Primecuts – This Week in the Journals

April 12, 2019


By Ryan Grattan, MD

Peer Reviewed 

With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature.  This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose. 

Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy[i]

Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic, demyelinating brain infection caused by reactivation of the polyomavirus JC that presents in patients with severe T-cell deficiency.  It is frequently fatal if immune system function cannot be restored. [ii]  Currently the only treatment strategy is to reconstitute the immune system.  However, there are increasing case reports of immune checkpoint inhibitor monoclonal antibodies against programmed cell death protein 1 (PD-1) that suggest these medications may have some efficacy in suppressing JC virus infections.

This small study enrolled eight patients with PML secondary to varying underlying conditions, including chronic lymphocytic leukemia, human immunodeficiency virus, lymphoma, and idiopathic lymphopenia.  JC viral load in the patient’s cerebrospinal fluid was measured at baseline and again at final visit.   Clinical disability was quantified with a modified Rankin scale and determined at baseline and again at final visit.  Lesion burden was evaluated on MRI.  Five patients had clinical improvement or stabilization of their disease and the remaining three had no meaningful response to treatment.  Patients with the same underlying predisposing condition did not necessarily have similar responses to treatment.  There was no evidence of Immune Reconstitution Inflammatory Syndrome (IRIS) aside from one patient who had a transient worsening of symptoms that was more likely attributable to brief worsening of PML.

Although small, this study suggests that immune checkpoint inhibitors may bolster host immune response to JC virus for some patients with PML.  Further evaluation to understand the in vivo characteristics that portend a response are warranted for this disease with severely limited treatment options.

The Effects of Long-term CPAP on Weight Change in Patients with Comorbid OSA and Cardiovascular Disease[iii]

Obstructive Sleep Apnea (OSA) likely affects multiple major weight-management factors, including metabolism and hormonal regulation of appetite.  It may promote sedentary behavior due to increased daytime somnolence.[iv]  Studies have found that serum levels of hormones that predispose to increased calorie intake are elevated in patients with OSA.[v]  However, basal metabolic rate is increased in patients with OSA,[vi] which may help to offset the hormonal and behavioral changes promoting weight gain.  Yet, treatment of OSA with continuous positive pressure ventilation (CPAP) may not alter factors equally, increasing concern that it can promote weight gain.  This study sought to understand the effect CPAP has on weight gain in patients with OSA.

The study was a post-hoc analysis performed on the data generated in the Sleep Apnea Cardiovascular Endpoints (SAVE) study.  In total 2,483 adults with moderate to severe OSA and history of cardiac or cerebrovascular events were enrolled in the SAVE study and randomly assigned to receive either CPAP and standard care or standard care alone.  Patients had on average a 3.78 year follow up period during which time anthropometric data was collected at specified durations.  Analysis of the SAVE data found that there was no significant difference in weight changes, BMI, or other anthropometric measures between the CPAP intervention group and the control group.  However, on further segmentation of the data, it was found that men using CPAP for four or more hours a night did on average have a 0.38 kg weight gain compared to men without CPAP use. (95% confidence interval 0.04 to 0.73; P = 0.031).  The study also recruited a significant number of participants from China and thus the findings may be less applicable to Western societies. Despite this, providers must consider the small weight gain found in this study versus the well-proven cardiovascular benefits of treating OSA.

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation[vii] – The COACT Trial

Out-of-hospital cardiac arrest requires resuscitation, diagnosis, and treatment in an exquisitely time sensitive manner.   The timing of diagnostic procedures is therefore critical in these situations.

The Coronary Angiography after Cardiac Arrest (COACT) trial was designed to assess if immediate coronary angiography provided significant survival benefit compared to delayed angiography for patients with cardiac arrest without signs of ST-segment elevation myocardial infarction (STEMI).  The study randomized 552 patients unconscious after cardiac arrest with an initially shockable rhythm to either immediate or delayed angiography.  Patients in the immediate group received angiography within two hours of randomization.  Patients in the delayed group had their angiography after neurologic recovery.  The primary endpoint was survival at 90 days.  Secondary end points primarily looked at the characteristics of survival at 90 days including cerebral performance, duration of mechanical ventilation, or need for renal-replacement therapy.  An additional secondary endpoint was the time to target temperature.  The study found no significant difference in number of patients alive at 90 days between immediate (64.5%) versus delayed (67.2%) angiography (odds ratio 0.89; 95% confidence interval 0.62 to 1.27; p=-0.51).  Secondary end points were also non-significant with the lone exception of time to target temperature.  The median time to temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed group (ratio of geometric means 1.19; 95% confidence interval 1.04 to 1.36).  This difference in median time to target temperature underscores the need for selectivity in this setting.

Interestingly, only 20% of patients were found to have acute unstable lesions.  There are patients who would likely benefit from immediate angiography, but they are the minority.  Additional studies are needed to help identify patients at higher risk for acute plaque rupture for whom immediate angiography is of increased value.

Use of Low-Dose Aspirin and Mortality After Prostate Cancer Diagnosis: A Nationwide Cohort Study[viii]

Prostate cancer is one of the most common cancers worldwide, with 1.28 million cases diagnosed in 2018[ix], and is estimated to be the second leading cause of cancer-related death in men in the U.S. [x]   The anticancer effect of aspirin in prostate cancer has been suggested, but evidence supporting its efficacy is mixed.[xi]

This association between aspirin and prostate cancer mortality was tested in a nationwide cohort study in Denmark.  Registry data on men with prostate adenocarcinoma first diagnosed between 2000 and 2011 were collected with the primary objective of assessing the use of low-dose aspirin within 1 year of diagnosis and differences in prostate-cancer specific and other-cause mortality.  Secondary analyses looked at the same endpoints but focused on low-dose aspirin use within 5 or 7.5 years from time of diagnosis.  In total 29,136 patients were included in the study and followed from 1 year after their diagnosis until the end of the follow-up period in December 2015.  Low-dose aspirin use was defined ≥ 2 prescriptions filled within the defined timeframes.  The primary objective did not achieve a significant difference with regards to prostate-cancer specific deaths.  However, it did find a significant increase in other-cause mortality (hazard ratio 1.12; confidence interval 1.05 to 1.20).  The secondary analyses showed a slight reduction in mortality at 5 (hazard ratio 0.91; confidence interval 0.83 to 1.01) and 7.5 years (hazard ratio 0.84, confidence interval 0.72 to 0.97).

The study’s findings are far from the definitive answer needed to confirm aspirin’s anticancer effects.  However, the findings elucidated in the secondary analyses again suggests that aspirin may have a role in decreasing prostate cancer related mortality; though this effect may only appear after many years of low-dose aspirin use.  Although the study authors did try to control for tumor grade in this study, it’s easy to make the argument that this finding may simply be the result of differences in disease severity within the population.

Mini Cuts

Quality and Experience of Outpatient Care in the United States for Adults With or Without Primary Care[xii]

This study evaluated 39 quality measures and 7 patient experience measures of medical care for patients with and without primary care providers (PCP).  They found patients with PCPs generally received better screening, basic diagnostic and preventative testing, diabetes care, and counseling as well as reporting better overall experience, communication, and access.  However they were at risk for more low-value antibiotic use and less use of high-value medical treatments including cardiovascular regimens.  With greater scrutiny on value of care given and arguments for healthcare reform, the study provides a road map of strengths to build upon and weaknesses to consider if moving towards a more primary-care centric model in the U.S.

Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer.[xiii]

In this meta-analysis, human gut microbiome genomic data was compiled into a gut microbial signature before being used to build a predictive model to identify patients at risk of developing colorectal cancer.  This finding may foreshadow the value of metagenomic studies in screening for cancers.

The electronic song “Scary Monsters and Nice Sprites” reduces host attack and mating success in the dengue vector Aedes aegypti[xiv]

This study examined the effects of music on the behaviors of a mosquito vector, Aedes aegypti, and found that electronic music can delay host attack, reduce blood feeding activity and disrupt mating patterns. The study has potential implications for the development of music-based anti-mosquito public health measures and may encourage hosts to broaden their musical horizons.

Dr. Ryan Grattan is a 1st year resident at NYU Langone Health

Peer reviewed by Scott Statman, MD, Chief Resident, Quality Improvement, Medicine, NYU Langone Health

Image courtesy of Wikimedia Commons

References

[i] Cortese I, Muranski P, Enose-Akahata Y, et al. Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy. NEJM. 2019 April. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1815039

[ii] Tan CS, Koralnik IJ.  Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurology.  2010 April.  Available at: https://www.ncbi.nlm.nih.gov/pubmed/?term=20298966

[iii] Qiong O, Chen B, Loffler K, et al.  The Effects of Long-term CPAP on Weight Change in Patients With Comorbid OSA and Cardiovascular Disease.  Chest.  2019 April.  Available at: https://journal.chestnet.org/article/S0012-3692(18)32482-6/fulltext#intraref0005

[iv] Basta M, Lin HM, Pejovic S, et al. Lack of regular exercise, depression, and degree of apnea are predictors of excessive daytime sleepiness in patients with sleep apnea: sex differences.  Journal of Clinical Sleep Medicine.  2008 Feb. Available at: https://www.ncbi.nlm.nih.gov/pubmed/18350958

[v] Patel SR, Palmer LJ, Larkin EK, et al.  Relationship between obstructive sleep apnea and diurnal leptin rhythms. Sleep. 2004 Mar.  Available at: https://www.ncbi.nlm.nih.gov/pubmed/15124716

[vi] Ucok K, Aycicek A, Sezer M, et al. Resting metabolic rate and anthropometric measurements in male sleep apnea patients.  Internal Medicine.  2011 April.  Available at: https://www.ncbi.nlm.nih.gov/pubmed/21498930

[vii] Lemkes JS, Janssens GN, van der Hoeven NW, et al.  Coronary Angiography after Cardiac Arrest without ST-Segment Elevation.  NEJM.  2019 April.  Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1816897

[viii] Skirver C, Dehlendorff C, Borre M, et al. Use of Low-Dose Aspirin and Mortality After Prostate Cancer Diagnosis: A Nationwide Cohort Study. Annals of Internal Medicine. 2019 April. Available from: https://annals.org/aim/article-abstract/2727206/use-low-dose-aspirin-mortality-after-prostate-cancer-diagnosis-nationwide

[ix] World Health Organization. Cancer Fact Sheet. 2018 Sept. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer

[x] American Cancer Society. Cancer Facts & Figures 2019. 2019. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf

[xi] Elwood PC, Morgan G, Pickering JE, et al. Aspirin in the Treatment of Cancer: Reductions in Metastatic Spread and in Mortality: A Systematic Review and Meta-Analyses of Published Studies.  PLoS One. 2016 Apr. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27096951

[xii] Levine DM, Landon BE, Linder JA.  Quality and Experience of Outpatient Care in the United States for Adults with or Without Primary Care. JAMA Internal Medicine. 2019 Jan. Available at: https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2721037

[xiii] Wirbel J, Pyl PT, et al.  Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer.  Nature Medicine.  2019 April.  Available at: https://www.ncbi.nlm.nih.gov/pubmed/30936547

[xiv] Dieng, H, The CC, et al. The electronic song “Scary Monsters and Nice Sprites” reduces host attach and mating success in the dengue vector Aedes aegypti. 2019 June. Available from: https://doi.org/10.1016/j.actatropica.2019.03.027

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