Publications by authors named "Cohen M"

11,702 Publications

Unexpected Internal Mammary Artery Perforation During Transradial Access for a Neuroendovascular Procedure.

JACC Case Rep 2021 Aug 7;3(9):1187-1190. Epub 2021 Apr 7.

Department of Neurological Surgery, University of Miami, Miami, Florida, USA.

During cerebral angiography via transradial access, the guidewire inadvertently entered the right internal mammary artery. This was not recognized because of its downward trajectory, and it was interpreted to be in the ascending aorta. Catheter manipulation perforated the right internal mammary artery, with development of pectoral hematoma. The perforation was sealed with coils and glue. .
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http://dx.doi.org/10.1016/j.jaccas.2021.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353564PMC
August 2021

Flexible fiber-based CO laser vs monopolar cautery for resection of oral cavity lesions: A single center randomized controlled trial assessing pain and quality of life following surgery.

Laryngoscope Investig Otolaryngol 2021 Aug 10;6(4):690-698. Epub 2021 Jul 10.

Department of Surgery Head and Neck Service, Memorial Sloan Kettering Cancer Center New York New York USA.

Importance: This study reports the impact of laser surgery on quality of life in patients with oral cavity lesions.

Objective: To compare postoperative pain and quality of life in patients treated with flexible fiberoptic CO laser vs electrocautery in patients with oral cavity precancerous lesions and early stage cancers.

Design: Randomized controlled trial.

Setting: Single center.

Participants: Patients with premalignant oral cavity lesions and early stage oral cancer.

Intervention: Patients were randomized to have surgical resection using either flexible fiber carbon dioxide laser (Laser) or electrocautery (EC). The patients were then followed over a period of 28 days to assess for outcomes including pain, quality of life, performance status, return to work, and return to diet. Quality of life was measured by the University of Washington Quality of Life (UWQOL) questionnaire and the performance status score (PSS).

Main Outcome Measure: The primary endpoint for this study was the numerical pain rating on postoperative day (POD) 7.

Results: Sixty-two patients were randomized (32 laser and 30 electrocautery). Lesions excised were carcinoma in 30(48%), dysplasia in 31(50%) and benign in 1(2%). There was no difference in the location of lesion, size of lesion, defect size, type of closure, resection time, and blood loss between Laser and EC arms. Patients who had Laser had less pain compared to EC (mean pain score on POD 7 L = 2.84 vs EC = 3.83,  = 0.11). better UW QOL scores and PSS scores, quicker return to normal diet (median days L = 26.0 vs EC = 28.5,  = 0.17) and faster return to work (median days L = 13.0 vs EC = 16.5,  = 0.14). However, these results were not statistically significant.

Conclusion: There was a trend for patients treated with laser to have less pain and better quality of life scores but these result were not statistically significant. Based on the actual observed difference, a large multicenter RCT with 90 patients in each arm is required to determine the clinical relevance of our results.
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http://dx.doi.org/10.1002/lio2.572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356859PMC
August 2021

Hot topics in interventional cardiology: Proceedings from the society for cardiovascular angiography and interventions (SCAI) 2021 think tank.

Catheter Cardiovasc Interv 2021 Aug 16. Epub 2021 Aug 16.

Department of Cardiology, Piedmont Heart Institute, Atlanta, Georgia, USA.

The Society for Cardiovascular Angiography and Interventions (SCAI) Think Tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community annually for high-level field-wide discussions. The 2021 Think Tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease. Each session was moderated by a senior content expert and co-moderated by a member of SCAI's Emerging Leader Mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialog from a broader base, and thereby aid SCAI, the industry community and external stakeholders in developing specific action items to move these areas forward.
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http://dx.doi.org/10.1002/ccd.29898DOI Listing
August 2021

International Survey of Operative Practices for Otologists and Neurotologists During the COVID-19 Crisis.

Otol Neurotol 2021 09;42(8):1275-1284

Department of Otorhinolaryngology - Head and Neck Surgery, University of Tuebingen, Tuebingen, Germany.

Objective: To investigate the influence of the COVID-19 pandemic on operative practices of otology and neurotology providers internationally.

Study Design: Cross-sectional survey.

Methods: A 78-question survey was distributed to otologists and neurotologists between May 12, 2020 and June 8, 2020 to assess the impact of the pandemic on surgical practices. Sections within the survey delineated time periods: prior to the crisis, onset of the crisis, during the crisis, postcrisis transition.

Results: Of 396 survey respondents, 284 participants from 38 countries met inclusion criteria.Respondents were 16.9% female and 82.4% male, with a most common age range of 40 to 49 years (36.3%). 69.8% of participants had been in practice for over 10 years and most respondents worked in an academic medical center (79.2%). The average operative weekly caseload was 5.3 (SD 3.9) per surgeon prior to the crisis, 0.7 (SD 1.2) during the COVID-19 crisis, and 3.5 (SD 3.3) for those who had begun a postcrisis transition at the time of survey administration (p < 0.001). 71.5% of providers did not perform an elective otologic or neurotologic operative procedure during the initial crisis period. 49.8% reported modifying their surgical technique due to the COVID-19 pandemic. Use of powered air-purifying respirators and filtering facepiece 2 or 3 (FFP2/FFP3) respirators were in minimal supply for 66.9% and 62.3% of respondents, respectively.

Conclusion: The COVID-19 pandemic impacted the otology and neurotology community globally, resulting in significant changes in operative volume and case selection. Modification of surgical technique and shortages of personal protective equipment were frequently reported.
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http://dx.doi.org/10.1097/MAO.0000000000003219DOI Listing
September 2021

Coronary Microvascular Dysfunction and the Risk of Atrial Fibrillation From an Artificial Intelligence-Enabled Electrocardiogram.

Circ Arrhythm Electrophysiol 2021 Aug 16;14(8):e009947. Epub 2021 Aug 16.

Department of Cardiovascular Medicine (A.A., M.T.C., T.T., Z.I.A., P.A.N., F.L.-J., M.S.C., J.D.S., I.O., S.K., P.A.F., A.L.), Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1161/CIRCEP.121.009947DOI Listing
August 2021

Pediatric Chair Turnover and Demographics.

J Pediatr 2021 Aug 12. Epub 2021 Aug 12.

Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL.

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http://dx.doi.org/10.1016/j.jpeds.2021.08.003DOI Listing
August 2021

Characterizing neural phase-space trajectories via Principal Louvain Clustering.

J Neurosci Methods 2021 Oct 9;362:109313. Epub 2021 Aug 9.

Radboud University Medical Center, Donders Centre for Medical Neuroscience, The Netherlands.

Background: With the growing size and richness of neuroscience datasets in terms of dimension, volume, and resolution, identifying spatiotemporal patterns in those datasets is increasingly important. Multivariate dimension-reduction methods are particularly adept at addressing these challenges.

New Method: In this paper, we propose a novel method, which we refer to as Principal Louvain Clustering (PLC), to identify clusters in a low-dimensional data subspace, based on time-varying trajectories of spectral dynamics across multisite local field potential (LFP) recordings in awake behaving mice. Data were recorded from prefrontal cortex, hippocampus, and parietal cortex in eleven mice while they explored novel and familiar environments.

Results: PLC-identified subspaces and clusters showed high consistency across animals, and were modulated by the animals' ongoing behavior.

Conclusions: PLC adds to an important growing literature on methods for characterizing dynamics in high-dimensional datasets, using a smaller number of parameters. The method is also applicable to other kinds of datasets, such as EEG or MEG.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109313DOI Listing
October 2021

Promoter Mutations Are Enriched in Oral Cavity Cancers and Associated With Locoregional Recurrence.

JCO Precis Oncol 2021 Aug 5;5. Epub 2021 Aug 5.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.

Telomerase reverse transcriptase () promoter mutations are prognostic in many cancers and have been observed in human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). However, the role of promoter mutations in HPV-negative HNSCCs remains poorly understood in these cancers, which have increased risk for locoregional failure (LRF).

Patients And Methods: We retrospectively identified patients who were diagnosed with HNSCC between July 1, 2004, and October 12, 2017, at Memorial Sloan Kettering Cancer Center and whose tumors underwent next-generation sequencing using the MSK-IMPACT panel. Patients with HPV-positive oropharyngeal squamous cell carcinoma (SCC) were excluded. Cumulative incidence of LRF, patterns of failure, and overall survival were measured.

Results: We identified 117 patients with SCC of the oral cavity (OSCC), larynx, hypopharynx, or HPV-negative oropharynx whose tumors underwent next-generation sequencing. Sequencing was performed on 95 tumors that were obtained after recurrence and 22 that were obtained before recurrence. promoter mutations were enriched in OSCC compared with laryngopharyngeal cancers (81.1% 7.0%; < .001), which was the largest genetic difference between these anatomic disease subsites. promoter mutations were associated with LRF in OSCCs (Gray's test, < .001) and in the overall cohort (Gray's test, < .001). On multivariate analysis, promoter mutations were associated with an increased risk for LRF (subdistribution hazard ratio, 2.82; 95% CI, 1.47 to 5.42; = .0019), independent of oral cavity primary site and mutation status.

Conclusion: promoter status is associated with the cumulative incidence of LRF and patterns of failure. promoter mutations may define a subset of OSCCs with unique pathogenesis that is associated with an increased risk of LRF. Validation in prospective cohorts is warranted.
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http://dx.doi.org/10.1200/PO.20.00515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345918PMC
August 2021

The effect of cardiac geometry variation according to sex and race on outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Arch Med Sci Atheroscler Dis 2021 19;6:e152-e159. Epub 2021 Jul 19.

Department of Cardiology, Westchester Medical Center, Valhalla, NY, USA.

Introduction: The prevalence and long-term consequences of differences in baseline cardiac geometry (as a result of hypertension) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are ill-defined. The primary purpose of this study was to clarify whether there were differences among sexual and racial groups in echocardiographic findings reflecting cardiac geometry and adaptation in patients undergoing PCI for ACS and whether this could explain the differences in outcomes seen between these groups.

Material And Methods: We analyzed 1-year follow-up data from a single institution, a retrospective, observational study that enrolled 1,153 patients who presented with ACS and were treated with PCI, for whom echocardiographic data were available.

Results: Normal, concentric hypertrophy, and eccentric hypertrophy in males vs. females were observed as follows: 29% vs. 19% ( = 0.001), 25% vs. 31% ( = 0.02), and 8% vs. 14% ( = 0.004), respectively. The primary endpoint of all-cause death ( = 89, 7.7%) occurred in 48 (10.5%) females and in 41 (8.2%) males, = 0.03. Major adverse cardiac events and bleeding (MACE-B - all-cause death, non-fatal myocardial infarction, stroke or hospitalization for bleeding) was higher among women than men (21.6% vs. 13.5%, = 0.0002). Males with eccentric hypertrophy (EH) had similar MACE-B outcomes as females with EH 1-year post-PCI (29% vs. 32%, respectively, = 0.77).

Conclusions: Females undergoing PCI for ACS are at higher risk for worse outcomes because they are more likely to express the eccentric hypertrophy phenotype; however, it did not account for the difference in adverse outcomes observed between sexes.
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http://dx.doi.org/10.5114/amsad.2021.107908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336437PMC
July 2021

Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women.

N Engl J Med 2021 08;385(7):595-608

From the Center for Clinical AIDS Research and Education, David Geffen School of Medicine, University of California, Los Angeles (R.J.L., R.M.K.), the Lundquist Institute at Harbor-UCLA Medical Center, Torrance (E.D.), the San Francisco Department of Public Health, San Francisco (H.S.), and Gilead Sciences, Foster City (J.F.R.) - all in California; the Fred Hutchinson Cancer Research Center, Seattle (D.D., B.H., L. Cottle, M.L., Z.W.); the Louisiana State University Health Sciences Center, New Orleans (M.E.C.); Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Rio de Janeiro (L. Coelho, B.G.), University of São Paulo (E.G.K.), and Centro de Referência e Treinamento DST-AIDS-SP (J.V.M.), São Paulo, and Hospital Nossa Senhora da Conceição, Porto Alegre (B.S.) - all in Brazil; Via Libre (R.C.), Universidad Nacional Mayor de San Marcos (J.A.G.-C.), and Asociacion Civil Impacta Salud y Educacion (P.G., J.V.H.), Lima, and Asociacion Civil Selva Amazonica, Iquitos (J.C.H.) - all in Peru; the Research Institute for Health Sciences, Chiang Mai University, Chiang Mai (S.C.), and the Institute of HIV Research and Innovation, Bangkok (N.P.) - both in Thailand; the Division of HIV-AIDS Prevention, Centers for Disease Control and Prevention (E.F.D.), the School of Medicine (C.F.K., C.R.), and Rollins School of Public Health (C.R.), Emory University - both in Atlanta; the Perelman School of Medicine, University of Pennsylvania, Philadelphia (I.F.), and Pennsylvania State University, State College (S.D.F.) - both in Pennsylvania; St. Jude Children's Research Hospital, Memphis, TN (A.H.G.); University of North Carolina at Chapel Hill, Chapel Hill (H.V.T., J.J.E., M.S.C.), FHI 360, Durham (A. Asmelash, M.B., C.B., J.L., N.D.S., K.G.-F., A.J., M.M.), and ViiV Healthcare, Research Triangle (K.Y.S., W.S., D.M., A.R.) - all in North Carolina; Hospital General de Agudos José María Ramos Mejia (M.H.L.) and Fundación Huésped (O.S.) - both in Buenos Aires; the Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa (K.M.); University of Alabama at Birmingham, Birmingham (E.T.O., J.M.); Rutgers New Jersey Medical School, Newark (S. Swaminathan); Weill Cornell Medicine, New York (R.M.G.); Johns Hopkins University, Baltimore (P.R., P.S., E.P.-M., M.M., C.H., T.T.B., S.H.E., J.S.); University of Colorado Anschutz Medical Campus, Aurora (P.A.); Massachusetts General Hospital, Boston (C.P.); University of Miami, Coral Gables, FL (S. Safren); the Office of AIDS Research (T.H.H.) and Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD (K.S., A. Adeyeye).

Background: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection.

Methods: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection.

Results: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified.

Conclusions: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).
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http://dx.doi.org/10.1056/NEJMoa2101016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448593PMC
August 2021

Nail gun injury with intraocular foreign body.

J Am Coll Emerg Physicians Open 2021 Aug 2;2(4):e12527. Epub 2021 Aug 2.

Mid Atlantic Retina Retina Service of Wills Eye Hospital Philadelphia Pennsylvania USA.

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http://dx.doi.org/10.1002/emp2.12527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329076PMC
August 2021

How Would You Manage This Male Patient With Hypogonadism? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Ann Intern Med 2021 08 10;174(8):1133-1142. Epub 2021 Aug 10.

Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts (H.L., M.L.C., M.S.I., G.W.S.).

Male hypogonadism is defined as an abnormally low serum testosterone concentration or sperm count. As men age, often in the context of obesity and other comorbid conditions, serum testosterone levels may decrease. Normalizing serum testosterone levels in male adults with hypogonadism may improve symptoms related to androgen deficiency, but controversies exist regarding the long-term benefits and risks of hormone supplementation in this setting. In 2020, the American College of Physicians published a clinical guideline for the use of testosterone supplementation in adult men based on a systematic review of available evidence. Among their recommendations were that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function and not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition. Here, two clinicians with expertise in this area, one a generalist and the other an endocrinologist, debate the management of a patient with sexual symptoms and a low serum testosterone level. They discuss the diagnosis of male hypogonadism, the indications for testosterone therapy, its potential benefits and risks, how it should be monitored, and how long it should be continued.
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http://dx.doi.org/10.7326/M21-2524DOI Listing
August 2021

Parental Views on the Role of Social Media in Pediatric Otolaryngology.

Ann Otol Rhinol Laryngol 2021 Aug 8:34894211037413. Epub 2021 Aug 8.

Boston University School of Medicine, Boston, MA, USA.

Objective: Social media is playing an increasingly important role in medicine as a tool for patients and their families to find information and connect with others. The goal of this study is to understand parental views on if and how social media should be incorporated into pediatric otolaryngology by physicians and hospitals.

Methods: A survey was distributed to parents of pediatric otolaryngologic patients to assess views on professional social media use by physicians and hospitals. The proportion of parents who answered with specific responses in the survey was computed using the SPSS frequency analysis function.

Results: One hundred five parents completed the survey. Ninety-six percent of respondents use social media, of which 92% use social media at least once a day (n = 93). Eighty-five percent of respondents said they definitely or probably would visit their physician's professional social media page (n = 90). Seventy-four percent would be interested in obtaining more information about the physician (n = 76). Forty-one percent would be interested in patient stories (n = 76). Twenty-eight percent would visit out of curiosity (n = 76). Twenty-six percent would want to gather more information about the hospital (n = 76). Seventeen percent would want to connect with other patients and their family members (n = 76). Sixty-seven percent of respondents believe it is important for physicians to have a professional social media page, and 79% of respondents believe it is important for hospitals to have a public social media page (n = 93).

Conclusion: The vast majority of parents of pediatric otolaryngologic patients use social media regularly and would want to gather information about their physician and hospital through social media. Therefore, physicians and hospitals should consider using social media as a valuable tool to connect with and relay information to patients and their family members.
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http://dx.doi.org/10.1177/00034894211037413DOI Listing
August 2021

Chemical genetic methodologies for identifying protein substrates of PARPs.

Trends Biochem Sci 2021 Aug 5. Epub 2021 Aug 5.

Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, USA. Electronic address:

Poly-ADP-ribose-polymerases (PARPs) are a family of 17 enzymes that regulate a diverse range of cellular processes in mammalian cells. PARPs catalyze the transfer of ADP-ribose from NAD to target molecules, most prominently amino acids on protein substrates, in a process known as ADP-ribosylation. Identifying the direct protein substrates of individual PARP family members is an essential first step for elucidating the mechanism by which PARPs regulate a particular pathway in cells. Two distinct chemical genetic (CG) strategies have been developed for identifying the direct protein substrates of individual PARP family members. In this review, we discuss the design principles behind these two strategies and how target identification has provided novel insight into the cellular function of individual PARPs and PARP-mediated ADP-ribosylation.
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http://dx.doi.org/10.1016/j.tibs.2021.07.002DOI Listing
August 2021

2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients.

Heart Rhythm 2021 Jul 29. Epub 2021 Jul 29.

St. Luke's Health System, Boise, Idaho.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consenus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology, (ACC) and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate follow-up in pediatric patients.
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http://dx.doi.org/10.1016/j.hrthm.2021.07.038DOI Listing
July 2021

Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications.

Genet Med 2021 Aug 6. Epub 2021 Aug 6.

Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX, USA.

Purpose: Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted.

Methods: We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record.

Results: Notably, 32% of patients had a genetic finding with clinical management implications, even after excluding PGx results, including 9% who were molecularly diagnosed with a Mendelian condition. Among surveyed physicians, 84% reported medical management changes based on these results, including specialist referrals, cardiac tests, and medication changes. LPA polymorphisms and high polygenic risk of CAD were found in 20% and 9% of patients, respectively, leading to diet, lifestyle, and other changes. Warfarin and simvastatin pharmacogenetic variants were present in roughly half of the cohort.

Conclusion: Our results support the use of genetic information in routine cardiovascular health management and provide a roadmap for accompanying research.
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http://dx.doi.org/10.1038/s41436-021-01294-8DOI Listing
August 2021

Identification of novel lipid metabolic biomarkers associated with poor adrenocortical carcinoma prognosis using integrated bioinformatics.

Surgery 2021 Aug 2. Epub 2021 Aug 2.

Department of Surgery, Michigan Medicine, Ann Arbor, MI; Departments of Pharmacology and Biomedical Engineering, University of Michigan, Ann Arbor, MI. Electronic address:

Background: Adrenocortical carcinoma while rare, often presents with advanced metastatic disease carrying a 5-year survival of <15%. Despite adrenocortical carcinoma tumors having high avidity for cholesterol, the role of lipids in adrenocortical carcinoma has not been well described. Therefore, we performed an integrated bioinformatic analysis to identify novel lipid biomarkers correlating with poor survival that may help identify adrenocortical carcinoma tumor progression or therapy resistance.

Methods: A meta-analysis of collated adrenocortical carcinoma studies from the correlation engine identified lipid metabolism genes differentially expressed between adrenocortical carcinoma and the normal adrenal, which were then selected for enrichment analysis by the Database for Annotation, Visualization and Integrated Discovery database. A protein-protein interaction network of genes was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. Top hub genes identified were validated using the Xena database. Survival analysis of hub genes was performed in the R2 genomic analysis platform using The Cancer Genome Atlas program data set.

Results: Examination of pathways by correlation engine identified a unique subset of lipid metabolism-related genes that are differentially regulated in adrenocortical carcinoma tumors versus normal tissues (P < .01). Enrichment pathway analysis in Database for Annotation, Visualization and Integrated Discovery indicated that genes involved in sphingolipid, steroid, and peroxisome proliferator-activated receptor-α metabolism is upregulated in adrenocortical carcinoma, whereas glycerol phospholipid, fatty acid, and phosphatidylinositol metabolism are downregulated. Survival analysis of differentially regulated genes indicated that upregulation of SGPL1, FDFT1, SQLE and downregulation of PIK3C2B, PIK3CD, SYNJ2, DGAT1, PLA2G16, PLD1, GPD1 are all significantly associated with poor overall survival (P < .05) in adrenocortical carcinoma patients.

Conclusion: Upregulation of sphingolipid and steroid synthesis genes and downregulation of phosphatidylinositol and glycerol phospholipid metabolism are associated with worse survival in patients with adrenocortical carcinoma.
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http://dx.doi.org/10.1016/j.surg.2021.04.049DOI Listing
August 2021

MSCopilot: New smartphone-based digital biomarkers correlate with Expanded Disability Status Scale scores in people with Multiple Sclerosis.

Mult Scler Relat Disord 2021 Jul 23;55:103164. Epub 2021 Jul 23.

Service de Neurologie, Hôpital Raymond Poincaré, Garches, UFR Simone Veil, UVSQ, INSERM U 1195, APHP, Université Paris Saclay, France.

Background: A previous clinical study showed the high specificity, sensitivity and reliability of MSCopilot, a software medical device designed by Ad Scientiam for the self-assessment of people with Multiple Sclerosis (PwMS), compared to the traditional Multiple Sclerosis Functional Composite (MSFC). We conducted further analyses to assess MSCopilot's performance with respect to the Expanded Disability Status Scale (EDSS).

Methods: The data of 116 PwMS were analysed. We studied the correlations between MSCopilot scores and the EDSS, and their ability to distinguish PwMS with high and low EDSS through a study of the distribution of the digital test scores as well as logistic regression models. The same analyses were performed using the MSFC tests.

Results: MSCopilot composite scores were as highly correlated to the EDSS (|r| = 0.65, p < 0.01) as their MSFC counterparts, confirming the known correlation of the MSFC with the EDSS. In a linear regression framework, the Walking digital tests have good explanatory power, especially for PwMS with EDSS > 3.5 (R²=0.47). The mean values of each MSCopilot subscore were significantly different between patients with an EDSS > 3.5 and others (p < 0.05), which could not be proved for the MSFC Cognition tests. MSCopilot4 was the best model to predict an EDSS score > 3.5 (AUC = 0.92).

Conclusion: These analyses confirm the reliability of MSCopilot and show interesting correlations with the EDSS (similar results obtained with the MSFC). MSCopilot was able to highlight nuances in the different stages of MS the MSFC could not capture.
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http://dx.doi.org/10.1016/j.msard.2021.103164DOI Listing
July 2021

SARS-CoV-2 Variants in Patients with Immunosuppression.

N Engl J Med 2021 08;385(6):562-566

From the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (L.C., T.B.); Johns Hopkins Bloomberg School of Public Health, Baltimore (C.B.), the Center for Infectious Disease Research (N.L.M.) and the U.S. Military HIV Research Program (M.R.), Walter Reed Army Institute of Research, Silver Spring, and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda (M.R.) - all in Maryland; and the Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill (M.S.C.).

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http://dx.doi.org/10.1056/NEJMsb2104756DOI Listing
August 2021

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19.

N Engl J Med 2021 Sep 4;385(13):1184-1195. Epub 2021 Aug 4.

From Regeneron Pharmaceuticals, Tarrytown, NY (M.P.O., E.F.-N., B.J.M., F.I., K.-C.C., N. Sarkar, P.H., I.H., J.D.D., K.C.T., D.R., A.M., A.T.H., J.D.H., Y.K., L.A.P., A.B., C.A.K., B.K., A.T.D., N. Stahl, L.L., N.B., G.H., G.D.Y., D.M.W.); the Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia (K.J.B.); the Departments of Global Health and Epidemiology and the Division of Allergy and Infectious Diseases, University of Washington, and the Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center - both in Seattle (R.V.B.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston (D.H.B.); the Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill (M.S.C., C.B.H.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD (D.R.B., M.A.M.); Clinical Trials of Florida (J.K.) and Medical Research of Westchester (R.P.-P.) - both in Miami; and the Catalina Research Institute, Montclair, CA (R.M.).

Background: REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown.

Methods: We randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase-quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity).

Results: Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P<0.001). In weeks 2 to 4, a total of 2 of 753 participants in the REGEN-COV group (0.3%) and 27 of 752 participants in the placebo group (3.6%) had symptomatic SARS-CoV-2 infection (relative risk reduction, 92.6%). REGEN-COV also prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%). Among symptomatic infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively), and the duration of a high viral load (>10 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted.

Conclusions: Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04452318.).
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http://dx.doi.org/10.1056/NEJMoa2109682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362593PMC
September 2021

Poverty, deprivation, and mortality risk among women with HIV in the United States.

Epidemiology 2021 Aug 3. Epub 2021 Aug 3.

Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC NoviSci Inc., Durham, NC Division of Infectious Diseases, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC Department of Clinical Pharmacy, The University of California San Francisco, San Francisco, CA Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, NY Department of Medicine, Stroger Hospital, Cook County Bureau of Health Services, Chicago, IL Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Department of Medicine, Georgetown University Medical Center, Washington, DC Department of Medicine, Albert Einstein College of Medicine, Bronx, NY Department of Medicine, The University of Mississippi Medical Center, Jackson, MS Department of Community Health Sciences, School of Public Health, State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY.

Background: Prior studies suggest neighborhood poverty and deprivation are associated with adverse health outcomes including death, but evidence is limited among persons with HIV, particularly women. We estimated changes in mortality risk from improvement in three measures of area-level socioeconomic context among participants of the Women's Interagency HIV Study.

Methods: Starting in October 2013, we linked geocoded residential census block groups to the 2015 Area Deprivation Index (ADI) and two 2012-2016 American Community Survey poverty variables, categorized into national tertiles. We used parametric g-computation to estimate, through March 2018, impacts on mortality of improving each income or poverty measure by one and two tertiles maximum versus no improvement.

Results: Of 1,596 women with HIV (median age 49), 91 (5.7%) were lost to follow-up and 83 (5.2%) died. Most women (62%) lived in a block group in the tertile with the highest proportions of individuals with income:poverty <1; 13% lived in areas in the tertile with the lowest proportions. Mortality risk differences comparing a one-tertile improvement (for those in the two highest poverty tertiles) in income:poverty <1 versus no improvement increased over time; the risk difference was -2.2% (95% confidence interval [CI], -3.7%, -0.64%) at 4 years. Estimates from family income below poverty level (-1.0%; 95% CI, -2.7%, 0.62%) and ADI (-1.5%; 95% CI, -2.8%, -0.21%) exposures were similar.

Conclusions: Consistent results from three distinct measures of area-level socioeconomic environment support the hypothesis that interventions to ameliorate neighborhood poverty or deprivation reduce mortality risk for US women with HIV.
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August 2021

Tendon grafts with preserved muscle demonstrate similar biomechanical properties to tendon grafts stripped of muscular attachments: a biomechanical evaluation in a porcine model.

J Exp Orthop 2021 Aug 2;8(1):57. Epub 2021 Aug 2.

Orthoapedic Surgeon From Universidade Federal de São Paulo, São Paulo, Brazil.

Purpose: (1) To evaluate the biomechanical properties of a porcine flexor digitorum superficialis tendon graft with preserved muscle fibers and (2) to compare these results with the biomechanical properties of a porcine tendon graft after removal of associated muscle.

Methods: Eighty-two porcine forelegs were dissected and the flexor digitorum superficialis muscle tendons were harvested. The study comprised of two groups: Group 1 (G1), harvested tendon with preserved muscle tissue; and Group 2 (G2), harvested contralateral tendon with removal of all muscle tissue. Tests in both groups were conducted using an electro-mechanical material testing machine (Instron, model 23-5S, Instron Corp., Canton, MA, USA) with a 500 N force transducer. Yield load, stiffness, and maximum load were evaluated and compared between groups.

Results: The behavior of the autografts during the tests followed the same stretching, deformation, and failure patterns as those observed in human autografts subjected to axial strain. There were no significant differences in the comparison between groups for ultimate load to failure (p = 0.105), stiffness (p = 0.097), and energy (p = 0.761).

Conclusion: In this porcine model biomechanical study, using autograft tendon with preserved muscle showed no statistically significant differences for yield load, stiffness, or maximum load compared to autograft tendon without preserved muscle. The preservation of muscle on the autograft tendon did not compromise the mechanical properties of the autograft.

Level Of Evidence: Level III Controlled laboratory study.
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http://dx.doi.org/10.1186/s40634-021-00375-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329107PMC
August 2021

2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients.

Cardiol Young 2021 Aug 2:1-104. Epub 2021 Aug 2.

St. Luke's Health System, Boise, Idaho.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consenus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology, (ACC) and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate follow-up in pediatric patients.
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http://dx.doi.org/10.1017/S1047951121003413DOI Listing
August 2021

2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients: Executive Summary.

Indian Pacing Electrophysiol J 2021 Jul 27. Epub 2021 Jul 27.

Evelina London Children's Hospital and St Thomas' Hospital, Guy's & St Thomas' NHS Foundation Trust, London, UK.

Guidelines for the implantation of cardiac implantable electronic devices (CIEDs) have evolved since publication of the initial ACC/AHA pacemaker guidelines in 1984. CIEDs have evolved to include novel forms of cardiac pacing, the development of implantable cardioverter-defibrillators (ICDs) and the introduction of devices for long term monitoring of heart rhythm and other physiologic parameters. In view of the increasing complexity of both devices and patients, practice guidelines, by necessity, have become increasingly specific. In 2018, the ACC/AHA/HRS published Guidelines on the Evaluation and Management of Patients with Bradycardia and Cardiac Conduction Delay, which were specific recommendations for patients >18 years of age. This age-specific threshold was established in view of the differing indications for CIEDs in young patients as well as size-specific technology factors. Therefore, the following document was developed to update and further delineate indications for the use and management of CIEDs in pediatric patients, defined as ≤21 years of age, with recognition that there is often overlap in the care of patents between 18 and 21 years of age. This document is an abbreviated expert consensus statement (ECS) intended to focus primarily on the indications for CIEDs in the setting of specific disease/diagnostic categories. This document will also provide guidance regarding the management of lead systems and follow-up evaluation for pediatric patients with CIEDs. The recommendations are presented in an abbreviated modular format, with each section including the complete table of recommendations along with a brief synopsis of supportive text and select references to provide some context for the recommendations. This document is not intended to provide an exhaustive discussion of the basis for each of the recommendations, which are further addressed in the comprehensive PACES-CIED document, with further data easily accessible in electronic searches or textbooks.
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http://dx.doi.org/10.1016/j.ipej.2021.07.006DOI Listing
July 2021

2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients.

Indian Pacing Electrophysiol J 2021 Jul 27. Epub 2021 Jul 27.

Evelina London Children's Hospital and St Thomas' Hospital, Guy's & St Thomas' NHS Foundation Trust, London, UK.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consenus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology, (ACC) and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate follow-up in pediatric patients.
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http://dx.doi.org/10.1016/j.ipej.2021.07.005DOI Listing
July 2021

COVID-19 vaccines that reduce symptoms but do not block infection need higher coverage and faster rollout to achieve population impact.

Sci Rep 2021 07 30;11(1):15531. Epub 2021 Jul 30.

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., M2-C200, P.O. Box 19024, Seattle, WA, 98109-1024, USA.

Trial results for two COVID-19 vaccines suggest at least 90% efficacy against symptomatic disease (VE). It remains unknown whether this efficacy is mediated by lowering SARS-CoV-2 infection susceptibility (VE) or development of symptoms after infection (VE). We aim to assess and compare the population impact of vaccines with different efficacy profiles (VE and VE) satisfying licensure criteria. We developed a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington. Rollout scenarios starting December 2020 were simulated with combinations of VE and VE resulting in up to 100% VE. We assumed no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported. Rollouts of 1 M vaccinations (5000 daily) using vaccines with 50% VE are projected to prevent 23-46% of infections and 31-46% of deaths over 1 year. In comparison, vaccines with 90% VE are projected to prevent 37-64% of infections and 46-64% of deaths over 1 year. In both cases, there is a greater reduction if VE is mediated mostly by VE. The use of a "symptom reducing" vaccine will require twice as many people vaccinated than a "susceptibility reducing" vaccine with the same 90% VE to prevent 50% of the infections and death over 1 year. Delaying the start of the vaccination by 3 months decreases the expected population impact by more than 50%. Vaccines which prevent COVID-19 disease but not SARS-CoV-2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.
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http://dx.doi.org/10.1038/s41598-021-94719-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324774PMC
July 2021

The non-canonical target PARP16 contributes to polypharmacology of the PARP inhibitor talazoparib and its synergy with WEE1 inhibitors.

Cell Chem Biol 2021 Jul 22. Epub 2021 Jul 22.

Department of Drug Discovery, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, University of South Florida, Tampa, FL 33620, USA. Electronic address:

PARP inhibitors (PARPis) display single-agent anticancer activity in small cell lung cancer (SCLC) and other neuroendocrine tumors independent of BRCA1/2 mutations. Here, we determine the differential efficacy of multiple clinical PARPis in SCLC cells. Compared with the other PARPis rucaparib, olaparib, and niraparib, talazoparib displays the highest potency across SCLC, including SLFN11-negative cells. Chemical proteomics identifies PARP16 as a unique talazoparib target in addition to PARP1. Silencing PARP16 significantly reduces cell survival, particularly in combination with PARP1 inhibition. Drug combination screening reveals talazoparib synergy with the WEE1/PLK1 inhibitor adavosertib. Global phosphoproteomics identifies disparate effects on cell-cycle and DNA damage signaling thereby illustrating underlying mechanisms of synergy, which is more pronounced for talazoparib than olaparib. Notably, silencing PARP16 further reduces cell survival in combination with olaparib and adavosertib. Together, these data suggest that PARP16 contributes to talazoparib's overall mechanism of action and constitutes an actionable target in SCLC.
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http://dx.doi.org/10.1016/j.chembiol.2021.07.008DOI Listing
July 2021

Association of Pharyngocutaneous Fistula With Cancer Outcomes in Patients After Laryngectomy: A Multicenter Collaborative Cohort Study.

JAMA Otolaryngol Head Neck Surg 2021 Jul 29. Epub 2021 Jul 29.

Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

Importance: Pharyngocutaneous fistula (PCF) results in an inflammatory reaction, but its association with the rate of locoregional and distant control, disease-free survival, and overall survival in laryngeal cancer remains uncertain.

Objective: To determine if pharyngocutaneous fistula after salvage laryngectomy is associated with locoregional and distant control, disease-free survival, and/or overall survival.

Design, Setting, And Participants: A multicenter collaborative retrospective cohort study conducted at 5 centers in Canada and the US of 550 patients who underwent salvage laryngectomy for recurrent laryngeal cancer from January 1, 2000, to December 31, 2014. The median follow-up time was 5.7 years (range, 0-18 years).

Main Outcomes And Measures: Outcomes examined included locoregional and distant control, disease-free survival, and overall survival. Fine and Gray competing risk regression and Cox-proportional hazard regression models were used for outcomes. Competing risks and the Kaplan-Meier methods were used to estimate outcomes at 3 years and 5 years.

Results: In all, 550 patients (mean [SD] age, 64 [10.4] years; men, 465 [85%]) met inclusion criteria. Pharyngocutaneous fistula occurred in 127 patients (23%). The difference in locoregional control between the group of patients with PCF (75%) and the non-PCF (72%) group was 3% (95% CI, -6% to 12%). The difference in overall survival between the group with PCF (44%) and the non-PCF group (52%) was 8% (95% CI, -2% to 20%). The difference in disease-free survival between PCF and non-PCF groups was 6% (95% CI, -4% to 16%). In the multivariable model, patients with PCF were at a 2-fold higher rate of distant metastases (hazard ratio, 2.00; 95% CI, 1.22 to 3.27). Distant control was reduced in those with PCF, a 13% (95% CI, 3% to 21%) difference in 5-year distant control.

Conclusions And Relevance: This multicenter retrospective cohort study found that development of PCF after salvage laryngectomy is associated with an increased risk for the development of distant metastases.
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http://dx.doi.org/10.1001/jamaoto.2021.1545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323048PMC
July 2021

Abortion Care Beyond 13 Weeks' Gestation: A Global Perspective.

Clin Obstet Gynecol 2021 09;64(3):460-474

Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon.

The majority of abortions are performed early in pregnancy, but later abortion accounts for a large proportion of abortion-related morbidity and mortality. People who need this care are often the most vulnerable-the poor, the young, those who experience violence, and those with significant health issues. In settings with access to safe care, studies demonstrate significant declines in abortion-related morbidity and mortality. This review focuses on evidence-based practices for induced abortion beyond 13 weeks' gestation and post-abortion care in both high- and low-resource settings. We also highlight key programmatic issues to consider when expanding the gestational age for abortion services.
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http://dx.doi.org/10.1097/GRF.0000000000000631DOI Listing
September 2021
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