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Congenital cardiac anesthesiologists practice in a unique environment with high risk for morbidity and mortality. Quality metrics can be used to focus clinical initiatives on evidence-based care and provide a target for local quality improvement measures. However, there has been no comprehensive review on appropriate quality metrics for congenital cardiac anesthesia to date. Members of the Quality and Safety Committee for the Congenital Cardiac Anesthesia Society proposed 31 possible candidate topics for metrics. Using a scoping review strategy, 3649 abstracts were reviewed with 30 articles meeting final criteria. Of these, 5 candidate metrics were unanimously proposed for local collection and national benchmarking efforts: use of a structured handover in the intensive care unit, use of an infection prevention bundle, use of blood conservation strategies, early extubation of cardiopulmonary bypass cases, and cardiac arrest under the care of a cardiac anesthesiologist. Many metrics were excluded due to a lack of primary data and perceived complexity beyond the scope of cardiac anesthesia practice. There is a need to develop more primary data including linking process measures with outcomes, developing risk-stratification for our patients, and collecting national data for benchmarking purposes., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 International Anesthesia Research Society.)

Description: In July 2024, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DOD) released a joint update of their 2019 clinical practice guideline (CPG) for the management of stroke rehabilitation. This synopsis is a condensed version of the 2024 CPG, highlighting the key aspects of the guideline development process and describing the major recommendations., Methods: The VA/DOD Evidence-Based Practice Work Group convened a joint VA/DOD guideline development work group (WG) that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy CPGs. The guideline WG conducted a patient focus group, developed key questions, and systematically searched and evaluated the literature (English-language publications from 1 July 2018 to 2 May 2023). The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to evaluate the evidence. The WG developed 47 recommendations along with algorithms for stroke rehabilitation in the inpatient and outpatient settings. Stakeholders outside the WG reviewed the CPG before approval by the VA/DOD Evidence-Based Practice Work Group., Recommendations: This synopsis summarizes where evidence is strongest to support guidelines in crucial areas relevant to primary care physicians: transition to community (case management, psychosocial or behavioral interventions); motor therapy (task-specific practice, mirror therapy, rhythmic auditory stimulation, electrical stimulation, botulinum toxin for spasticity); dysphagia, aphasia, and cognition (chin tuck against resistance, respiratory muscle strength training); and mental health (selective serotonin reuptake inhibitor use, psychotherapy, mindfulness-based therapies for treatment but not prevention of depression)., Competing Interests: Disclosures: Disclosure forms are available with the article online.

Objective: The US Department of Veterans Affairs (VA) and Department of Defense (DOD) Work Group revised the 2013 VA/DOD Clinical Practice Guideline (CPG) for the Management of Bipolar Disorder (BD). This paper reviews the 2023 CPG and its development process, including how recommendations were made for evidence-based treatment in BD., Methods: Subject experts and key stakeholders developed 20 key questions and reviewed the published literature after a systematic search using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) method. The evidence was then evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. Recommendations were based on quality and strength of evidence and informed by other factors, including feasibility, patient perspectives, and the unique needs of people with BD. Peer review by an external group of experts then resulted in completion of the CPG., Recommendations: While the scope of the CPG is broad, this synopsis focuses on clinically relevant recommendations related to the identification and management of BD, including the acute and maintenance phases of illness., (© Copyright 2025 Physicians Postgraduate Press, Inc.)

Transradial arterial access has transformed the field of coronary interventions, where it has several advantages over femoral access, such as reduced bleeding and access site complications, improved patient comfort, shorter time to ambulation after the procedure, reduced length of hospital stay, and potentially reduced mortality rates. Because of these benefits, as well as the concurrent expanding indications for various endovascular therapies, there is growing interest in adopting radial access for peripheral vascular interventions. However, radial access can present challenges, and specialized equipment for peripheral interventions through this route are under development. Nevertheless, a growing number of studies, largely comprising single-center and registry data, have broadly suggested that transradial arterial access is likely to be safe and associated with reduced bleeding and local access site complications for most peripheral interventions compared with transfemoral access. Large, prospective randomized trials are lacking, and the question of any effect on mortality rates has not been addressed. Whereas the field of transradial arterial access for peripheral vascular interventions is in development, it is clear that this approach, at least with available equipment, will not be suitable for all patients, and careful case selection is paramount. Furthermore, the remaining knowledge gaps must be addressed, and robust outcome data obtained, to allow full understanding of the factors that determine optimal patient, lesion, and equipment selection. Nevertheless, the use of transradial arterial access for peripheral vascular interventions holds great promise, particularly if the necessary technologic advances are rapid and favorable clinical trial data continue to emerge.

Description: Headache medicine and therapeutics evidence have been rapidly expanding and evolving since the 2020 U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) clinical practice guideline (CPG) for the management of headache. Therefore, the CPG was revised in 2023, earlier than the standard 5-year cycle. This article reviews the 2023 CPG recommendations relevant to primary care clinicians for treatment and prevention of migraine and tension-type headache (TTH)., Methods: Subject experts from the VA and the DoD developed 12 key questions, which guided a systematic search using predefined inclusion and exclusion criteria. After reviewing evidence from 5 databases published between 6 March 2019 and 16 August 2022, the work group considered the strength and quality of the evidence, patient preferences, and benefits versus harms on critical outcomes before making consensus recommendations., Recommendations: The revised CPG includes 52 recommendations on evaluation, pharmacotherapy, invasive interventions, and nonpharmacologic interventions for selected primary and secondary headache disorders. In addition to triptans and aspirin-acetaminophen-caffeine, newer calcitonin gene-related peptide (CGRP) inhibitors (gepants) are options for treatment of acute migraine. Medications to prevent episodic migraine (EM) include angiotensin-receptor blockers, lisinopril, magnesium, topiramate, valproate, memantine, the newer CGRP monoclonal antibodies, and atogepant. AbobotulinumtoxinA can be used for prevention of chronic migraine but not EM. Gabapentin is not recommended for prevention of EM. Ibuprofen (400 mg) and acetaminophen (1000 mg) can be used for treatment of TTH, and amitriptyline for prevention of chronic TTH. Physical therapy or aerobic exercise can be used in management of TTH and migraines., Competing Interests: Disclosures: Disclosure forms are available with the article online.

Introduction: This Clinical Practical Guideline provides recommendations based on a systematic review of the evidence to address critical decision points in the management of pregnancy. The guideline is intended to improve patient outcomes and local management of patients who are pregnant. This CPG is based on a systematic review of both clinical and epidemiological evidence and was developed by a panel of multidisciplinary experts. The Work Group provides clear and comprehensive evidence-based recommendations incorporating current information and practices targeting practitioners throughout the DoD and VA Health Care systems. The guideline is intended to improve patient outcomes and local management of patients who are pregnant. This CPG does not address every aspect of routine pregnancy care and is not intended to be a comprehensive guide to all care needed in pregnancy. It also addresses some clinically important and generally accepted standards of pregnancy care interventions that do not have sufficient high-quality evidence to support standalone recommendations. Additionally, it highlights emerging topics that have the potential to impact pregnancy care in the future and identifies gaps in the literature that warrant further research., Materials and Methods: The development of all VA/DoD guidelines is directed by the Evidence-Based Practice Guideline Work Group and adheres to the standards for trustworthy guidelines that were set by the National Academy of Medicine. A patient focus group was convened to assess important aspects of treatment for patients and to gain information about patient values and preferences. The Lewin Group, a contracted third party with expertise in CPG development, facilitated meetings and the development of key questions using the population, intervention, comparison, outcome, timing, and setting format. Consensus was achieved among the Work Group through an iterative process involving discussions on conference calls and in person during the recommendation development meeting. An independent third party, ECRI, conducted the systematic evidence review, which the guideline Work Group then used to develop recommendations using the Grading of Recommendations Assessment, Development and Evaluation system (7-9). The search methods and results are detailed in the full guideline., Results: This CPG provides 28 clinical practice recommendations that cover selected topics that the Work Group deemed had high priority need for evidence-based standards. The recommendations are divided into 3 main categories: routine care, complicated obstetrics, and mental health. An algorithm delineating recommended interventions and appropriate timing of these interventions over the course of the pregnancy and postpartum period was also created., Conclusion: The CPG is not intended to define standards of care nor address all care needed in pregnancy; it does provide comprehensive guidance for routine pregnancy care. It aligns with the VA and DOD's goal of providing care that is consistent in quality and utilization of resources in efforts to reduce errors and inappropriate variations in practices. In total, the Work Group identified 71 items needing further study, including areas requiring stronger evidence to support current recommendations and newer topics that will guide future guideline development., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Despite abundant clinical innovation and burgeoning scientific investigation, pulmonary embolism (PE) has continued to pose a diagnostic and management challenge worldwide. Aging populations, patients living with a mounting number of chronic medical conditions, particularly cancer, and increasingly prevalent health care disparities herald a growing burden of PE. In the meantime, navigating expanding strategies for immediate and long-term anticoagulation, as well as advanced therapies, including catheter-based interventions for patients with more severe PE, has become progressively daunting. Accordingly, clinicians frequently turn to evidence-based clinical practice guidelines for diagnostic and management recommendations. However, numerous international guidelines, heterogeneity in recommendations, as well as areas of uncertainty or omission may leave the readers and clinicians without a clear management pathway. In this review of international PE guidelines, we highlight key areas of consistency, difference, and lack of recommendations (silence) with an emphasis on critical clinical and research needs., Competing Interests: Funding Support and Author Disclosures Outside of the submitted work, Dr Bikdeli is supported by a Career Development Award from the American Heart Association and VIVA Physicians (#938814); was supported by the Scott Schoen and Nancy Adams IGNITE Award; is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and the Heart and Vascular Center Junior Faculty Award from Brigham and Women’s Hospital; was a consulting expert, on behalf of the plaintiff, for litigation related to 2 specific brand models of IVC filters (he has not been involved in the litigation in 2022-2024 nor has he received any compensation in 2022-2024); is a member of the Medical Advisory Board for the North American Thrombosis Forum; serves in the Data Safety and Monitory Board of the NAIL-IT trial funded by the National Heart, Lung, and Blood Institute, and Translational Sciences; and is a collaborating consultant with the International Consulting Associates and the U.S. Food and Drug Administration in study to generate knowledge about utilization, predictors, retrieval, and safety of IVC filters. Dr Barco has received institutional research support from Boston Scientific, Medtronic, Bayer, and Sanofi; and has received personal fees/honoraria from Boston Scientific, Penumbra, and Viatris. Dr Giannakoulas has received fees for lectures and/or consultations from Actelion/Janssen, Bayer, Boehringer Ingelheim, ELPEN Pharmaceuticals, Ferrer-Galenica, GlaxoSmithKline, Gossamer-Bio, Merck Sharp and Dohme, Pfizer, Lilly, and United Therapeutics. Dr Jimenez has served as a speaker for Bristol Myers Squibb, ROVI, and Sanofi. Dr Lang, in addition to being an investigator in trials involving these companies, has relationships including consultancy service, research grants, and membership of scientific advisory boards for drug companies including AOP-Health, Actelion-Janssen, Merck Sharp and Dohme, United Therapeutics, Medtronic, Neutrolis, and Novo Nordisk; has served as a consultant for AOP Health, Merck Sharp and Dohme, PULNOVO, United Therapeutics, and Janssen; has received grants from AOP Health; and has served on the Speakers Bureau for Merck Sharp and Dohme and Janssen. Dr Klok has received research funding from Bayer, Bristol Myers Squibb, BSCI, AstraZeneca, Merck Sharp and Dohme, Leo Pharma, Actelion, Farm-X, the Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Foundation, The Dutch Heart Foundation, and the Horizon Europe Program, all outside of this work and paid to his institution. Dr Weitz holds the Canada Research Chair (Tier 1) in Thrombosis and the Heart and Stroke Foundation J.F. Mustard Chair in Cardiovascular Research. Dr Piazza has received research grants (paid to his institution) from Bristol Myers Squibb/Pfizer, Janssen, Alexion, Bayer, Amgen, BSC, Esperion, and the National Institutes of Health (1R01HL164717-01); and has received consulting fees for advisory roles from BSC, Amgen, PERC, NAMSA, Bristol Myers Squibb, Janssen, Penumbra, and Thrombolex. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cancer-associated venous thromboembolism (VTE) is a major source of oncologic cost, morbidity and mortality. Identifying high-risk patients for prophylactic anticoagulation is challenging and adds to clinician burden. Circulating tumor DNA (ctDNA) sequencing assays ('liquid biopsies') are widely implemented, but their utility for VTE prognostication is unknown. Here we analyzed three plasma sequencing cohorts: a pan-cancer discovery cohort of 4,141 patients with non-small cell lung cancer (NSCLC) or breast, pancreatic and other cancers; a prospective validation cohort consisting of 1,426 patients with the same cancer types; and an international generalizability cohort of 463 patients with advanced NSCLC. ctDNA detection was associated with VTE independent of clinical and radiographic features. A machine learning model trained on liquid biopsy data outperformed previous risk scores (discovery, validation and generalizability c-indices 0.74, 0.73 and 0.67, respectively, versus 0.57, 0.61 and 0.54 for the Khorana score). In real-world data, anticoagulation was associated with lower VTE rates if ctDNA was detected (n = 2,522, adjusted hazard ratio (HR) = 0.50, 95% confidence interval (CI): 0.30-0.81); ctDNA - patients (n = 1,619) did not benefit from anticoagulation (adjusted HR = 0.89, 95% CI: 0.40-2.0). These results provide preliminary evidence that liquid biopsies may improve VTE risk stratification in addition to clinical parameters. Interventional, randomized prospective studies are needed to confirm the clinical utility of liquid biopsies for guiding anticoagulation in patients with cancer., (© 2024. The Author(s).)

Background: In the setting of limited funding and high expectations for quality care, safety net hospitals play a crucial role in treating pediatric trauma patients. This study aimed to compare outcomes and hospitalization costs of pediatric trauma patients in safety net hospitals across the United States. Methods: The Nationwide Readmissions Database for 2016-2020 was queried for all patients under the age of 18 years hospitalized for traumatic injury. Patients admitted to safety net hospitals were propensity matched 1:1 to all other patients. The primary outcome was mortality. The secondary outcomes were readmission within 1-year, mean length of stay (LOS), total charges, and total hospitalization costs including readmissions. Results: There were 176,325 patients meeting inclusion criteria, and 30,869 were admitted to safety net hospitals. All safety net patients were successfully matched across predictors, and 61,738 patients were included. The overall mortality rate was 1.4% (n = 834), and the mortality risk was similar in safety net hospitals (OR 1.11 [.96-1.27] P = .15). The overall readmission rate, mean LOS, and mean total cost were similar for safety net hospitals when compared to all hospitals. However, the overall mean total charge was $78,724 (±$224,884) and was lower in safety net hospitals ($76,575 [±$198,342], P = .02). Discussion: Safety net hospitals deliver comparable outcomes as other health care facilities when caring for pediatric trauma patients. Notably, these hospitals appear to undercharge for their services, despite incurring similar costs in the process. These results shed light on the resilience of safety net hospitals in delivering quality and cost-effective care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The rise of value-based purchasing has led to decreased compensation for hospital-acquired conditions, including surgical site infections (SSI). This study aims to assess the risk factors for SSI in children and teenagers undergoing gastrointestinal surgery across US hospitals., Methods: The 2018-2020 Nationwide Readmissions Database was queried for patients undergoing gastrointestinal surgery under the age of 18. The primary outcome was SSI during index admission or readmission within a year. Comparison groups were elective, trauma, and emergent surgery based on anatomic location and urgency. Univariable comparison used chi-squared tests for relevant variables. Confounders were addressed through multivariable logistic regression with significant variables from univariable analysis., Results: 113 108 total patients met the study criteria. The SSI rate during admission or readmission was 2.9% (n = 3254). Infections during admission and readmission were 1.4% (n = 1560) and 1.5% (n = 1694), respectively. The most common site was organ space (48.6%, n = 1657). Increased infection risk was associated with trauma (OR 1.80 [1.51-2.16] P < .001), emergency surgery (OR 1.31 [1.17-1.47] P < .001), large bowel surgery (OR 2.78 [2.26-3.43] P < .001), and those with three or more comorbidities (OR 2.03 [1.69-2.45] P < .001). Investor-owned hospitals (OR .65 [.56-.76] P < .001) and highest quartile income (OR .80 [.73-.88] P < .001) were associated with decreased infection risk., Conclusions: Pediatric patients undergoing gastrointestinal surgery face an elevated risk of SSI, especially in trauma and emergency surgeries, particularly with multiple comorbidities. Meanwhile, a reduced risk is observed in high-income and investor-owned hospital settings. Hospitals and surgeons caring for high risk patients should advocate for risk adjustment in value-based payment systems., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Many veterans with serious illnesses, such as end-stage kidney disease requiring dialysis and advanced cancer requiring treatment infusions, must make complex decisions about their current and future medical care. Advance care planning (ACP) is a process where individuals identify, express, and communicate their personal values, life goals, and preferences for care. ACP may be feasible in chemotherapy infusion centers or chronic dialysis centers during patient treatment., Materials and Methods: We assessed the feasibility of a licensed vocational nurse (LVN) facilitator to help veterans review the PREPARE for Your Care program (www.prepareforyourcare.org) and complete an advance directive (AD) in an outpatient hemodialysis unit or a chemotherapy infusion center. PREPARE For Your Care is an evidence-based online program with written pamphlets and ADs that prepares patients to participate with clinicians in making medical decisions. We measured the time to complete a session and the level of assistance required from LVNs via LVN self-report. Self-reported ease-of-use, comfort, and helpfulness were assessed on a 10-point Likert scale from 1 (not at all) to 10 (very)., Results: Twenty-eight patients were enrolled (mean age ± SD: 67 ± 11 years); all (100%) completed PREPARE and the AD within 1 session. The mean completion time was 100 (±40) minutes. Most of the patients required considerable assistance from the LVN. The mean scores were 8.0 of 10 for ease-of-use (±2.3), 7.7 of 10 (±2.8) for comfort, and 8.2 of 10 (±2.3) for helpfulness., Conclusions: This pilot study demonstrates that using PREPARE as an ACP tool for veterans may be feasible for patients during hemodialysis and chemotherapy infusion. Patients required considerable assistance from the LVN to complete PREPARE. Hemodialysis and chemotherapy infusion are opportunities when patients have time and space to consider ACP., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Venous thromboembolism (VTE) in pediatric trauma patients is under-investigated. The purpose of this study was to perform an evaluation of the risk factors for VTE after pediatric trauma, including readmissions across the United States. The Nationwide Readmissions Database for 2016-2020 was queried for all patients under the age of 18 years admitted for trauma. 276 670 patients were identified; 2063 (.8%) were diagnosed with VTE. Among those with VTE, 300 (15%) were identified during a readmission. Higher rates of VTE were seen in ages 15-17 years (n = 1,294, 1.3%, P < .001), penetrating injuries (n = 478, .9%, P < .001), and assault (n = 271, 2.7%, P < .001). The strongest risk factor for VTE was prolonged mechanical ventilation (OR 5.5 [4.9-6.3] P < .001). Our study found that a significant portion of post-traumatic VTE in children and teenagers occur during readmissions. A deeper understanding of the risk factors outlined here can guide enhanced clinical protocols, ensuring early detection and prevention of this complication., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Over the last 25 years, clinical practice guidelines have emerged as a means to standardize and improve care. As pharmaceutical innovations develop, guidelines are updated to incorporate new interventions. However, the extent to which pharmacotherapies are represented as treatment options in guideline recommendations has not been well elucidated. This study aimed to quantify the role pharmacotherapy has played in clinical practice guidelines across a range of chronic diseases over the past 20 years., Methods: Clinical practice guidelines published from 2000 to 2021 were identified for five chronic diseases: ischemic heart disease (IHD), non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), Alzheimer's disease (AD), and type 2 diabetes (T2D). Guidelines were reviewed and data on treatment recommendations were collected, including the type of intervention, line of therapy, and, for pharmacotherapies, year of regulatory approval and year of inclusion in guidelines., Results: In total, 92 clinical practice guidelines were reviewed. Among the 184 discrete recommended interventions across the five disease areas, 146 (79.3%) were pharmacotherapies, 21 (11.4%) were behavioral modifications, 6 (3.3%) were surgical interventions, and 11 (6%) were other interventions. Across guidelines, when a line of therapy was specified, behavioral modifications and pharmacotherapies were most frequently recommended as first-line interventions, whereas surgical interventions were more often recommended for subsequent lines of treatment. The time from regulatory approval of novel pharmacotherapies to inclusion in guideline recommendations varied considerably by disease area and geography., Conclusions: Across the reviewed disease areas, behavioral interventions and pharmacotherapies are shown to be critical components of clinical practice. Over the last 20 years, novel pharmaceutical innovations have been incorporated into clinical practice guideline recommendations; however, with varying speeds of adoption. Given the increasing pace of pharmacologic innovation, timely updates of clinical practice guidelines are critical to evolving the standard of care and practicing evidence-based medicine., Competing Interests: Meaghan Roach, Natalie Land, Jacquelyn W. Chou, and John R. Maclean are employees of PRECISIONheor, a consulting firm that received research funding from Janssen Pharmaceuticals in relation to this project. Jennifer Hernandez, and Reina Rau were employees of PRECISIONheor at the time this study was conducted. Meaghan Roach, Jacquelyn W. Chou, and John R. Maclean own equity interest in PRECISIONheor's parent company, Precision Medicine Group. Stacey S. Hickson and Danielle F. Rollmann are employees of Janssen Pharmaceuticals Inc., (Copyright © 2024 Meaghan Roach et al.)

Background and Objectives: Myasthenia gravis (MG) is a rare neuromuscular disorder where IgG antibodies damage the communication between nerves and muscles, leading to muscle weakness that can be severe and have a significant impact on patients' lives. MG exacerbations include myasthenic crisis with respiratory failure, the most serious manifestation of MG. Recent studies have found MG prevalence increasing, especially in older patients. This study examined trends in hospital admissions and in-hospital mortality for adult patients with MG and readmissions and postdischarge mortality in older (65 years or older) adults with MG., Methods: Data from the Nationwide Inpatient Sample (NIS), an all-payer national database of hospital discharges, were used to characterize trends in hospitalizations and in-hospital mortality related to MG exacerbations and MG crisis among adult patients aged 18 years or older. The Medicare Limited Data Set, a deidentified, longitudinal research database with demographic, enrollment, and claims data was used to assess hospitalizations, length of stay (LOS), readmissions, and 30-day postdischarge mortality among fee-for-service Medicare beneficiaries aged 65 years or older. The study period was 2010-2019. Multinomial logit models and Poisson regression were used to test for significance of trends., Results: Hospitalization rates for 19,715 unique adult patients and 56,822 admissions increased from 2010 to 2019 at an average annualized rate of 4.9% (MG noncrisis: 4.4%; MG crisis: 6.8%; all p < 0.001). Readmission rates were approximately 20% in each study year for both crisis and noncrisis hospitalizations; the in-hospital mortality rate averaged 1.8%. Among patients aged 65 years or older, annualized increases in hospitalizations were estimated at 5.2%, 4.2%, and 7.7% for all, noncrisis, and crisis hospitalizations, respectively (all p < 0.001). The average LOS was stable over the study period, ranging from 11.3 to 13.1 days, but was consistently longer for MG crisis admissions. Mortality among patients aged 65 years or older was higher compared with that in all patients, averaging 5.0% across each of the study years., Discussion: Increasing hospitalization rates suggest a growing burden associated with MG, especially among older adults. While readmission and mortality rates have remained stable, the increasing hospitalization rates indicate that the raw numbers of readmissions-and deaths-are also increasing. Mortality rates are considerably higher in older patients hospitalized with MG.

This study furthers the investigation of how pituitary adenylate cyclase activating polypeptide (PACAP) and the PAC1 receptor (PAC1R) regulate the homeostatic energy balance circuitry. We hypothesized that apoptotic ablation of PACAP neurones in the hypothalamic ventromedial nucleus (VMN) would affect both energy intake and energy expenditure. We also hypothesized that selective PAC1R knockdown would impair the PACAP-induced excitation in anorexigenic proopiomelanocortin (POMC) neurones and inhibition of orexigenic neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurones in the hypothalamic arcuate nucleus (ARC). The results show CASPASE-3-induced ablation of VMN PACAP neurones leads to increased energy intake and meal frequency as well as decreased energy expenditure in lean animals. The effects were more robust in obese males, whereas we saw the opposite effects in obese females. We then utilized visualized whole-cell patch clamp recordings in hypothalamic slices. PAC1R knockdown in POMC neurones diminishes the PACAP-induced depolarization, increase in firing, decreases in energy intake and meal size, as well as increases in CO 2 production and O 2 consumption. Similarly, the lack of expression of the PAC1R in NPY/AgRP neurones greatly attenuates the PACAP-induced hyperpolarization, suppression of firing, decreases in energy intake and meal frequency, as well as increases in energy expenditure. The PACAP response in NPY/AgRP neurones switched from predominantly inhibitory to excitatory in fasted animals. Finally, the anorexigenic effect of PACAP was potentiated when oestradiol was injected into the ARC in ovariectomized females. This study demonstrates the critical role of anorexigenic VMN PACAP neurones and the PAC1R in exciting POMC and inhibiting NPY/AgRP neurons to control homeostatic feeding., (© 2023 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Background: Given the inequities in access to health care resources like COVID-19 vaccination, health systems should carefully consider how to reach underrepresented groups. Reflecting on vaccine rollout efforts holds insight on the role of community engagement and informatics support in promoting health equity., Objectives: This study aimed to assess the effectiveness of four outreach strategies deployed by University of Washington (UW) Medicine in improving vaccine equity over traditional vaccine scheduling online or by phone, we report on appointment scheduling and completion of appointments (i.e., vaccine administration) through (1) automated outreach to individuals from underrepresented groups, (2) temporary "pop-up" clinics in neighborhoods highly impacted by COVID-19, (3) vulnerable population clinics, and (4) mobile vaccine vans., Methods: We conducted a 6-month retrospective analysis of electronic health records (EHR) to describe the sociodemographic characteristics of individuals who scheduled appointments using the outreach strategies and characteristics associated with a greater likelihood of vaccine administration based on appointment completion. To help explain trends in the EHR data, we engaged 10 health system leaders and staff who spearheaded the outreach strategies in follow-up conversations to identify qualitative insights into what worked and why., Results: Compared with traditional scheduling, all outreach strategies except vulnerable population clinics had higher vaccine appointment completion rates, including automated outreach ( N  = 3,734 [94.7%], p  < 0.001), pop-up clinics ( N  = 4,391 [96.0%], p  < 0.001), and mobile vans ( N  = 4,198 [99.1%], p  < 0.001); and lower cancellation rates, including automated outreach ( N  = 166 [1.1%], p  < 0.001), pop-up clinics ( N  = 155 [0.6%], p  < 0.001), and mobile vans ( N  = 0 [0%], p  < 0.001). Qualitative insights emphasized ongoing community partnerships and information resources in successful outreach., Conclusion: Vaccine equity outreach strategies improved the proportion of patients who scheduled and completed vaccination appointments among populations disproportionately impacted by COVID-19. Engaging community partners and equity-focused informatics tools can facilitate outreach. Lessons from these outreach strategies carry practical implications for health systems to amplify their health equity efforts., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Over the last few years, targeted therapy has become the mainstay maintenance treatment of patients with ovarian cancer including patients with BRCA1/BRCA2 mutations. Poly ADP ribose polymerase inhibitors (PARPi) are effective in the treatment of patients who are in complete or partial remission. PARPi are known to cause hematological adverse events (AEs), but have not been compared directly to each other. Objective: Primary objective was to compare the incidence of hematological and non-hematological AEs associated with the use of PARPi. Methods: This was a single institution, retrospective study evaluating patients who were treated with PARPi for ovarian cancer from January 2017 to October 2020. Patients were stratified according to which PARP inhibitor they received. Results: Ninety-two patients were included in final analysis. Thirty-one (33.7%) patients received niraparib and 61 (66.3%) patients received olaparib. Median age of patients were 64.3 (range, 33.8 to 92.3) years, 66 (71.7%) were white, and 84 (91.3%) had an ECOG PS of 0/1. Patients in the niraparib group experienced a higher rate of hematologic AEs, with 11 (35.5%), 20 (64.5%), and 18 (58.1%) experiencing neutropenia, anemia, and thrombocytopenia, respectively. Eight (13.1%), 24 (39.3%), and 16 (26.2%) patients in the olaparib group experienced neutropenia, anemia, and thrombocytopenia, respectively. Conclusion: This single institution retrospective study outlines the hematological toxicities observed between two PARPi. Our results suggested that niraparib tended to be associated with a higher risk for hematologic toxicities than olaparib. Anemia was the most common hematologic toxicity which was consistent with what has been widely documented in the literature.

Vibrio vulnificus is an opportunistic gram-negative rod-shaped bacteria found in warm, low salinity waters. Transmission through open wounds or consumption of contaminated seafood can lead to wound infections, sepsis, and potentially death. A 44-year-old man with a history of poly-substance abuse, cirrhosis, and recent oyster consumption presented to the emergency department in June with acute onset bilateral leg pain associated with rash and fever. Within 6 hours of his arrival, the rash rapidly progressed to large bullae with extensive necrosis ascending to the level of the abdomen, and he developed septic shock. Despite prompt surgical intervention and appropriate antibiotic and resuscitative therapies, the patient had progressive multi-system organ failure and died 7 days after admission. Concurrent necrotizing fasciitis with sepsis secondary to V. vulnificus infection is rare and potentially fatal, as demonstrated in this case., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. The development and progression of atherosclerotic CVD are largely dependent on a multitude of modifiable and nonmodifiable risk factors. Current therapeutic strategies involve risk factor modification, especially dyslipidemia. The treatment of dyslipidemia continues to be dynamic, and in this paper, we review the current strategies for risk assessment, diagnosis, and treatment. As treatments for the management of dyslipidemia continue to evolve with ever-increasing options for therapeutic targets, an understanding of lipid-lowering therapies remains an essential topic of understanding for all health care providers., (Published by Elsevier Inc.)

Background: Non-elderly trauma patients represent the largest portion of preventable years of life loss in the US. The purpose of this study was to compare outcomes in patients admitted to investor-owned vs public and not-for-profit hospitals across the US., Material and Methods: The Nationwide Readmissions Database 2018 was queried for trauma patients with an Injury Severity Score greater than 15 and age 18-65 years. The primary outcome was mortality; secondary outcomes were prolonged length of stay (LOS) greater than 30 days, readmission within 30 days, and readmission to a different hospital. Patients admitted to investor-owned hospitals were compared to public and not-for-profit hospitals. Univariable analysis was performed using chi-squared tests. Multivariable logistic regression was performed for each outcome., Results: 157 945 patients were included with 11.0% (n = 17 346) admitted to investor-owned hospitals. The overall mortality rate and prolonged LOS were similar for both groups. The overall readmission rate was 9.2% (n = 13 895), with the rate in investor-owned hospitals at 10.5% (n = 1,739, P < .001). Multivariable logistic regression revealed investor-owned hospitals had an increased risk of readmission (OR 1.2 [1.1-1.3] P < .001) and readmission to a different hospital (OR 1.3 [1.2-1.5] P < .001)., Discussion: Severely injured trauma patients have similar rates of mortality and prolonged length of stay in investor-owned vs public and not-for-profit hospitals. However, patients admitted to investor-owned hospitals have an increased risk of readmission and readmission to different hospitals. Efforts to improve outcomes after trauma must consider hospital ownership and readmission to different hospitals.

Introduction: Maintaining trust in the patient-doctor relationship requires transparency in the details of the financial relationships between physicians and drug and medical device corporations. These details are publicly available through the Open Payments database, and patients are encouraged to ask surgeons to interpret their implications. The purpose of this study was to better equip surgeons in responding to these inquiries and to compare the distribution of these payments by gender and specialty., Methods: The 2021 Open Payments dataset was searched for all payments to surgeons from the 14 different specialties recognized by the American College of Surgeons. The total payments per surgeon were compared by calculating the mean and median payments. The Gini index, a measure of income inequality, was also calculated for each specialty., Results: There were 96 724 surgeons who received over $755 million in payments from drug and medical device companies. There were 72 245 (74.7%) men and 24 479 (25.3%) women. The total amount of payments to men was $712 million (94.2%) and for women it was $44 million (5.8%). The overall Gini index was .9508. The specialty with the highest Gini index was pediatric surgery (.9844) and the lowest was cardiothoracic surgery (.8656)., Discussion: Male surgeons received disproportionately higher payments from drug and device corporations than female surgeons. Surgeons should be aware of their own standing within the Open Payments database in order to respond appropriately to patient inquiries.

Background: Impostor phenomenon, also referred to as imposter syndrome or impostorism, was initially identified among high achieving women who felt undeserving of their successes because they felt they were earned through luck or chance, rather than skill or experience. It's prevalence has been identified in many health professions; however, there are no known studies of Registered Dietitians' (RDs) perceptions of impostor phenomenon. This study assesses the following among RDs: [1] prevalence of impostor phenomenon and differences in impostor phenomenon levels, if any, based on [2] highest educational level achieved and [3] years of experience as an RD., Methods: A cross-sectional survey was sent electronically to 5,000 RDs credentialed by the Commission on Dietetic Registration in the United States. Respondents' agreement with 20 impostor phenomenon statements from the Clance Impostor Phenomenon Scale were measured. The sum score from the scale was used to classify levels of impostor phenomenon. Descriptive statistics and chi square analyses for comparison were evaluated., Results: Of the 445 (9%) who began the survey, 266 (5%) completed it and were included in analyses. Over 76% of 266 individuals reported at least moderate impostorism (score of 40 or fewer points out of 100). No difference was seen based on educational level (p = .898); however, those with less than five years' experience reported higher impostor phenomenon (p < .05). Among those with five to 39 years' experience, over 40% reported moderate impostorism., Conclusion: Impostor phenomenon is prevalent among RDs. Moderate impostorism was pervasive among all those with less than 40 years' experience and could potentially negatively impact these respondents. Future research could explore ways to reduce impostor phenomenon in RDs., (© 2023. The Author(s).)

Objective: To characterize treatment decision-making processes and formalize consensus regarding key factors headache specialists consider in treatment decisions for patients with migraine, considering novel therapies., Background: Migraine therapies have long been subject to binary classification, acute versus preventive, due to limitations of available drugs. The emergence of novel therapies that can be used more flexibly creates an opportunity to rethink this binary classification. To determine the role of these novel therapies in treatment, it is critical to understand whether existing guidelines reflect clinical practice and to establish consensus around factors driving management., Methods: A three-round modified Delphi process was conducted with migraine clinical experts. Round 1 consisted of an online questionnaire; Round 2 involved an online discussion of aggregated Round 1 results; and Round 3 allowed participants to revise Round 1 responses, incorporating Round 2 insights. Questions elicited likelihood ratings (0 = highly unlikely to 100 = highly likely), rankings, and estimates on treatment decision-making., Results: Nineteen experts completed three Delphi rounds. Experts strongly agreed on definitions for "acute" (median = 100, inter-quartile range [IQR] = 5) and "preventive" treatment (median = 90, IQR = 15), but noted a need for treatment customization for patients (median = 100, IQR = 6). Experts noted certain aspects of guidelines may no longer apply based on established tolerability and efficacy of newer acute and preventive agents (median = 91, IQR = 17). Further, experts agreed on a treatment category referred to as "situational prevention" (or "short-term prevention") for patients with reliable and predictable migraine triggers (median = 100, IQR = 10) or time-limited periods when headache avoidance is important (median = 100, IQR = 12)., Conclusions: Using the modified Delphi method, a panel of migraine experts identified the importance of customizing treatment for people with migraine and the utility of "situational prevention," given the ability of new treatment options to meet this need and the potential to clinically identify patients and time periods when this approach would add value., (© 2023 Biohaven Pharmaceuticals. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Identifying a circulating biomarker predictive of immune checkpoint inhibitor (ICI) benefit in patients with small cell lung cancer (SCLC) remains an unmet need. Characteristics of peripheral and intratumoral T-cell receptor (TCR) repertoires have been shown to predict clinical outcomes in non-small cell lung cancer (NSCLC). Recognizing a knowledge gap, we sought to characterize circulating TCR repertoires and their relationship with clinical outcomes in SCLC., Methods: SCLC patients with limited (n=4) and extensive (n=10) stage disease were prospectively enrolled for blood collection and chart review. Targeted next-generation sequencing of TCR beta and alpha chains of peripheral blood samples was performed. Unique TCR clonotypes were defined by identical CDR3, V gene, and J gene nucleotide sequences of the beta chain and subsequently used to calculate TCR diversity indices., Results: Patients with stable versus progressive and limited versus extensive stage disease did not demonstrate significant differences in V gene usage. Kaplan-Meier curve and log-rank analysis did not identify a statistical difference in progression-free survival (PFS) (P=0.900) or overall survival (OS) (P=0.200) between high and low on-treatment TCR diversity groups, although the high diversity group exhibited a trend toward increased OS., Conclusions: We report the second study investigating peripheral TCR repertoire diversity in SCLC. With a limited sample size, no statistically significant associations between peripheral TCR diversity and clinical outcomes were observed, though further study is warranted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-666/coif). MLA is listed as a coinventor on a provisional patent application for methods to predict therapeutic outcomes using blood-based gene expression patterns, that is owned by Vanderbilt University Medical Center, and is currently unlicensed. JMB receives research support from Genentech/Roche, Bristol Myers Squibb, and Incyte Corporation, has received consulting/expert witness fees from Novartis, and is an inventor on patents regarding immunotherapy targets and biomarkers in cancer. AB, TS, LL, JG, JH, and ML are current or former employees of Resolution Bioscience, a part of Agilent. WTI has served as a consultant for Bristol Myers Squibb, OncLive, Clinical Care Options, Chardan, Outcomes Insights, Cello Health, and Curio Science. He reports advisory board participation for Genentech, Jazz Pharma, G1 Therapeutics, Mirati, and Takeda. The other authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

BACKGROUND The purpose of this study is to discuss a patient with a history of conditions, including arthrogryposis, gastroschisis, and malignant hyperthermia, who presented with cecal volvulus requiring urgent surgical intervention. CASE REPORT A 29-year-old woman with a history of arthrogryposis, gastroschisis, malignant hyperthermia, and multiple childhood abdominal surgeries presents to the Emergency Department (ED) with 2 days of abdominal pain and bloody diarrhea. A CT abdomen/pelvis revealed findings concerning for a cecal volvulus. The patient was premedicated and monitored closely by the anesthesia team due to her history of malignant hyperthermia. She underwent an exploratory laparotomy, where a dilated cecum and proximal ascending colon were found to be completely volvulized around the mesentery. Manual bowel detorsion was performed, which resulted in reperfusion of the ischemic-appearing bowel, which then appeared viable. She recovered well after the procedure and was discharged on postoperative day 5. CONCLUSIONS This case highlights a patient who presented with a combination of 4 findings: arthrogryposis, gastroschisis, malignant hyperthermia, and cecal volvulus. With arthrogryposis reported to be associated with gastroschisis and malignant hyperthermia, this report not only corroborates this association, but also aims to draw attention to the fact that these conditions have potential to occur jointly with cecal volvulus. Given the patient's history of gastroschisis requiring extensive abdominal surgeries that contribute as risk factors for cecal volvulus, it is possible there may be other arthrogryposis patients who present with cecal volvulus similar to that seen in this patient.

Objective: To address the current lack of specified data existing regarding the perioperative characteristics and outcomes in a novel patient population, which may bridge the current understanding of how patient characteristics and perioperative management may influence the postoperative hospital course before cardiac transplantation., Design: A retrospective electronic chart review included all patients with failing single- ventricle (SV) physiology receiving ventricular assist device (VAD) support at a high-volume pediatric VAD center between April 5, 2010, and December 1, 2020, using institution-based electronic medical records for retrospective analysis., Setting: At a single pediatric hospital., Participants: Fourteen pediatric patients with failing SV physiology receiving ventricular assist device therapy (SVAD)., Interventions: None., Measurements and Main Results: Preoperative, intraoperative, and postoperative patient demographic and medical data were obtained from prior inpatient progress notes, laboratory values, anesthetic records, cardiac catheterization reports, echocardiography reports, and postoperative surgical notes entered during inpatient encounters at the time of SVAD placement. Between April 5, 2010, and December 1, 2020, 16 VAD device implants supported 14 pediatric patients with failing SV physiology. Most patients presented with a preoperative diagnosis of hypoplastic left heart syndrome (N = 9, 64.3%). A total of 6 patients expired on VAD therapy (43%), 7 (50%) survived to receive a cardiac transplant, and 1 patient currently remains on device therapy., Conclusion: Although our institutional approach represents a single perspective, we anticipate that our experience institutional experience may prove helpful to others caring for peditric patients with single ventricle physiology undergoing ventricular assist device placement and promote collaborative efforts to improve their care., Competing Interests: Conflict of Interest None., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

We tested the hypothesis that N/OFQ neurones in the arcuate nucleus (N/OFQ ARC ) inhibit proopiomelanocortin (POMC ARC ) neurones in a diet- and hormone-dependent manner to promote a more extensive rebound hyperphagia upon re-feeding following an 18 h fast. We utilized intact male or ovariectomized (OVX) female mice subjected to ad libitum-feeding or fasting conditions. N/OFQ ARC neurones under negative energy balance conditions displayed heightened sensitivity as evidenced by a decreased rheobase threshold, increased firing frequency, and increased burst duration and frequency compared to ad libitum-feeding conditions. Stimulation of N/OFQ ARC neurones more robustly inhibited POMC ARC neurones under fasting conditions compared to ad libitum-feeding conditions. N/OFQ ARC inhibition of POMC ARC neurones is hormone dependent as chemostimulation of N/OFQ ARC neurones from fasted males and OVX females produced a sizable outward current in POMC ARC neurones. Oestradiol (E 2 ) markedly attenuated the N/OFQ-induced POMC ARC outward current. Additionally, N/OFQ tonically inhibits POMC ARC neurones to a greater degree under fasting conditions than in ad libitum-feeding conditions as evidenced by the abrogation of N/OFQ-nociceptin opioid peptide (NOP) receptor signalling and inhibition of N/OFQ release via chemoinhibition of N/OFQ ARC neurones. Intra-arcuate nucleus application of N/OFQ further elevated the hyperphagic response and increased meal size during the 6 h re-feed period, and these effects were mimicked by chemostimulation of N/OFQ ARC neurones in vivo. E 2 attenuated the robust N/OFQ-induced rebound hyperphagia seen in vehicle-treated OVX females. These data demonstrate that N/OFQ ARC neurones play a vital role in mitigating the impact of negative energy balance by inhibiting the excitability of anorexigenic neural substrates, an effect that is diminished by E 2 in females. KEY POINTS: Nociceptin/orphanin FQ (N/OFQ) promotes increased energy intake and decreased energy expenditure under conditions of positive energy balance in a sex- and hormone-dependent manner. Here it is shown that under conditions of negative energy balance, i.e. fasting, N/OFQ inhibits anorexigenic proopiomelanocortin (POMC) neurones to a greater degree compared to homeostatic conditions due to fasting-induced hyperexcitability of N/OFQ neurones. Additionally, N/OFQ promotes a sustained increase in rebound hyperphagia and increase in meal size during the re-feed period following a fast. These results promote greater understanding of how energy balance influences the anorexigenic circuitry of the hypothalamus, and aid in understanding the neurophysiological pathways implicated in eating disorders promoting cachexia., (© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Little is known about real-world outcomes for first-line and anti-PD-1 second-line treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC). Patients & methods: Retrospective data of advanced/metastatic ESCC patients treated between 2011 and 2021 were collected from Flatiron Health. Median duration of therapy (mDoT) and median overall survival (mOS) were evaluated for patients initiating first-line and anti-PD-1 second-line therapy. Results: Among patients receiving first-line therapy (n = 948), mDoT was 1.4 months and mOS was 16.0 months, with mOS of 16.0 and 18.0 months for the non-immunotherapy and immunotherapy cohorts, respectively. Among patients receiving anti-PD-1 second-line therapy (n = 60), mDoT was 5.7 months and mOS was 10.1 months. Conclusion: Patients with advanced/metastatic ESCC have short duration of therapy, and overall survival remains limited. This real-world study underscores the need for efficacious treatments for advanced/metastatic ESCC in the first- and second-line setting. Direct comparisons of emerging therapies in the real world are urgently needed.

"Pedestrian struck by train" represents one of the highest magnitude blunt force traumas. Despite the severity of injuries, these patients can have good outcomes. A 25-year-old male presented after being struck by a train. He had several injuries, including extensive complex pelvic fractures, right external iliac artery and vein laceration, and right femur and tibia fracture. He was taken to the operating room for damage control surgery and attempted revascularization of the right lower extremity. The extremity became ischemic and required above knee amputation followed by hip disarticulation and hemipelvectomy. His pelvic wounds were treated with negative pressure wound therapy and gradually closed. He was eventually discharged to a rehab facility for continued recovery. This case highlights the interventions that allowed a young man who was struck by a train to survive. He improved significantly since undergoing hemipelvectomy, indicating that severe pelvic injuries from high energy trauma may necessitate hemipelvectomy.

Objective To determine community pharmacists' experience with foreign language and American Sign Language (ASL) interpretation services. Design A survey was drafted to gather information about pharmacists' familiarity with ASL and foreign language interpreting services as well as the frequency with which pharmacists encountered patients who needed these services. Setting Independent and chain community pharmacies in Spokane County, Washington, USA. Participants Fifty-two community pharmacies were identified using a provider-credential search. Fifty-one pharmacists (98%) agreed to participate and completed the survey. Interventions Surveys were initially conducted in person, but after the COVID-19 pandemic began data collection was halted and restarted via phone in accordance with the Washington State University Office of Research Support and Operations. Results Four out of 51 pharmacists surveyed (7.84%) indicated that they were fluent in a language besides English. Pharmacists reported encountering patients who spoke Spanish (31%), Russian (31%), ASL (8%), Arabic (5%), Mandarin Chinese (5%), Vietnamese (5%), Marshallese (5%), and Ukrainian (2%). Some pharmacists (8%) reported not encountering patients who spoke other languages besides English. Most pharmacists (72.5%) indicated their company offered interpreting services for foreign languages, but less than half of pharmacists surveyed (43.1%) had experience using these services. Forty-five percent of pharmacists surveyed did not know whether their company offered an interpreting service for ASL, and only 23.5% indicated that they had experience using ASL interpreting services. Conclusion Pharmacists are less familiar with services for patients who speak ASL and are less likely to have experience with ASL interpretation services than they are to have assisted foreign-language-speaking patients.

Pituitary adenylate cyclase-activating polypeptide (PACAP) binds to PACAP-specific (PAC1) receptors in multiple hypothalamic areas, especially those regulating energy balance. PACAP neurons in the ventromedial nucleus (VMN) exert anorexigenic effects within the homeostatic energy balance circuitry. Since PACAP can also reduce the consumption of palatable food, we tested the hypothesis that VMN PACAP neurons project to the ventral tegmental area (VTA) to inhibit A 10 dopamine neurons via PAC1 receptors and K ATP channels, and thereby suppress binge-like consumption. We performed electrophysiological recordings in mesencephalic slices from male PACAP-Cre and tyrosine hydroxylase (TH)-Cre mice. Initially, we injected PACAP (30 pmol) into the VTA, where it suppressed binge intake in wildtype male but not female mice. Subsequent tract tracing studies uncovered projections of VMN PACAP neurons to the VTA. Optogenetic stimulation of VMN PACAP neurons in voltage clamp induced an outward current and increase in conductance in VTA neurons, and a hyperpolarization and decrease in firing in current clamp. These effects were markedly attenuated by the K ATP channel blocker tolbutamide (100 μM) and PAC1 receptor antagonist PACAP 6-38 (200 nM). In recordings from A 10 dopamine neurons in TH-Cre mice, we replicated the outward current by perfusing PACAP 1-38 (100 nM). This response was again completely blocked by tolbutamide and PACAP 6-38 , and associated with a hyperpolarization and decrease in firing. These findings demonstrate that PACAP activates PAC1 receptors and K ATP channels to inhibit A 10 dopamine neurons and sex-dependently suppress binge-like consumption. Accordingly, they advance our understanding of how PACAP regulates energy homeostasis via the hedonic energy balance circuitry., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Cardiac catheterization and cardiovascular magnetic resonance (CMR) imaging have distinct diagnostic roles in the congenital heart disease (CHD) population. Invasive CMR (iCMR) allows for a more thorough assessment of cardiac hemodynamics at the same time under the same conditions. It is assumed but not proven that iCMR gives an incremental value by providing more accurate flow quantification., Methods: Subjects with CHD underwent real-time 1.5 T iCMR using a passive catheter tracking technique with partial saturation pulse of 40° to visualize the gadolinium-filled balloon, CMR-conditional guidewire, and cardiac structures simultaneously to aid in completion of right (RHC) and left heart catheterization (LHC). Repeat iCMR and catheterization measurements were performed to compare reliability by the Pearson (PCC) and concordance correlation coefficients (CCC)., Results: Thirty CHD (20 single ventricle and 10 bi-ventricular) subjects with a median age and weight of 8.3 years (2-33) and 27.7 kg (9.2-80), respectively,  successfully underwent iCMR RHC and LHC. No catheter related complications were encountered. Time taken for first pass RHC and LHC/aortic pull back was 5.1, and 2.9 min, respectively. Total success rate to obtain required data points to complete Fick principle calculations for all patients was 321/328 (98%). One patient with multiple shunts was an outlier and excluded from further analysis. The PCC for catheter-derived pulmonary blood flow (Qp) (0.89, p < 0.001) is slightly lower than iCMR-derived Qp (0.96, p < 0.001), whereas catheter-derived systemic blood flow (Qs) (0.62, p = < 0.001) was considerably lower than iCMR-derived Qs (0.94, p < 0.001). CCC agreement for Qp at baseline (C1-CCC = 0.65, 95% CI 0.41-0.81) and retested conditions (C2-CCC = 0.78, 95% CI 0.58-0.89) were better than for Qs at baseline (C1-CCC = 0.22, 95% CI - 0.15-0.53) and retested conditions (C2-CCC = 0.52, 95% CI 0.17-0.76)., Conclusion: This study further validates hemodynamic measurements obtained via iCMR. iCMR-derived flows have considerably higher test-retest reliability for Qs. iCMR evaluations allow for more reproducible hemodynamic assessments in the CHD population., (© 2021. The Author(s).)

A multispecialty nursing team plays a crucial role in key decision making, education, prevention, screening, assessment, diagnosis, management, data collection and dissemination of best practices during the novel coronavirus disease (COVID-19) pandemic. Using examples from a large, tertiary medical center in Los Angeles, this paper highlights contributions made by multispecialty nursing specialties to optimize health and safety for patients and frontline health care workers. Recognizing nurses' ongoing critical role encourages and informs further collaboration and serves as a catalyst to innovation for a healthier tomorrow. The result of the COVID-19 pandemic will be felt for years to come., (© 2020 The Authors.)

Energy homeostasis is regulated in coordinate fashion by the brain-gut axis, the homeostatic energy balance circuitry in the hypothalamus and the hedonic energy balance circuitry comprising the mesolimbcortical A 10 dopamine pathway. Collectively, these systems convey and integrate information regarding nutrient status and the rewarding properties of ingested food, and formulate it into a behavioral response that attempts to balance fluctuations in consumption and food-seeking behavior. In this review we start with a functional overview of the homeostatic and hedonic energy balance circuitries; identifying the salient neural, hormonal and humoral components involved. We then delve into how the function of these circuits differs in males and females. Finally, we turn our attention to the ever-emerging roles of nociceptin/orphanin FQ (N/OFQ) and pituitary adenylate cyclase-activating polypeptide (PACAP)-two neuropeptides that have garnered increased recognition for their regulatory impact in energy homeostasis-to further probe how the imposed regulation of energy balance circuitry by these peptides is affected by sex and altered under positive (e.g., obesity) and negative (e.g., fasting) energy balance states. It is hoped that this work will impart a newfound appreciation for the intricate regulatory processes that govern energy homeostasis, as well as how recent insights into the N/OFQ and PACAP systems can be leveraged in the treatment of conditions ranging from obesity to anorexia.

The polyglutamine expansion of huntingtin (mHTT) causes Huntington disease (HD) and neurodegeneration, but the mechanisms remain unclear. Here, we found that mHtt promotes ribosome stalling and suppresses protein synthesis in mouse HD striatal neuronal cells. Depletion of mHtt enhances protein synthesis and increases the speed of ribosomal translocation, while mHtt directly inhibits protein synthesis in vitro. Fmrp, a known regulator of ribosome stalling, is upregulated in HD, but its depletion has no discernible effect on protein synthesis or ribosome stalling in HD cells. We found interactions of ribosomal proteins and translating ribosomes with mHtt. High-resolution global ribosome footprint profiling (Ribo-Seq) and mRNA-Seq indicates a widespread shift in ribosome occupancy toward the 5' and 3' end and unique single-codon pauses on selected mRNA targets in HD cells, compared to controls. Thus, mHtt impedes ribosomal translocation during translation elongation, a mechanistic defect that can be exploited for HD therapeutics.

The association of obesity with cardiovascular disease is well established. However, the interplay of obesity and vascular dysfunction in peripheral tissues such as skeletal muscle, which plays a key in role metabolic homeostasis, requires further study. In particular, there is a paucity of data with regard to sex-differences. Therefore, using a murine model (C57BL/6) of high-fat diet-induced obesity and insulin resistance, we investigated changes in vascular function in gluteus maximus muscle of female and male mice. Diet-induced obesity resulted in alterations in microvascular function. Obese male mice displayed impaired vasoconstriction in second order arterioles compared to lean, male mice, whereas arterioles of obese, female mice displayed significant impairments of both vasodilation and vasoconstrictor responses compared to lean, female mice. Overall, this study identifies distinct differences in how obesity impacts the female and male murine response to skeletal muscle vascular function. This work advances our understanding of sex-specific risk of metabolic complications of obesity and indicates the need for expansion of this study as well as detailed investigation of sex-specific differences in obesity pathology in the future., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Published by Elsevier Ltd.)

The neuropeptide nociceptin/orphanin FQ (N/OFQ) inhibits neuronal activity via its cognate nociceptin opioid peptide (NOP) receptor throughout the peripheral and central nervous systems, including those areas involved in the homeostatic and hedonic regulation of energy homeostasis. We thus tested the hypothesis that N/OFQ neurons in the hypothalamic arcuate nucleus (ARC) and ventral tegmental area (VTA) act via NOP receptor signaling to inhibit nearby anorexigenic proopiomelanocortin (POMC) and A 10 dopamine neuronal excitability, respectively, and thereby modulate ingestion of palatable food. Electrophysiologic recordings were performed in slices prepared from transgenic male and ovariectomized (OVX) female N/OFQ-cre/enhanced green fluorescent protein-POMC, N/OFQ-cre and tyrosine hydroxylase-cre animals to see if optogenetically-stimulated peptide release from N/OFQ neurons could directly inhibit these neuronal populations. Binge-feeding behavioral experiments were also conducted where animals were exposed to a high-fat-diet (HFD) for one hour each day for five days and monitored for energy intake. Photostimulation of ARC and VTA N/OFQ neurons produces an outward current in POMC and A 10 dopamine neurons receiving input from these cells. This is associated with a hyperpolarization and decreased firing. These features are also sex hormone- and diet-dependent; with estradiol-treated slices from OVX females being less sensitive, and obese males being more sensitive, to N/OFQ. Limited access to HFD causes a dramatic escalation in consumption, such that animals eat 25-45% of their daily intake during that one-hour exposure. Moreover, the NOP receptor-mediated regulation of these energy balance circuits are engaged, as N/OFQ injected directly into the VTA or ARC respectively diminishes or potentiates this binge-like increase in a manner heightened by diet-induced obesity or dampened by estradiol in females. Collectively, these findings provide key support for the idea that N/OFQ regulates appetitive behavior in sex-, site- and diet-specific ways, along with important insights into aberrant patterns of feeding behavior pertinent to the pathogenesis of food addiction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: We examined whether pituitary adenylate cyclase-activating polypeptide (PACAP) excites proopiomelanocortin (POMC) neurons via PAC1 receptor mediation and transient receptor potential cation (TRPC) channel activation., Methods: Electrophysiological recordings were done in slices from both intact male and ovariectomized (OVX) female PACAP-Cre mice and eGFP-POMC mice., Results: In recordings from POMC neurons in eGFP-POMC mice, PACAP induced a robust inward current and increase in conductance in voltage clamp, and a depolarization and increase in firing in current clamp. These postsynaptic actions were abolished by inhibitors of the PAC1 receptor, TRPC channels, phospholipase C, phosphatidylinositol-3-kinase, and protein kinase C. Estradiol augmented the PACAP-induced inward current, depolarization, and increased firing, which was abrogated by estrogen receptor (ER) antagonists. In optogenetic recordings from POMC neurons in PACAP-Cre mice, high-frequency photostimulation induced inward currents, depolarizations, and increased firing that were significantly enhanced by Gq-coupled membrane ER signaling in an ER antagonist-sensitive manner. Importantly, the PACAP-induced excitation of POMC neurons was notably reduced in obese, high-fat (HFD)-fed males. In vivo experiments revealed that intra-arcuate nucleus (ARC) PACAP as well as chemogenetic and optogenetic stimulation of ventromedial nucleus (VMN) PACAP neurons produced a significant decrease in energy intake accompanied by an increase in energy expenditure, effects blunted by HFD in males and partially potentiated by estradiol in OVX females., Conclusions: These findings reveal that the PACAP-induced activation of PAC1 receptor and TRPC5 channels at VMN PACAP/ARC POMC synapses is potentiated by estradiol and attenuated under conditions of diet-induced obesity/insulin resistance. As such, they advance our understanding of how PACAP regulates the homeostatic energy balance circuitry under normal and pathophysiological circumstances., (© 2020 S. Karger AG, Basel.)

Description: In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations., Methods: On 6 August to 9 August 2019, the VA/DoD Evidence-Based Practice Work Group (EBPWG) convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system., Recommendations: This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.

Background: Today's standard of care, in the congenital heart disease (CHD) population, involves performing cardiac catheterization under x-ray fluoroscopy and cardiac magnetic resonance (CMR) imaging separately. The unique ability of CMR to provide real-time functional imaging in multiple views without ionizing radiation exposure has the potential to be a powerful tool for diagnostic and interventional procedures. Limiting fluoroscopic radiation exposure remains a challenge for pediatric interventional cardiologists. This pilot study's objective is to establish feasibility of right (RHC) and left heart catheterization (LHC) during invasive CMR (iCMR) procedures at our institution in the CHD population. Furthermore, we aim to improve simultaneous visualization of the catheter balloon tip, MR-conditional guidewire, and cardiac/vessel anatomy during iCMR procedures., Methods: Subjects with CHD were enrolled in a pilot study for iCMR procedures at 1.5 T with an MR-conditional guidewire. The CMR area is located adjacent to a standard catheterization laboratory. Using the interactive scanning mode for real-time control of the imaging location, a dilute gadolinium-filled balloon-tip catheter was used in combination with an MR-conditional guidewire to obtain cardiac saturations and hemodynamics. A recently developed catheter tracking technique using a real-time single-shot balanced steady-state free precession (bSSFP), flip angle (FA) 35-45°, echo time (TE) 1.3 ms, repetition time (TR) 2.7 ms, 40° partial saturation (pSAT) pre-pulse was used to visualize the gadolinium-filled balloon, MR-conditional guidewire, and cardiac structures simultaneously. MR-conditional guidewire visualization was enabled due to susceptibility artifact created by distal markers. Pre-clinical phantom testing was performed to determine the optimum imaging FA-pSAT combination., Results: The iCMR procedure was successfully performed to completion in 31/34 (91%) subjects between August 1st, 2017 to December 13th, 2018. Median age and weight were 7.7 years and 25.2 kg (range: 3 months - 33 years and 8 - 80 kg). Twenty-one subjects had single ventricle (SV) anatomy: one subject was referred for pre-Glenn evaluation, 11 were pre-Fontan evaluations and 9 post-Fontan evaluations for protein losing enteropathy (PLE) and/or cyanosis. Thirteen subjects had bi-ventricular (BiV) anatomy, 4 were referred for coarctation of the aorta (CoA) evaluations, 3 underwent vaso-reactivity testing with inhaled nitric oxide, 3 investigated RV volume dimensions, two underwent branch PA stenosis evaluation, and the remaining subject was status post heart transplant. No catheter related complications were encountered. Average time taken for first pass RHC, LHC/aortic pull back, and to cross the Fontan fenestration was 5.2, 3.0, and 6.5 min, respectively. Total success rate to obtain required data points to complete Fick principle calculations for all patients was 331/337 (98%). Subjects were transferred to the x-ray fluoroscopy lab if further intervention was required including Fontan fenestration device closure, balloon angioplasty of pulmonary arteries/conduits, CoA stenting, and/or coiling of aortopulmonary (AP) collaterals. Starting with subject #10, an MR-conditional guidewire was used in all subsequent subjects (15 SV and 10 BiV) with a success rate of 96% (24/25). Real-time CMR-guided RHC (25/25 subjects, 100%), retrograde and prograde LHC/aortic pull back (24/25 subjects, 96%), CoA crossing (3/4 subjects, 75%) and Fontan fenestration test occlusion (2/3 subjects, 67%) were successfully performed in the majority of subjects when an MR-conditional guidewire was utilized., Conclusion: Feasibility for detailed diagnostic RHC, LHC, and Fontan fenestration test occlusion iCMR procedures in SV and BiV pediatric subjects with complex CHD is demonstrated with the aid of an MR-conditional guidewire. A novel real-time pSAT GRE sequence with optimized FA-pSAT angle has facilitated simultaneous visualization of the catheter balloon tip, MR-conditional guidewire, and cardiac/vessel anatomy during iCMR procedures.

Introduction: Despite initial effectiveness of ALK receptor tyrosine kinase inhibitors (TKIs) in patients with ALK+ NSCLC, therapeutic resistance will ultimately develop. Serial tracking of genetic alterations detected in circulating tumor DNA (ctDNA) can be an informative strategy to identify response and resistance. This study evaluated the utility of analyzing ctDNA as a function of response to ensartinib, a potent second-generation ALK TKI., Methods: Pre-treatment plasma was collected from 76 patients with ALK+ NSCLC who were ALK TKI-naive or had received prior ALK TKI, and analyzed for specific genetic alterations. Longitudinal plasma samples were analyzed from a subset (n = 11) of patients. Analysis of pre-treatment tumor biopsy specimens from 22 patients was compared with plasma., Results: Disease-associated genetic alterations were detected in 74% (56 of 76) of patients, the most common being EML4-ALK. Concordance of ALK fusion between plasma and tissue was 91% (20 of 22 blood and tissue samples). Twenty-four ALK kinase domain mutations were detected in 15 patients, all had previously received an ALK TKI; G1269A was the most prevalent (4 of 24). Patients with a detectable EML4-ALK variant 1 (V1) fusion had improved response (9 of 17 patients; 53%) to ensartinib compared to patients with EML4-ALK V3 fusion (one of seven patients; 14%). Serial changes in ALK alterations were observed during therapy., Conclusions: Clinical utility of ctDNA was shown, both at pre-treatment by identifying a potential subgroup of ALK+ NSCLC patients who may derive more benefit from ensartinib and longitudinally by tracking resistance. Prospective application of this technology may translate to improved outcomes for NSCLC patients treated with ALK TKIs., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Heart failure (HF) is a significant cause of cardiovascular morbidity and mortality for women in the United States. There are clear sex-specific differences between men and women in etiology, disease progression, and outcomes. HF with preserved ejection fraction is the most common type of HF in women, with hypertensive heart disease playing a pivotal role in its etiology. The Practice Guidelines do not endorse sex-specific recommendations for standard medical therapy of HF management. Women are underrepresented in HF clinical trials, leading to a lacking evidence base supporting sex-specific therapy. Further studies are needed to evaluate targeted HF therapies in women., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cell-to-cell communication is a key element of microvascular blood flow control, including rapidly carrying signals through the vascular endothelium in response to local stimuli. This cell-to-cell communication is negatively impacted during inflammation through the disruption of junctional integrity. Such disruption is associated with promoting the onset of cardiovascular diseases as a result of altered microvascular blood flow regulation. Therefore, understanding the mechanisms how inflammation drives microvascular dysfunction and compounds that mitigate such inflammation and dysfunction are of great interest for development. As such we aimed to investigate extracts of mushrooms as potential novel compounds. Using intravital microscopy, the medicinal mushroom, Inonotus obliquus was observed, to attenuate histamine-induced inflammation conducted vasodilation in second-order arterioles in the gluteus maximus muscle of C57BL/6 mice. Mast cell activation by C48/80 similarly disrupted endothelial junctions and conducted vasodilation but only histamine was blocked by the histamine antagonist, pyrilamine not C48/80 suggesting the importance of mast cell activation. Data presented here supports that histamine induced inflammation is a major disruptor of junctional integrity, and highlights the important anti-inflammatory properties of Inonotus obliquus focusing future assessment of mast cells as putative target for Inonotus obliquus., Competing Interests: The authors have declared that no competing interests exist.

Background: Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is commercially available and increasingly adopted in clinical practice despite a paucity of prospective data to support its use., Methods: Patients with advanced lung cancers who had no known oncogenic driver or developed resistance to current targeted therapy (n = 210) underwent plasma NGS, targeting 21 genes. A subset of patients had concurrent tissue NGS testing using a 468-gene panel (n = 106). Oncogenic driver detection, test turnaround time (TAT), concordance, and treatment response guided by plasma NGS were measured. All statistical tests were two-sided., Results: Somatic mutations were detected in 64.3% (135/210) of patients. ctDNA detection was lower in patients who were on systemic therapy at the time of plasma collection compared with those who were not (30/70, 42.9% vs 105/140, 75.0%; OR = 0.26, 95% CI = 0.1 to 0.5, P < .001). The median TAT of plasma NGS was shorter than tissue NGS (9 vs 20 days; P < .001). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 56.6% (60/106, 95% CI = 46.6% to 66.2%). Among patients who tested plasma NGS positive, 89.6% (60/67; 95% CI = 79.7% to 95.7%) were also concordant on tissue NGS and 60.6% (60/99; 95% CI = 50.3% to 70.3%) vice versa. Patients who tested plasma NGS positive for oncogenic drivers had tissue NGS concordance of 96.1% (49/51, 95% CI = 86.5% to 99.5%), and directly led to matched targeted therapy in 21.9% (46/210) with clinical response., Conclusions: Plasma ctDNA NGS detected a variety of oncogenic drivers with a shorter TAT compared with tissue NGS and matched patients to targeted therapy with clinical response. Positive findings on plasma NGS were highly concordant with tissue NGS and can guide immediate therapy; however, a negative finding in plasma requires further testing. Our findings support the potential incorporation of plasma NGS into practice guidelines., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Orphanin FQ (aka nociceptin; N/OFQ) binds to its nociceptin opioid peptide (NOP) receptor expressed in proopiomelanocortin (POMC) neurons within the arcuate nucleus (ARC), a critical anorexigenic component of the hypothalamic energy balance circuitry. It inhibits POMC neurons by modifying neuronal excitability both pre- and postsynaptically. We tested the hypothesis that N/OFQ inhibits neurotransmission at synapses involving steroidogenic factor (SF)-1 neurons in the ventromedial nucleus (VMN) and ARC POMC neurons in a sex- and diet-dependent fashion., Methods: Electrophysiological recordings were done in intact male and in cycling and ovariectomized female NR5A1-Cre and eGFP-POMC mice. Energy homeostasis was assessed in wildtype animals following intra-ARC injections of N/OFQ or its saline vehicle., Results: N/OFQ (1 μM) decreased light-evoked excitatory postsynaptic current (leEPSC) amplitude more so in males than in diestrus or proestrus females, which was further accentuated in high-fat diet (HFD)-fed males. N/OFQ elicited a more robust outward current and increase in conductance in males than in diestrus, proestrus, and estrus females. These pleiotropic actions of N/OFQ were abrogated by the NOP receptor antagonist BAN ORL-24 (10 μM). In ovariectomized female eGFP-POMC mice, 17β-estradiol (E 2 ; 100 nM) attenuated the N/OFQ-induced postsynaptic response. SF-1 neurons from NR5A1-Cre mice also displayed a robust N/OFQ-induced outward current and increase in conductance that was sexually differentiated and suppressed by E 2 . Finally, intra-ARC injections of N/OFQ increased energy intake and decreased energy expenditure, which was further potentiated by exposure to HFD and diminished by estradiol benzoate (20 μg/kg; s.c.)., Conclusion: These findings show that males are more responsive to the pleiotropic actions of N/OFQ at anorexigenic VMN SF-1/ARC POMC synapses, and this responsiveness can be further enhanced under conditions of diet-induced obesity/insulin resistance.

We present a 40 year old asymptomatic man with mild left main artery narrowing who demonstrated extreme discordance between symptom presentation and ischemic burden i.e. visual (angiographic) and ischemic (functional) mismatch. The use of an appropriately selected screening stress test can lead to an appropriate decision for revascularization, supported by landmark risk assessment documents and revascularization trials., (Published by Elsevier Inc.)