancy Revealing Multiple Pulmonary Arteriovenous Malformations And A New Diagnosis Of Hereditary Hemorrhagic Telangiectasia

Pedro J. Baez, MD

Adenoid Cystic Adenocarcinoma: A Rare Esophageal Malignancy Misdiagnosed As COPD

Brette Guckian, DO

Management Of Pulmonary Cement Emboli After Kyphoplasty

Brinn Demars, DO

Tumor Emboli In The Pulmonary Artery Secondary To Chondrosarcoma: A Rare Presentation Mimicking Pulmonary Thromboembolism

Aakriti Arora

A Case Of Pulmonary Hypertension As A Possible Extracranial Manifestation Of Moyamoya Disease

Racine Elaine Reinoso

Clot In Transit: The Role Of Point-Of-Care Ultrasound In Early Diagnosis And Improved Outcomes

Qiraat Azeem, MD

A Case Of Autosomal-Dominant Hyper-IgE Syndrome Masquerading As Cystic Fibrosis

Jason R. Ballengee, DO

Third-Trimester Pregnancy Complicated By Non-Small Cell Lung Cancer Initially Presenting With Central Airway Obstruction And Stenosis

Sam Shafer

Caught In The Fray: Neurosarcoidosis Presenting As Chronic Respiratory Failure

Takkin Lo, MD, MPH

China White In Asthmatic Recreational Drug Users: Does It Contribute To Pneumatocele Development?

Sanjeev Shrestha, MD

Successful Treatment Of Microscopic Polyangiitis Using Novel Steroid-Sparing Agent Avacopan

Kristina Menchaca, MD

Cardiac Tamponade Without The Beck Triad: A Complication Of Severe Hypothyroidism

Olivia Millay, BS

Spontaneous Coronary Artery Dissection Of Left Anterior Descending Artery Complicated By Ventricular Septal Rupture

Akruti P. Prabhakar, DO

Delayed Lead Perforation Of The Right Atrium In The Presence Of Persistent Left Superior Vena Cava: A Rare Coincidence

Kevin Hsu, MD

A Modified Valsalva Maneuver For Ventilated And Sedated Patients With Unstable Supraventricular Tachycardia

Nang San Hti Lar Seng

Cardiovascular Manifestations Of Paraaortic Paragangliomas

Rocio Castillo-Larios

Membranous Dehiscence After Tracheal Resection And Reconstruction Healed Spontaneously With Conservative Treatment

Fizza Sajid, DO

A Young Broken Heart, Reversed

Janeen Grant-Sittol, MD

Inhaled Tranexamic Acid Use For Massive Hemoptysis In Vasculitis-Induced Bronchoalveolar Hemorrhage

Raman G. Kutty, Md, PhD

Progressive Lung Infiltrates In Patient With Acquired Immunodeficiency: A Rare Case Of GLILD

Tanwe Shende

Mycobacterium Shimoidei: A Rare Nontuberculous Infection In A U.S. Patient

Sarah M. Upson, MD

Not Your Typical Lactic Acidosis

Prachi Saluja, MD

Late-Onset Immune Thrombotic Thrombocytopenic Purpura (TTP) After Asymptomatic COVID-19 Infection

Steven S. Wu, MD

Type 1 Multiple Endocrine Neoplasia-Associated Tracheobronchial Tumors Managed By Rigid Bronchoscopy-Directed Multimodal Tumor Destruction

Konstantin Golubykh, MD

The Reversal That Helped: Role Of Bedside Echocardiography In Takotsubo Cardiomyopathy

Eric Salomon, MD

Obstructive Tracheobronchial Pulmonary Aspergillosis Managed With Local Bronchoscopic Intervention Alone

Daniel Hoesterey, MD

A Rare Case Of Critical Illness Due To Eczema Herpeticum With Disseminated Herpes Simplex Virus Infection

Awab U. Khan, DO

Severe Colchicine Toxicity In A Suicide Attempt Causing Multiorgan Failure: A Survival Story

Jacob Cebulko

Disseminated Strongyloidiasis In A Patient With Acute Lymphocytic Leukemia

Hasan Baher, MD

Hiding In Plain Sight: Disseminated Pulmonary TB

Navneet Ramesh

Multimodal Management Of Gastric Variceal Bleeding In Hemorrhagic Shock

Jason L. Peng, MD

Improving Compliance With Continuous Anterior Chest Compression In ARDS Caused By COVID-19: A Case Series

Sushan Gupta, MD

Complete Resolution Of Vasoreactive Pulmonary Artery Hypertension In Chronic Hypersensitive Pneumonitis

Mamta S. Chhabria, MD

A Fistulous Issue: Gastropleural Fistula As A Complication Of Gastrectomy

Anita Singh, DO, MBA

Identifying A Novel Surfactant Protein Mutation In A Family With Pulmonary Fibrosis

Rana Prathap Padappayil, MBBS

Delayed Cerebral Venous Sinus Thrombosis (CSVT) After An Invasive Meningioma Resection: An Uncommon Presentation Of A Common Complication

Rubabin Tooba, MD

The Morphing Cavity: An Image Series Of A Patient’s Pulmonary Infarction Over Time

Sally Ziatabar, DO

A Rare Case Of Disseminated Blastomycosis

Sumukh Arun Kumar

Incidental Pulmonary Cavitary Lesions As An Uncommon Presentation Of Lemierre Syndrome

Sophia Emetu

Pet Peeve: Dyspnea From Undiagnosed Pasteurella Multocida Empyema

Chidambaram Ramasamy, MD

A Case Of Diffuse Alveolar-Septal Pulmonary Amyloidosis And Cardiomyopathy

Rachel Swier

Acid-Fast Bacteria In Bronchiectasis: If The Glass Slipper Does Not Fit, Non-TB Mycobacteria, Consider Tsukamurella

Catherine Durant, MD

Idiopathic Multicentric Castleman Disease With Tafro Syndrome And Sjögren Syndrome

Ali Al-Hilli, MD, MSc

Sarcoidosis-Like Reaction During Treatment For Metastatic Breast Cancer With CDK 4/6 Inhibitors: Just An Epiphenomenon Or A Causal Relationship?

Scott Slusarenko, DO

Rapidly Progressive Perimyocarditis In SARS-CoV-2 Infection

Agatha M. Formoso, MD

Two Infants Presenting With Polymicrobial Pneumonia And Hypoxemic Respiratory Failure Associated With Heterozygous Variants In Carmil2 And Itk

Juan Adams-Chahin

The Silence Of “Lam”: A Case Of Tuberous Sclerosis Complex Associated With Lymphangioleiomyomatosis (Lam)

Kathleen Capaccione, MD

Lung Cancer Is Not Always The Answer: Exploring The Differential Diagnosis Of Thoracic Masses

Joann Wongvravit, DO

West Nile-Induced Myasthenia Gravis Crisis: An Unexpected Case Of Respiratory Failure

Ethan Karle, Do

A Rare Cause Of Community-Acquired Bacterial Pneumonia In A Patient With Poorly Controlled Diabetes

Taylor C. Becker, MD

Calcified Cavitary Conundrum: Delayed Diagnosis Of Histoplasmosis

Anneka Hutton, MD

Disseminated Listeriosis: A Deadly Triplicate

Omar Kandah, DO

COVID-19 Cardiac Tamponade With Cardiogenic Shock In A Previously Vaccinated Young Adult: A Case Report

Cihan Caglayan, MD

Partial Anomalous Pulmonary Venous Connection Diagnosed After Central Venous Catheter Placement

Michelle Jones, DO

Delayed Hemophagocytic Lymphohistiocytosis (HLH) Diagnosis In A Patient With Pulmonary Sarcoidosis And Newly Diagnosed T-Cell Lymphoma: A Case Report

Mariah Evarts, MD

A Normotensive Woman With Profound Lactic Acidosis And Stress-Induced Cardiomyopathy

Rachel V. Tan, MD

A Four-Boding Future: Polyviral Infection With SARS-CoV-2, Parainfluenza Virus Type 3, Influenza A, And Adenovirus

Thanh Hoang

Recurrent Syncope From Intermittent Torsades In Loperamide Abuse

Alissa Ali, MD

Ground Glass Opacities In A Patient Receiving Treatment With All-Trans Retinoic Acid And Arsenic Trioxide

Sean M. Masi, DO, MBA

Ferritin-Guided Therapeutic Plasma Exchange (TPE) Administration In COVID-19-Induced Cytokine Storm Syndrome: A Case Series

Anjali Sachdeva

Successful Biopsy Of Aortopulmonary Window Lymph Node With Robotic-Assisted Bronchoscopy

Rehan Saeed, MD

Multiple Sclerosis After COVID-19: A Sign Of Things To Come?

Harshitha Mergey Devender

Invasive Pulmonary Aspergillosis Associated With Nonspecific Interstitial Pneumonia Causing Recurrent Respiratory Failure



Be sure to check out the other award winners on page 20 in the January issue of CHEST Physician: https://tinyurl.com/2bcdcbj3 .

A new randomized, open-label French trial offers more evidence that the discontinuation of oxytocin treatment after the earliest stages of labor may be safe. Stopping oxytocin didn’t appear to affect neonatal outcomes, compared with continual use of the medication. However, the first stage of labor lasted slightly longer – not surprisingly – in those in the intervention group, and many of those who stopped oxytocin treatment resumed it later.

“Our trial did not show any impact of oxytocin discontinuation in the active [labor] stage on neonatal morbidity cesarean delivery, postpartum hemorrhage, birth experience, and postpartum depression,” said Aude Girault, MD, PhD, of Paris Cité University, in a presentation in San Francisco at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The goal of the STOPOXY study is to build upon previous research that found oxytocin discontinuation didn’t boost the risk of cesarean delivery rates, uterine hyperstimulation, and abnormal fetal heart rate, Dr. Girault said. “These studies were underpowered to show any effects on neonatal morbidity,” so she and colleagues decided to dig deeper into the issue by launching the new trial.

From 2020 to 2022, researchers assigned 2,367 women who received oxytocin before 4 centimeters dilation to either continue with the drug (n = 1,192) or discontinue it before reaching 6 centimeters dilation (n = 1,175). Overall, the women were pregnant for the first time (around 55%) with a median age around 32 years and body mass index around 24.1 kg/m². All had live, singleton, full-term babies.

More than a third – 37% – of those who discontinued oxytocin resumed treatment with the medication, while 5% of those in the control group stopped taking it.

The neonatal morbidity rate – defined via a composite variable based on umbilical arterial pH, umbilical arterial lactates, Apgar score, and/or neonatal ICU admission – was 10.0% in the intervention group and 10.1% in the control group (P = .94), the researchers reported. Cesarean delivery rates were similar (18.8% vs. 16.5%, respectively; P = .22). Apart from the duration of the active first stage, which was significantly higher in the intervention group (100 min [ interquartile range, 50-208 min] vs. 90 min [IQR, 45-150 min]; P = .001), there were no significant differences between the groups.

Dr. Girault said this increase in labor duration was “moderate and clinically debatable.”

In an interview, oncologist-gynecologist George Saade, MD, of the University of Texas Medical Branch, Galveston, noted that “oxytocin is frequently used for either induction or augmentation of labor ... with the goal of improving maternal and neonatal outcomes.”

Oxytocin itself is not expensive, Dr. Saade said. “However, when it is given, the patient requires more monitoring, which may increase cost.”

There’s debate over the proper use of oxytocin, which is available in a synthetic version as Pitocin, and researchers have been trying to understand whether it can safely be discontinued early in labor.

Potential side effects of oxytocin include heart disorders such as arrhythmia, asphyxia, neonatal seizure, and jaundice, low Apgar score, and fetal death. A boxed warning says: “Because the available data are inadequate to evaluate the benefits-to-risks considerations, oxytocin is not indicated for elective induction of labor.”

However, “overall oxytocin is commonly used and very safe as long as careful protocols are followed,” David N. Hackney, MD, MS, of University Hospitals Cleveland, said in an interview. “The medication itself does not have many negative side effects. With very high doses there can be a concern for water intoxication, though this is clinically very uncommon. Some prior studies have raised concerns about the use of oxytocin and subsequent long-term neurodevelopmental outcomes, though these associations are likely confounders and the mainstream opinion is that these are not truly biologically causative associations.”

A 2021 study in The BMJ randomly assigned 1,200 women to continue or discontinue oxytocin. There was a slight increase in cesarean sections in the discontinuation group but significantly lower risks of uterine hyperstimulation and abnormal fetal heart rate.

Dr. Hackney, who didn’t take part in the new study, said the trial is “well conducted and well executed.” However, it needs peer review before any of its findings should change practice.

He added that differences in delivery protocols between the United States and France should be considered. As he noted, Dr. Girault mentioned in a Q&A after her presentation that delayed second-stage labor is more common in France than in the United States.

The study was funded by the French National Ministry of Health. Disclosures for the authors were not provided. Dr. Saade and Dr. Hackney have no disclosures.

A new randomized, open-label French trial offers more evidence that the discontinuation of oxytocin treatment after the earliest stages of labor may be safe. Stopping oxytocin didn’t appear to affect neonatal outcomes, compared with continual use of the medication. However, the first stage of labor lasted slightly longer – not surprisingly – in those in the intervention group, and many of those who stopped oxytocin treatment resumed it later.

“Our trial did not show any impact of oxytocin discontinuation in the active [labor] stage on neonatal morbidity cesarean delivery, postpartum hemorrhage, birth experience, and postpartum depression,” said Aude Girault, MD, PhD, of Paris Cité University, in a presentation in San Francisco at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The goal of the STOPOXY study is to build upon previous research that found oxytocin discontinuation didn’t boost the risk of cesarean delivery rates, uterine hyperstimulation, and abnormal fetal heart rate, Dr. Girault said. “These studies were underpowered to show any effects on neonatal morbidity,” so she and colleagues decided to dig deeper into the issue by launching the new trial.

From 2020 to 2022, researchers assigned 2,367 women who received oxytocin before 4 centimeters dilation to either continue with the drug (n = 1,192) or discontinue it before reaching 6 centimeters dilation (n = 1,175). Overall, the women were pregnant for the first time (around 55%) with a median age around 32 years and body mass index around 24.1 kg/m². All had live, singleton, full-term babies.

More than a third – 37% – of those who discontinued oxytocin resumed treatment with the medication, while 5% of those in the control group stopped taking it.

The neonatal morbidity rate – defined via a composite variable based on umbilical arterial pH, umbilical arterial lactates, Apgar score, and/or neonatal ICU admission – was 10.0% in the intervention group and 10.1% in the control group (P = .94), the researchers reported. Cesarean delivery rates were similar (18.8% vs. 16.5%, respectively; P = .22). Apart from the duration of the active first stage, which was significantly higher in the intervention group (100 min [ interquartile range, 50-208 min] vs. 90 min [IQR, 45-150 min]; P = .001), there were no significant differences between the groups.

Dr. Girault said this increase in labor duration was “moderate and clinically debatable.”

In an interview, oncologist-gynecologist George Saade, MD, of the University of Texas Medical Branch, Galveston, noted that “oxytocin is frequently used for either induction or augmentation of labor ... with the goal of improving maternal and neonatal outcomes.”

Oxytocin itself is not expensive, Dr. Saade said. “However, when it is given, the patient requires more monitoring, which may increase cost.”

There’s debate over the proper use of oxytocin, which is available in a synthetic version as Pitocin, and researchers have been trying to understand whether it can safely be discontinued early in labor.

Potential side effects of oxytocin include heart disorders such as arrhythmia, asphyxia, neonatal seizure, and jaundice, low Apgar score, and fetal death. A boxed warning says: “Because the available data are inadequate to evaluate the benefits-to-risks considerations, oxytocin is not indicated for elective induction of labor.”

However, “overall oxytocin is commonly used and very safe as long as careful protocols are followed,” David N. Hackney, MD, MS, of University Hospitals Cleveland, said in an interview. “The medication itself does not have many negative side effects. With very high doses there can be a concern for water intoxication, though this is clinically very uncommon. Some prior studies have raised concerns about the use of oxytocin and subsequent long-term neurodevelopmental outcomes, though these associations are likely confounders and the mainstream opinion is that these are not truly biologically causative associations.”

A 2021 study in The BMJ randomly assigned 1,200 women to continue or discontinue oxytocin. There was a slight increase in cesarean sections in the discontinuation group but significantly lower risks of uterine hyperstimulation and abnormal fetal heart rate.

Dr. Hackney, who didn’t take part in the new study, said the trial is “well conducted and well executed.” However, it needs peer review before any of its findings should change practice.

He added that differences in delivery protocols between the United States and France should be considered. As he noted, Dr. Girault mentioned in a Q&A after her presentation that delayed second-stage labor is more common in France than in the United States.

The study was funded by the French National Ministry of Health. Disclosures for the authors were not provided. Dr. Saade and Dr. Hackney have no disclosures.

A new randomized, open-label French trial offers more evidence that the discontinuation of oxytocin treatment after the earliest stages of labor may be safe. Stopping oxytocin didn’t appear to affect neonatal outcomes, compared with continual use of the medication. However, the first stage of labor lasted slightly longer – not surprisingly – in those in the intervention group, and many of those who stopped oxytocin treatment resumed it later.

“Our trial did not show any impact of oxytocin discontinuation in the active [labor] stage on neonatal morbidity cesarean delivery, postpartum hemorrhage, birth experience, and postpartum depression,” said Aude Girault, MD, PhD, of Paris Cité University, in a presentation in San Francisco at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The goal of the STOPOXY study is to build upon previous research that found oxytocin discontinuation didn’t boost the risk of cesarean delivery rates, uterine hyperstimulation, and abnormal fetal heart rate, Dr. Girault said. “These studies were underpowered to show any effects on neonatal morbidity,” so she and colleagues decided to dig deeper into the issue by launching the new trial.

From 2020 to 2022, researchers assigned 2,367 women who received oxytocin before 4 centimeters dilation to either continue with the drug (n = 1,192) or discontinue it before reaching 6 centimeters dilation (n = 1,175). Overall, the women were pregnant for the first time (around 55%) with a median age around 32 years and body mass index around 24.1 kg/m². All had live, singleton, full-term babies.

More than a third – 37% – of those who discontinued oxytocin resumed treatment with the medication, while 5% of those in the control group stopped taking it.

The neonatal morbidity rate – defined via a composite variable based on umbilical arterial pH, umbilical arterial lactates, Apgar score, and/or neonatal ICU admission – was 10.0% in the intervention group and 10.1% in the control group (P = .94), the researchers reported. Cesarean delivery rates were similar (18.8% vs. 16.5%, respectively; P = .22). Apart from the duration of the active first stage, which was significantly higher in the intervention group (100 min [ interquartile range, 50-208 min] vs. 90 min [IQR, 45-150 min]; P = .001), there were no significant differences between the groups.

Dr. Girault said this increase in labor duration was “moderate and clinically debatable.”

In an interview, oncologist-gynecologist George Saade, MD, of the University of Texas Medical Branch, Galveston, noted that “oxytocin is frequently used for either induction or augmentation of labor ... with the goal of improving maternal and neonatal outcomes.”

Oxytocin itself is not expensive, Dr. Saade said. “However, when it is given, the patient requires more monitoring, which may increase cost.”

There’s debate over the proper use of oxytocin, which is available in a synthetic version as Pitocin, and researchers have been trying to understand whether it can safely be discontinued early in labor.

Potential side effects of oxytocin include heart disorders such as arrhythmia, asphyxia, neonatal seizure, and jaundice, low Apgar score, and fetal death. A boxed warning says: “Because the available data are inadequate to evaluate the benefits-to-risks considerations, oxytocin is not indicated for elective induction of labor.”

However, “overall oxytocin is commonly used and very safe as long as careful protocols are followed,” David N. Hackney, MD, MS, of University Hospitals Cleveland, said in an interview. “The medication itself does not have many negative side effects. With very high doses there can be a concern for water intoxication, though this is clinically very uncommon. Some prior studies have raised concerns about the use of oxytocin and subsequent long-term neurodevelopmental outcomes, though these associations are likely confounders and the mainstream opinion is that these are not truly biologically causative associations.”

A 2021 study in The BMJ randomly assigned 1,200 women to continue or discontinue oxytocin. There was a slight increase in cesarean sections in the discontinuation group but significantly lower risks of uterine hyperstimulation and abnormal fetal heart rate.

Dr. Hackney, who didn’t take part in the new study, said the trial is “well conducted and well executed.” However, it needs peer review before any of its findings should change practice.

He added that differences in delivery protocols between the United States and France should be considered. As he noted, Dr. Girault mentioned in a Q&A after her presentation that delayed second-stage labor is more common in France than in the United States.

The study was funded by the French National Ministry of Health. Disclosures for the authors were not provided. Dr. Saade and Dr. Hackney have no disclosures.

Catatonia is a psychomotor syndrome identified by its clinical phenotype. Unlike common psychiatric syndromes such as major depression that are characterized by self-report of symptoms, catatonia is identified chiefly by empirically evaluated signs on clinical evaluation. Its signs are recognized through observation, physical examination, or elicitation by clinical maneuvers or the presentation of stimuli. However, catatonia is often overlooked even though its clinical signs are often visibly apparent, including to the casual observer.

Why is catatonia underdiagnosed? A key modifiable factor appears to be a prevalent misunderstanding over what catatonia looks like.¹ We have sought to address this in a few ways.

First identified was the need for comprehensive educational resources on how to assess for and recognize catatonia. Using the Bush-Francis Catatonia Rating Scale – the most widely used scale for catatonia in both research and clinical settings and the most cited publication in the catatonia literature– our team developed the BFCRS Training Manual and Coding Guide.^2,3 This manual expands on the definitions of each BFCRS item based on how it was originally operationalized by the scale’s authors. Subsequently, we created a comprehensive set of educational resources including videos illustrating how to assess for catatonia, a video for each of the 23 items on the BFCRS, and self-assessment tools. All resources are freely available online at https://bfcrs.urmc.edu.⁴

Through this project it became apparent that there are many discrepancies across the field regarding the phenotype of catatonia. Specifically, a recent review inspired by this project set about to characterize the scope of distinctions across diagnostic systems and rating scales.⁵ For instance, each diagnostic system and rating scale includes a unique set of signs, approaches diagnostic thresholds differently, and often operationalizes clinical features in ways that lead either to criterion overlap (for example, combativeness would be scored both as combativeness and agitation on ICD-11) or contradictions with other systems or scales (for example, varied definitions of waxy flexibility). In the face of so many inconsistencies, what is a clinician to do? What follows is a discussion of how to apply the insights from this recent review in clinical and research settings.

Starting with DSM-5-TR and ICD-11 – the current editions of the two leading diagnostic systems – one might ask: How do they compare?^6,7 Overall, these two systems are broadly aligned in terms of the catatonic syndrome. Both systems identify individual clinical signs (as opposed to symptom complexes). Both require three features as a diagnostic threshold. Most of the same clinical signs are included in both systems, and the definitions of individual items are largely equivalent. Additionally, both systems allow for diagnosis of catatonia in association with psychiatric and medical conditions and include a category for unspecified catatonia.

Despite these core agreements, though, there are several important distinctions. First, whereas all 12 signs included in DSM-5-TR count toward an ICD-11 catatonia diagnosis, the opposite cannot be said. ICD-11 includes several features that are not in DSM-5-TR: rigidity, verbigeration, withdrawal, staring, ambitendency, impulsivity, and combativeness. Next, autonomic abnormality, which signifies the most severe type of catatonia called malignant catatonia, is included as a potential comorbidity in ICD-11 but not mentioned in DSM-5-TR. Third, ICD-11 includes a separate diagnosis for substance-induced catatonia, whereas this condition would be diagnosed as unspecified catatonia in DSM-5-TR.

There are also elements missing from both systems. The most notable of these is that neither system specifies the period over which findings must be present for diagnosis. By clinical convention, the practical definition of 24 hours is appropriate in most instances. The clinical features identified during direct evaluation are usually sufficient for diagnosis, but additional signs observed or documented over the prior 24 hours should be incorporated as part of the clinical evaluation. Another distinction is how to handle clinical features before and after lorazepam challenge. As noted in the BFCRS Training Manual, it would be appropriate to compare “state assessments” (that is, restricted to features identified only during direct, in-person assessment) from before and after lorazepam administration to document improvement.⁴

Whereas DSM-5-TR and ICD-11 are broadly in agreement, comparing these systems with catatonia rating scales reveals many sources of potential confusion, but also concrete guidance on operationalizing individual items.⁵ How exactly should each of catatonia’s clinical signs be defined? Descriptions differ, and thresholds of duration and frequency vary considerably across scales. As a result, clinicians who use different scales and then convert these results to diagnostic criteria are liable to come to different clinical conclusions. For instance, both echophenomena and negativism must be elicited more than five times to be scored per Northoff,⁸ but even a single convincing instance of either would be scored on the BFCRS as “occasional.”²

Such discrepancies are important because, whereas the psychometric properties of several catatonia scales have been documented, there are no analogous studies on the DSM-5-TR and ICD-11 criteria. Therefore, it is essential for clinicians and researchers to document how diagnostic criteria have been operationalized. The most practical and evidence-based way to do this is to use a clinically validated scale and convert these to diagnostic criteria, yet in doing so a few modifications will be necessary.

Of the available clinical scales, the BFCRS is best positioned for clinical use. The BFCRS has been validated clinically and has good reliability, detailed item definitions and audiovisual examples available. In addition, it is the only scale with a published semistructured evaluation (see initial paper and Training Manual), which takes about 5 minutes.2,4 In terms of utility, all 12 signs included by DSM-5-TR are among the first 14 items on the BFCRS, which constitutes a standalone tool known as the Bush-Francis Catatonia Screening Instrument (BFCSI, see Table).

Many fundamental questions remain about catatonia,but the importance of a shared understanding of its clinical features is clear.⁹ Catatonia should be on the differential whenever a patient exhibits a markedly altered level of activity or grossly abnormal behavior, especially when inappropriate to context. We encourage readers to familiarize themselves with the phenotype of catatonia through online educational resources⁴ because the optimal care of patients with catatonia requires – at a minimum – that we know what we’re looking for.

Dr. Oldham is assistant professor of psychiatry at the University of Rochester (N.Y.) Medical Center. Dr. Francis is professor of psychiatry at Penn State University, Hershey. The authors declare no relevant conflicts of interest. Funding for the educational project hosted at https://bfcrs.urmc.edu was provided by the department of psychiatry at the University of Rochester Medical Center. Dr. Oldham is currently supported by a K23 career development award from the National Institute on Aging (AG072383). The educational resources referenced in this piece could not have been created were it not for the intellectual and thespian collaboration of Joshua R. Wortzel, MD, who is currently a fellow in child and adolescent psychiatry at Brown University, Providence, R.I. The authors are also indebted to Hochang B. Lee, MD, for his gracious support of this project.

References

1. Wortzel JR et al. J Clin Psychiatry. 2021 Aug 17;82(5):21m14025. doi: 10.4088/JCP.21m14025.

2. Bush G et al. Acta Psychiatr Scand. 1996 Feb;93(2):129-36. doi: 10.1111/j.1600-0447.1996.tb09814.x.

3. Weleff J et al. J Acad Consult Liaison Psychiatry. 2023 Jan-Feb;64(1):13-27. doi:10.1016/j.jaclp.2022.07.002.

4. Oldham MA et al. Bush-Francis Catatonia Rating Scale Assessment Resources. University of Rochester Medical Center, Department of Psychiatry. https://bfcrs.urmc.edu.

5. Oldham MA. Schizophr Res. 2022 Aug 19;S0920-9964(22)00294-8. doi: 10.1016/j.schres.2022.08.002.

6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. Washington, D.C.: American Psychiatric Association Publishing, 2022.

7. World Health Organization. ICD-11 for Mortality and Morbidity Stastistics. 2022. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/486722075.

8. Northoff G et al. Mov Disord. May 1999;14(3):404-16. doi: 10.1002/1531-8257(199905)14:3<404::AID-MDS1004>3.0.CO;2-5.

9. Walther S et al. The Lancet Psychiatry. 2019 Jul;6(7):610-9. doi: 10.1016/S2215-0366(18)30474-7.

Catatonia is a psychomotor syndrome identified by its clinical phenotype. Unlike common psychiatric syndromes such as major depression that are characterized by self-report of symptoms, catatonia is identified chiefly by empirically evaluated signs on clinical evaluation. Its signs are recognized through observation, physical examination, or elicitation by clinical maneuvers or the presentation of stimuli. However, catatonia is often overlooked even though its clinical signs are often visibly apparent, including to the casual observer.

Why is catatonia underdiagnosed? A key modifiable factor appears to be a prevalent misunderstanding over what catatonia looks like.¹ We have sought to address this in a few ways.

First identified was the need for comprehensive educational resources on how to assess for and recognize catatonia. Using the Bush-Francis Catatonia Rating Scale – the most widely used scale for catatonia in both research and clinical settings and the most cited publication in the catatonia literature– our team developed the BFCRS Training Manual and Coding Guide.^2,3 This manual expands on the definitions of each BFCRS item based on how it was originally operationalized by the scale’s authors. Subsequently, we created a comprehensive set of educational resources including videos illustrating how to assess for catatonia, a video for each of the 23 items on the BFCRS, and self-assessment tools. All resources are freely available online at https://bfcrs.urmc.edu.⁴

Through this project it became apparent that there are many discrepancies across the field regarding the phenotype of catatonia. Specifically, a recent review inspired by this project set about to characterize the scope of distinctions across diagnostic systems and rating scales.⁵ For instance, each diagnostic system and rating scale includes a unique set of signs, approaches diagnostic thresholds differently, and often operationalizes clinical features in ways that lead either to criterion overlap (for example, combativeness would be scored both as combativeness and agitation on ICD-11) or contradictions with other systems or scales (for example, varied definitions of waxy flexibility). In the face of so many inconsistencies, what is a clinician to do? What follows is a discussion of how to apply the insights from this recent review in clinical and research settings.

Starting with DSM-5-TR and ICD-11 – the current editions of the two leading diagnostic systems – one might ask: How do they compare?^6,7 Overall, these two systems are broadly aligned in terms of the catatonic syndrome. Both systems identify individual clinical signs (as opposed to symptom complexes). Both require three features as a diagnostic threshold. Most of the same clinical signs are included in both systems, and the definitions of individual items are largely equivalent. Additionally, both systems allow for diagnosis of catatonia in association with psychiatric and medical conditions and include a category for unspecified catatonia.

Despite these core agreements, though, there are several important distinctions. First, whereas all 12 signs included in DSM-5-TR count toward an ICD-11 catatonia diagnosis, the opposite cannot be said. ICD-11 includes several features that are not in DSM-5-TR: rigidity, verbigeration, withdrawal, staring, ambitendency, impulsivity, and combativeness. Next, autonomic abnormality, which signifies the most severe type of catatonia called malignant catatonia, is included as a potential comorbidity in ICD-11 but not mentioned in DSM-5-TR. Third, ICD-11 includes a separate diagnosis for substance-induced catatonia, whereas this condition would be diagnosed as unspecified catatonia in DSM-5-TR.

There are also elements missing from both systems. The most notable of these is that neither system specifies the period over which findings must be present for diagnosis. By clinical convention, the practical definition of 24 hours is appropriate in most instances. The clinical features identified during direct evaluation are usually sufficient for diagnosis, but additional signs observed or documented over the prior 24 hours should be incorporated as part of the clinical evaluation. Another distinction is how to handle clinical features before and after lorazepam challenge. As noted in the BFCRS Training Manual, it would be appropriate to compare “state assessments” (that is, restricted to features identified only during direct, in-person assessment) from before and after lorazepam administration to document improvement.⁴

Whereas DSM-5-TR and ICD-11 are broadly in agreement, comparing these systems with catatonia rating scales reveals many sources of potential confusion, but also concrete guidance on operationalizing individual items.⁵ How exactly should each of catatonia’s clinical signs be defined? Descriptions differ, and thresholds of duration and frequency vary considerably across scales. As a result, clinicians who use different scales and then convert these results to diagnostic criteria are liable to come to different clinical conclusions. For instance, both echophenomena and negativism must be elicited more than five times to be scored per Northoff,⁸ but even a single convincing instance of either would be scored on the BFCRS as “occasional.”²

Such discrepancies are important because, whereas the psychometric properties of several catatonia scales have been documented, there are no analogous studies on the DSM-5-TR and ICD-11 criteria. Therefore, it is essential for clinicians and researchers to document how diagnostic criteria have been operationalized. The most practical and evidence-based way to do this is to use a clinically validated scale and convert these to diagnostic criteria, yet in doing so a few modifications will be necessary.

Of the available clinical scales, the BFCRS is best positioned for clinical use. The BFCRS has been validated clinically and has good reliability, detailed item definitions and audiovisual examples available. In addition, it is the only scale with a published semistructured evaluation (see initial paper and Training Manual), which takes about 5 minutes.2,4 In terms of utility, all 12 signs included by DSM-5-TR are among the first 14 items on the BFCRS, which constitutes a standalone tool known as the Bush-Francis Catatonia Screening Instrument (BFCSI, see Table).

Many fundamental questions remain about catatonia,but the importance of a shared understanding of its clinical features is clear.⁹ Catatonia should be on the differential whenever a patient exhibits a markedly altered level of activity or grossly abnormal behavior, especially when inappropriate to context. We encourage readers to familiarize themselves with the phenotype of catatonia through online educational resources⁴ because the optimal care of patients with catatonia requires – at a minimum – that we know what we’re looking for.

Dr. Oldham is assistant professor of psychiatry at the University of Rochester (N.Y.) Medical Center. Dr. Francis is professor of psychiatry at Penn State University, Hershey. The authors declare no relevant conflicts of interest. Funding for the educational project hosted at https://bfcrs.urmc.edu was provided by the department of psychiatry at the University of Rochester Medical Center. Dr. Oldham is currently supported by a K23 career development award from the National Institute on Aging (AG072383). The educational resources referenced in this piece could not have been created were it not for the intellectual and thespian collaboration of Joshua R. Wortzel, MD, who is currently a fellow in child and adolescent psychiatry at Brown University, Providence, R.I. The authors are also indebted to Hochang B. Lee, MD, for his gracious support of this project.

References

1. Wortzel JR et al. J Clin Psychiatry. 2021 Aug 17;82(5):21m14025. doi: 10.4088/JCP.21m14025.

2. Bush G et al. Acta Psychiatr Scand. 1996 Feb;93(2):129-36. doi: 10.1111/j.1600-0447.1996.tb09814.x.

3. Weleff J et al. J Acad Consult Liaison Psychiatry. 2023 Jan-Feb;64(1):13-27. doi:10.1016/j.jaclp.2022.07.002.

4. Oldham MA et al. Bush-Francis Catatonia Rating Scale Assessment Resources. University of Rochester Medical Center, Department of Psychiatry. https://bfcrs.urmc.edu.

5. Oldham MA. Schizophr Res. 2022 Aug 19;S0920-9964(22)00294-8. doi: 10.1016/j.schres.2022.08.002.

6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. Washington, D.C.: American Psychiatric Association Publishing, 2022.

7. World Health Organization. ICD-11 for Mortality and Morbidity Stastistics. 2022. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/486722075.

8. Northoff G et al. Mov Disord. May 1999;14(3):404-16. doi: 10.1002/1531-8257(199905)14:3<404::AID-MDS1004>3.0.CO;2-5.

9. Walther S et al. The Lancet Psychiatry. 2019 Jul;6(7):610-9. doi: 10.1016/S2215-0366(18)30474-7.

Catatonia is a psychomotor syndrome identified by its clinical phenotype. Unlike common psychiatric syndromes such as major depression that are characterized by self-report of symptoms, catatonia is identified chiefly by empirically evaluated signs on clinical evaluation. Its signs are recognized through observation, physical examination, or elicitation by clinical maneuvers or the presentation of stimuli. However, catatonia is often overlooked even though its clinical signs are often visibly apparent, including to the casual observer.

Why is catatonia underdiagnosed? A key modifiable factor appears to be a prevalent misunderstanding over what catatonia looks like.¹ We have sought to address this in a few ways.

First identified was the need for comprehensive educational resources on how to assess for and recognize catatonia. Using the Bush-Francis Catatonia Rating Scale – the most widely used scale for catatonia in both research and clinical settings and the most cited publication in the catatonia literature– our team developed the BFCRS Training Manual and Coding Guide.^2,3 This manual expands on the definitions of each BFCRS item based on how it was originally operationalized by the scale’s authors. Subsequently, we created a comprehensive set of educational resources including videos illustrating how to assess for catatonia, a video for each of the 23 items on the BFCRS, and self-assessment tools. All resources are freely available online at https://bfcrs.urmc.edu.⁴

Through this project it became apparent that there are many discrepancies across the field regarding the phenotype of catatonia. Specifically, a recent review inspired by this project set about to characterize the scope of distinctions across diagnostic systems and rating scales.⁵ For instance, each diagnostic system and rating scale includes a unique set of signs, approaches diagnostic thresholds differently, and often operationalizes clinical features in ways that lead either to criterion overlap (for example, combativeness would be scored both as combativeness and agitation on ICD-11) or contradictions with other systems or scales (for example, varied definitions of waxy flexibility). In the face of so many inconsistencies, what is a clinician to do? What follows is a discussion of how to apply the insights from this recent review in clinical and research settings.

Starting with DSM-5-TR and ICD-11 – the current editions of the two leading diagnostic systems – one might ask: How do they compare?^6,7 Overall, these two systems are broadly aligned in terms of the catatonic syndrome. Both systems identify individual clinical signs (as opposed to symptom complexes). Both require three features as a diagnostic threshold. Most of the same clinical signs are included in both systems, and the definitions of individual items are largely equivalent. Additionally, both systems allow for diagnosis of catatonia in association with psychiatric and medical conditions and include a category for unspecified catatonia.

Despite these core agreements, though, there are several important distinctions. First, whereas all 12 signs included in DSM-5-TR count toward an ICD-11 catatonia diagnosis, the opposite cannot be said. ICD-11 includes several features that are not in DSM-5-TR: rigidity, verbigeration, withdrawal, staring, ambitendency, impulsivity, and combativeness. Next, autonomic abnormality, which signifies the most severe type of catatonia called malignant catatonia, is included as a potential comorbidity in ICD-11 but not mentioned in DSM-5-TR. Third, ICD-11 includes a separate diagnosis for substance-induced catatonia, whereas this condition would be diagnosed as unspecified catatonia in DSM-5-TR.

There are also elements missing from both systems. The most notable of these is that neither system specifies the period over which findings must be present for diagnosis. By clinical convention, the practical definition of 24 hours is appropriate in most instances. The clinical features identified during direct evaluation are usually sufficient for diagnosis, but additional signs observed or documented over the prior 24 hours should be incorporated as part of the clinical evaluation. Another distinction is how to handle clinical features before and after lorazepam challenge. As noted in the BFCRS Training Manual, it would be appropriate to compare “state assessments” (that is, restricted to features identified only during direct, in-person assessment) from before and after lorazepam administration to document improvement.⁴

Whereas DSM-5-TR and ICD-11 are broadly in agreement, comparing these systems with catatonia rating scales reveals many sources of potential confusion, but also concrete guidance on operationalizing individual items.⁵ How exactly should each of catatonia’s clinical signs be defined? Descriptions differ, and thresholds of duration and frequency vary considerably across scales. As a result, clinicians who use different scales and then convert these results to diagnostic criteria are liable to come to different clinical conclusions. For instance, both echophenomena and negativism must be elicited more than five times to be scored per Northoff,⁸ but even a single convincing instance of either would be scored on the BFCRS as “occasional.”²

Such discrepancies are important because, whereas the psychometric properties of several catatonia scales have been documented, there are no analogous studies on the DSM-5-TR and ICD-11 criteria. Therefore, it is essential for clinicians and researchers to document how diagnostic criteria have been operationalized. The most practical and evidence-based way to do this is to use a clinically validated scale and convert these to diagnostic criteria, yet in doing so a few modifications will be necessary.

Of the available clinical scales, the BFCRS is best positioned for clinical use. The BFCRS has been validated clinically and has good reliability, detailed item definitions and audiovisual examples available. In addition, it is the only scale with a published semistructured evaluation (see initial paper and Training Manual), which takes about 5 minutes.2,4 In terms of utility, all 12 signs included by DSM-5-TR are among the first 14 items on the BFCRS, which constitutes a standalone tool known as the Bush-Francis Catatonia Screening Instrument (BFCSI, see Table).

Many fundamental questions remain about catatonia,but the importance of a shared understanding of its clinical features is clear.⁹ Catatonia should be on the differential whenever a patient exhibits a markedly altered level of activity or grossly abnormal behavior, especially when inappropriate to context. We encourage readers to familiarize themselves with the phenotype of catatonia through online educational resources⁴ because the optimal care of patients with catatonia requires – at a minimum – that we know what we’re looking for.

Dr. Oldham is assistant professor of psychiatry at the University of Rochester (N.Y.) Medical Center. Dr. Francis is professor of psychiatry at Penn State University, Hershey. The authors declare no relevant conflicts of interest. Funding for the educational project hosted at https://bfcrs.urmc.edu was provided by the department of psychiatry at the University of Rochester Medical Center. Dr. Oldham is currently supported by a K23 career development award from the National Institute on Aging (AG072383). The educational resources referenced in this piece could not have been created were it not for the intellectual and thespian collaboration of Joshua R. Wortzel, MD, who is currently a fellow in child and adolescent psychiatry at Brown University, Providence, R.I. The authors are also indebted to Hochang B. Lee, MD, for his gracious support of this project.

References

1. Wortzel JR et al. J Clin Psychiatry. 2021 Aug 17;82(5):21m14025. doi: 10.4088/JCP.21m14025.

2. Bush G et al. Acta Psychiatr Scand. 1996 Feb;93(2):129-36. doi: 10.1111/j.1600-0447.1996.tb09814.x.

3. Weleff J et al. J Acad Consult Liaison Psychiatry. 2023 Jan-Feb;64(1):13-27. doi:10.1016/j.jaclp.2022.07.002.

4. Oldham MA et al. Bush-Francis Catatonia Rating Scale Assessment Resources. University of Rochester Medical Center, Department of Psychiatry. https://bfcrs.urmc.edu.

5. Oldham MA. Schizophr Res. 2022 Aug 19;S0920-9964(22)00294-8. doi: 10.1016/j.schres.2022.08.002.

6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. Washington, D.C.: American Psychiatric Association Publishing, 2022.

7. World Health Organization. ICD-11 for Mortality and Morbidity Stastistics. 2022. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/486722075.

8. Northoff G et al. Mov Disord. May 1999;14(3):404-16. doi: 10.1002/1531-8257(199905)14:3<404::AID-MDS1004>3.0.CO;2-5.

9. Walther S et al. The Lancet Psychiatry. 2019 Jul;6(7):610-9. doi: 10.1016/S2215-0366(18)30474-7.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

Migraine is a condition that particularly affects the population of reproductive-aged women. A significant amount of the literature discusses the effect of estrogen as a migraine trigger and specifically migraine with aura as a vascular risk factor. One topic that is not discussed in the literature is whether migraine could be a risk for miscarriage, also known as spontaneous abortion. The National Institutes of Health (NIH)-funded study by Crowe and colleagues looks at this risk, especially as it relates to the frequency of migraine, the use of acute migraine medications, and caffeine intake.

This was a broad study, including nearly 2000 patients with migraine, and was a continuation of a prior ongoing NIH-funded epidemiologic study. The initial study enrolled nearly 8000 participants, all of whom were women aged 21-45 years, were in a pregnancy planning stage, and were followed for up to 12 months or until a reported pregnancy. Questionnaires were given preconception, as well as early in pregnancy (defined as 8-9 weeks' gestation), and late in pregnancy (defined as 32 weeks' gestation).

During this study 19% of pregnancies ended in spontaneous abortion. A history of migraine preconception was not associated with spontaneous abortion risk on the basis of hazard ratios. There was a slight risk in those taking some migraine medication daily, either prophylactic or analgesic. Frequency of migraine itself was not noted as a risk for spontaneous abortion.

It is necessary that this important study be followed by further investigations looking at specific medication classes and their potential risk for spontaneous abortion. Migraine itself does not appear to be a risk for miscarriage; however, there remains the possibility that some preventive or acute medications may elevate this risk. At the current moment, there is not enough information to draw a conclusion. All clinicians who treat people with migraine, particularly women who are in their reproductive years, should continue to have conversations regarding pregnancy planning and the adjustment of both preventive and acute medications prior to conception.

Neck pain is a common comorbidity of both chronic and acute migraine, and botulinum toxin is a US Food and Drug Administration–approved treatment both for chronic migraine and certain painful neck conditions, including cervical dystonia. Migraine itself can be a disabling condition; when migraine is combined with other painful comorbidities the likelihood of disability becomes increased significantly. The standard PREEMPT protocol for botulinum toxin injection in chronic migraine of 155 units includes a number of injections in the trapezius and cervical paraspinal muscles. Many clinicians will give additional injections into these muscles and other areas around the neck, specifically targeting areas of neck and shoulder spasm and tenderness. Onan and colleagues investigated the quality of life and disability scores of patients who received these additional injections.

This was an open study, in which participants were given an additional 30 units of botulinum toxin into the general neck areas in a follow-the-pain protocol. The authors, used as a primary outcome, the reduction in the Migraine Disability Assessment (MIDAS) and Neck Disability Index (NDI) scores at 4 weeks and 3 months. The secondary outcome was the Headache Impact Test (HIT-6) score. An objective assessment of neck mobility or a quantification of trigger points were not calculated.

All scores, both the primary and secondary outcomes, were significantly decreased, and quality of life was also noted to be significantly improved with these additional injections. Most clinicians receive a 200-unit vial of botulinum toxin for each of their chronic migraine protocol injections. There is a growing body of evidence to argue that the additional units of botulinum toxin significantly improve outcomes, both regarding headache and neck pain. This study argues for delivering these additional injections of botulinum toxin, especially when neck pain is more prominent.

Much has been written about diet triggers and migraine recently. There has been some evidence for specific diet changes, ie, the addition of foods or nutrients that can be helpful or preventive for migraine. There is some evidence for the addition of omega-3 fatty acids. Huang and He investigated the effect of a high fiber diet on migraine frequency and severity.

This was a cross-sectional study involving data collected from the NIH/Centers for Disease Control and Prevention–sponsored National Health and Nutrition Examination Survey trial from 1999 to 2004. In the studied population, severe headache and migraine was present in approximately 20%, and dietary fiber intake was delineated on the basis of whether it was more than or less than 100 g/d. This study assessed dietary intake of fiber, via a 24-hour dietary recall that was conducted by trained interviewers during two interviews conducted over the course of 2 years.

A total of 12,000 participants were included in the study. There was a significant decrease in migraine severity between those with a higher and lower dietary fiber intake. The incidence of severe headache or migraine, as defined by frequency and severity, decreased in participants who had a dietary fiber intake > 100 g/d. The authors found that for every 10 g/d increase in dietary fiber intake, the prevalence of severe headache or migraine decreased by approximately 11%.

Although much has been written about the association between diet and migraine, most of the literature focuses on the avoidance of specific dietary triggers. A different consideration now exists, one that will likely increase compliance with dietary recommendations. Specifically, people treating patients with migraine can make recommendations regarding dietary changes that focus on adding specific healthy foods or other changes that can actually be associated with improving migraine frequency long-term. Recommending healthy fats, such as omega-3 fatty acids, and high fiber should be done for nearly all patients with migraine.

Migraine is a condition that particularly affects the population of reproductive-aged women. A significant amount of the literature discusses the effect of estrogen as a migraine trigger and specifically migraine with aura as a vascular risk factor. One topic that is not discussed in the literature is whether migraine could be a risk for miscarriage, also known as spontaneous abortion. The National Institutes of Health (NIH)-funded study by Crowe and colleagues looks at this risk, especially as it relates to the frequency of migraine, the use of acute migraine medications, and caffeine intake.

This was a broad study, including nearly 2000 patients with migraine, and was a continuation of a prior ongoing NIH-funded epidemiologic study. The initial study enrolled nearly 8000 participants, all of whom were women aged 21-45 years, were in a pregnancy planning stage, and were followed for up to 12 months or until a reported pregnancy. Questionnaires were given preconception, as well as early in pregnancy (defined as 8-9 weeks' gestation), and late in pregnancy (defined as 32 weeks' gestation).

During this study 19% of pregnancies ended in spontaneous abortion. A history of migraine preconception was not associated with spontaneous abortion risk on the basis of hazard ratios. There was a slight risk in those taking some migraine medication daily, either prophylactic or analgesic. Frequency of migraine itself was not noted as a risk for spontaneous abortion.

It is necessary that this important study be followed by further investigations looking at specific medication classes and their potential risk for spontaneous abortion. Migraine itself does not appear to be a risk for miscarriage; however, there remains the possibility that some preventive or acute medications may elevate this risk. At the current moment, there is not enough information to draw a conclusion. All clinicians who treat people with migraine, particularly women who are in their reproductive years, should continue to have conversations regarding pregnancy planning and the adjustment of both preventive and acute medications prior to conception.

Neck pain is a common comorbidity of both chronic and acute migraine, and botulinum toxin is a US Food and Drug Administration–approved treatment both for chronic migraine and certain painful neck conditions, including cervical dystonia. Migraine itself can be a disabling condition; when migraine is combined with other painful comorbidities the likelihood of disability becomes increased significantly. The standard PREEMPT protocol for botulinum toxin injection in chronic migraine of 155 units includes a number of injections in the trapezius and cervical paraspinal muscles. Many clinicians will give additional injections into these muscles and other areas around the neck, specifically targeting areas of neck and shoulder spasm and tenderness. Onan and colleagues investigated the quality of life and disability scores of patients who received these additional injections.

This was an open study, in which participants were given an additional 30 units of botulinum toxin into the general neck areas in a follow-the-pain protocol. The authors, used as a primary outcome, the reduction in the Migraine Disability Assessment (MIDAS) and Neck Disability Index (NDI) scores at 4 weeks and 3 months. The secondary outcome was the Headache Impact Test (HIT-6) score. An objective assessment of neck mobility or a quantification of trigger points were not calculated.

All scores, both the primary and secondary outcomes, were significantly decreased, and quality of life was also noted to be significantly improved with these additional injections. Most clinicians receive a 200-unit vial of botulinum toxin for each of their chronic migraine protocol injections. There is a growing body of evidence to argue that the additional units of botulinum toxin significantly improve outcomes, both regarding headache and neck pain. This study argues for delivering these additional injections of botulinum toxin, especially when neck pain is more prominent.

Much has been written about diet triggers and migraine recently. There has been some evidence for specific diet changes, ie, the addition of foods or nutrients that can be helpful or preventive for migraine. There is some evidence for the addition of omega-3 fatty acids. Huang and He investigated the effect of a high fiber diet on migraine frequency and severity.

This was a cross-sectional study involving data collected from the NIH/Centers for Disease Control and Prevention–sponsored National Health and Nutrition Examination Survey trial from 1999 to 2004. In the studied population, severe headache and migraine was present in approximately 20%, and dietary fiber intake was delineated on the basis of whether it was more than or less than 100 g/d. This study assessed dietary intake of fiber, via a 24-hour dietary recall that was conducted by trained interviewers during two interviews conducted over the course of 2 years.

A total of 12,000 participants were included in the study. There was a significant decrease in migraine severity between those with a higher and lower dietary fiber intake. The incidence of severe headache or migraine, as defined by frequency and severity, decreased in participants who had a dietary fiber intake > 100 g/d. The authors found that for every 10 g/d increase in dietary fiber intake, the prevalence of severe headache or migraine decreased by approximately 11%.

Although much has been written about the association between diet and migraine, most of the literature focuses on the avoidance of specific dietary triggers. A different consideration now exists, one that will likely increase compliance with dietary recommendations. Specifically, people treating patients with migraine can make recommendations regarding dietary changes that focus on adding specific healthy foods or other changes that can actually be associated with improving migraine frequency long-term. Recommending healthy fats, such as omega-3 fatty acids, and high fiber should be done for nearly all patients with migraine.

Migraine is a condition that particularly affects the population of reproductive-aged women. A significant amount of the literature discusses the effect of estrogen as a migraine trigger and specifically migraine with aura as a vascular risk factor. One topic that is not discussed in the literature is whether migraine could be a risk for miscarriage, also known as spontaneous abortion. The National Institutes of Health (NIH)-funded study by Crowe and colleagues looks at this risk, especially as it relates to the frequency of migraine, the use of acute migraine medications, and caffeine intake.

This was a broad study, including nearly 2000 patients with migraine, and was a continuation of a prior ongoing NIH-funded epidemiologic study. The initial study enrolled nearly 8000 participants, all of whom were women aged 21-45 years, were in a pregnancy planning stage, and were followed for up to 12 months or until a reported pregnancy. Questionnaires were given preconception, as well as early in pregnancy (defined as 8-9 weeks' gestation), and late in pregnancy (defined as 32 weeks' gestation).

During this study 19% of pregnancies ended in spontaneous abortion. A history of migraine preconception was not associated with spontaneous abortion risk on the basis of hazard ratios. There was a slight risk in those taking some migraine medication daily, either prophylactic or analgesic. Frequency of migraine itself was not noted as a risk for spontaneous abortion.

It is necessary that this important study be followed by further investigations looking at specific medication classes and their potential risk for spontaneous abortion. Migraine itself does not appear to be a risk for miscarriage; however, there remains the possibility that some preventive or acute medications may elevate this risk. At the current moment, there is not enough information to draw a conclusion. All clinicians who treat people with migraine, particularly women who are in their reproductive years, should continue to have conversations regarding pregnancy planning and the adjustment of both preventive and acute medications prior to conception.

Neck pain is a common comorbidity of both chronic and acute migraine, and botulinum toxin is a US Food and Drug Administration–approved treatment both for chronic migraine and certain painful neck conditions, including cervical dystonia. Migraine itself can be a disabling condition; when migraine is combined with other painful comorbidities the likelihood of disability becomes increased significantly. The standard PREEMPT protocol for botulinum toxin injection in chronic migraine of 155 units includes a number of injections in the trapezius and cervical paraspinal muscles. Many clinicians will give additional injections into these muscles and other areas around the neck, specifically targeting areas of neck and shoulder spasm and tenderness. Onan and colleagues investigated the quality of life and disability scores of patients who received these additional injections.

This was an open study, in which participants were given an additional 30 units of botulinum toxin into the general neck areas in a follow-the-pain protocol. The authors, used as a primary outcome, the reduction in the Migraine Disability Assessment (MIDAS) and Neck Disability Index (NDI) scores at 4 weeks and 3 months. The secondary outcome was the Headache Impact Test (HIT-6) score. An objective assessment of neck mobility or a quantification of trigger points were not calculated.

All scores, both the primary and secondary outcomes, were significantly decreased, and quality of life was also noted to be significantly improved with these additional injections. Most clinicians receive a 200-unit vial of botulinum toxin for each of their chronic migraine protocol injections. There is a growing body of evidence to argue that the additional units of botulinum toxin significantly improve outcomes, both regarding headache and neck pain. This study argues for delivering these additional injections of botulinum toxin, especially when neck pain is more prominent.

Much has been written about diet triggers and migraine recently. There has been some evidence for specific diet changes, ie, the addition of foods or nutrients that can be helpful or preventive for migraine. There is some evidence for the addition of omega-3 fatty acids. Huang and He investigated the effect of a high fiber diet on migraine frequency and severity.

This was a cross-sectional study involving data collected from the NIH/Centers for Disease Control and Prevention–sponsored National Health and Nutrition Examination Survey trial from 1999 to 2004. In the studied population, severe headache and migraine was present in approximately 20%, and dietary fiber intake was delineated on the basis of whether it was more than or less than 100 g/d. This study assessed dietary intake of fiber, via a 24-hour dietary recall that was conducted by trained interviewers during two interviews conducted over the course of 2 years.

A total of 12,000 participants were included in the study. There was a significant decrease in migraine severity between those with a higher and lower dietary fiber intake. The incidence of severe headache or migraine, as defined by frequency and severity, decreased in participants who had a dietary fiber intake > 100 g/d. The authors found that for every 10 g/d increase in dietary fiber intake, the prevalence of severe headache or migraine decreased by approximately 11%.

Although much has been written about the association between diet and migraine, most of the literature focuses on the avoidance of specific dietary triggers. A different consideration now exists, one that will likely increase compliance with dietary recommendations. Specifically, people treating patients with migraine can make recommendations regarding dietary changes that focus on adding specific healthy foods or other changes that can actually be associated with improving migraine frequency long-term. Recommending healthy fats, such as omega-3 fatty acids, and high fiber should be done for nearly all patients with migraine.

The recent debate about how best to address the growing epidemic of obesity in children and adolescents has pitted different professional organizations against each other. While there is little controversy that both obesity and eating disorders represent important public health concerns, each deserving of clinical attention, how best to address one without worsening the other has been the crux of the discussion.

Sparking the dispute was a recent publication from the American Academy of Pediatrics that outlines the scope of the obesity problem and makes specific recommendations for assessment and treatment.¹ The ambitious 100-page document, with 801 citations, puts new emphasis on the medical and psychological costs associated with obesity and advocates that pediatric primary care clinicians be more assertive in its treatment. While the guidelines certainly don’t urge the use of medications or surgery options as first-line treatment, the new recommendations do put them on the table as options.

In response, the Academy of Eating Disorders issued a public statement outlining several concerns regarding these guidelines that centered around a lack of a detailed plan to screen and address eating disorders; concerns that pediatricians don’t have the level of training and “skills” to conduct these conversations with patients and families with enough sensitivity; and worries about the premature use of antiobesity medications and surgeries in this population.²

It is fair to say that the critique was sharply worded, invoking physicians’ Hippocratic oath, criticizing their training, and suggesting that the guidelines could be biased by pharmaceutical industry influence (of note, the authors of the guidelines reported no ties to any pharmaceutical company). The AED urged that the guidelines be “revised” after consultation with other groups, including them.

Not unexpectedly, this response, especially coming from a group whose leadership and members are primarily nonphysicians, triggered its own sharp rebukes, including a recent commentary that counter-accused some of the eating disorder clinicians of being more concerned with their pet diets than actual health improvements.³

After everyone takes some deep breaths, it’s worth looking to see if there is some middle ground to explore here. The AAP document, to my reading, shows some important acknowledgments of the stigma associated with being overweight, even coming from pediatricians themselves. One passage reads, “Pediatricians and other PHCPs [primary health care providers] have been – and remain – a source of weight bias. They first need to uncover and address their own attitudes regarding children with obesity. Understanding weight stigma and bias, and learning how to reduce it in the clinical setting, sets the stage for productive discussions and improved relationships between families and pediatricians or other PHCPs.”

The guidelines also include some suggestions for how to talk to youth and families about obesity in less stigmatizing ways and offer a fairly lengthy summary of motivational interviewing techniques as they might apply to obesity discussions and lifestyle change. There is also a section on the interface between obesity and eating disorders with suggestions for further reading on their assessment and management.⁴

Indeed, research has looked specifically at how to minimize the triggering of eating disorders when addressing weight problems, a concern that has been raised by pediatricians themselves as documented in a qualitative study that also invoked the “do no harm” principle.⁵ One study asked more than 2,000 teens about how various conversations about weight affected their behavior.⁶ A main finding from that study was that conversations that focused on healthy eating rather than weight per se were less likely to be associated with unhealthy weight control behaviors. This message was emphasized in a publication that came from the AAP itself; it addresses the interaction between eating disorders and obesity.⁷ Strangely, however, the suggestion to try to minimize the focus on weight in discussions with patients isn’t well emphasized in the publication.

Overall, though, the AAP guidelines offer a well-informed and balanced approach to helping overweight youth. Pediatricians and other pediatric primary care clinicians are frequently called upon to engage in extremely sensitive and difficult discussions with patients and families on a wide variety of topics and most do so quite skillfully, especially when given the proper time and tools. While it is an area in which many of us, including mental health professionals, could do better, it’s no surprise that the AED’s disparaging of pediatricians’ communication competence came off as insulting. Similarly, productive dialogue would be likely enhanced if both sides avoided unfounded speculation about bias and motive and worked from a good faith perspective that all of us are engaged in this important discussion because of a desire to improve the lives of kids.

From my reading, it is quite a stretch to conclude that this document is urging a hasty and financially driven descent into GLP-1 analogues and bariatric surgery. That said, this wouldn’t be the first time a professional organization issues detailed, thoughtful, and nuanced care guidelines only to have them “condensed” within the practical confines of a busy office practice. Leaders would do well to remember that there remains much work to do to empower clinicians to be able to follow these guidelines as intended.
 

Dr. Rettew is a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland. His latest book is “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood.”

References

1. Hampl SE et al. Pediatrics. 2023;151(2):e2022060640.

2. Academy of Eating Disorders. Jan. 26, 2023. Accessed February 2, 2023. Available at The Academy for Eating Disorders Releases a Statement on the Recent American Academy of Pediatrics Clinical Practice Guideline for Weight-Related Care: First, Do No Harm (newswise.com).

3. Freedhoff Y. MDedge Pediatrics 2023. Available at https://www.mdedge.com/pediatrics/article/260894/obesity/weight-bias-affects-views-kids-obesity-recommendations?channel=52.

4. Hornberger LL, Lane MA et al. Pediatrics. 2021;147(1):e202004027989.

5. Loth KA, Lebow J et al. Global Pediatric Health. 2021;8:1-9.

6. Berge JM et al. JAMA Pediatrics. 2013;167(8):746-53.

7. Golden NH et al. Pediatrics. 2016;138(3):e20161649.

The recent debate about how best to address the growing epidemic of obesity in children and adolescents has pitted different professional organizations against each other. While there is little controversy that both obesity and eating disorders represent important public health concerns, each deserving of clinical attention, how best to address one without worsening the other has been the crux of the discussion.

Sparking the dispute was a recent publication from the American Academy of Pediatrics that outlines the scope of the obesity problem and makes specific recommendations for assessment and treatment.¹ The ambitious 100-page document, with 801 citations, puts new emphasis on the medical and psychological costs associated with obesity and advocates that pediatric primary care clinicians be more assertive in its treatment. While the guidelines certainly don’t urge the use of medications or surgery options as first-line treatment, the new recommendations do put them on the table as options.

In response, the Academy of Eating Disorders issued a public statement outlining several concerns regarding these guidelines that centered around a lack of a detailed plan to screen and address eating disorders; concerns that pediatricians don’t have the level of training and “skills” to conduct these conversations with patients and families with enough sensitivity; and worries about the premature use of antiobesity medications and surgeries in this population.²

It is fair to say that the critique was sharply worded, invoking physicians’ Hippocratic oath, criticizing their training, and suggesting that the guidelines could be biased by pharmaceutical industry influence (of note, the authors of the guidelines reported no ties to any pharmaceutical company). The AED urged that the guidelines be “revised” after consultation with other groups, including them.

Not unexpectedly, this response, especially coming from a group whose leadership and members are primarily nonphysicians, triggered its own sharp rebukes, including a recent commentary that counter-accused some of the eating disorder clinicians of being more concerned with their pet diets than actual health improvements.³

After everyone takes some deep breaths, it’s worth looking to see if there is some middle ground to explore here. The AAP document, to my reading, shows some important acknowledgments of the stigma associated with being overweight, even coming from pediatricians themselves. One passage reads, “Pediatricians and other PHCPs [primary health care providers] have been – and remain – a source of weight bias. They first need to uncover and address their own attitudes regarding children with obesity. Understanding weight stigma and bias, and learning how to reduce it in the clinical setting, sets the stage for productive discussions and improved relationships between families and pediatricians or other PHCPs.”

The guidelines also include some suggestions for how to talk to youth and families about obesity in less stigmatizing ways and offer a fairly lengthy summary of motivational interviewing techniques as they might apply to obesity discussions and lifestyle change. There is also a section on the interface between obesity and eating disorders with suggestions for further reading on their assessment and management.⁴

Indeed, research has looked specifically at how to minimize the triggering of eating disorders when addressing weight problems, a concern that has been raised by pediatricians themselves as documented in a qualitative study that also invoked the “do no harm” principle.⁵ One study asked more than 2,000 teens about how various conversations about weight affected their behavior.⁶ A main finding from that study was that conversations that focused on healthy eating rather than weight per se were less likely to be associated with unhealthy weight control behaviors. This message was emphasized in a publication that came from the AAP itself; it addresses the interaction between eating disorders and obesity.⁷ Strangely, however, the suggestion to try to minimize the focus on weight in discussions with patients isn’t well emphasized in the publication.

Overall, though, the AAP guidelines offer a well-informed and balanced approach to helping overweight youth. Pediatricians and other pediatric primary care clinicians are frequently called upon to engage in extremely sensitive and difficult discussions with patients and families on a wide variety of topics and most do so quite skillfully, especially when given the proper time and tools. While it is an area in which many of us, including mental health professionals, could do better, it’s no surprise that the AED’s disparaging of pediatricians’ communication competence came off as insulting. Similarly, productive dialogue would be likely enhanced if both sides avoided unfounded speculation about bias and motive and worked from a good faith perspective that all of us are engaged in this important discussion because of a desire to improve the lives of kids.

From my reading, it is quite a stretch to conclude that this document is urging a hasty and financially driven descent into GLP-1 analogues and bariatric surgery. That said, this wouldn’t be the first time a professional organization issues detailed, thoughtful, and nuanced care guidelines only to have them “condensed” within the practical confines of a busy office practice. Leaders would do well to remember that there remains much work to do to empower clinicians to be able to follow these guidelines as intended.
 

Dr. Rettew is a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland. His latest book is “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood.”

References

1. Hampl SE et al. Pediatrics. 2023;151(2):e2022060640.

2. Academy of Eating Disorders. Jan. 26, 2023. Accessed February 2, 2023. Available at The Academy for Eating Disorders Releases a Statement on the Recent American Academy of Pediatrics Clinical Practice Guideline for Weight-Related Care: First, Do No Harm (newswise.com).

3. Freedhoff Y. MDedge Pediatrics 2023. Available at https://www.mdedge.com/pediatrics/article/260894/obesity/weight-bias-affects-views-kids-obesity-recommendations?channel=52.

4. Hornberger LL, Lane MA et al. Pediatrics. 2021;147(1):e202004027989.

5. Loth KA, Lebow J et al. Global Pediatric Health. 2021;8:1-9.

6. Berge JM et al. JAMA Pediatrics. 2013;167(8):746-53.

7. Golden NH et al. Pediatrics. 2016;138(3):e20161649.

The recent debate about how best to address the growing epidemic of obesity in children and adolescents has pitted different professional organizations against each other. While there is little controversy that both obesity and eating disorders represent important public health concerns, each deserving of clinical attention, how best to address one without worsening the other has been the crux of the discussion.

Sparking the dispute was a recent publication from the American Academy of Pediatrics that outlines the scope of the obesity problem and makes specific recommendations for assessment and treatment.¹ The ambitious 100-page document, with 801 citations, puts new emphasis on the medical and psychological costs associated with obesity and advocates that pediatric primary care clinicians be more assertive in its treatment. While the guidelines certainly don’t urge the use of medications or surgery options as first-line treatment, the new recommendations do put them on the table as options.

In response, the Academy of Eating Disorders issued a public statement outlining several concerns regarding these guidelines that centered around a lack of a detailed plan to screen and address eating disorders; concerns that pediatricians don’t have the level of training and “skills” to conduct these conversations with patients and families with enough sensitivity; and worries about the premature use of antiobesity medications and surgeries in this population.²

It is fair to say that the critique was sharply worded, invoking physicians’ Hippocratic oath, criticizing their training, and suggesting that the guidelines could be biased by pharmaceutical industry influence (of note, the authors of the guidelines reported no ties to any pharmaceutical company). The AED urged that the guidelines be “revised” after consultation with other groups, including them.

Not unexpectedly, this response, especially coming from a group whose leadership and members are primarily nonphysicians, triggered its own sharp rebukes, including a recent commentary that counter-accused some of the eating disorder clinicians of being more concerned with their pet diets than actual health improvements.³

After everyone takes some deep breaths, it’s worth looking to see if there is some middle ground to explore here. The AAP document, to my reading, shows some important acknowledgments of the stigma associated with being overweight, even coming from pediatricians themselves. One passage reads, “Pediatricians and other PHCPs [primary health care providers] have been – and remain – a source of weight bias. They first need to uncover and address their own attitudes regarding children with obesity. Understanding weight stigma and bias, and learning how to reduce it in the clinical setting, sets the stage for productive discussions and improved relationships between families and pediatricians or other PHCPs.”

The guidelines also include some suggestions for how to talk to youth and families about obesity in less stigmatizing ways and offer a fairly lengthy summary of motivational interviewing techniques as they might apply to obesity discussions and lifestyle change. There is also a section on the interface between obesity and eating disorders with suggestions for further reading on their assessment and management.⁴

Indeed, research has looked specifically at how to minimize the triggering of eating disorders when addressing weight problems, a concern that has been raised by pediatricians themselves as documented in a qualitative study that also invoked the “do no harm” principle.⁵ One study asked more than 2,000 teens about how various conversations about weight affected their behavior.⁶ A main finding from that study was that conversations that focused on healthy eating rather than weight per se were less likely to be associated with unhealthy weight control behaviors. This message was emphasized in a publication that came from the AAP itself; it addresses the interaction between eating disorders and obesity.⁷ Strangely, however, the suggestion to try to minimize the focus on weight in discussions with patients isn’t well emphasized in the publication.

Overall, though, the AAP guidelines offer a well-informed and balanced approach to helping overweight youth. Pediatricians and other pediatric primary care clinicians are frequently called upon to engage in extremely sensitive and difficult discussions with patients and families on a wide variety of topics and most do so quite skillfully, especially when given the proper time and tools. While it is an area in which many of us, including mental health professionals, could do better, it’s no surprise that the AED’s disparaging of pediatricians’ communication competence came off as insulting. Similarly, productive dialogue would be likely enhanced if both sides avoided unfounded speculation about bias and motive and worked from a good faith perspective that all of us are engaged in this important discussion because of a desire to improve the lives of kids.

From my reading, it is quite a stretch to conclude that this document is urging a hasty and financially driven descent into GLP-1 analogues and bariatric surgery. That said, this wouldn’t be the first time a professional organization issues detailed, thoughtful, and nuanced care guidelines only to have them “condensed” within the practical confines of a busy office practice. Leaders would do well to remember that there remains much work to do to empower clinicians to be able to follow these guidelines as intended.
 

Dr. Rettew is a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland. His latest book is “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood.”

References

1. Hampl SE et al. Pediatrics. 2023;151(2):e2022060640.

2. Academy of Eating Disorders. Jan. 26, 2023. Accessed February 2, 2023. Available at The Academy for Eating Disorders Releases a Statement on the Recent American Academy of Pediatrics Clinical Practice Guideline for Weight-Related Care: First, Do No Harm (newswise.com).

3. Freedhoff Y. MDedge Pediatrics 2023. Available at https://www.mdedge.com/pediatrics/article/260894/obesity/weight-bias-affects-views-kids-obesity-recommendations?channel=52.

4. Hornberger LL, Lane MA et al. Pediatrics. 2021;147(1):e202004027989.

5. Loth KA, Lebow J et al. Global Pediatric Health. 2021;8:1-9.

6. Berge JM et al. JAMA Pediatrics. 2013;167(8):746-53.

7. Golden NH et al. Pediatrics. 2016;138(3):e20161649.

Here we are, 1 month into the new year, and it already feels like my time as President of the American College of Chest Physicians will pass too quickly. One of my goals is to share some thoughts on issues important to our profession by contributing quarterly to CHEST Physician. CHEST has always been like an extended family to me, and I look forward to having this regular touchpoint with all of you.

For my first written contribution, I want to focus on the future of medicine through medical education and involvement in professional associations because I am, at heart, a medical educator.

During my address at the CHEST Annual Meeting 2022, I spoke on how CHEST provided me with networking, mentoring, and volunteer opportunities that were critical in advancing my career. Those same opportunities should be extended to everyone in pulmonary, critical care, and sleep medicine – whether a current member or prospective member.
 

Lighting a fire

Attending my first CHEST Annual Meeting was possible due to my nomination for a leadership development course. The connections I made during the meeting really lit a fire within me. We need to engage with early career clinicians and provide them the same exposure and encouragement that I received.

To instill this fire in the next generation, I encourage each of our established members, years (or decades) into their careers, to pass along their expertise to someone who is just starting out, whether it be a trainee or a junior faculty member. If this applies to you: encourage a new attending who has never been to a CHEST event to attend with you; invite a fellow or resident to submit an abstract or case report to the journal CHEST® with your oversight; or simply volunteer to speak at your medical school or residency program about why you chose PCCM and the career it has given you.

Think back to when you were embarking on your journey toward where you are now – what would it have meant to be able to get career advice or even just a friendly conversation started with someone at your current level?
 

CHEST offerings and accreditations

Beyond bringing someone to a CHEST Annual Meeting – which you should definitely do – work with your learners at medical schools and residency programs to expose them to CHEST much earlier in their careers. The Trainings and Transitions Committee is an excellent resource to guide newer clinicians and can provide a vital source of encouragement and support. If your institution doesn’t have a simulation learning center or if it has limited offerings, the hands-on learning opportunities offered at CHEST headquarters may be a fit. Accredited by the Society for Simulation in Healthcare (SSH) and the Accreditation Council for Continuing Medical Education (ACCME), CHEST currently offers 24 courses with four new courses planned for 2023 in a wide variety of areas, including courses on ultrasound and bronchoscopy.

There are so many ways to introduce early career clinicians to CHEST, and it can begin with one personal outreach. If you are working on a project for CHEST right now, consider inviting an early career clinician to join you on it – this may be the opportunity that will change their career. It did for me.

As medical professionals, each of us plays an important role in the future of medicine, and the CHEST organization can bring us together to strengthen our impact.

If you are interested in brainstorming ideas for how to engage your medical students, residents, or fellows, please feel free to contact me or anyone at CHEST to help create a plan.

I look forward to the next time we connect.

Doreen J. Addrizzo-Harris, MD, FCCP

CHEST President

Here we are, 1 month into the new year, and it already feels like my time as President of the American College of Chest Physicians will pass too quickly. One of my goals is to share some thoughts on issues important to our profession by contributing quarterly to CHEST Physician. CHEST has always been like an extended family to me, and I look forward to having this regular touchpoint with all of you.

For my first written contribution, I want to focus on the future of medicine through medical education and involvement in professional associations because I am, at heart, a medical educator.

During my address at the CHEST Annual Meeting 2022, I spoke on how CHEST provided me with networking, mentoring, and volunteer opportunities that were critical in advancing my career. Those same opportunities should be extended to everyone in pulmonary, critical care, and sleep medicine – whether a current member or prospective member.
 

Lighting a fire

Attending my first CHEST Annual Meeting was possible due to my nomination for a leadership development course. The connections I made during the meeting really lit a fire within me. We need to engage with early career clinicians and provide them the same exposure and encouragement that I received.

To instill this fire in the next generation, I encourage each of our established members, years (or decades) into their careers, to pass along their expertise to someone who is just starting out, whether it be a trainee or a junior faculty member. If this applies to you: encourage a new attending who has never been to a CHEST event to attend with you; invite a fellow or resident to submit an abstract or case report to the journal CHEST® with your oversight; or simply volunteer to speak at your medical school or residency program about why you chose PCCM and the career it has given you.

Think back to when you were embarking on your journey toward where you are now – what would it have meant to be able to get career advice or even just a friendly conversation started with someone at your current level?
 

CHEST offerings and accreditations

Beyond bringing someone to a CHEST Annual Meeting – which you should definitely do – work with your learners at medical schools and residency programs to expose them to CHEST much earlier in their careers. The Trainings and Transitions Committee is an excellent resource to guide newer clinicians and can provide a vital source of encouragement and support. If your institution doesn’t have a simulation learning center or if it has limited offerings, the hands-on learning opportunities offered at CHEST headquarters may be a fit. Accredited by the Society for Simulation in Healthcare (SSH) and the Accreditation Council for Continuing Medical Education (ACCME), CHEST currently offers 24 courses with four new courses planned for 2023 in a wide variety of areas, including courses on ultrasound and bronchoscopy.

There are so many ways to introduce early career clinicians to CHEST, and it can begin with one personal outreach. If you are working on a project for CHEST right now, consider inviting an early career clinician to join you on it – this may be the opportunity that will change their career. It did for me.

As medical professionals, each of us plays an important role in the future of medicine, and the CHEST organization can bring us together to strengthen our impact.

If you are interested in brainstorming ideas for how to engage your medical students, residents, or fellows, please feel free to contact me or anyone at CHEST to help create a plan.

I look forward to the next time we connect.

Doreen J. Addrizzo-Harris, MD, FCCP

CHEST President

Here we are, 1 month into the new year, and it already feels like my time as President of the American College of Chest Physicians will pass too quickly. One of my goals is to share some thoughts on issues important to our profession by contributing quarterly to CHEST Physician. CHEST has always been like an extended family to me, and I look forward to having this regular touchpoint with all of you.

For my first written contribution, I want to focus on the future of medicine through medical education and involvement in professional associations because I am, at heart, a medical educator.

During my address at the CHEST Annual Meeting 2022, I spoke on how CHEST provided me with networking, mentoring, and volunteer opportunities that were critical in advancing my career. Those same opportunities should be extended to everyone in pulmonary, critical care, and sleep medicine – whether a current member or prospective member.
 

Lighting a fire

Attending my first CHEST Annual Meeting was possible due to my nomination for a leadership development course. The connections I made during the meeting really lit a fire within me. We need to engage with early career clinicians and provide them the same exposure and encouragement that I received.

To instill this fire in the next generation, I encourage each of our established members, years (or decades) into their careers, to pass along their expertise to someone who is just starting out, whether it be a trainee or a junior faculty member. If this applies to you: encourage a new attending who has never been to a CHEST event to attend with you; invite a fellow or resident to submit an abstract or case report to the journal CHEST® with your oversight; or simply volunteer to speak at your medical school or residency program about why you chose PCCM and the career it has given you.

Think back to when you were embarking on your journey toward where you are now – what would it have meant to be able to get career advice or even just a friendly conversation started with someone at your current level?
 

CHEST offerings and accreditations

Beyond bringing someone to a CHEST Annual Meeting – which you should definitely do – work with your learners at medical schools and residency programs to expose them to CHEST much earlier in their careers. The Trainings and Transitions Committee is an excellent resource to guide newer clinicians and can provide a vital source of encouragement and support. If your institution doesn’t have a simulation learning center or if it has limited offerings, the hands-on learning opportunities offered at CHEST headquarters may be a fit. Accredited by the Society for Simulation in Healthcare (SSH) and the Accreditation Council for Continuing Medical Education (ACCME), CHEST currently offers 24 courses with four new courses planned for 2023 in a wide variety of areas, including courses on ultrasound and bronchoscopy.

There are so many ways to introduce early career clinicians to CHEST, and it can begin with one personal outreach. If you are working on a project for CHEST right now, consider inviting an early career clinician to join you on it – this may be the opportunity that will change their career. It did for me.

As medical professionals, each of us plays an important role in the future of medicine, and the CHEST organization can bring us together to strengthen our impact.

If you are interested in brainstorming ideas for how to engage your medical students, residents, or fellows, please feel free to contact me or anyone at CHEST to help create a plan.

I look forward to the next time we connect.

Doreen J. Addrizzo-Harris, MD, FCCP

CHEST President

HMG-CoA reductase inhibitors (statins) have been shown to effectively reduce low-density lipoprotein cholesterol (LDL-C) as well as morbidity and mortality in patients who have either atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD.^1-12 However, research shows that up to 20% of patients are unable to tolerate statin therapy due to muscle-related adverse events (AEs).¹³ This presents a substantial clinical challenge, as current management strategies for patients with statin-associated muscle symptoms, such as intermittent administration of statins and ezetimibe, seldom achieve the > 50% LDL-C reduction recommended by the 2018 American Heart Association/American College of Cardiology Clinical Practice Guidelines.¹⁴ Additionally, statin-intolerant patients who have antihyperlipidemic medication lowered or discontinued are at an increased risk of future cardiovascular events.¹⁵ Observational data also show that about 70% of adult patients (primarily with genetic lipid disorders such as heterozygous familial hypercholesterolemia) do not achieve an LDL-C level < 100 mg/dL despite treatment with maximum doses of statins with or without ezetimibe.^16,17

PCSK9 inhibitors (PCSK9i) have robust efficacy data to support use in patients who do not meet their LDL-C goal despite maximally tolerated lipid therapy.¹⁴ However, long-term safety data for PCSK9i are not as robust as its efficacy data. Specifically, safety data relating to muscle-related AEs, which are the most widely recognized AE associated with statins, have only been reported in a few clinical trials with varying incidence rates, levels of significance, and relatively small study populations. Furthermore, the real-world prevalence of muscle-related PCSK9i AEs is unknown. Clinical guidance for management strategies for muscle-related AEs associated with PCSK9i is largely lacking. For this study, muscle-related AEs were defined as any new or unusual muscle soreness, weakness, cramping, aches, and stiffness that persists, is generally bilateral, and typically affects the large muscles. It is important to note, that muscle-related AEs associated with statins, ezetimibe, and PCSK9i can be attributed to the nocebo effect.

According to the prescribing information for alirocumab and evolocumab, myalgia, muscle spasms, and musculoskeletal pain each occurred in < 5% of the study populations.^18,19 From these data, muscle-related PCSK9i AEs are thought to be relatively rare, based on the ODYSSEY-OUTCOME and FOURIER trials, which did not enroll statin-intolerant patients.^20,21 However, currently available safety data from 3 small, randomized clinical trials specifically in statin-intolerant patients taking a PCSK9i suggest that muscle-related AEs occur at a rate of 12.2% to 32.5% and discontinuation rates varied from 0% to 15.9%.^22-25 As the incidence rates of muscle-related AEs in the prescribing information and clinical trials varied widely, this study will provide quantitative data on the percentage of patients that developed muscle-related PCSK9i AEs in a veteran population to help shed light on a topic that is not well studied.

Methods

This was a single-center, retrospective chart review of patients prescribed a PCSK9i between December 1, 2017, and September 1, 2021, and were managed in a pharmacy-led patient aligned care team (PACT) clinic at the Wilkes-Barre US Department of Veterans Affairs (VA) Medical Center (WBVAMC) in Pennsylvania. This study was approved by the Coatesville VA Medical Center Institutional Review Board, which oversees research conducted at WBVAMC. Veterans aged ≥ 18 years were included in the study. Patients were excluded if they had a history of serious hypersensitivity reaction to a PCSK9i or rhabdomyolysis or did not meet the VA criteria for use.²⁶

The primary outcome was the percentage of patients who developed a muscle-related AE while on a PCSK9i in a PACT clinic. Data were further analyzed based on patients who (1) tolerated a full PCSK9i dose; (2) tolerated alternative PCSK9i following initial intolerance; (3) required a PCSK9i dose reduction, or (4) discontinued PCSK9i. A secondary outcome was the percentage of statin- and/or ezetimibe-intolerant patients in these 4 groups. Another secondary outcome was the management strategies taken for patients who were on a reduced (monthly) dose of PCSK9i who did not reach their LDL-C goal. Management strategies that were assessed included restarting weekly statin, restarting weekly ezetimibe, increasing the dose of the same PCSK9i administered monthly, and switching to an alternative PCSK9i.

Data were collected using the VA Computerized Patient Record System (CPRS) and stored in a secure, locked spreadsheet. Baseline patient demographic characteristics collected included age (at PCSK9i start); sex; race; and PCSK9i name, dose, and frequency. We recorded when a patient switched PCSK9i, whether or not it was due to a muscle-related AE, and the name of the original PCSK9i. Also collected were lipid therapy intolerances prior to PCSK9i initiation (ie, intolerance to statin, ezetimibe, or both).

Patients were considered statin intolerant due to a muscle-related AE in accordance with the VA PCSK9i Criteria for Use, which requires trial of at least 3 statins, one of which was trialed at the lowest dosage approved by the US Food and Drug Administration (FDA) and resulted in intolerable skeletal muscle AEs that worsened during treatment and resolved when the statin was stopped. For our study purposes, patients taking alternative day dosing of statins due to muscle-related AEs (ie, 2- or 3-times weekly dosing) were not considered statin intolerant; however, patients taking once-weekly statin dosing were considered statin intolerant. Patients were considered ezetimibe intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when ezetimibe was stopped. Patients were considered PCSK9i intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when the PCSK9i was stopped. Patients with non–muscle-related intolerances to statins, ezetimibe, and PCSK9i were not considered statin, ezetimibe, and PCSK9i intolerant.

Alirocumab was initiated at 75 mg subcutaneous (SQ) once every 2 weeks or evolocumab 140 mg SQ once every 2 weeks in our study. The protocol allowed for a dose reduction of alirocumab 75 mg SQ once monthly if a patient experienced AEs, but this dose reduction strategy was not used for any patients on evolocumab in this study. Of note, alirocumab 75 mg SQ once monthly is not an FDA-approved dosing strategy. However, it is similar in concept to the alternative statin dosing (ie, alternate day dosing, once-weekly dosing) and may avoid the need to discontinue PCSK9i therapy altogether.

A review of the CPRS also documented whether a muscle-related AE occurred while the patient was on a PCSK9i (if yes, the specific AE was recorded), the result of PCSK9i therapy (tolerated full dose, required a dose reduction, switched medication, or discontinued), and management strategies taken for patients who did not meet their LDL-C goal while on a reduced (monthly) PCSK9i dose. Prior lipid therapy intolerances, PCSK9i-related AEs, results of PCSK9i therapy, and management strategies for patients who did not meet LDL-C goal while on a reduced PCSK9i dose were obtained by reviewing the PACT pharmacist’s clinic notes and assessment, along with clinic notes and medication history listed within the CPRS.

Statistical Analysis

Descriptive statistics were used for the demographic characteristics of study patients. The primary outcome was calculated as a binary measure (yes/no) of whether the patient developed a muscle-related AE while on a PCSK9i. The secondary outcome of statin, ezetimibe, or statin and ezetimibe intolerances in subgroups also was calculated as a binary measure.

Results

For the study, 156 charts were reviewed and 137 patients were included (Figure).

For the secondary results, 4 patients (2.9%) tolerated an alternate PCSK9i (evolocumab 140 mg SQ every 2 weeks) after initial intolerance to PCSK9i, 16 (11.7%) required a dose reduction, and 6 (4.4%) discontinued PCSK9i due to a muscle-related AE.

Discussion

This retrospective study found 17.5% of patients experienced muscle-related PCSK9i AEs. These occurred at a higher rate than reported in the prescribing information (< 5%) and were similar to the incidence rates reported in the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE clinical trials (12.0%-32.5%), which is what we hypothesized.^18,19,22-25 It is important to note that the incidence rates of muscle-related AEs reported in the prescribing information for alirocumab and evolocumab were based on trials that did not include statin- and/or ezetimibe-intolerant patients; whereas many patients in our study and patients in the clinical trials were statin and/or ezetimibe intolerant.

Additionally, a new study by Donald and colleagues found an incidence rate of 32% to 36% for muscle-related PCSK9i AEs.²⁷ Collectively, the data from clinical trials and our study indicate that patients with prior intolerances to statin and/or ezetimibe appear to have a higher likelihood of developing a muscle-related PCSK9i intolerance. In our study, 23 of 24 patients who developed a muscle-related PCSK9i AE had a prior history of statin and/or ezetimibe intolerances. This should alert clinicians prescribing PCSK9i in patients with a history of statin and/or ezetimibe intolerance to counsel their patients on the possibility of muscle-related PCSK9i AEs and management strategies. However, it is important to note that there was a substantial number of patients in our study who were statin and/or ezetimibe intolerant due to a prior muscle-related AE who tolerated the full dose of PCSK9i.

To our knowledge, this was the first trial to evaluate muscle-related PCSK9i AEs in a veteran population. Additionally, our study appears to be the first to use 2 PCSK9i dosing strategies that are not FDA approved: Dose reduction for patients who experienced a muscle-related AE on alirocumab 75 mg SQ every 2 weeks and dose escalation for patients who did not meet their LDL-C goal on alirocumab 75 mg SQ monthly following an initial intolerance to 2-week dosing. The dose-reduction strategy allowed patients who experienced a muscle-related AE to alirocumab 75 mg to reduce administration from every 2 weeks to monthly.

This strategy was only performed with alirocumab, the preferred PCSK9i at WBVAMC, but the same dose-reduction strategy can theoretically be used with evolocumab as well. Reduced monthly dosing of alirocumab allowed patients with a prior intolerance to remain on a lower dosage without discontinuation. This is important because as noted by Myers and colleagues, individuals without access to PCSK9i were found to have a significantly higher incidence ratio of cardiovascular events compared with those taking PCSK9i.¹⁵ Also of note, > 30% of patients on the reduced monthly dose of alirocumab still met their LDL-C goal. Therefore, using this dose-reduction strategy (instead of patients discontinuing therapy altogether due to a muscle-related intolerance) can lessen the risk of major adverse cardiovascular events (MACE) as well as mitigate muscle-related AEs that occurred while on 2-week PCSK9i dosing regimens. While we acknowledge that this reduced monthly dose of either alirocumab or evolocumab is not FDA approved, it is similar to alternative statin dosing that also is not FDA approved but may minimize the need to discontinue PCSK9i therapy. It would be beneficial if these dosing strategies were investigated by future research.

The dose-escalation strategy for patients who did not meet their LDL-C goal while on the reduced, monthly dose of alirocumab also was unique. Alirocumab was increased from 75 mg SQ once monthly to 150 mg SQ once monthly. Interestingly, we found that through the end of the chart review period, all patients tolerated the increase well, despite having an initial muscle-related AE to alirocumab 75 mg every 2 weeks, which is the same total monthly dosage. This approach is similar to that of once-weekly statin dosing or a drug holiday and may be explained by the long half-life of PCSK9i. Regardless of the mechanism, this finding suggests that an increased monthly dose of PCSK9i is a potential alternative for patients who cannot tolerate the FDA-approved dose. However, the ability for patients to achieve goal LDL-C on the monthly dosage requires future study.

Limitations

The results of this study should be considered with the following limitations. First, this was a retrospective chart review performed over a prespecified period. Any muscle-related AEs or LDL-C lowering effects from PCSK9i that occurred outside the review period were not captured. Our study was small and only included 137 patients, though it was similar in size to the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE trials.^22-24 Additionally, the study was primarily composed of White men and may not be representative of other populations. Some muscle-related PCSK9i AEs may be attributed to the nocebo. Last, our study did not capture patients on a PCSK9i who were not followed in the PACT clinic.

Conclusions

We found that muscle-related PCSK9i AEs occurred at a similar rate as those reported in previous clinical trials and exceeded the incidence rate reported in the prescribing information for alirocumab and evolocumab. It appears that patients who have a prior muscle-related intolerance to a statin and/or ezetimibe had a higher likelihood of developing a muscle-related PCSK9i AE. In our study, only 1 patient developed a muscle-related PCSK9i AE who did not have a prior history of muscle-related intolerance to either a statin or ezetimibe. However, in our study, a substantial percentage of patients with statin and/or ezetimibe intolerances tolerated the full PCSK9i dose well, proving that PCSK9i are still a reasonable alternative for patients with prior intolerances to statins and/or ezetimibe.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the US Department of Veterans Affairs Medical Center, Wilkes-Barre, Pennsylvania.

HMG-CoA reductase inhibitors (statins) have been shown to effectively reduce low-density lipoprotein cholesterol (LDL-C) as well as morbidity and mortality in patients who have either atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD.^1-12 However, research shows that up to 20% of patients are unable to tolerate statin therapy due to muscle-related adverse events (AEs).¹³ This presents a substantial clinical challenge, as current management strategies for patients with statin-associated muscle symptoms, such as intermittent administration of statins and ezetimibe, seldom achieve the > 50% LDL-C reduction recommended by the 2018 American Heart Association/American College of Cardiology Clinical Practice Guidelines.¹⁴ Additionally, statin-intolerant patients who have antihyperlipidemic medication lowered or discontinued are at an increased risk of future cardiovascular events.¹⁵ Observational data also show that about 70% of adult patients (primarily with genetic lipid disorders such as heterozygous familial hypercholesterolemia) do not achieve an LDL-C level < 100 mg/dL despite treatment with maximum doses of statins with or without ezetimibe.^16,17

PCSK9 inhibitors (PCSK9i) have robust efficacy data to support use in patients who do not meet their LDL-C goal despite maximally tolerated lipid therapy.¹⁴ However, long-term safety data for PCSK9i are not as robust as its efficacy data. Specifically, safety data relating to muscle-related AEs, which are the most widely recognized AE associated with statins, have only been reported in a few clinical trials with varying incidence rates, levels of significance, and relatively small study populations. Furthermore, the real-world prevalence of muscle-related PCSK9i AEs is unknown. Clinical guidance for management strategies for muscle-related AEs associated with PCSK9i is largely lacking. For this study, muscle-related AEs were defined as any new or unusual muscle soreness, weakness, cramping, aches, and stiffness that persists, is generally bilateral, and typically affects the large muscles. It is important to note, that muscle-related AEs associated with statins, ezetimibe, and PCSK9i can be attributed to the nocebo effect.

According to the prescribing information for alirocumab and evolocumab, myalgia, muscle spasms, and musculoskeletal pain each occurred in < 5% of the study populations.^18,19 From these data, muscle-related PCSK9i AEs are thought to be relatively rare, based on the ODYSSEY-OUTCOME and FOURIER trials, which did not enroll statin-intolerant patients.^20,21 However, currently available safety data from 3 small, randomized clinical trials specifically in statin-intolerant patients taking a PCSK9i suggest that muscle-related AEs occur at a rate of 12.2% to 32.5% and discontinuation rates varied from 0% to 15.9%.^22-25 As the incidence rates of muscle-related AEs in the prescribing information and clinical trials varied widely, this study will provide quantitative data on the percentage of patients that developed muscle-related PCSK9i AEs in a veteran population to help shed light on a topic that is not well studied.

Methods

This was a single-center, retrospective chart review of patients prescribed a PCSK9i between December 1, 2017, and September 1, 2021, and were managed in a pharmacy-led patient aligned care team (PACT) clinic at the Wilkes-Barre US Department of Veterans Affairs (VA) Medical Center (WBVAMC) in Pennsylvania. This study was approved by the Coatesville VA Medical Center Institutional Review Board, which oversees research conducted at WBVAMC. Veterans aged ≥ 18 years were included in the study. Patients were excluded if they had a history of serious hypersensitivity reaction to a PCSK9i or rhabdomyolysis or did not meet the VA criteria for use.²⁶

The primary outcome was the percentage of patients who developed a muscle-related AE while on a PCSK9i in a PACT clinic. Data were further analyzed based on patients who (1) tolerated a full PCSK9i dose; (2) tolerated alternative PCSK9i following initial intolerance; (3) required a PCSK9i dose reduction, or (4) discontinued PCSK9i. A secondary outcome was the percentage of statin- and/or ezetimibe-intolerant patients in these 4 groups. Another secondary outcome was the management strategies taken for patients who were on a reduced (monthly) dose of PCSK9i who did not reach their LDL-C goal. Management strategies that were assessed included restarting weekly statin, restarting weekly ezetimibe, increasing the dose of the same PCSK9i administered monthly, and switching to an alternative PCSK9i.

Data were collected using the VA Computerized Patient Record System (CPRS) and stored in a secure, locked spreadsheet. Baseline patient demographic characteristics collected included age (at PCSK9i start); sex; race; and PCSK9i name, dose, and frequency. We recorded when a patient switched PCSK9i, whether or not it was due to a muscle-related AE, and the name of the original PCSK9i. Also collected were lipid therapy intolerances prior to PCSK9i initiation (ie, intolerance to statin, ezetimibe, or both).

Patients were considered statin intolerant due to a muscle-related AE in accordance with the VA PCSK9i Criteria for Use, which requires trial of at least 3 statins, one of which was trialed at the lowest dosage approved by the US Food and Drug Administration (FDA) and resulted in intolerable skeletal muscle AEs that worsened during treatment and resolved when the statin was stopped. For our study purposes, patients taking alternative day dosing of statins due to muscle-related AEs (ie, 2- or 3-times weekly dosing) were not considered statin intolerant; however, patients taking once-weekly statin dosing were considered statin intolerant. Patients were considered ezetimibe intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when ezetimibe was stopped. Patients were considered PCSK9i intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when the PCSK9i was stopped. Patients with non–muscle-related intolerances to statins, ezetimibe, and PCSK9i were not considered statin, ezetimibe, and PCSK9i intolerant.

Alirocumab was initiated at 75 mg subcutaneous (SQ) once every 2 weeks or evolocumab 140 mg SQ once every 2 weeks in our study. The protocol allowed for a dose reduction of alirocumab 75 mg SQ once monthly if a patient experienced AEs, but this dose reduction strategy was not used for any patients on evolocumab in this study. Of note, alirocumab 75 mg SQ once monthly is not an FDA-approved dosing strategy. However, it is similar in concept to the alternative statin dosing (ie, alternate day dosing, once-weekly dosing) and may avoid the need to discontinue PCSK9i therapy altogether.

A review of the CPRS also documented whether a muscle-related AE occurred while the patient was on a PCSK9i (if yes, the specific AE was recorded), the result of PCSK9i therapy (tolerated full dose, required a dose reduction, switched medication, or discontinued), and management strategies taken for patients who did not meet their LDL-C goal while on a reduced (monthly) PCSK9i dose. Prior lipid therapy intolerances, PCSK9i-related AEs, results of PCSK9i therapy, and management strategies for patients who did not meet LDL-C goal while on a reduced PCSK9i dose were obtained by reviewing the PACT pharmacist’s clinic notes and assessment, along with clinic notes and medication history listed within the CPRS.

Statistical Analysis

Descriptive statistics were used for the demographic characteristics of study patients. The primary outcome was calculated as a binary measure (yes/no) of whether the patient developed a muscle-related AE while on a PCSK9i. The secondary outcome of statin, ezetimibe, or statin and ezetimibe intolerances in subgroups also was calculated as a binary measure.

Results

For the study, 156 charts were reviewed and 137 patients were included (Figure).

For the secondary results, 4 patients (2.9%) tolerated an alternate PCSK9i (evolocumab 140 mg SQ every 2 weeks) after initial intolerance to PCSK9i, 16 (11.7%) required a dose reduction, and 6 (4.4%) discontinued PCSK9i due to a muscle-related AE.

Discussion

This retrospective study found 17.5% of patients experienced muscle-related PCSK9i AEs. These occurred at a higher rate than reported in the prescribing information (< 5%) and were similar to the incidence rates reported in the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE clinical trials (12.0%-32.5%), which is what we hypothesized.^18,19,22-25 It is important to note that the incidence rates of muscle-related AEs reported in the prescribing information for alirocumab and evolocumab were based on trials that did not include statin- and/or ezetimibe-intolerant patients; whereas many patients in our study and patients in the clinical trials were statin and/or ezetimibe intolerant.

Additionally, a new study by Donald and colleagues found an incidence rate of 32% to 36% for muscle-related PCSK9i AEs.²⁷ Collectively, the data from clinical trials and our study indicate that patients with prior intolerances to statin and/or ezetimibe appear to have a higher likelihood of developing a muscle-related PCSK9i intolerance. In our study, 23 of 24 patients who developed a muscle-related PCSK9i AE had a prior history of statin and/or ezetimibe intolerances. This should alert clinicians prescribing PCSK9i in patients with a history of statin and/or ezetimibe intolerance to counsel their patients on the possibility of muscle-related PCSK9i AEs and management strategies. However, it is important to note that there was a substantial number of patients in our study who were statin and/or ezetimibe intolerant due to a prior muscle-related AE who tolerated the full dose of PCSK9i.

To our knowledge, this was the first trial to evaluate muscle-related PCSK9i AEs in a veteran population. Additionally, our study appears to be the first to use 2 PCSK9i dosing strategies that are not FDA approved: Dose reduction for patients who experienced a muscle-related AE on alirocumab 75 mg SQ every 2 weeks and dose escalation for patients who did not meet their LDL-C goal on alirocumab 75 mg SQ monthly following an initial intolerance to 2-week dosing. The dose-reduction strategy allowed patients who experienced a muscle-related AE to alirocumab 75 mg to reduce administration from every 2 weeks to monthly.

This strategy was only performed with alirocumab, the preferred PCSK9i at WBVAMC, but the same dose-reduction strategy can theoretically be used with evolocumab as well. Reduced monthly dosing of alirocumab allowed patients with a prior intolerance to remain on a lower dosage without discontinuation. This is important because as noted by Myers and colleagues, individuals without access to PCSK9i were found to have a significantly higher incidence ratio of cardiovascular events compared with those taking PCSK9i.¹⁵ Also of note, > 30% of patients on the reduced monthly dose of alirocumab still met their LDL-C goal. Therefore, using this dose-reduction strategy (instead of patients discontinuing therapy altogether due to a muscle-related intolerance) can lessen the risk of major adverse cardiovascular events (MACE) as well as mitigate muscle-related AEs that occurred while on 2-week PCSK9i dosing regimens. While we acknowledge that this reduced monthly dose of either alirocumab or evolocumab is not FDA approved, it is similar to alternative statin dosing that also is not FDA approved but may minimize the need to discontinue PCSK9i therapy. It would be beneficial if these dosing strategies were investigated by future research.

The dose-escalation strategy for patients who did not meet their LDL-C goal while on the reduced, monthly dose of alirocumab also was unique. Alirocumab was increased from 75 mg SQ once monthly to 150 mg SQ once monthly. Interestingly, we found that through the end of the chart review period, all patients tolerated the increase well, despite having an initial muscle-related AE to alirocumab 75 mg every 2 weeks, which is the same total monthly dosage. This approach is similar to that of once-weekly statin dosing or a drug holiday and may be explained by the long half-life of PCSK9i. Regardless of the mechanism, this finding suggests that an increased monthly dose of PCSK9i is a potential alternative for patients who cannot tolerate the FDA-approved dose. However, the ability for patients to achieve goal LDL-C on the monthly dosage requires future study.

Limitations

The results of this study should be considered with the following limitations. First, this was a retrospective chart review performed over a prespecified period. Any muscle-related AEs or LDL-C lowering effects from PCSK9i that occurred outside the review period were not captured. Our study was small and only included 137 patients, though it was similar in size to the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE trials.^22-24 Additionally, the study was primarily composed of White men and may not be representative of other populations. Some muscle-related PCSK9i AEs may be attributed to the nocebo. Last, our study did not capture patients on a PCSK9i who were not followed in the PACT clinic.

Conclusions

We found that muscle-related PCSK9i AEs occurred at a similar rate as those reported in previous clinical trials and exceeded the incidence rate reported in the prescribing information for alirocumab and evolocumab. It appears that patients who have a prior muscle-related intolerance to a statin and/or ezetimibe had a higher likelihood of developing a muscle-related PCSK9i AE. In our study, only 1 patient developed a muscle-related PCSK9i AE who did not have a prior history of muscle-related intolerance to either a statin or ezetimibe. However, in our study, a substantial percentage of patients with statin and/or ezetimibe intolerances tolerated the full PCSK9i dose well, proving that PCSK9i are still a reasonable alternative for patients with prior intolerances to statins and/or ezetimibe.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the US Department of Veterans Affairs Medical Center, Wilkes-Barre, Pennsylvania.

HMG-CoA reductase inhibitors (statins) have been shown to effectively reduce low-density lipoprotein cholesterol (LDL-C) as well as morbidity and mortality in patients who have either atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD.^1-12 However, research shows that up to 20% of patients are unable to tolerate statin therapy due to muscle-related adverse events (AEs).¹³ This presents a substantial clinical challenge, as current management strategies for patients with statin-associated muscle symptoms, such as intermittent administration of statins and ezetimibe, seldom achieve the > 50% LDL-C reduction recommended by the 2018 American Heart Association/American College of Cardiology Clinical Practice Guidelines.¹⁴ Additionally, statin-intolerant patients who have antihyperlipidemic medication lowered or discontinued are at an increased risk of future cardiovascular events.¹⁵ Observational data also show that about 70% of adult patients (primarily with genetic lipid disorders such as heterozygous familial hypercholesterolemia) do not achieve an LDL-C level < 100 mg/dL despite treatment with maximum doses of statins with or without ezetimibe.^16,17

PCSK9 inhibitors (PCSK9i) have robust efficacy data to support use in patients who do not meet their LDL-C goal despite maximally tolerated lipid therapy.¹⁴ However, long-term safety data for PCSK9i are not as robust as its efficacy data. Specifically, safety data relating to muscle-related AEs, which are the most widely recognized AE associated with statins, have only been reported in a few clinical trials with varying incidence rates, levels of significance, and relatively small study populations. Furthermore, the real-world prevalence of muscle-related PCSK9i AEs is unknown. Clinical guidance for management strategies for muscle-related AEs associated with PCSK9i is largely lacking. For this study, muscle-related AEs were defined as any new or unusual muscle soreness, weakness, cramping, aches, and stiffness that persists, is generally bilateral, and typically affects the large muscles. It is important to note, that muscle-related AEs associated with statins, ezetimibe, and PCSK9i can be attributed to the nocebo effect.

According to the prescribing information for alirocumab and evolocumab, myalgia, muscle spasms, and musculoskeletal pain each occurred in < 5% of the study populations.^18,19 From these data, muscle-related PCSK9i AEs are thought to be relatively rare, based on the ODYSSEY-OUTCOME and FOURIER trials, which did not enroll statin-intolerant patients.^20,21 However, currently available safety data from 3 small, randomized clinical trials specifically in statin-intolerant patients taking a PCSK9i suggest that muscle-related AEs occur at a rate of 12.2% to 32.5% and discontinuation rates varied from 0% to 15.9%.^22-25 As the incidence rates of muscle-related AEs in the prescribing information and clinical trials varied widely, this study will provide quantitative data on the percentage of patients that developed muscle-related PCSK9i AEs in a veteran population to help shed light on a topic that is not well studied.

Methods

This was a single-center, retrospective chart review of patients prescribed a PCSK9i between December 1, 2017, and September 1, 2021, and were managed in a pharmacy-led patient aligned care team (PACT) clinic at the Wilkes-Barre US Department of Veterans Affairs (VA) Medical Center (WBVAMC) in Pennsylvania. This study was approved by the Coatesville VA Medical Center Institutional Review Board, which oversees research conducted at WBVAMC. Veterans aged ≥ 18 years were included in the study. Patients were excluded if they had a history of serious hypersensitivity reaction to a PCSK9i or rhabdomyolysis or did not meet the VA criteria for use.²⁶

The primary outcome was the percentage of patients who developed a muscle-related AE while on a PCSK9i in a PACT clinic. Data were further analyzed based on patients who (1) tolerated a full PCSK9i dose; (2) tolerated alternative PCSK9i following initial intolerance; (3) required a PCSK9i dose reduction, or (4) discontinued PCSK9i. A secondary outcome was the percentage of statin- and/or ezetimibe-intolerant patients in these 4 groups. Another secondary outcome was the management strategies taken for patients who were on a reduced (monthly) dose of PCSK9i who did not reach their LDL-C goal. Management strategies that were assessed included restarting weekly statin, restarting weekly ezetimibe, increasing the dose of the same PCSK9i administered monthly, and switching to an alternative PCSK9i.

Data were collected using the VA Computerized Patient Record System (CPRS) and stored in a secure, locked spreadsheet. Baseline patient demographic characteristics collected included age (at PCSK9i start); sex; race; and PCSK9i name, dose, and frequency. We recorded when a patient switched PCSK9i, whether or not it was due to a muscle-related AE, and the name of the original PCSK9i. Also collected were lipid therapy intolerances prior to PCSK9i initiation (ie, intolerance to statin, ezetimibe, or both).

Patients were considered statin intolerant due to a muscle-related AE in accordance with the VA PCSK9i Criteria for Use, which requires trial of at least 3 statins, one of which was trialed at the lowest dosage approved by the US Food and Drug Administration (FDA) and resulted in intolerable skeletal muscle AEs that worsened during treatment and resolved when the statin was stopped. For our study purposes, patients taking alternative day dosing of statins due to muscle-related AEs (ie, 2- or 3-times weekly dosing) were not considered statin intolerant; however, patients taking once-weekly statin dosing were considered statin intolerant. Patients were considered ezetimibe intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when ezetimibe was stopped. Patients were considered PCSK9i intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when the PCSK9i was stopped. Patients with non–muscle-related intolerances to statins, ezetimibe, and PCSK9i were not considered statin, ezetimibe, and PCSK9i intolerant.

Alirocumab was initiated at 75 mg subcutaneous (SQ) once every 2 weeks or evolocumab 140 mg SQ once every 2 weeks in our study. The protocol allowed for a dose reduction of alirocumab 75 mg SQ once monthly if a patient experienced AEs, but this dose reduction strategy was not used for any patients on evolocumab in this study. Of note, alirocumab 75 mg SQ once monthly is not an FDA-approved dosing strategy. However, it is similar in concept to the alternative statin dosing (ie, alternate day dosing, once-weekly dosing) and may avoid the need to discontinue PCSK9i therapy altogether.

A review of the CPRS also documented whether a muscle-related AE occurred while the patient was on a PCSK9i (if yes, the specific AE was recorded), the result of PCSK9i therapy (tolerated full dose, required a dose reduction, switched medication, or discontinued), and management strategies taken for patients who did not meet their LDL-C goal while on a reduced (monthly) PCSK9i dose. Prior lipid therapy intolerances, PCSK9i-related AEs, results of PCSK9i therapy, and management strategies for patients who did not meet LDL-C goal while on a reduced PCSK9i dose were obtained by reviewing the PACT pharmacist’s clinic notes and assessment, along with clinic notes and medication history listed within the CPRS.

Statistical Analysis

Descriptive statistics were used for the demographic characteristics of study patients. The primary outcome was calculated as a binary measure (yes/no) of whether the patient developed a muscle-related AE while on a PCSK9i. The secondary outcome of statin, ezetimibe, or statin and ezetimibe intolerances in subgroups also was calculated as a binary measure.

Results

For the study, 156 charts were reviewed and 137 patients were included (Figure).

For the secondary results, 4 patients (2.9%) tolerated an alternate PCSK9i (evolocumab 140 mg SQ every 2 weeks) after initial intolerance to PCSK9i, 16 (11.7%) required a dose reduction, and 6 (4.4%) discontinued PCSK9i due to a muscle-related AE.

Discussion

This retrospective study found 17.5% of patients experienced muscle-related PCSK9i AEs. These occurred at a higher rate than reported in the prescribing information (< 5%) and were similar to the incidence rates reported in the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE clinical trials (12.0%-32.5%), which is what we hypothesized.^18,19,22-25 It is important to note that the incidence rates of muscle-related AEs reported in the prescribing information for alirocumab and evolocumab were based on trials that did not include statin- and/or ezetimibe-intolerant patients; whereas many patients in our study and patients in the clinical trials were statin and/or ezetimibe intolerant.

Additionally, a new study by Donald and colleagues found an incidence rate of 32% to 36% for muscle-related PCSK9i AEs.²⁷ Collectively, the data from clinical trials and our study indicate that patients with prior intolerances to statin and/or ezetimibe appear to have a higher likelihood of developing a muscle-related PCSK9i intolerance. In our study, 23 of 24 patients who developed a muscle-related PCSK9i AE had a prior history of statin and/or ezetimibe intolerances. This should alert clinicians prescribing PCSK9i in patients with a history of statin and/or ezetimibe intolerance to counsel their patients on the possibility of muscle-related PCSK9i AEs and management strategies. However, it is important to note that there was a substantial number of patients in our study who were statin and/or ezetimibe intolerant due to a prior muscle-related AE who tolerated the full dose of PCSK9i.

To our knowledge, this was the first trial to evaluate muscle-related PCSK9i AEs in a veteran population. Additionally, our study appears to be the first to use 2 PCSK9i dosing strategies that are not FDA approved: Dose reduction for patients who experienced a muscle-related AE on alirocumab 75 mg SQ every 2 weeks and dose escalation for patients who did not meet their LDL-C goal on alirocumab 75 mg SQ monthly following an initial intolerance to 2-week dosing. The dose-reduction strategy allowed patients who experienced a muscle-related AE to alirocumab 75 mg to reduce administration from every 2 weeks to monthly.

This strategy was only performed with alirocumab, the preferred PCSK9i at WBVAMC, but the same dose-reduction strategy can theoretically be used with evolocumab as well. Reduced monthly dosing of alirocumab allowed patients with a prior intolerance to remain on a lower dosage without discontinuation. This is important because as noted by Myers and colleagues, individuals without access to PCSK9i were found to have a significantly higher incidence ratio of cardiovascular events compared with those taking PCSK9i.¹⁵ Also of note, > 30% of patients on the reduced monthly dose of alirocumab still met their LDL-C goal. Therefore, using this dose-reduction strategy (instead of patients discontinuing therapy altogether due to a muscle-related intolerance) can lessen the risk of major adverse cardiovascular events (MACE) as well as mitigate muscle-related AEs that occurred while on 2-week PCSK9i dosing regimens. While we acknowledge that this reduced monthly dose of either alirocumab or evolocumab is not FDA approved, it is similar to alternative statin dosing that also is not FDA approved but may minimize the need to discontinue PCSK9i therapy. It would be beneficial if these dosing strategies were investigated by future research.

The dose-escalation strategy for patients who did not meet their LDL-C goal while on the reduced, monthly dose of alirocumab also was unique. Alirocumab was increased from 75 mg SQ once monthly to 150 mg SQ once monthly. Interestingly, we found that through the end of the chart review period, all patients tolerated the increase well, despite having an initial muscle-related AE to alirocumab 75 mg every 2 weeks, which is the same total monthly dosage. This approach is similar to that of once-weekly statin dosing or a drug holiday and may be explained by the long half-life of PCSK9i. Regardless of the mechanism, this finding suggests that an increased monthly dose of PCSK9i is a potential alternative for patients who cannot tolerate the FDA-approved dose. However, the ability for patients to achieve goal LDL-C on the monthly dosage requires future study.

Limitations

The results of this study should be considered with the following limitations. First, this was a retrospective chart review performed over a prespecified period. Any muscle-related AEs or LDL-C lowering effects from PCSK9i that occurred outside the review period were not captured. Our study was small and only included 137 patients, though it was similar in size to the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE trials.^22-24 Additionally, the study was primarily composed of White men and may not be representative of other populations. Some muscle-related PCSK9i AEs may be attributed to the nocebo. Last, our study did not capture patients on a PCSK9i who were not followed in the PACT clinic.

Conclusions

We found that muscle-related PCSK9i AEs occurred at a similar rate as those reported in previous clinical trials and exceeded the incidence rate reported in the prescribing information for alirocumab and evolocumab. It appears that patients who have a prior muscle-related intolerance to a statin and/or ezetimibe had a higher likelihood of developing a muscle-related PCSK9i AE. In our study, only 1 patient developed a muscle-related PCSK9i AE who did not have a prior history of muscle-related intolerance to either a statin or ezetimibe. However, in our study, a substantial percentage of patients with statin and/or ezetimibe intolerances tolerated the full PCSK9i dose well, proving that PCSK9i are still a reasonable alternative for patients with prior intolerances to statins and/or ezetimibe.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the US Department of Veterans Affairs Medical Center, Wilkes-Barre, Pennsylvania.