User login
‘Achilles heels’ open doors to myeloma advances
NEW YORK – Three “Achilles heels” of multiple myeloma offer exciting promise for additional advances that will begin to see therapeutic payoffs within the next year, according to Kenneth C. Anderson, MD.
The three targets – excess protein production, immune suppression, and genomic abnormalities – can be addressed by focusing on protein degradation, restoring anti–multiple myeloma immunity, and targeting and overcoming genomic abnormalities, respectively, Dr. Anderson of Dana-Farber Cancer Institute in Boston said at Imedex: Lymphoma & Myeloma, an international congress on hematologic malignancies.
“So if you block those so-called DUBs, you block this same pathway upstream of the proteasome,” he said.
One DUB inhibitor (P5091) was shown in a preclinical trial to overcome bortezomib resistance in multiple myeloma, as was another novel, more user-friendly agent (b-AP15) that blocks USP14/UCHL5 and can be active with immunomodulatory drugs. A clinical trial of b-AP15 is ongoing, Dr. Anderson said.
In contrast to the conventional approach of inhibiting proteins and signaling pathways needed for the survival of the cancer cells, a new technology called “degronimids” turns on the cereblon gene and delivers protein-degrading machinery to targeted proteins. Cereblon, a protein-degrading enzyme that forms part of the ubiquitin E3 ligase complex, tags proteins in the cell for destruction, he noted.
As for immune suppression, he said, the selective plasma cell antigen BCMA (B-cell maturation antigen) is “probably a better target than either CD38 or SLAMF7,” and has already been targeted with an auristatin immunotoxin that induced strong anti–multiple myeloma effects.
“Excitingly, there is this concept of BCMA-BiTEs (B-cell maturation antigen–bispecific T-cell engagers) where we have one linkage of BCMA to the myeloma cell and CD3 attracting a local immune response,” he said.
Other promising new approaches with respect to immune suppression involve checkpoint inhibitors, histone deacetylase (HDAC) inhibitors, and chimeric antigen receptor (CAR) T-cells, he added.
Genomic abnormalities represent another potential vulnerability, and venetoclax (Venclexta) could prove to be the first precision medicine for multiple myeloma, he suggested.
In myeloma, “we are trying to treat the abnormality, but what about treating the genetic consequences of this abnormality,” he said, adding that clinical trials that target the consequences of genomic heterogeneity or instability are on the horizon.
Dr. Anderson reported serving as a consultant for, or receiving other financial support from Acetylon, Bristol-Myers Squibb, C4 Therapeutics, Celgene, Gilead, Millennium, and OncoPep.
NEW YORK – Three “Achilles heels” of multiple myeloma offer exciting promise for additional advances that will begin to see therapeutic payoffs within the next year, according to Kenneth C. Anderson, MD.
The three targets – excess protein production, immune suppression, and genomic abnormalities – can be addressed by focusing on protein degradation, restoring anti–multiple myeloma immunity, and targeting and overcoming genomic abnormalities, respectively, Dr. Anderson of Dana-Farber Cancer Institute in Boston said at Imedex: Lymphoma & Myeloma, an international congress on hematologic malignancies.
“So if you block those so-called DUBs, you block this same pathway upstream of the proteasome,” he said.
One DUB inhibitor (P5091) was shown in a preclinical trial to overcome bortezomib resistance in multiple myeloma, as was another novel, more user-friendly agent (b-AP15) that blocks USP14/UCHL5 and can be active with immunomodulatory drugs. A clinical trial of b-AP15 is ongoing, Dr. Anderson said.
In contrast to the conventional approach of inhibiting proteins and signaling pathways needed for the survival of the cancer cells, a new technology called “degronimids” turns on the cereblon gene and delivers protein-degrading machinery to targeted proteins. Cereblon, a protein-degrading enzyme that forms part of the ubiquitin E3 ligase complex, tags proteins in the cell for destruction, he noted.
As for immune suppression, he said, the selective plasma cell antigen BCMA (B-cell maturation antigen) is “probably a better target than either CD38 or SLAMF7,” and has already been targeted with an auristatin immunotoxin that induced strong anti–multiple myeloma effects.
“Excitingly, there is this concept of BCMA-BiTEs (B-cell maturation antigen–bispecific T-cell engagers) where we have one linkage of BCMA to the myeloma cell and CD3 attracting a local immune response,” he said.
Other promising new approaches with respect to immune suppression involve checkpoint inhibitors, histone deacetylase (HDAC) inhibitors, and chimeric antigen receptor (CAR) T-cells, he added.
Genomic abnormalities represent another potential vulnerability, and venetoclax (Venclexta) could prove to be the first precision medicine for multiple myeloma, he suggested.
In myeloma, “we are trying to treat the abnormality, but what about treating the genetic consequences of this abnormality,” he said, adding that clinical trials that target the consequences of genomic heterogeneity or instability are on the horizon.
Dr. Anderson reported serving as a consultant for, or receiving other financial support from Acetylon, Bristol-Myers Squibb, C4 Therapeutics, Celgene, Gilead, Millennium, and OncoPep.
NEW YORK – Three “Achilles heels” of multiple myeloma offer exciting promise for additional advances that will begin to see therapeutic payoffs within the next year, according to Kenneth C. Anderson, MD.
The three targets – excess protein production, immune suppression, and genomic abnormalities – can be addressed by focusing on protein degradation, restoring anti–multiple myeloma immunity, and targeting and overcoming genomic abnormalities, respectively, Dr. Anderson of Dana-Farber Cancer Institute in Boston said at Imedex: Lymphoma & Myeloma, an international congress on hematologic malignancies.
“So if you block those so-called DUBs, you block this same pathway upstream of the proteasome,” he said.
One DUB inhibitor (P5091) was shown in a preclinical trial to overcome bortezomib resistance in multiple myeloma, as was another novel, more user-friendly agent (b-AP15) that blocks USP14/UCHL5 and can be active with immunomodulatory drugs. A clinical trial of b-AP15 is ongoing, Dr. Anderson said.
In contrast to the conventional approach of inhibiting proteins and signaling pathways needed for the survival of the cancer cells, a new technology called “degronimids” turns on the cereblon gene and delivers protein-degrading machinery to targeted proteins. Cereblon, a protein-degrading enzyme that forms part of the ubiquitin E3 ligase complex, tags proteins in the cell for destruction, he noted.
As for immune suppression, he said, the selective plasma cell antigen BCMA (B-cell maturation antigen) is “probably a better target than either CD38 or SLAMF7,” and has already been targeted with an auristatin immunotoxin that induced strong anti–multiple myeloma effects.
“Excitingly, there is this concept of BCMA-BiTEs (B-cell maturation antigen–bispecific T-cell engagers) where we have one linkage of BCMA to the myeloma cell and CD3 attracting a local immune response,” he said.
Other promising new approaches with respect to immune suppression involve checkpoint inhibitors, histone deacetylase (HDAC) inhibitors, and chimeric antigen receptor (CAR) T-cells, he added.
Genomic abnormalities represent another potential vulnerability, and venetoclax (Venclexta) could prove to be the first precision medicine for multiple myeloma, he suggested.
In myeloma, “we are trying to treat the abnormality, but what about treating the genetic consequences of this abnormality,” he said, adding that clinical trials that target the consequences of genomic heterogeneity or instability are on the horizon.
Dr. Anderson reported serving as a consultant for, or receiving other financial support from Acetylon, Bristol-Myers Squibb, C4 Therapeutics, Celgene, Gilead, Millennium, and OncoPep.
EXPERT ANALYSIS FROM IMEDEX: LYMPHOMA & MYELOMA
Pulmonary embolism common in patients hospitalized for syncope
When specifically looked for, pulmonary embolism was identified in approximately 17% of adults hospitalized for a first episode of syncope, according to a report published in the New England Journal of Medicine.
Most medical textbooks include pulmonary embolism (PE) in the differential diagnosis of syncope, but “current international guidelines, including those from the European Society of Cardiology and the American Heart Association, pay little attention to establishing a diagnostic workup for PE in these patients. Hence, when a patient is admitted to a hospital for an episode of syncope, PE – a potentially fatal disease that can be effectively treated – is rarely considered as a possible cause,” said Paolo Prandoni, MD, PhD, of the vascular medicine unit, University of Padua (Italy), and his associates in the PESY (Prevalence of Pulmonary Embolism in Patients With Syncope) trial.
The investigators used a systematic diagnostic work-up to determine the prevalence of PE in a cross-sectional study involving 560 adults hospitalized for syncope at 11 medical centers across Italy during a 2.5-year period. Most of these patients were elderly (mean age, 76 years), and most had clinical evidence indicating that a factor other than PE had caused their fainting. For this study, syncope was defined as a transient loss of consciousness with rapid onset, short duration (less than 1 minute), and spontaneous resolution, with obvious causes ruled out (such as epileptic seizure, stroke, or head trauma).
The “unexpectedly high” prevalence of PE was 17.3% overall, and it was consistent, ranging from 15% to 20%, across all 11 hospitals. The prevalence was even higher, at 25.4%, in the subgroup of 205 patients who had syncope of undetermined origin, as well as in 12.7% of the subgroup of 355 patients considered to have an alternative explanation for the disorder, Dr. Prandoni and his associates wrote (N Engl J Med. 2016 Oct 20. doi: 10.1056/NEJMoa1602172).
The researchers noted that this study likely underestimates the actual prevalence of PE among patients with syncope because it did not include patients who were not hospitalized, such as those who received only ambulatory care and those who presented to an emergency department but were not admitted.
The study was supported by the University of Padua. Dr. Prandoni and his associates reported having no relevant financial disclosures.
When specifically looked for, pulmonary embolism was identified in approximately 17% of adults hospitalized for a first episode of syncope, according to a report published in the New England Journal of Medicine.
Most medical textbooks include pulmonary embolism (PE) in the differential diagnosis of syncope, but “current international guidelines, including those from the European Society of Cardiology and the American Heart Association, pay little attention to establishing a diagnostic workup for PE in these patients. Hence, when a patient is admitted to a hospital for an episode of syncope, PE – a potentially fatal disease that can be effectively treated – is rarely considered as a possible cause,” said Paolo Prandoni, MD, PhD, of the vascular medicine unit, University of Padua (Italy), and his associates in the PESY (Prevalence of Pulmonary Embolism in Patients With Syncope) trial.
The investigators used a systematic diagnostic work-up to determine the prevalence of PE in a cross-sectional study involving 560 adults hospitalized for syncope at 11 medical centers across Italy during a 2.5-year period. Most of these patients were elderly (mean age, 76 years), and most had clinical evidence indicating that a factor other than PE had caused their fainting. For this study, syncope was defined as a transient loss of consciousness with rapid onset, short duration (less than 1 minute), and spontaneous resolution, with obvious causes ruled out (such as epileptic seizure, stroke, or head trauma).
The “unexpectedly high” prevalence of PE was 17.3% overall, and it was consistent, ranging from 15% to 20%, across all 11 hospitals. The prevalence was even higher, at 25.4%, in the subgroup of 205 patients who had syncope of undetermined origin, as well as in 12.7% of the subgroup of 355 patients considered to have an alternative explanation for the disorder, Dr. Prandoni and his associates wrote (N Engl J Med. 2016 Oct 20. doi: 10.1056/NEJMoa1602172).
The researchers noted that this study likely underestimates the actual prevalence of PE among patients with syncope because it did not include patients who were not hospitalized, such as those who received only ambulatory care and those who presented to an emergency department but were not admitted.
The study was supported by the University of Padua. Dr. Prandoni and his associates reported having no relevant financial disclosures.
When specifically looked for, pulmonary embolism was identified in approximately 17% of adults hospitalized for a first episode of syncope, according to a report published in the New England Journal of Medicine.
Most medical textbooks include pulmonary embolism (PE) in the differential diagnosis of syncope, but “current international guidelines, including those from the European Society of Cardiology and the American Heart Association, pay little attention to establishing a diagnostic workup for PE in these patients. Hence, when a patient is admitted to a hospital for an episode of syncope, PE – a potentially fatal disease that can be effectively treated – is rarely considered as a possible cause,” said Paolo Prandoni, MD, PhD, of the vascular medicine unit, University of Padua (Italy), and his associates in the PESY (Prevalence of Pulmonary Embolism in Patients With Syncope) trial.
The investigators used a systematic diagnostic work-up to determine the prevalence of PE in a cross-sectional study involving 560 adults hospitalized for syncope at 11 medical centers across Italy during a 2.5-year period. Most of these patients were elderly (mean age, 76 years), and most had clinical evidence indicating that a factor other than PE had caused their fainting. For this study, syncope was defined as a transient loss of consciousness with rapid onset, short duration (less than 1 minute), and spontaneous resolution, with obvious causes ruled out (such as epileptic seizure, stroke, or head trauma).
The “unexpectedly high” prevalence of PE was 17.3% overall, and it was consistent, ranging from 15% to 20%, across all 11 hospitals. The prevalence was even higher, at 25.4%, in the subgroup of 205 patients who had syncope of undetermined origin, as well as in 12.7% of the subgroup of 355 patients considered to have an alternative explanation for the disorder, Dr. Prandoni and his associates wrote (N Engl J Med. 2016 Oct 20. doi: 10.1056/NEJMoa1602172).
The researchers noted that this study likely underestimates the actual prevalence of PE among patients with syncope because it did not include patients who were not hospitalized, such as those who received only ambulatory care and those who presented to an emergency department but were not admitted.
The study was supported by the University of Padua. Dr. Prandoni and his associates reported having no relevant financial disclosures.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: When specifically looked for, pulmonary embolism was identified in approximately 17% of adults hospitalized for a first episode of syncope.
Major finding: The “unexpectedly high” prevalence of PE was 17.3% overall, and it was consistent, ranging from 15% to 20%, across all 11 hospitals in the study.
Data source: A cross-sectional study involving 560 adults hospitalized for syncope at 11 Italian medical centers during a 2.5 year period.
Disclosures: This study was supported by the University of Padua (Italy). Dr. Prandoni and his associates reported having no relevant financial disclosures.
Older adults with active, remitted MDD may miss positive facial expressions
Older adults with both active and remitted major depressive disorder (MDD) may have a tougher time processing happy faces than do their counterparts without depression, a cross-sectional study of 59 veterans suggests.
“Sensitivity recognition of moderately intense happy expression appears to reflect a perceptual bias in major depression among older adults,” report Paulo R. Shiroma, MD, of the Minneapolis Veterans Affairs Medical Center, and his associates.
The researchers recruited the subjects from October 2011 to September 2013, from primary care practices. The participants were divided into three groups – one with active major depressive disorder, another with MDD in remission, and one with no history of depression. Most of the veterans were white and married, and all were aged 55 years and older. Only veterans who were free of antidepressants or other psychotropic medications for at least 2 weeks were included in the study. They were compensated monetarily for participating in the study, reported Dr. Shiroma (Psychiatry Res. 2016 Sep 30:243;287-91).
Dr. Shiroma and his associates assessed the participants using several scales, including the 15-item Geriatric Depression Scale (GDS-15) and the 17-item Hamilton Depression Rating Scale (HDRS-17). The veterans also were asked to complete a facial emotional recognition task, which involved looking at facial images depicting 12 neutral expressions and 48 happy expressions on a computer in a quiet room. Among other things, the participants were asked to respond as quickly as possible to the question: “Do you see a happy face?”
The researchers found a significant correlation between GDS-15 (P = .02) and HDRS-17 (P = .05) scores, and emotion recognition. Specifically, they found that the mean sensitivity among the never-depressed patients was 83.9%, compared with a mean sensitivity of 75.5% among the participants with active MDD and 75.4% among those with MDD that was in remission. No significant different differences were found in reaction time.
They cited several limitations. Veterans made up the entire study sample, and the results might not be generalizable. In addition, the prevalence of MDD in VA populations is 12%, compared with 7% in the general U.S. population, Dr. Shiroma and his associates wrote. Also, studies suggest that women may be more accurate in recognizing subtle facial displays of emotion.
Previous studies suggest that reducing “emotion-related negative bias” is associated with an improvement in depressive symptoms after 3 months of treatment with antidepressants. A recent trial analyzed the impact of emotion recognition training on mood among people with depressive symptoms using technology such as computers and smartphones (Trials. 2013 Jun 1;14:161). In light of those findings, Dr. Shiroma and his associates wrote, “similar intervention within the specific social and psychological aspects of the aging process could also be attempted.”
Dr. Shiroma reported having no conflicts of interest.
Older adults with both active and remitted major depressive disorder (MDD) may have a tougher time processing happy faces than do their counterparts without depression, a cross-sectional study of 59 veterans suggests.
“Sensitivity recognition of moderately intense happy expression appears to reflect a perceptual bias in major depression among older adults,” report Paulo R. Shiroma, MD, of the Minneapolis Veterans Affairs Medical Center, and his associates.
The researchers recruited the subjects from October 2011 to September 2013, from primary care practices. The participants were divided into three groups – one with active major depressive disorder, another with MDD in remission, and one with no history of depression. Most of the veterans were white and married, and all were aged 55 years and older. Only veterans who were free of antidepressants or other psychotropic medications for at least 2 weeks were included in the study. They were compensated monetarily for participating in the study, reported Dr. Shiroma (Psychiatry Res. 2016 Sep 30:243;287-91).
Dr. Shiroma and his associates assessed the participants using several scales, including the 15-item Geriatric Depression Scale (GDS-15) and the 17-item Hamilton Depression Rating Scale (HDRS-17). The veterans also were asked to complete a facial emotional recognition task, which involved looking at facial images depicting 12 neutral expressions and 48 happy expressions on a computer in a quiet room. Among other things, the participants were asked to respond as quickly as possible to the question: “Do you see a happy face?”
The researchers found a significant correlation between GDS-15 (P = .02) and HDRS-17 (P = .05) scores, and emotion recognition. Specifically, they found that the mean sensitivity among the never-depressed patients was 83.9%, compared with a mean sensitivity of 75.5% among the participants with active MDD and 75.4% among those with MDD that was in remission. No significant different differences were found in reaction time.
They cited several limitations. Veterans made up the entire study sample, and the results might not be generalizable. In addition, the prevalence of MDD in VA populations is 12%, compared with 7% in the general U.S. population, Dr. Shiroma and his associates wrote. Also, studies suggest that women may be more accurate in recognizing subtle facial displays of emotion.
Previous studies suggest that reducing “emotion-related negative bias” is associated with an improvement in depressive symptoms after 3 months of treatment with antidepressants. A recent trial analyzed the impact of emotion recognition training on mood among people with depressive symptoms using technology such as computers and smartphones (Trials. 2013 Jun 1;14:161). In light of those findings, Dr. Shiroma and his associates wrote, “similar intervention within the specific social and psychological aspects of the aging process could also be attempted.”
Dr. Shiroma reported having no conflicts of interest.
Older adults with both active and remitted major depressive disorder (MDD) may have a tougher time processing happy faces than do their counterparts without depression, a cross-sectional study of 59 veterans suggests.
“Sensitivity recognition of moderately intense happy expression appears to reflect a perceptual bias in major depression among older adults,” report Paulo R. Shiroma, MD, of the Minneapolis Veterans Affairs Medical Center, and his associates.
The researchers recruited the subjects from October 2011 to September 2013, from primary care practices. The participants were divided into three groups – one with active major depressive disorder, another with MDD in remission, and one with no history of depression. Most of the veterans were white and married, and all were aged 55 years and older. Only veterans who were free of antidepressants or other psychotropic medications for at least 2 weeks were included in the study. They were compensated monetarily for participating in the study, reported Dr. Shiroma (Psychiatry Res. 2016 Sep 30:243;287-91).
Dr. Shiroma and his associates assessed the participants using several scales, including the 15-item Geriatric Depression Scale (GDS-15) and the 17-item Hamilton Depression Rating Scale (HDRS-17). The veterans also were asked to complete a facial emotional recognition task, which involved looking at facial images depicting 12 neutral expressions and 48 happy expressions on a computer in a quiet room. Among other things, the participants were asked to respond as quickly as possible to the question: “Do you see a happy face?”
The researchers found a significant correlation between GDS-15 (P = .02) and HDRS-17 (P = .05) scores, and emotion recognition. Specifically, they found that the mean sensitivity among the never-depressed patients was 83.9%, compared with a mean sensitivity of 75.5% among the participants with active MDD and 75.4% among those with MDD that was in remission. No significant different differences were found in reaction time.
They cited several limitations. Veterans made up the entire study sample, and the results might not be generalizable. In addition, the prevalence of MDD in VA populations is 12%, compared with 7% in the general U.S. population, Dr. Shiroma and his associates wrote. Also, studies suggest that women may be more accurate in recognizing subtle facial displays of emotion.
Previous studies suggest that reducing “emotion-related negative bias” is associated with an improvement in depressive symptoms after 3 months of treatment with antidepressants. A recent trial analyzed the impact of emotion recognition training on mood among people with depressive symptoms using technology such as computers and smartphones (Trials. 2013 Jun 1;14:161). In light of those findings, Dr. Shiroma and his associates wrote, “similar intervention within the specific social and psychological aspects of the aging process could also be attempted.”
Dr. Shiroma reported having no conflicts of interest.
Navigating the ambiguity around whether to admit or discharge
In my first week of intern year, I learned the criteria for admission to an inpatient psychiatric unit: imminent harm to self, imminent harm to others, or the inability to care for self.1 The standard risk assessment. In residency training, each patient encounter trains us in the challenging practice of risk assessment in potentially dangerous situations. One quickly learns the anxiety a moderate risk patient will cause.
Less discussed than the risk assessment, but certainly, a frequent challenge facing psychiatry residents is whether an admission is “good” or “bad.” The bad admission reflects the type of patient and situation, when you, the psychiatrist, basically know that inpatient admission is likely inappropriate.2 Usually, these occur when your hands are tied by structural and systemic pressures. Perhaps the patient is a known “high utilizer” whose admission is primarily motivated by homelessness or lack of community mental health resources.3 Or maybe the bad admission is a patient with a personality disorder who is consistently readmitted by each resident in the program with seemingly little improvement after each admission.4 Bad admissions are the type of patient who, as the overnight resident, you feel a touch embarrassed signing out to the fresh resident there to relieve you in the morning. In these cases, I find myself making various justifications: It was a busy night; there was no collateral; no family; no friends; no outpatient support. I tell myself, I just couldn’t manage a safe enough discharge. I couldn’t mitigate the risk enough.
If the situation allows in the midst of the tumult, I create an intimate space to interview my patient. I pull up a chair and lean in to listen. To maintain an empathetic stance, I must recognize and control my biases toward high utilizers, drug use, homelessness, noncompliance, and the other host of factors that may influence my judgment. Between the hours of 1 a.m. and 6 a.m., fatigue, in particular, will breed negative countertransference. Before I sit down to listen, I repeat my mantra to myself: The least I can offer is kindness. Then the assessment and the decision-making process that leads to an admission or a discharge begins.
When I’m on call, I am torn by my obligations: to the patient, their safety and well-being; to the health care system and distributive justice; to making the “right” decision to admit or discharge; to my nursing staff and their safety; to my supervisors and my fellow residents who will judge and must deal with my clinical decision to admit or discharge. Some of these obligations that I struggle to balance are outlined as core competencies by the Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology, and called the Psychiatry Milestone Project.5 I am supposed to be thinking about these issues as I work up a patient, evaluating, and making purposeful trade-offs. The educational language of these core competencies does not capture the tensions of these complicated on-call experiences.
The most useful thing I have learned this year is that the decision to admit or discharge is not a binary decision. The very act of assessment through an interview and making a plan with the patient is valuable in itself as risk mitigation. Only recently as a second-year resident have I fully realized how my presence could have therapeutic effects. Even a brief interview in the emergency department can be generative. I try to bring calm to the chaos around the patient. I listen, elicit protective factors and coping skills, and try to mobilize hope and internal strength building capabilities just as we are taught in my residency program.
However, I admittedly continue to dread my overnight calls. As a second-year resident, I am still uncomfortable with the ambiguity in some decisions to admit or discharge. Nonetheless, I recognize these experiences are only helping me become a better psychiatrist with every night I spend running between the ED and the psychiatric unit. To get through this process of residency, I have formulated another mantra: Every call and every patient is a learning experience.
References
1. BMC Health Serv Res. 2006;6:150.
2. Health Policy. 2000 Oct;53(3):157-84.
3. Adm Policy Ment Health. 2012 May;39(3):200-9.
4. Psychiatr Serv. 2015 Jan 1;66(1):15-20.
5. “The Psychiatry Milestone Project”: Assessment Tools. A Joint Initiative of the Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology.
Dr. Posada is a second-year resident in the psychiatry & behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at the George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, health disparities, and psychosomatic medicine.
In my first week of intern year, I learned the criteria for admission to an inpatient psychiatric unit: imminent harm to self, imminent harm to others, or the inability to care for self.1 The standard risk assessment. In residency training, each patient encounter trains us in the challenging practice of risk assessment in potentially dangerous situations. One quickly learns the anxiety a moderate risk patient will cause.
Less discussed than the risk assessment, but certainly, a frequent challenge facing psychiatry residents is whether an admission is “good” or “bad.” The bad admission reflects the type of patient and situation, when you, the psychiatrist, basically know that inpatient admission is likely inappropriate.2 Usually, these occur when your hands are tied by structural and systemic pressures. Perhaps the patient is a known “high utilizer” whose admission is primarily motivated by homelessness or lack of community mental health resources.3 Or maybe the bad admission is a patient with a personality disorder who is consistently readmitted by each resident in the program with seemingly little improvement after each admission.4 Bad admissions are the type of patient who, as the overnight resident, you feel a touch embarrassed signing out to the fresh resident there to relieve you in the morning. In these cases, I find myself making various justifications: It was a busy night; there was no collateral; no family; no friends; no outpatient support. I tell myself, I just couldn’t manage a safe enough discharge. I couldn’t mitigate the risk enough.
If the situation allows in the midst of the tumult, I create an intimate space to interview my patient. I pull up a chair and lean in to listen. To maintain an empathetic stance, I must recognize and control my biases toward high utilizers, drug use, homelessness, noncompliance, and the other host of factors that may influence my judgment. Between the hours of 1 a.m. and 6 a.m., fatigue, in particular, will breed negative countertransference. Before I sit down to listen, I repeat my mantra to myself: The least I can offer is kindness. Then the assessment and the decision-making process that leads to an admission or a discharge begins.
When I’m on call, I am torn by my obligations: to the patient, their safety and well-being; to the health care system and distributive justice; to making the “right” decision to admit or discharge; to my nursing staff and their safety; to my supervisors and my fellow residents who will judge and must deal with my clinical decision to admit or discharge. Some of these obligations that I struggle to balance are outlined as core competencies by the Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology, and called the Psychiatry Milestone Project.5 I am supposed to be thinking about these issues as I work up a patient, evaluating, and making purposeful trade-offs. The educational language of these core competencies does not capture the tensions of these complicated on-call experiences.
The most useful thing I have learned this year is that the decision to admit or discharge is not a binary decision. The very act of assessment through an interview and making a plan with the patient is valuable in itself as risk mitigation. Only recently as a second-year resident have I fully realized how my presence could have therapeutic effects. Even a brief interview in the emergency department can be generative. I try to bring calm to the chaos around the patient. I listen, elicit protective factors and coping skills, and try to mobilize hope and internal strength building capabilities just as we are taught in my residency program.
However, I admittedly continue to dread my overnight calls. As a second-year resident, I am still uncomfortable with the ambiguity in some decisions to admit or discharge. Nonetheless, I recognize these experiences are only helping me become a better psychiatrist with every night I spend running between the ED and the psychiatric unit. To get through this process of residency, I have formulated another mantra: Every call and every patient is a learning experience.
References
1. BMC Health Serv Res. 2006;6:150.
2. Health Policy. 2000 Oct;53(3):157-84.
3. Adm Policy Ment Health. 2012 May;39(3):200-9.
4. Psychiatr Serv. 2015 Jan 1;66(1):15-20.
5. “The Psychiatry Milestone Project”: Assessment Tools. A Joint Initiative of the Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology.
Dr. Posada is a second-year resident in the psychiatry & behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at the George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, health disparities, and psychosomatic medicine.
In my first week of intern year, I learned the criteria for admission to an inpatient psychiatric unit: imminent harm to self, imminent harm to others, or the inability to care for self.1 The standard risk assessment. In residency training, each patient encounter trains us in the challenging practice of risk assessment in potentially dangerous situations. One quickly learns the anxiety a moderate risk patient will cause.
Less discussed than the risk assessment, but certainly, a frequent challenge facing psychiatry residents is whether an admission is “good” or “bad.” The bad admission reflects the type of patient and situation, when you, the psychiatrist, basically know that inpatient admission is likely inappropriate.2 Usually, these occur when your hands are tied by structural and systemic pressures. Perhaps the patient is a known “high utilizer” whose admission is primarily motivated by homelessness or lack of community mental health resources.3 Or maybe the bad admission is a patient with a personality disorder who is consistently readmitted by each resident in the program with seemingly little improvement after each admission.4 Bad admissions are the type of patient who, as the overnight resident, you feel a touch embarrassed signing out to the fresh resident there to relieve you in the morning. In these cases, I find myself making various justifications: It was a busy night; there was no collateral; no family; no friends; no outpatient support. I tell myself, I just couldn’t manage a safe enough discharge. I couldn’t mitigate the risk enough.
If the situation allows in the midst of the tumult, I create an intimate space to interview my patient. I pull up a chair and lean in to listen. To maintain an empathetic stance, I must recognize and control my biases toward high utilizers, drug use, homelessness, noncompliance, and the other host of factors that may influence my judgment. Between the hours of 1 a.m. and 6 a.m., fatigue, in particular, will breed negative countertransference. Before I sit down to listen, I repeat my mantra to myself: The least I can offer is kindness. Then the assessment and the decision-making process that leads to an admission or a discharge begins.
When I’m on call, I am torn by my obligations: to the patient, their safety and well-being; to the health care system and distributive justice; to making the “right” decision to admit or discharge; to my nursing staff and their safety; to my supervisors and my fellow residents who will judge and must deal with my clinical decision to admit or discharge. Some of these obligations that I struggle to balance are outlined as core competencies by the Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology, and called the Psychiatry Milestone Project.5 I am supposed to be thinking about these issues as I work up a patient, evaluating, and making purposeful trade-offs. The educational language of these core competencies does not capture the tensions of these complicated on-call experiences.
The most useful thing I have learned this year is that the decision to admit or discharge is not a binary decision. The very act of assessment through an interview and making a plan with the patient is valuable in itself as risk mitigation. Only recently as a second-year resident have I fully realized how my presence could have therapeutic effects. Even a brief interview in the emergency department can be generative. I try to bring calm to the chaos around the patient. I listen, elicit protective factors and coping skills, and try to mobilize hope and internal strength building capabilities just as we are taught in my residency program.
However, I admittedly continue to dread my overnight calls. As a second-year resident, I am still uncomfortable with the ambiguity in some decisions to admit or discharge. Nonetheless, I recognize these experiences are only helping me become a better psychiatrist with every night I spend running between the ED and the psychiatric unit. To get through this process of residency, I have formulated another mantra: Every call and every patient is a learning experience.
References
1. BMC Health Serv Res. 2006;6:150.
2. Health Policy. 2000 Oct;53(3):157-84.
3. Adm Policy Ment Health. 2012 May;39(3):200-9.
4. Psychiatr Serv. 2015 Jan 1;66(1):15-20.
5. “The Psychiatry Milestone Project”: Assessment Tools. A Joint Initiative of the Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology.
Dr. Posada is a second-year resident in the psychiatry & behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at the George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, health disparities, and psychosomatic medicine.
Evaluating the Malignant Potential of Nevus Spilus
ACIP approves change to hepatitis B vaccination guidelines
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted in favor of changes to the current recommendations that would remove the permissive language for the hepatitis B birth dose to be administered after discharge from the hospital.
The revised language will state that for all medically stable infants weighing greater than or equal to 2,000 g at birth and born to hepatitis B surface antigen–negative mothers, the first dose of vaccine should be administered within 24 hours of birth. Originally, the recommendations were to state that vaccination should take place before hospital discharge, but this language was changed via a unanimously approved amendment to broaden the scope of the guidelines. Furthermore, the recommendations state that only single-antigen hepatitis B vaccine should be used for the birth dose.
“The language regarding vaccination within 24 hours of birth is consistent with what the [World Health Organization] says,” she explained.
The proposed changes came after the hepatitis B workgroup held five teleconference meetings between February and September of this year to discuss and determine what changes, if any, need to be made. A draft was prepared and presented at the ACIP meeting, at which the changes were unanimously approved by the 14-member advisory committee.
The recommendations agreed upon will be submitted for approval to CDC Director Tom Frieden, MD, and, if approved, will be published by Jan. 1, 2017, at which point they will go into effect.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted in favor of changes to the current recommendations that would remove the permissive language for the hepatitis B birth dose to be administered after discharge from the hospital.
The revised language will state that for all medically stable infants weighing greater than or equal to 2,000 g at birth and born to hepatitis B surface antigen–negative mothers, the first dose of vaccine should be administered within 24 hours of birth. Originally, the recommendations were to state that vaccination should take place before hospital discharge, but this language was changed via a unanimously approved amendment to broaden the scope of the guidelines. Furthermore, the recommendations state that only single-antigen hepatitis B vaccine should be used for the birth dose.
“The language regarding vaccination within 24 hours of birth is consistent with what the [World Health Organization] says,” she explained.
The proposed changes came after the hepatitis B workgroup held five teleconference meetings between February and September of this year to discuss and determine what changes, if any, need to be made. A draft was prepared and presented at the ACIP meeting, at which the changes were unanimously approved by the 14-member advisory committee.
The recommendations agreed upon will be submitted for approval to CDC Director Tom Frieden, MD, and, if approved, will be published by Jan. 1, 2017, at which point they will go into effect.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted in favor of changes to the current recommendations that would remove the permissive language for the hepatitis B birth dose to be administered after discharge from the hospital.
The revised language will state that for all medically stable infants weighing greater than or equal to 2,000 g at birth and born to hepatitis B surface antigen–negative mothers, the first dose of vaccine should be administered within 24 hours of birth. Originally, the recommendations were to state that vaccination should take place before hospital discharge, but this language was changed via a unanimously approved amendment to broaden the scope of the guidelines. Furthermore, the recommendations state that only single-antigen hepatitis B vaccine should be used for the birth dose.
“The language regarding vaccination within 24 hours of birth is consistent with what the [World Health Organization] says,” she explained.
The proposed changes came after the hepatitis B workgroup held five teleconference meetings between February and September of this year to discuss and determine what changes, if any, need to be made. A draft was prepared and presented at the ACIP meeting, at which the changes were unanimously approved by the 14-member advisory committee.
The recommendations agreed upon will be submitted for approval to CDC Director Tom Frieden, MD, and, if approved, will be published by Jan. 1, 2017, at which point they will go into effect.
Computed tomography angiography after NCCT delays thrombectomy
BALTIMORE – Performing computed tomography angiography (CTA) following noncontrast computed tomography (NCCT) to obtain a high-resolution image of the large-vessel occlusion significantly delays the time to thrombectomy.
In clinical practice, omitting CTA in patients whose middle cerebral artery visualized on NCCT reveals the hyperdense sign may speed the time to thrombectomy and improve outcome. The findings of a retrospective cohort study of prospectively collected data were presented by Kunakorn Atchaneeyasakul, MD, of the University of Miami, as a poster and a brief oral presentation at the annual meeting of the American Neurological Association.
This study retrospectively compared the time from imaging to groin puncture, which is the first step in thrombectomy, in patients who received NCCT followed by CTA with those who received just NCCT for anterior circulation occlusion at the tertiary care University of Miami medical center. Of the 289 patients who received thrombectomy, 255 were excluded because of transfer from another hospital, occurrence of stroke while hospitalized, or use of other imaging prior to thrombectomy.
The remaining 34 patients were all evaluated with thin (0.625-mm) NCCT with automated image reconstruction. Fourteen received NCCT only, and 20 received CTA in addition to NCCT. The two groups were similar in mean age (64-71 years), gender (50% were female in each group), prevalence of hypertension (64% and 70% in the NCCT and NCCT + CTA group, respectively), and prevalence of diabetes, hyperlipidemia, atrial fibrillation, smoking, occlusion site, modified Rankin Scale score at discharge, and National Institutes of Health Stroke Scale scores at presentation and discharge. All 14 NCCT patients received intravenous tPA in contrast to 11 of the 20 (55%) NCCT + CTA patients (P = .003).
The middle cerebral artery was visualized on NCCT in about 85% of patients in each treatment group. Reperfusion was successful in 64% and 80% of patients receiving NCCT and NCCT + CTA, respectively (P = .31).
The total duration of imaging was 2 minutes (range, 1-6) in the NCCT group. The duration was significantly longer in the NCCT + CTA group (28 minutes; range, 23-65; P less than .001). The time from imaging to groin puncture was 68 minutes (range, 32-99) in the NCCT group. This was more than 30 minutes shorter than the NCCT + CTA group (104 minutes; range, 79-128; P = .030).
The times from emergency department admission to NCCT and from admission to groin puncture were similar in both groups.
“Avoiding advanced imaging in patients with anterior circulation large-vessel occlusion in whom thin-section NCCT with maximum-intensity projections reveals a hyperdense sign significantly shortens the imaging to groin puncture time,” concluded Dr. Atchaneeyasakul.
In the scenario, the detection of hyperdense middle cerebral artery would fast track the patient to the angiography suite, forgoing CTA. The result, according to Dr. Atchaneeyasakul, could alleviate a delay in thrombectomy, which could better preserve brain function.
Funding information was not provided.
BALTIMORE – Performing computed tomography angiography (CTA) following noncontrast computed tomography (NCCT) to obtain a high-resolution image of the large-vessel occlusion significantly delays the time to thrombectomy.
In clinical practice, omitting CTA in patients whose middle cerebral artery visualized on NCCT reveals the hyperdense sign may speed the time to thrombectomy and improve outcome. The findings of a retrospective cohort study of prospectively collected data were presented by Kunakorn Atchaneeyasakul, MD, of the University of Miami, as a poster and a brief oral presentation at the annual meeting of the American Neurological Association.
This study retrospectively compared the time from imaging to groin puncture, which is the first step in thrombectomy, in patients who received NCCT followed by CTA with those who received just NCCT for anterior circulation occlusion at the tertiary care University of Miami medical center. Of the 289 patients who received thrombectomy, 255 were excluded because of transfer from another hospital, occurrence of stroke while hospitalized, or use of other imaging prior to thrombectomy.
The remaining 34 patients were all evaluated with thin (0.625-mm) NCCT with automated image reconstruction. Fourteen received NCCT only, and 20 received CTA in addition to NCCT. The two groups were similar in mean age (64-71 years), gender (50% were female in each group), prevalence of hypertension (64% and 70% in the NCCT and NCCT + CTA group, respectively), and prevalence of diabetes, hyperlipidemia, atrial fibrillation, smoking, occlusion site, modified Rankin Scale score at discharge, and National Institutes of Health Stroke Scale scores at presentation and discharge. All 14 NCCT patients received intravenous tPA in contrast to 11 of the 20 (55%) NCCT + CTA patients (P = .003).
The middle cerebral artery was visualized on NCCT in about 85% of patients in each treatment group. Reperfusion was successful in 64% and 80% of patients receiving NCCT and NCCT + CTA, respectively (P = .31).
The total duration of imaging was 2 minutes (range, 1-6) in the NCCT group. The duration was significantly longer in the NCCT + CTA group (28 minutes; range, 23-65; P less than .001). The time from imaging to groin puncture was 68 minutes (range, 32-99) in the NCCT group. This was more than 30 minutes shorter than the NCCT + CTA group (104 minutes; range, 79-128; P = .030).
The times from emergency department admission to NCCT and from admission to groin puncture were similar in both groups.
“Avoiding advanced imaging in patients with anterior circulation large-vessel occlusion in whom thin-section NCCT with maximum-intensity projections reveals a hyperdense sign significantly shortens the imaging to groin puncture time,” concluded Dr. Atchaneeyasakul.
In the scenario, the detection of hyperdense middle cerebral artery would fast track the patient to the angiography suite, forgoing CTA. The result, according to Dr. Atchaneeyasakul, could alleviate a delay in thrombectomy, which could better preserve brain function.
Funding information was not provided.
BALTIMORE – Performing computed tomography angiography (CTA) following noncontrast computed tomography (NCCT) to obtain a high-resolution image of the large-vessel occlusion significantly delays the time to thrombectomy.
In clinical practice, omitting CTA in patients whose middle cerebral artery visualized on NCCT reveals the hyperdense sign may speed the time to thrombectomy and improve outcome. The findings of a retrospective cohort study of prospectively collected data were presented by Kunakorn Atchaneeyasakul, MD, of the University of Miami, as a poster and a brief oral presentation at the annual meeting of the American Neurological Association.
This study retrospectively compared the time from imaging to groin puncture, which is the first step in thrombectomy, in patients who received NCCT followed by CTA with those who received just NCCT for anterior circulation occlusion at the tertiary care University of Miami medical center. Of the 289 patients who received thrombectomy, 255 were excluded because of transfer from another hospital, occurrence of stroke while hospitalized, or use of other imaging prior to thrombectomy.
The remaining 34 patients were all evaluated with thin (0.625-mm) NCCT with automated image reconstruction. Fourteen received NCCT only, and 20 received CTA in addition to NCCT. The two groups were similar in mean age (64-71 years), gender (50% were female in each group), prevalence of hypertension (64% and 70% in the NCCT and NCCT + CTA group, respectively), and prevalence of diabetes, hyperlipidemia, atrial fibrillation, smoking, occlusion site, modified Rankin Scale score at discharge, and National Institutes of Health Stroke Scale scores at presentation and discharge. All 14 NCCT patients received intravenous tPA in contrast to 11 of the 20 (55%) NCCT + CTA patients (P = .003).
The middle cerebral artery was visualized on NCCT in about 85% of patients in each treatment group. Reperfusion was successful in 64% and 80% of patients receiving NCCT and NCCT + CTA, respectively (P = .31).
The total duration of imaging was 2 minutes (range, 1-6) in the NCCT group. The duration was significantly longer in the NCCT + CTA group (28 minutes; range, 23-65; P less than .001). The time from imaging to groin puncture was 68 minutes (range, 32-99) in the NCCT group. This was more than 30 minutes shorter than the NCCT + CTA group (104 minutes; range, 79-128; P = .030).
The times from emergency department admission to NCCT and from admission to groin puncture were similar in both groups.
“Avoiding advanced imaging in patients with anterior circulation large-vessel occlusion in whom thin-section NCCT with maximum-intensity projections reveals a hyperdense sign significantly shortens the imaging to groin puncture time,” concluded Dr. Atchaneeyasakul.
In the scenario, the detection of hyperdense middle cerebral artery would fast track the patient to the angiography suite, forgoing CTA. The result, according to Dr. Atchaneeyasakul, could alleviate a delay in thrombectomy, which could better preserve brain function.
Funding information was not provided.
AT ANA 2016
Key clinical point:
Major finding: Time from imaging to groin puncture was 68 minutes for NCCT vs. 104 minutes for NCCT + CTA.
Data source: Retrospective cohort study of prospectively collected data.
Disclosures: Dr. Atchaneeyasakul had no disclosures.
VIDEO: Pre–gastric bypass antibiotics alter gut microbiome
WASHINGTON – Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.
Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.
Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.
Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.
Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.
At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.
Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.
Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.
“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”
Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”
Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.
Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.
He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.
Dr. Jahansouz said that he had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
WASHINGTON – Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.
Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.
Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.
Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.
Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.
At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.
Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.
Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.
“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”
Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”
Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.
Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.
He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.
Dr. Jahansouz said that he had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
WASHINGTON – Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.
Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.
Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.
Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.
Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.
At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.
Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.
Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.
“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”
Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”
Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.
Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.
He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.
Dr. Jahansouz said that he had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
EXPERT ANALYSIS FROM THE ACS CLINICAL CONGRESS
FBN-1 Overexpression Linked to Testicular Tumor Development
Researchers from Comenius University in Bratislava, Slovakia, have shown for the first time that fibrillin-1 (FBN-1) is overexpressed in testicular germ cell tumors (TGCTs). Their data suggest that progression of germ cell neoplasia in situ (GCNIS) to overt germ cell tumor is connected with decreased FBN-1 production. Fibrillin is a glycoprotein essential in forming the elastic fibers in connective tissue.
The researchers evaluated 350 tumor specimens and 85 adjacent nonneoplastic testicular tissues in 203 patients. They detected FBN-1 expression in 68 (97%) GCNIS, 21 (96%) yolk sac tumors, 85 (87%) seminomas, 78 (83%) embryonal carcinomas, 35 (71%) teratomas, 3 (18%) choriocarcinomas, and 1 (1%) nonneoplastic tissue. The highest FBN-1 positivity was found in GCNIS, with overexpression of FBN-1 in 77% of cases. The fact that the highest expression was observed in seminomas and the lowest in choriocarcinomas, the researchers say, suggests a reduction of FBN-1 expression with the process of differentiation.
Related: Is Chemotherapy a Good Choice for Neuroendocrine Tumors?
GCNIS represents the preinvasive stage of most TGCTs in adults. GCNIS cells are believed to be germ cells that have failed to mature normally, the researchers note. The appearance of FBN-1 expression in germ cells in the stage of GCNIS, they suggest, can be an early event in the process of malignant transformation.
Source:
Cierna Z, Mego M, Jurisica I, et al. BMC Cancer. 2016;16:597
doi: 10.1186/s12885-016-2644-z.
Researchers from Comenius University in Bratislava, Slovakia, have shown for the first time that fibrillin-1 (FBN-1) is overexpressed in testicular germ cell tumors (TGCTs). Their data suggest that progression of germ cell neoplasia in situ (GCNIS) to overt germ cell tumor is connected with decreased FBN-1 production. Fibrillin is a glycoprotein essential in forming the elastic fibers in connective tissue.
The researchers evaluated 350 tumor specimens and 85 adjacent nonneoplastic testicular tissues in 203 patients. They detected FBN-1 expression in 68 (97%) GCNIS, 21 (96%) yolk sac tumors, 85 (87%) seminomas, 78 (83%) embryonal carcinomas, 35 (71%) teratomas, 3 (18%) choriocarcinomas, and 1 (1%) nonneoplastic tissue. The highest FBN-1 positivity was found in GCNIS, with overexpression of FBN-1 in 77% of cases. The fact that the highest expression was observed in seminomas and the lowest in choriocarcinomas, the researchers say, suggests a reduction of FBN-1 expression with the process of differentiation.
Related: Is Chemotherapy a Good Choice for Neuroendocrine Tumors?
GCNIS represents the preinvasive stage of most TGCTs in adults. GCNIS cells are believed to be germ cells that have failed to mature normally, the researchers note. The appearance of FBN-1 expression in germ cells in the stage of GCNIS, they suggest, can be an early event in the process of malignant transformation.
Source:
Cierna Z, Mego M, Jurisica I, et al. BMC Cancer. 2016;16:597
doi: 10.1186/s12885-016-2644-z.
Researchers from Comenius University in Bratislava, Slovakia, have shown for the first time that fibrillin-1 (FBN-1) is overexpressed in testicular germ cell tumors (TGCTs). Their data suggest that progression of germ cell neoplasia in situ (GCNIS) to overt germ cell tumor is connected with decreased FBN-1 production. Fibrillin is a glycoprotein essential in forming the elastic fibers in connective tissue.
The researchers evaluated 350 tumor specimens and 85 adjacent nonneoplastic testicular tissues in 203 patients. They detected FBN-1 expression in 68 (97%) GCNIS, 21 (96%) yolk sac tumors, 85 (87%) seminomas, 78 (83%) embryonal carcinomas, 35 (71%) teratomas, 3 (18%) choriocarcinomas, and 1 (1%) nonneoplastic tissue. The highest FBN-1 positivity was found in GCNIS, with overexpression of FBN-1 in 77% of cases. The fact that the highest expression was observed in seminomas and the lowest in choriocarcinomas, the researchers say, suggests a reduction of FBN-1 expression with the process of differentiation.
Related: Is Chemotherapy a Good Choice for Neuroendocrine Tumors?
GCNIS represents the preinvasive stage of most TGCTs in adults. GCNIS cells are believed to be germ cells that have failed to mature normally, the researchers note. The appearance of FBN-1 expression in germ cells in the stage of GCNIS, they suggest, can be an early event in the process of malignant transformation.
Source:
Cierna Z, Mego M, Jurisica I, et al. BMC Cancer. 2016;16:597
doi: 10.1186/s12885-016-2644-z.
ACOS under-recognized, under-treated
Exacerbations in bronchodilator-responsive asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) were more frequent and severe than in COPD with emphysema, but only a minority of patients were treated to prevent them, in a review of 1,005 patients from the Annals of the American Thoracic Society.
All the subjects were current or former smokers culled from the COPDGene Study, a multicenter observational study looking for the genetic roots of COPD susceptibility; 385 patients met the investigators’ criteria for ACOS with bronchodilator response (ACOS-BDR), which included a history of asthma or hay fever, airway obstruction with significant bronchodilator responsiveness, and less then 15% emphysema on chest CT.
Another 620 subjects met criteria for COPD with emphysema, including airway obstruction without bronchodilator reversibility, and more than 15% emphysema on chest CT (Ann Am Thorac Soc. 2016 Sep;13(9):1483-9).
Although the ACOS patients had better lung function, they had similar severity and frequency of exacerbations, compared with the COPD group. After adjustment for forced expiratory volume in 1 second percent predicted and other factors, the patients with ACOS-BDR were actually more likely to have severe and frequent exacerbations. Possible explanations for this are that they were more likely to smoke and have gastroesophageal reflux disease and obstructive sleep apnea, all of which increase the risk of exacerbations.
Even so, ACOS-BDR patients were less likely to be on a long-acting beta-agonist (6.8% versus 13.9%); a long-acting muscarinic antagonist (20% versus 60.8%); or a combination long-acting beta-agonist/inhaled corticosteroid (29.9% versus 55.6%).
“Only a small percentage of them were being treated ... Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations,” said investigators led by James Cosentino, DO, of Temple University School of Medicine, Philadelphia. Patients with ACOS “are a particularly high-risk group.” They deserve “special attention, and practitioners need to be diligent in evaluation of them.”
ACOS is being increasingly recognized as a distinct clinical entity with perhaps a worse prognosis than either asthma or COPD alone. The goal of the study was to better characterize the disease.
To that end, the team found four features that seemed to distinguish ACOS-BDR from COPD with emphysema: ACOS-BDR patients were younger (60.6 versus 65.9 years old); heavier (body mass index 29.6 versus 25.1 kg/m2; more likely to be African American (26.8% versus 14.4%); and more likely to be current smokers (50.9% versus 20.7%).
It’s “likely that current smoking in subjects with ACOS, coupled with the long duration of asthma, leads to inflammation and small airway remodeling with development of symptoms earlier in the disease course than that seen in those with COPD with emphysema,” the investigators said.
“Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations. Recognition and treatment of comorbidities and aggressive smoking cessation may also play a key role in preventing exacerbations and alleviating the morbidity associated with ACOS; however, future studies on the treatment of ACOS are needed,” they said.
The majority of subjects with ACOS-BDR met criteria for Global Initiative for Chronic Obstructive Lung Disease grade B, indicating a high degree of symptoms despite less severe airflow obstruction.
The funding source wasn’t reported. Dr. Cosentino had no conflicts. Other authors disclosed personal fees from Concert Pharmaceuticals, CSA Medical, CSL Behring, Gala Therapeutics, and Novartis.
The importance of this study is that it used readily available metrics to define ACOS in a COPD population. Although diffusion capacity was not reported, quantification of emphysema on chest CT scans combined with history and spirometry provide a reasonable approach to distinguishing ACOS-BDR from COPD with emphysema.
Although subjects with COPD had smoked more heavily as measured by cigarette pack-years, subjects with ACOS were much more likely to be current smokers... Subjects with ACOS also had a higher prevalence of comorbidities such as sleep apnea, diabetes mellitus, hypertension, and hypercholesterolemia as compared with patients with COPD. Having a higher BMI, to near obesity, and a greater prevalence of gastroesophageal reflux disease raises questions related to diet, lifestyle, and nutrition as potential contributors to ACOS pathophysiology.
In the future, the use of diagnostic terms such as “asthma,” “COPD,” and “ACOS,” will likely give way to the more unifying diagnosis of obstructive airway disease (OAD)... OAD would be further delineated on the basis of molecular phenotyping, genomic, and systems biology approaches, in combination with more traditional clinical and physiological parameters... This new mindset can help us solve the problem of obstructive airway disease taxonomy and develop not only better treatments, but eventually invent lasting cures – if we are so lucky.
Amir Zeki, MD , is an assistant professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of California, Davis. Nizar Jarjour, MD , is a professor of medicine and head of the allergy, pulmonary, and critical care division at the University of Wisconsin, Madison. Dr. Zeki had no disclosures. Dr. Jarjour reported consulting fees from AstraZeneca, Daiichi Sankyo, and Teva. They made their comments in an editorial ( Ann Am Thorac Soc. 2016 Sep;13(9):1440-2 ).
The importance of this study is that it used readily available metrics to define ACOS in a COPD population. Although diffusion capacity was not reported, quantification of emphysema on chest CT scans combined with history and spirometry provide a reasonable approach to distinguishing ACOS-BDR from COPD with emphysema.
Although subjects with COPD had smoked more heavily as measured by cigarette pack-years, subjects with ACOS were much more likely to be current smokers... Subjects with ACOS also had a higher prevalence of comorbidities such as sleep apnea, diabetes mellitus, hypertension, and hypercholesterolemia as compared with patients with COPD. Having a higher BMI, to near obesity, and a greater prevalence of gastroesophageal reflux disease raises questions related to diet, lifestyle, and nutrition as potential contributors to ACOS pathophysiology.
In the future, the use of diagnostic terms such as “asthma,” “COPD,” and “ACOS,” will likely give way to the more unifying diagnosis of obstructive airway disease (OAD)... OAD would be further delineated on the basis of molecular phenotyping, genomic, and systems biology approaches, in combination with more traditional clinical and physiological parameters... This new mindset can help us solve the problem of obstructive airway disease taxonomy and develop not only better treatments, but eventually invent lasting cures – if we are so lucky.
Amir Zeki, MD , is an assistant professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of California, Davis. Nizar Jarjour, MD , is a professor of medicine and head of the allergy, pulmonary, and critical care division at the University of Wisconsin, Madison. Dr. Zeki had no disclosures. Dr. Jarjour reported consulting fees from AstraZeneca, Daiichi Sankyo, and Teva. They made their comments in an editorial ( Ann Am Thorac Soc. 2016 Sep;13(9):1440-2 ).
The importance of this study is that it used readily available metrics to define ACOS in a COPD population. Although diffusion capacity was not reported, quantification of emphysema on chest CT scans combined with history and spirometry provide a reasonable approach to distinguishing ACOS-BDR from COPD with emphysema.
Although subjects with COPD had smoked more heavily as measured by cigarette pack-years, subjects with ACOS were much more likely to be current smokers... Subjects with ACOS also had a higher prevalence of comorbidities such as sleep apnea, diabetes mellitus, hypertension, and hypercholesterolemia as compared with patients with COPD. Having a higher BMI, to near obesity, and a greater prevalence of gastroesophageal reflux disease raises questions related to diet, lifestyle, and nutrition as potential contributors to ACOS pathophysiology.
In the future, the use of diagnostic terms such as “asthma,” “COPD,” and “ACOS,” will likely give way to the more unifying diagnosis of obstructive airway disease (OAD)... OAD would be further delineated on the basis of molecular phenotyping, genomic, and systems biology approaches, in combination with more traditional clinical and physiological parameters... This new mindset can help us solve the problem of obstructive airway disease taxonomy and develop not only better treatments, but eventually invent lasting cures – if we are so lucky.
Amir Zeki, MD , is an assistant professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of California, Davis. Nizar Jarjour, MD , is a professor of medicine and head of the allergy, pulmonary, and critical care division at the University of Wisconsin, Madison. Dr. Zeki had no disclosures. Dr. Jarjour reported consulting fees from AstraZeneca, Daiichi Sankyo, and Teva. They made their comments in an editorial ( Ann Am Thorac Soc. 2016 Sep;13(9):1440-2 ).
Exacerbations in bronchodilator-responsive asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) were more frequent and severe than in COPD with emphysema, but only a minority of patients were treated to prevent them, in a review of 1,005 patients from the Annals of the American Thoracic Society.
All the subjects were current or former smokers culled from the COPDGene Study, a multicenter observational study looking for the genetic roots of COPD susceptibility; 385 patients met the investigators’ criteria for ACOS with bronchodilator response (ACOS-BDR), which included a history of asthma or hay fever, airway obstruction with significant bronchodilator responsiveness, and less then 15% emphysema on chest CT.
Another 620 subjects met criteria for COPD with emphysema, including airway obstruction without bronchodilator reversibility, and more than 15% emphysema on chest CT (Ann Am Thorac Soc. 2016 Sep;13(9):1483-9).
Although the ACOS patients had better lung function, they had similar severity and frequency of exacerbations, compared with the COPD group. After adjustment for forced expiratory volume in 1 second percent predicted and other factors, the patients with ACOS-BDR were actually more likely to have severe and frequent exacerbations. Possible explanations for this are that they were more likely to smoke and have gastroesophageal reflux disease and obstructive sleep apnea, all of which increase the risk of exacerbations.
Even so, ACOS-BDR patients were less likely to be on a long-acting beta-agonist (6.8% versus 13.9%); a long-acting muscarinic antagonist (20% versus 60.8%); or a combination long-acting beta-agonist/inhaled corticosteroid (29.9% versus 55.6%).
“Only a small percentage of them were being treated ... Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations,” said investigators led by James Cosentino, DO, of Temple University School of Medicine, Philadelphia. Patients with ACOS “are a particularly high-risk group.” They deserve “special attention, and practitioners need to be diligent in evaluation of them.”
ACOS is being increasingly recognized as a distinct clinical entity with perhaps a worse prognosis than either asthma or COPD alone. The goal of the study was to better characterize the disease.
To that end, the team found four features that seemed to distinguish ACOS-BDR from COPD with emphysema: ACOS-BDR patients were younger (60.6 versus 65.9 years old); heavier (body mass index 29.6 versus 25.1 kg/m2; more likely to be African American (26.8% versus 14.4%); and more likely to be current smokers (50.9% versus 20.7%).
It’s “likely that current smoking in subjects with ACOS, coupled with the long duration of asthma, leads to inflammation and small airway remodeling with development of symptoms earlier in the disease course than that seen in those with COPD with emphysema,” the investigators said.
“Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations. Recognition and treatment of comorbidities and aggressive smoking cessation may also play a key role in preventing exacerbations and alleviating the morbidity associated with ACOS; however, future studies on the treatment of ACOS are needed,” they said.
The majority of subjects with ACOS-BDR met criteria for Global Initiative for Chronic Obstructive Lung Disease grade B, indicating a high degree of symptoms despite less severe airflow obstruction.
The funding source wasn’t reported. Dr. Cosentino had no conflicts. Other authors disclosed personal fees from Concert Pharmaceuticals, CSA Medical, CSL Behring, Gala Therapeutics, and Novartis.
Exacerbations in bronchodilator-responsive asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) were more frequent and severe than in COPD with emphysema, but only a minority of patients were treated to prevent them, in a review of 1,005 patients from the Annals of the American Thoracic Society.
All the subjects were current or former smokers culled from the COPDGene Study, a multicenter observational study looking for the genetic roots of COPD susceptibility; 385 patients met the investigators’ criteria for ACOS with bronchodilator response (ACOS-BDR), which included a history of asthma or hay fever, airway obstruction with significant bronchodilator responsiveness, and less then 15% emphysema on chest CT.
Another 620 subjects met criteria for COPD with emphysema, including airway obstruction without bronchodilator reversibility, and more than 15% emphysema on chest CT (Ann Am Thorac Soc. 2016 Sep;13(9):1483-9).
Although the ACOS patients had better lung function, they had similar severity and frequency of exacerbations, compared with the COPD group. After adjustment for forced expiratory volume in 1 second percent predicted and other factors, the patients with ACOS-BDR were actually more likely to have severe and frequent exacerbations. Possible explanations for this are that they were more likely to smoke and have gastroesophageal reflux disease and obstructive sleep apnea, all of which increase the risk of exacerbations.
Even so, ACOS-BDR patients were less likely to be on a long-acting beta-agonist (6.8% versus 13.9%); a long-acting muscarinic antagonist (20% versus 60.8%); or a combination long-acting beta-agonist/inhaled corticosteroid (29.9% versus 55.6%).
“Only a small percentage of them were being treated ... Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations,” said investigators led by James Cosentino, DO, of Temple University School of Medicine, Philadelphia. Patients with ACOS “are a particularly high-risk group.” They deserve “special attention, and practitioners need to be diligent in evaluation of them.”
ACOS is being increasingly recognized as a distinct clinical entity with perhaps a worse prognosis than either asthma or COPD alone. The goal of the study was to better characterize the disease.
To that end, the team found four features that seemed to distinguish ACOS-BDR from COPD with emphysema: ACOS-BDR patients were younger (60.6 versus 65.9 years old); heavier (body mass index 29.6 versus 25.1 kg/m2; more likely to be African American (26.8% versus 14.4%); and more likely to be current smokers (50.9% versus 20.7%).
It’s “likely that current smoking in subjects with ACOS, coupled with the long duration of asthma, leads to inflammation and small airway remodeling with development of symptoms earlier in the disease course than that seen in those with COPD with emphysema,” the investigators said.
“Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations. Recognition and treatment of comorbidities and aggressive smoking cessation may also play a key role in preventing exacerbations and alleviating the morbidity associated with ACOS; however, future studies on the treatment of ACOS are needed,” they said.
The majority of subjects with ACOS-BDR met criteria for Global Initiative for Chronic Obstructive Lung Disease grade B, indicating a high degree of symptoms despite less severe airflow obstruction.
The funding source wasn’t reported. Dr. Cosentino had no conflicts. Other authors disclosed personal fees from Concert Pharmaceuticals, CSA Medical, CSL Behring, Gala Therapeutics, and Novartis.
FROM THE ANNALS OF THE AMERICAN THORACIC SOCIETY
Key clinical point:
Major finding: ACOS-BDR patients were less likely to be on a long-acting beta-agonist (6.8% versus 13.9%); a long-acting muscarinic antagonist (20% versus 60.8%); or a combination long-acting beta-agonist/inhaled corticosteroid (29.9% versus 55.6%).
Data source: 1,005 patients from the COPDGene study.
Disclosures: The funding source wasn’t reported. Authors disclosed personal fees from Concert Pharmaceuticals, CSA Medical, CSL Behring, Gala Therapeutics, and Novartis.