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Pulmonary vascular & cardiovascular network: Cardiovascular medicine & surgery section
Targeted temperature management (TTM) after cardiac arrest: How cool?
Recent randomized control trials, TTM2 (Dankiewicz J. N Engl J Med. 2021;384:2283) and HYPERION (Lascarrou J-B. N Engl J Med. 2019;381:2327), of therapeutic hypothermia, as opposed to normothermia, in patients who remain comatose after return of spontaneous circulation (ROSC) after cardiac arrest have produced conflicting results regarding survival and neurologic benefit. TTM2 reported no benefit to cooling to 33°C, while HYPERION found improved neurologic outcome at 90 days in patients cooled to 33°C. The European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recently released an evidence review and guideline for adults who remain comatose after cardiac arrest (Sandroni C. Intensive Care Med. 2022;48:261). These guidelines recommend continuous monitoring of core temperature in all patients who remain comatose after cardiac arrest, and preventing fever (>37.7°C) for 72 hours, but with no recommendation of target temperature of 32°C vs 36°C.
Differences in patient populations, presenting rhythm during arrest, duration of CPR, and time to target temperature likely each contribute to the disparate conclusions of previous trials. For example, HYPERION enrolled patients with out of hospital cardiac arrest with initial nonshockable rhythms and found benefit to cooling to 33°C. In comparison, TTM2 enrolled all patients with ROSC following arrest (regardless of rhythm), including patients with in-hospital cardiac arrest and found no benefit in therapeutic cooling. Differences in patient populations are underscored by the widely differing percentage of patients with good neurologic outcome in their respective control groups: approximately 30% in the TTM2 trial and 6% in HYPERION. The guidelines leave significant room for clinical judgment in employing therapeutic cooling but encourage the continuous monitoring of core temperature and active avoidance of fever.
Fiore Mastroianna, MD
Section Member-at-Large
Chest infections & disaster response network: Chest infections section
Update on LTBI treatment: Ensuring success by simplifying, shortening, and completing treatment
My patient has a positive IGRA test result – what’s next?
If TB disease is ruled out by clinical, radiographic, and microbiologic assessment (if indicated), then latent TB infection (LTBI) is established, and treatment should be offered, guided by shared-decision making between provider and patient.
What options are available?
While the former standard 9-month regimen of isoniazid-monotherapy can be shortened to 6 months, shorter rifamycin-based regimens are now preferred in most cases and include:
4 months rifampin daily, 3 months isoniazid plus rifampin daily, or 3 months isoniazid plus rifapentine weekly. In addition, 1 month of isoniazid plus rifapentine daily has recently been shown to be effective in people with HIV.
How to choose?
Rifamycin-based regimens have been shown to have less hepatotoxicity and higher completion rates. Drug-drug interactions are of potential concern, for example, in patients receiving anticoagulation or treatment for HIV. The clinician should be aware of rifamycins causing a flu-like illness that may be treatment-limiting. In patients with known contact to drug-resistant TB, regimens are individualized.
How to monitor?
Adherence and completion are the keys to success. Directly observed therapy may be indicated in certain scenarios. Baseline and monthly blood work is recommended for people with risk factors for hepatic or bone marrow toxicity. More importantly, patients should be instructed to discontinue LTBI medications and call the clinician with any new symptoms. HIV testing should be offered to all patients if status is unknown. Clinicians are encouraged to reach out to one of four regional TB Centers of Excellence for guidance.
Sebastian Kurz, MD, FCCP
Amee Patrawalla, MD, MPH, FCCP
Section Members-at-Large
References
Testing and Treatment of Latent Tuberculosis Infection in the United States: Clinical Recommendations. A Guide for Health Care Providers and Public Health Programs. Copyright © 2021 by the National Society of Tuberculosis Clinicians and National Tuberculosis Controllers Association
1. Shah, D. Latent tuberculosis infection. N Engl J Med. 2021;385:2271-80.
2. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-115.
3. Swindells et. al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med. 2019;380:1001-11.
Thoracic oncology & chest procedures network: Lung cancer section
Adjuvant and neoadjuvant therapies in early stage lung cancer
Since the discovery of the epidermal growth factor receptor (EGFR) mutation in 2004 and the development of checkpoint blockade in 2006, personalized treatment options for non–small cell lung cancer (NSCLC) have exploded, but targeted systemic therapy medications were only recommended among patients with metastatic or locally advanced disease (Rivera MP, Matthay RA. Clin Chest Med. 2020;41[1]:ix-xi). However, in November 2020, the National Comprehensive Cancer Network (NCCN) updated guidelines to recommend EGFR testing in surgically resected stage IB-IIIA adenocarcinoma, and to consider adjuvant osimerintib in those who were mutation-positive (NCCN. Nov 2020). Interim analysis of an ongoing phase-3 trial showed 89% of patients in the osimertinib group were alive and disease-free at 24 months compared with 52% in the placebo group (hazard ratio 0.20, P < .001) (Wu YL, et al. N Engl J Med. 2020;383[18]:1711-23).
The FDA has also recently approved the use of neoadjuvant and adjuvant immunotherapy in combination with platinum-based chemotherapy. Nivolumab is now approved as neoadjuvant therapy in patients with resectable IB-IIIA NSCLC regardless of PDL-1 status. The Checkmate-816 trial showed increased median event-free survival in the immunotherapy plus chemotherapy group of 31.6 months vs 20.8 months in the chemotherapy-only group (FDA.gov. 2022, Mar 4). Atezolizumab is also now approved for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on ≥ 1% of tumor cells. Median disease-free survival was not reached in patients in the atezolizumab groups vs 35.3 months in the best supportive care group (FDA.gov. 2021, Oct 15). With so many advances in the personalized treatment among all stages of NSCLC, this is a hopeful new chapter in the care of patients with NSCLC.
More information: https://www.nccn.org/guidelines/guidelines-process/transparency-process-and-recommendations/GetFileFromFileManager?fileManagerId=11259
Sohini Ghosh, MD
Section Member-at-Large
Diffuse lung disease and lung transplant network: Lung transplant section
Continuous distribution for lung transplant: Overhauling the wait list
Determining how to allocate the scarce resource of donor lungs to patients is a difficult task and evaluated continuously for potential improvement. Since 2005, in the United States, lung transplant recipients have been selected based primarily on location within a Donor Service Area and by lung allocation score (LAS), a composite score of urgency for transplant. This was updated in 2017 to an allocation by highest LAS within 250 nautical miles from the donor hospital. Factors such as blood type compatibility and height are also considered. Implementation of the LAS improved the sickest patients’ access to transplants while not worsening 1-year mortality (Egan TM. Semin Respir Crit Care Med. 2018;39[02]:126-37). Unfortunately, geographic hard boundaries mean a high proportion of low LAS (<50) patients receive local donors while high LAS patients receive national offers or die while on the waitlist (Iribarne A, et al. Clin Transplant. 2016:30:688-93).
A new model that employs continuous distribution has been developed based on concerns regarding equity and improving allocation. This model would prioritize patients based on factors including medical priority, efficient management of organ placement (distance), expected posttransplant outcomes, and patient access (equity). By creating a composite of these without a geographic boundary, patients would be considered more on urgency within realistic constraints of distance and outcomes. 
The Organ Procurement and Transplantation Network has officially approved continuous distribution, with implementation planned for 2022; details regarding the new scoring system are to be published and further research will need to be undertaken to determine if it meets the goal of overall improvement in patient access, equity, and outcomes.
Grant A. Turner, MD, MHA
Laura Frye, MD
Section Members-at-Large
Critical care network: Non-respiratory critical care section
Update from the non-respiratory critical care section
As you’ve probably noticed, there have been some changes here at CHEST involving the Networks. Leadership here at CHEST has been hard at work restructuring the networks to make them more closely aligned with relevant clinical disciplines, and, ultimately, allow for greater participation. I am proud to have been given stewardship of the new Non-Respiratory Critical Care Section of the Critical Care Network.
So, what exactly is Non-Respiratory Critical Care? Well, that’s where I need your help. You see this network is meant to reflect the needs and wants of CHEST members like you. We need you, dear readers, to join in this venture and help us guide the content that this section will ultimately create for our members.
If you’re interested in critical care, but you don’t see your particular area of interest anywhere else in the current structure ... guess what? You’ve found the right place!
My Infectious Diseases and Nephro peeps? Welcome! Are you a surgical or anesthesia intensivist? Don’t be shy. ECMO people, let’s hear some chatter!Is therapeutic hypothermia your thing? Come on in. The water’s freezing. 33 degrees just like you folks like it. Or is it 36? Not sure. Anyway, see what I’m talking about? We really need your help!You can get involved by clicking on the Membership & Community tab at the CHEST website. Once you’re a member, you can even nominate yourself to run for the Steering Committee elections which are held periodically. Hope to see you soon!
Deep Ramachandran, MD, FCCP
Section Chair
Sleep medicine network: Non-respiratory sleep section
Unusual suspects? Breakthrough in the treatment of idiopathic hypersomnia
Idiopathic hypersomnia (IH) is a rare and debilitating disorder defined by its excessive daytime sleepiness, sleep inertia, prolonged nighttime sleep, and long, unrefreshing naps (AASM. ICSD 3rd ed. 2014). Gamma-aminobutyric acid (GABA) is one of the main inhibitory neurotransmitters in the nervous system. It is through the potentiation of GABA that substances such as alcohol and benzodiazepines yield their effects. It is also hypothesized that the “brain fog” experienced in IH may be a consequence of either higher levels of an endogenous benzodiazepines in the cerebral spinal fluid or the presence of a GABA-enhancing peptide (Rye DB. Science Transl Med. 2012;Med 4:161ra151).
Sodium oxybate (SXB), a compound that likely has its therapeutic effect through the potentiation of GABA receptors, is an effective treatment option for cataplexy and sleepiness in narcolepsy. Although there may be some overlap between narcolepsy and IH in both diagnosis and treatment (Bassetti C, et al. Brain. 1997;120:1423), it would perhaps be entirely counterintuitive (given SXB’s pharmacology) to imagine using SXB as a plausible treatment option in IH. It was, however, investigated in the treatment of refractory hypersomnia and IH. In the retrospective study looking at 46 subjects treated with SXB, 71% experienced improvement of their severe sleep inertia, 55% had a decrease in their excessive daytime sleepiness, and 52% reported a shortened nighttime sleep time (Leu-Semenescu S, et al. Sleep Med. 2016;17:38).
In a recent double-blind, randomized control trial, the lower-sodium oxybate (LXB) was trialed in 154 patients with IH. It demonstrated statistically significant and clinically meaningful improvements (compared with placebo) in the Epworth Sleepiness Scale score (P <.0001) and in the Idiopathic Hypersomnia Severity Scale (P <.0001). The effects were seen both during the up titration of LXB and the benefits were maintained during the stable phase of the intervention (Dauvilliers Y, et al. Lancet Neurol. 2022;21(1):53). In August 2021, LXB (initially launched in 2020 for the treatment of narcolepsy) is now the first FDA-approved medication to treat IH in adults. It is curious, however, that LXB’s understood therapeutic effects are secondary to the “potentiation” of the very GABA receptor we have believed to be the root cause of the debilitating symptoms in IH. Could this discovery lend to further insights into the origins of this condition?
Ruckshanda Majid, MD, FCCP
Pulmonary vascular & cardiovascular network: Cardiovascular medicine & surgery section
Targeted temperature management (TTM) after cardiac arrest: How cool?
Recent randomized control trials, TTM2 (Dankiewicz J. N Engl J Med. 2021;384:2283) and HYPERION (Lascarrou J-B. N Engl J Med. 2019;381:2327), of therapeutic hypothermia, as opposed to normothermia, in patients who remain comatose after return of spontaneous circulation (ROSC) after cardiac arrest have produced conflicting results regarding survival and neurologic benefit. TTM2 reported no benefit to cooling to 33°C, while HYPERION found improved neurologic outcome at 90 days in patients cooled to 33°C. The European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recently released an evidence review and guideline for adults who remain comatose after cardiac arrest (Sandroni C. Intensive Care Med. 2022;48:261). These guidelines recommend continuous monitoring of core temperature in all patients who remain comatose after cardiac arrest, and preventing fever (>37.7°C) for 72 hours, but with no recommendation of target temperature of 32°C vs 36°C.
Differences in patient populations, presenting rhythm during arrest, duration of CPR, and time to target temperature likely each contribute to the disparate conclusions of previous trials. For example, HYPERION enrolled patients with out of hospital cardiac arrest with initial nonshockable rhythms and found benefit to cooling to 33°C. In comparison, TTM2 enrolled all patients with ROSC following arrest (regardless of rhythm), including patients with in-hospital cardiac arrest and found no benefit in therapeutic cooling. Differences in patient populations are underscored by the widely differing percentage of patients with good neurologic outcome in their respective control groups: approximately 30% in the TTM2 trial and 6% in HYPERION. The guidelines leave significant room for clinical judgment in employing therapeutic cooling but encourage the continuous monitoring of core temperature and active avoidance of fever.
Fiore Mastroianna, MD
Section Member-at-Large
Chest infections & disaster response network: Chest infections section
Update on LTBI treatment: Ensuring success by simplifying, shortening, and completing treatment
My patient has a positive IGRA test result – what’s next?
If TB disease is ruled out by clinical, radiographic, and microbiologic assessment (if indicated), then latent TB infection (LTBI) is established, and treatment should be offered, guided by shared-decision making between provider and patient.
What options are available?
While the former standard 9-month regimen of isoniazid-monotherapy can be shortened to 6 months, shorter rifamycin-based regimens are now preferred in most cases and include:
4 months rifampin daily, 3 months isoniazid plus rifampin daily, or 3 months isoniazid plus rifapentine weekly. In addition, 1 month of isoniazid plus rifapentine daily has recently been shown to be effective in people with HIV.
How to choose?
Rifamycin-based regimens have been shown to have less hepatotoxicity and higher completion rates. Drug-drug interactions are of potential concern, for example, in patients receiving anticoagulation or treatment for HIV. The clinician should be aware of rifamycins causing a flu-like illness that may be treatment-limiting. In patients with known contact to drug-resistant TB, regimens are individualized.
How to monitor?
Adherence and completion are the keys to success. Directly observed therapy may be indicated in certain scenarios. Baseline and monthly blood work is recommended for people with risk factors for hepatic or bone marrow toxicity. More importantly, patients should be instructed to discontinue LTBI medications and call the clinician with any new symptoms. HIV testing should be offered to all patients if status is unknown. Clinicians are encouraged to reach out to one of four regional TB Centers of Excellence for guidance.
Sebastian Kurz, MD, FCCP
Amee Patrawalla, MD, MPH, FCCP
Section Members-at-Large
References
Testing and Treatment of Latent Tuberculosis Infection in the United States: Clinical Recommendations. A Guide for Health Care Providers and Public Health Programs. Copyright © 2021 by the National Society of Tuberculosis Clinicians and National Tuberculosis Controllers Association
1. Shah, D. Latent tuberculosis infection. N Engl J Med. 2021;385:2271-80.
2. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-115.
3. Swindells et. al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med. 2019;380:1001-11.
Thoracic oncology & chest procedures network: Lung cancer section
Adjuvant and neoadjuvant therapies in early stage lung cancer
Since the discovery of the epidermal growth factor receptor (EGFR) mutation in 2004 and the development of checkpoint blockade in 2006, personalized treatment options for non–small cell lung cancer (NSCLC) have exploded, but targeted systemic therapy medications were only recommended among patients with metastatic or locally advanced disease (Rivera MP, Matthay RA. Clin Chest Med. 2020;41[1]:ix-xi). However, in November 2020, the National Comprehensive Cancer Network (NCCN) updated guidelines to recommend EGFR testing in surgically resected stage IB-IIIA adenocarcinoma, and to consider adjuvant osimerintib in those who were mutation-positive (NCCN. Nov 2020). Interim analysis of an ongoing phase-3 trial showed 89% of patients in the osimertinib group were alive and disease-free at 24 months compared with 52% in the placebo group (hazard ratio 0.20, P < .001) (Wu YL, et al. N Engl J Med. 2020;383[18]:1711-23).
The FDA has also recently approved the use of neoadjuvant and adjuvant immunotherapy in combination with platinum-based chemotherapy. Nivolumab is now approved as neoadjuvant therapy in patients with resectable IB-IIIA NSCLC regardless of PDL-1 status. The Checkmate-816 trial showed increased median event-free survival in the immunotherapy plus chemotherapy group of 31.6 months vs 20.8 months in the chemotherapy-only group (FDA.gov. 2022, Mar 4). Atezolizumab is also now approved for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on ≥ 1% of tumor cells. Median disease-free survival was not reached in patients in the atezolizumab groups vs 35.3 months in the best supportive care group (FDA.gov. 2021, Oct 15). With so many advances in the personalized treatment among all stages of NSCLC, this is a hopeful new chapter in the care of patients with NSCLC.
More information: https://www.nccn.org/guidelines/guidelines-process/transparency-process-and-recommendations/GetFileFromFileManager?fileManagerId=11259
Sohini Ghosh, MD
Section Member-at-Large
Diffuse lung disease and lung transplant network: Lung transplant section
Continuous distribution for lung transplant: Overhauling the wait list
Determining how to allocate the scarce resource of donor lungs to patients is a difficult task and evaluated continuously for potential improvement. Since 2005, in the United States, lung transplant recipients have been selected based primarily on location within a Donor Service Area and by lung allocation score (LAS), a composite score of urgency for transplant. This was updated in 2017 to an allocation by highest LAS within 250 nautical miles from the donor hospital. Factors such as blood type compatibility and height are also considered. Implementation of the LAS improved the sickest patients’ access to transplants while not worsening 1-year mortality (Egan TM. Semin Respir Crit Care Med. 2018;39[02]:126-37). Unfortunately, geographic hard boundaries mean a high proportion of low LAS (<50) patients receive local donors while high LAS patients receive national offers or die while on the waitlist (Iribarne A, et al. Clin Transplant. 2016:30:688-93).
A new model that employs continuous distribution has been developed based on concerns regarding equity and improving allocation. This model would prioritize patients based on factors including medical priority, efficient management of organ placement (distance), expected posttransplant outcomes, and patient access (equity). By creating a composite of these without a geographic boundary, patients would be considered more on urgency within realistic constraints of distance and outcomes.
The Organ Procurement and Transplantation Network has officially approved continuous distribution, with implementation planned for 2022; details regarding the new scoring system are to be published and further research will need to be undertaken to determine if it meets the goal of overall improvement in patient access, equity, and outcomes.
Grant A. Turner, MD, MHA
Laura Frye, MD
Section Members-at-Large
Critical care network: Non-respiratory critical care section
Update from the non-respiratory critical care section
As you’ve probably noticed, there have been some changes here at CHEST involving the Networks. Leadership here at CHEST has been hard at work restructuring the networks to make them more closely aligned with relevant clinical disciplines, and, ultimately, allow for greater participation. I am proud to have been given stewardship of the new Non-Respiratory Critical Care Section of the Critical Care Network.
So, what exactly is Non-Respiratory Critical Care? Well, that’s where I need your help. You see this network is meant to reflect the needs and wants of CHEST members like you. We need you, dear readers, to join in this venture and help us guide the content that this section will ultimately create for our members.
If you’re interested in critical care, but you don’t see your particular area of interest anywhere else in the current structure ... guess what? You’ve found the right place!
My Infectious Diseases and Nephro peeps? Welcome! Are you a surgical or anesthesia intensivist? Don’t be shy. ECMO people, let’s hear some chatter!Is therapeutic hypothermia your thing? Come on in. The water’s freezing. 33 degrees just like you folks like it. Or is it 36? Not sure. Anyway, see what I’m talking about? We really need your help!You can get involved by clicking on the Membership & Community tab at the CHEST website. Once you’re a member, you can even nominate yourself to run for the Steering Committee elections which are held periodically. Hope to see you soon!
Deep Ramachandran, MD, FCCP
Section Chair
Sleep medicine network: Non-respiratory sleep section
Unusual suspects? Breakthrough in the treatment of idiopathic hypersomnia
Idiopathic hypersomnia (IH) is a rare and debilitating disorder defined by its excessive daytime sleepiness, sleep inertia, prolonged nighttime sleep, and long, unrefreshing naps (AASM. ICSD 3rd ed. 2014). Gamma-aminobutyric acid (GABA) is one of the main inhibitory neurotransmitters in the nervous system. It is through the potentiation of GABA that substances such as alcohol and benzodiazepines yield their effects. It is also hypothesized that the “brain fog” experienced in IH may be a consequence of either higher levels of an endogenous benzodiazepines in the cerebral spinal fluid or the presence of a GABA-enhancing peptide (Rye DB. Science Transl Med. 2012;Med 4:161ra151).
Sodium oxybate (SXB), a compound that likely has its therapeutic effect through the potentiation of GABA receptors, is an effective treatment option for cataplexy and sleepiness in narcolepsy. Although there may be some overlap between narcolepsy and IH in both diagnosis and treatment (Bassetti C, et al. Brain. 1997;120:1423), it would perhaps be entirely counterintuitive (given SXB’s pharmacology) to imagine using SXB as a plausible treatment option in IH. It was, however, investigated in the treatment of refractory hypersomnia and IH. In the retrospective study looking at 46 subjects treated with SXB, 71% experienced improvement of their severe sleep inertia, 55% had a decrease in their excessive daytime sleepiness, and 52% reported a shortened nighttime sleep time (Leu-Semenescu S, et al. Sleep Med. 2016;17:38).
In a recent double-blind, randomized control trial, the lower-sodium oxybate (LXB) was trialed in 154 patients with IH. It demonstrated statistically significant and clinically meaningful improvements (compared with placebo) in the Epworth Sleepiness Scale score (P <.0001) and in the Idiopathic Hypersomnia Severity Scale (P <.0001). The effects were seen both during the up titration of LXB and the benefits were maintained during the stable phase of the intervention (Dauvilliers Y, et al. Lancet Neurol. 2022;21(1):53). In August 2021, LXB (initially launched in 2020 for the treatment of narcolepsy) is now the first FDA-approved medication to treat IH in adults. It is curious, however, that LXB’s understood therapeutic effects are secondary to the “potentiation” of the very GABA receptor we have believed to be the root cause of the debilitating symptoms in IH. Could this discovery lend to further insights into the origins of this condition?
Ruckshanda Majid, MD, FCCP
Pulmonary vascular & cardiovascular network: Cardiovascular medicine & surgery section
Targeted temperature management (TTM) after cardiac arrest: How cool?
Recent randomized control trials, TTM2 (Dankiewicz J. N Engl J Med. 2021;384:2283) and HYPERION (Lascarrou J-B. N Engl J Med. 2019;381:2327), of therapeutic hypothermia, as opposed to normothermia, in patients who remain comatose after return of spontaneous circulation (ROSC) after cardiac arrest have produced conflicting results regarding survival and neurologic benefit. TTM2 reported no benefit to cooling to 33°C, while HYPERION found improved neurologic outcome at 90 days in patients cooled to 33°C. The European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recently released an evidence review and guideline for adults who remain comatose after cardiac arrest (Sandroni C. Intensive Care Med. 2022;48:261). These guidelines recommend continuous monitoring of core temperature in all patients who remain comatose after cardiac arrest, and preventing fever (>37.7°C) for 72 hours, but with no recommendation of target temperature of 32°C vs 36°C.
Differences in patient populations, presenting rhythm during arrest, duration of CPR, and time to target temperature likely each contribute to the disparate conclusions of previous trials. For example, HYPERION enrolled patients with out of hospital cardiac arrest with initial nonshockable rhythms and found benefit to cooling to 33°C. In comparison, TTM2 enrolled all patients with ROSC following arrest (regardless of rhythm), including patients with in-hospital cardiac arrest and found no benefit in therapeutic cooling. Differences in patient populations are underscored by the widely differing percentage of patients with good neurologic outcome in their respective control groups: approximately 30% in the TTM2 trial and 6% in HYPERION. The guidelines leave significant room for clinical judgment in employing therapeutic cooling but encourage the continuous monitoring of core temperature and active avoidance of fever.
Fiore Mastroianna, MD
Section Member-at-Large
Chest infections & disaster response network: Chest infections section
Update on LTBI treatment: Ensuring success by simplifying, shortening, and completing treatment
My patient has a positive IGRA test result – what’s next?
If TB disease is ruled out by clinical, radiographic, and microbiologic assessment (if indicated), then latent TB infection (LTBI) is established, and treatment should be offered, guided by shared-decision making between provider and patient.
What options are available?
While the former standard 9-month regimen of isoniazid-monotherapy can be shortened to 6 months, shorter rifamycin-based regimens are now preferred in most cases and include:
4 months rifampin daily, 3 months isoniazid plus rifampin daily, or 3 months isoniazid plus rifapentine weekly. In addition, 1 month of isoniazid plus rifapentine daily has recently been shown to be effective in people with HIV.
How to choose?
Rifamycin-based regimens have been shown to have less hepatotoxicity and higher completion rates. Drug-drug interactions are of potential concern, for example, in patients receiving anticoagulation or treatment for HIV. The clinician should be aware of rifamycins causing a flu-like illness that may be treatment-limiting. In patients with known contact to drug-resistant TB, regimens are individualized.
How to monitor?
Adherence and completion are the keys to success. Directly observed therapy may be indicated in certain scenarios. Baseline and monthly blood work is recommended for people with risk factors for hepatic or bone marrow toxicity. More importantly, patients should be instructed to discontinue LTBI medications and call the clinician with any new symptoms. HIV testing should be offered to all patients if status is unknown. Clinicians are encouraged to reach out to one of four regional TB Centers of Excellence for guidance.
Sebastian Kurz, MD, FCCP
Amee Patrawalla, MD, MPH, FCCP
Section Members-at-Large
References
Testing and Treatment of Latent Tuberculosis Infection in the United States: Clinical Recommendations. A Guide for Health Care Providers and Public Health Programs. Copyright © 2021 by the National Society of Tuberculosis Clinicians and National Tuberculosis Controllers Association
1. Shah, D. Latent tuberculosis infection. N Engl J Med. 2021;385:2271-80.
2. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-115.
3. Swindells et. al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med. 2019;380:1001-11.
Thoracic oncology & chest procedures network: Lung cancer section
Adjuvant and neoadjuvant therapies in early stage lung cancer
Since the discovery of the epidermal growth factor receptor (EGFR) mutation in 2004 and the development of checkpoint blockade in 2006, personalized treatment options for non–small cell lung cancer (NSCLC) have exploded, but targeted systemic therapy medications were only recommended among patients with metastatic or locally advanced disease (Rivera MP, Matthay RA. Clin Chest Med. 2020;41[1]:ix-xi). However, in November 2020, the National Comprehensive Cancer Network (NCCN) updated guidelines to recommend EGFR testing in surgically resected stage IB-IIIA adenocarcinoma, and to consider adjuvant osimerintib in those who were mutation-positive (NCCN. Nov 2020). Interim analysis of an ongoing phase-3 trial showed 89% of patients in the osimertinib group were alive and disease-free at 24 months compared with 52% in the placebo group (hazard ratio 0.20, P < .001) (Wu YL, et al. N Engl J Med. 2020;383[18]:1711-23).
The FDA has also recently approved the use of neoadjuvant and adjuvant immunotherapy in combination with platinum-based chemotherapy. Nivolumab is now approved as neoadjuvant therapy in patients with resectable IB-IIIA NSCLC regardless of PDL-1 status. The Checkmate-816 trial showed increased median event-free survival in the immunotherapy plus chemotherapy group of 31.6 months vs 20.8 months in the chemotherapy-only group (FDA.gov. 2022, Mar 4). Atezolizumab is also now approved for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on ≥ 1% of tumor cells. Median disease-free survival was not reached in patients in the atezolizumab groups vs 35.3 months in the best supportive care group (FDA.gov. 2021, Oct 15). With so many advances in the personalized treatment among all stages of NSCLC, this is a hopeful new chapter in the care of patients with NSCLC.
More information: https://www.nccn.org/guidelines/guidelines-process/transparency-process-and-recommendations/GetFileFromFileManager?fileManagerId=11259
Sohini Ghosh, MD
Section Member-at-Large
Diffuse lung disease and lung transplant network: Lung transplant section
Continuous distribution for lung transplant: Overhauling the wait list
Determining how to allocate the scarce resource of donor lungs to patients is a difficult task and evaluated continuously for potential improvement. Since 2005, in the United States, lung transplant recipients have been selected based primarily on location within a Donor Service Area and by lung allocation score (LAS), a composite score of urgency for transplant. This was updated in 2017 to an allocation by highest LAS within 250 nautical miles from the donor hospital. Factors such as blood type compatibility and height are also considered. Implementation of the LAS improved the sickest patients’ access to transplants while not worsening 1-year mortality (Egan TM. Semin Respir Crit Care Med. 2018;39[02]:126-37). Unfortunately, geographic hard boundaries mean a high proportion of low LAS (<50) patients receive local donors while high LAS patients receive national offers or die while on the waitlist (Iribarne A, et al. Clin Transplant. 2016:30:688-93).
A new model that employs continuous distribution has been developed based on concerns regarding equity and improving allocation. This model would prioritize patients based on factors including medical priority, efficient management of organ placement (distance), expected posttransplant outcomes, and patient access (equity). By creating a composite of these without a geographic boundary, patients would be considered more on urgency within realistic constraints of distance and outcomes.
The Organ Procurement and Transplantation Network has officially approved continuous distribution, with implementation planned for 2022; details regarding the new scoring system are to be published and further research will need to be undertaken to determine if it meets the goal of overall improvement in patient access, equity, and outcomes.
Grant A. Turner, MD, MHA
Laura Frye, MD
Section Members-at-Large
Critical care network: Non-respiratory critical care section
Update from the non-respiratory critical care section
As you’ve probably noticed, there have been some changes here at CHEST involving the Networks. Leadership here at CHEST has been hard at work restructuring the networks to make them more closely aligned with relevant clinical disciplines, and, ultimately, allow for greater participation. I am proud to have been given stewardship of the new Non-Respiratory Critical Care Section of the Critical Care Network.
So, what exactly is Non-Respiratory Critical Care? Well, that’s where I need your help. You see this network is meant to reflect the needs and wants of CHEST members like you. We need you, dear readers, to join in this venture and help us guide the content that this section will ultimately create for our members.
If you’re interested in critical care, but you don’t see your particular area of interest anywhere else in the current structure ... guess what? You’ve found the right place!
My Infectious Diseases and Nephro peeps? Welcome! Are you a surgical or anesthesia intensivist? Don’t be shy. ECMO people, let’s hear some chatter!Is therapeutic hypothermia your thing? Come on in. The water’s freezing. 33 degrees just like you folks like it. Or is it 36? Not sure. Anyway, see what I’m talking about? We really need your help!You can get involved by clicking on the Membership & Community tab at the CHEST website. Once you’re a member, you can even nominate yourself to run for the Steering Committee elections which are held periodically. Hope to see you soon!
Deep Ramachandran, MD, FCCP
Section Chair
Sleep medicine network: Non-respiratory sleep section
Unusual suspects? Breakthrough in the treatment of idiopathic hypersomnia
Idiopathic hypersomnia (IH) is a rare and debilitating disorder defined by its excessive daytime sleepiness, sleep inertia, prolonged nighttime sleep, and long, unrefreshing naps (AASM. ICSD 3rd ed. 2014). Gamma-aminobutyric acid (GABA) is one of the main inhibitory neurotransmitters in the nervous system. It is through the potentiation of GABA that substances such as alcohol and benzodiazepines yield their effects. It is also hypothesized that the “brain fog” experienced in IH may be a consequence of either higher levels of an endogenous benzodiazepines in the cerebral spinal fluid or the presence of a GABA-enhancing peptide (Rye DB. Science Transl Med. 2012;Med 4:161ra151).
Sodium oxybate (SXB), a compound that likely has its therapeutic effect through the potentiation of GABA receptors, is an effective treatment option for cataplexy and sleepiness in narcolepsy. Although there may be some overlap between narcolepsy and IH in both diagnosis and treatment (Bassetti C, et al. Brain. 1997;120:1423), it would perhaps be entirely counterintuitive (given SXB’s pharmacology) to imagine using SXB as a plausible treatment option in IH. It was, however, investigated in the treatment of refractory hypersomnia and IH. In the retrospective study looking at 46 subjects treated with SXB, 71% experienced improvement of their severe sleep inertia, 55% had a decrease in their excessive daytime sleepiness, and 52% reported a shortened nighttime sleep time (Leu-Semenescu S, et al. Sleep Med. 2016;17:38).
In a recent double-blind, randomized control trial, the lower-sodium oxybate (LXB) was trialed in 154 patients with IH. It demonstrated statistically significant and clinically meaningful improvements (compared with placebo) in the Epworth Sleepiness Scale score (P <.0001) and in the Idiopathic Hypersomnia Severity Scale (P <.0001). The effects were seen both during the up titration of LXB and the benefits were maintained during the stable phase of the intervention (Dauvilliers Y, et al. Lancet Neurol. 2022;21(1):53). In August 2021, LXB (initially launched in 2020 for the treatment of narcolepsy) is now the first FDA-approved medication to treat IH in adults. It is curious, however, that LXB’s understood therapeutic effects are secondary to the “potentiation” of the very GABA receptor we have believed to be the root cause of the debilitating symptoms in IH. Could this discovery lend to further insights into the origins of this condition?
Ruckshanda Majid, MD, FCCP