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Introduction: Nitazene compounds are high potency, synthetic opioids, recently detected in the United States illicit opioid supply. This is a scoping review to summarize the available body of literature on naloxone and hospitalization reports in response to nitazene compound overdose., Methods: This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for Scoping Reviews. PubMed, ProQuest, and Google Scholar were accessed. Articles were limited to full-text peer-reviewed publications appearing in scholarly journals between January 2018 and December 2024. Total naloxone dose (in mg, primary outcome) and total length of stay (LOS, in hours, secondary outcome) were recorded., Results: Of 109 articles screened, 103 were excluded (44 non-human; 35 no nitazene exposure, 9 no naloxone administered, 9 post-mortem data only, 3 non-overdose, 2 non-English, and 1 full text unavailable), leaving 6 articles included. Data were described on 19 distinct patients with nitazene compound overdose (meto-, isoto-, proto-, and eto-nitazene), all of whom had naloxone data, and 10 of whom had LOS data. Median total naloxone doses were the following: metonitazene 6.00mg; etonitazene 3.06mg; isotonitazene 3.00mg; protonitazene 1mg (p=0.4). Mean hospital LOS were the following: metonitazene 360 hours; etonitazene 122.25 hrs; isotonitazene 32.67 hrs; protonitazene 20 hrs., Conclusion: This scoping review reveals a paucity of data on nitazene compound overdoses and identifies a gap in our current opioid crisis response. Most nitazene cases reviewed involved hospitalization, had high naloxone dosing, and relatively long LOS. Differences in naloxone dose and hospital LOS could underscore the unpredictable and potent nature of these substances., Competing Interests: Declarations. Conflict of Interest: The authors report no commercial or other conflicts of interest., (© 2025. American College of Medical Toxicology.)

Purpose: High-grade gliomas (HGG) represent the most aggressive primary brain tumors in adults, characterized by high recurrence rates due to incomplete resection. This review explores the effectiveness of emerging intraoperative therapies that may extend survival by targeting residual tumor cells. The main research question addressed is: What recent intraoperative techniques show promise for complementing surgical resection in HGG treatment?, Methods: A comprehensive literature review was conducted, examining recent studies on intraoperative therapeutic modalities that support surgical resection of HGG. Techniques reviewed include laser interstitial thermal therapy (LITT), intraoperative brachytherapy, photodynamic therapy (PDT), sonodynamic therapy (SDT), and focused ultrasound (FUS). Each modality was evaluated based on clinical application, evidence of effectiveness, and potential for integration into standard HGG treatment protocols., Results: Findings indicate that these therapies offer distinct mechanisms to target residual tumor cells: LITT provides localized thermal ablation; intraoperative brachytherapy delivers sustained radiation; PDT and SDT activate cytotoxic agents in tumor cells; and FUS enables precise energy delivery. Each method has shown varying levels of clinical success, with PDT and LITT currently more widely implemented, while SDT and FUS are promising but under investigation., Conclusion: Intraoperative therapies hold potential to improve surgical outcomes for HGG by reducing residual tumor burden. While further clinical studies are needed to optimize these techniques, early evidence supports their potential to enhance the effectiveness of surgical resection and improve patient survival in HGG management., Competing Interests: Declarations. Competing interests: Dr. Hadjipanayis has received consulting fees from Synaptive Medical, Stryker Corporation, Hemerion Therapeutics, and Integra. All other authors have no competing financial interests. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Data on the potential protective effect of psychological safety (PS) on well-being and satisfaction among physicians are lacking., Objective: We sought to examine (1) prevalence of PS; (2) relationship between PS, burnout, and intent to leave one's job (ILJ); and (3) demographic and occupational factors associated with PS within our physician faculty., Design: Participants: An institution-wide survey was sent to all faculty within our eight-hospital health system, between July and September 2022., Main Measures: PS was assessed using the seven-item Fearless Organization Questionnaire and burnout with the Maslach Burnout Inventory-2. Demographics and a measure of ILJ were assessed. Multivariable logistic regression analyses were conducted to determine associations between PS, burnout, ILJ, and demographic and occupational correlates of PS., Key Results: A total of 867 out of 3086 total estimated clinical faculty members (28.1%) participated in the survey. The majority were 40 and older (67.4%), female (51.9%), white (60.0%), and married/partnered (80.4%); worked in ambulatory care departments (53.7%); and ranked assistant or associate professors (75.8%). On average, 57.6% of physicians evaluated their workplace as psychologically safe (range across items = 40.9-69.9%), with 35.2% screening positive for burnout and 13.4% reporting ILJ. After adjusting for demographic and occupational characteristics, each standard deviation unit increase in PS scores was associated with 27% lower odds of screening positive for burnout (odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.63-0.84) and 38% lower odds of ILJ (OR = 0.62, 95% CI = 0.52-0.74). Female gender was associated with lower scores of PS., Conclusions: A majority of faculty physicians reported working in a psychologically safe environment. Greater PS was associated with lower odds of burnout and ILJ. Investment in gender and diversity equity training may be one concrete step in advancing PS in the workplace., Competing Interests: Declarations:. Conflict of Interest:: Lauren Peccoralo and Jonathan Ripp were partially supported by HRSA grant U3NHP45398 and Lauren Peccoralo was partially supported by the CTSA grant UL1TR004419 from the National Center for Advancing Translational Sciences, by the AMA EHR Use Research Grant and the NIH FIRST Cohort Cluster Hiring U54 CA267776. Lauren Peccoralo received honoraria from Chinese American Medical Society, Maine Medical Center, Atrium Health Wake Forest Baptist, American Society of Health-System Pharmacists, Stanford University, University of Montana and Baylor, and Scott & White Health. Jonathan Ripp received honoraria for numerous speaking engagements at professional societies, academic medical centers, and healthcare institutions; serves as a course director for the Institute for Healthcare Improvement; worked as a consultant for the well-being program at the NYU School of Medicine Long Island; served as a non-fiduciary board member of the Lorna Breen Foundation; served on a temporary advisory board established by PEPSICO to inform employee well-being efforts; and provides consultation to Marvin Behavioral Health, Inc. Robert H. Pietrzak is a research consultant to the Office of Well-Being and Resilience at the Icahn School of Medicine at Mount Sinai. Robert H. Pietrzak and Eleonore de Guillebon declare that they do not have a conflict of interest. Prior Presentations:: Presented by Eleonore de Guillebon at the American Conference of Physician Health on October 12, 2023. Human Research Exempt Determination:: Exempt status determined by the Mount Sinai Health System IRB on June 23, 2022., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Purpose: This study is to evaluate duration of oocyte cryostorage and association with thaw survival, fertilization, blastulation, ploidy rates, and pregnancy outcomes in patients seeking fertility preservation., Methods: Retrospective cohort study to evaluate clinical outcomes in patients who underwent fertility preservation from 2011 to 2023 via oocyte vitrification for non-oncologic indications. Primary outcome was thaw survival rate. Secondary outcomes included rates of fertilization, blastulation and embryo ploidy, as well asn pregnancy outcomes. Demographic, controlled ovarian stimulation, and laboratory data were collected for each patient. Analyses were conducted using Kruskal-Wallis, Fisher's exact test, or Chi-squared test, as appropriate. A multivariate logistic regression analysis was utilized, and adjusted odds ratios with 95% confidence intervals were calculated using Group A as the reference group., Results: A total of 5995 oocytes met inclusion criteria. These were divided into quartiles based on duration of cryostorage. Group A included oocytes in cryostorage for 0-2 years; Group B, 3-5 years; and Group C, 6-11 years. Significant differences were found when comparing thaw survival (p < 0.0001), fertilization (p = 0.0009), and blastulation rates (p = 0.0002) among groups; however, no significant differences were seen after multivariate GEE regression analysis. No significant differences were seen in rates of euploidy (p = 0.70), live birth (p = 0.81), and clinical pregnancy (p = 0.58) among groups. After analyzing years in cryostorage as a continuous variable and controlling for confounders, duration of cryostorage was not related to odds of thaw, fertilization, blastulation, euploid rates, or pregnancy outcomes., Conclusion: Length of time in cryostorage is not associated with compromised rates of oocyte thaw survival, fertilization, blastulation, ploidy, or pregnancy outcomes., Competing Interests: Declarations. Competing interests: Alan Copperman is the Medical Director of Progyny., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Meningiomas are central nervous system tumors whose incidence increases with age. Benign meningioma pathogenesis involves germline or somatic mutation of target genes, such as NF2, leading to clonal expansion. We used an established cancer epidemiology model to investigate the number of rate-limiting steps sufficient for benign meningioma development., Methods: Incidence data was obtained from the Surveillance, Epidemiology and End Results Program (SEER) for nonmalignant meningioma from 2004 to 2020. Age-adjusted incidence rates per 100,000 person-years were divided into 5-year bands. This was repeated for vestibular schwannomas as a negative control. The Armitage-Doll methodology was applied. Mathematical solutions correcting for volatile tumor microenvironments were applied to fit higher-order models using polynomial regression when appropriate. A 75:25 training:test split was utilized for validation., Results: 222,509 cases of benign meningiomas were identified. We noted strong linear relationships between log-transformed incidence and age across the cohort and multiple subpopulations: male, white, black, Hispanic, Asian/Pacific Islander, and American Indian subpopulations all demonstrated R 2  = 0.99. Slopes were between 3.1 and 3.4, suggesting a four-step process for benign meningioma development. Female patients exhibited nonlinear deviations, but the corrected model demonstrated R 2  = 0.99 with a four-hit pathway. This model performed robustly on test data with R 2  = 0.99. Vestibular schwannomas demonstrated a slope of 2.1 with R 2  = 0.99, suggesting a separate three-step process., Conclusion: Four mutations are uniquely required for the development of benign meningiomas. Correcting for volatile tumor microenvironments reliably accounted for nonlinear deviations in behavior. Further studies are warranted to elucidate genomic findings suggestive of key mutations in this pathway., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Antiangiogenic drugs may cause vascular normalization and correct hypoxia in tumors, shifting cells to mitochondrial respiration as the primary source of energy. In turn, the addition of an inhibitor of mitochondrial respiration to antiangiogenic therapy holds potential to induce synthetic lethality. This study evaluated the mitochondrial inhibitor ME-344 in combination with bevacizumab in patients with refractory metastatic colorectal cancer (mCRC). Patients were eligible if they had disease progression after standard therapies, adequate hematologic, hepatic and renal function, and no contraindications to bevacizumab. ME-344 was administered intravenously on days 1, 8 and 15 and bevacizumab on days 1 and 15 of 28-day cycles until disease progression or intolerance. The primary efficacy endpoint was progression-free survival (PFS) at week 16. In the 23 patients enrolled, the median age was 58 years, median number of prior lines of therapy was 4, and median interval from last therapy was 3 months. The most common adverse events (all grades/grade ≥ 3) were fatigue (48%/13%), abdominal pain (35%/4%), diarrhea (30%/4%) and constipation (30%/0%). No patient had an objective response; 9 patients (39%) achieved stable disease. The 16-week PFS was 30.6% (95% confidence interval [CI]: 12.2-51.3), the median PFS was 1.9 months (95% CI: 1.6-4.7), and the median overall survival was 6.7 months (95% CI: 3.4-not reached). ME-344 plus bevacizumab was well tolerated. Disease control was limited in this heavily pretreated patient population. Additional investigations in earlier lines are indicated, and extended-release ME-344 formulations may provide longer drug exposure to maximize benefit. (Trial registration number ClinicalTrials.gov NCT05824559. Registration date 22 March 2022)., Competing Interests: Declarations. Ethical approval: This study was performed in line with the ethical principles that have their origin in the Declaration of Helsinki, and the ICH Harmonised Tripartite Guideline for GCP and all applicable regulations. This study and all pertinent documents were reviewed and approved by the Institutional Review Board of each participating institution. Consent to participate: All participants provided written informed consent to participate in the study prior to the initiation of any study-specific procedures. Competing interests: Patrick M. Boland is on the advisory board of AbbVie, Bristol Myers Squib, BeiGene and Taiho and has a research grant from CARIS. Kristen K. Ciombor is a consultant/advisory board for Pfizer, Incyte, Exelixis, Bayer, ALX, Tempus, Taiho, Agenus, Merck, Beigene, and has received research grants from BMS, Array, Incyte, Daiichi Sankyo, Nucana, Merck, Pfizer, Calithera, Genentech, Seagen, and Syndax. Vaia Florou is a consultant/advisory board member of Deciphera, Springwork Therapeutics, and Aadi Biosciences. Michael J. Pishvaian is a consultant/ad hoc advisory board for Astra Zeneca, Ideaya, Seattle Genetics, Merus, Merck, Moderna, Pfizer, Novartis, Astellas, and Serna Bio. He is on the Steering Committee/Advisory Board for Astellas and Merck. He has received travel, accommodations and expenses support from Astellas and RenovoRx. He owns equity in Perthera. He has received institutional research funding from Tesaro, Arcus Bio, Ideaya, Repare Tx, Novartis, Pfizer, Merck, Tizonia, Biomed Valley Discoveries, Amgen, RenovoRx, Boerhinger Ingelheim, Astellas, Hutchinson Medipharma, Takeda, Actuate, MEI Pharma, Elevation Oncology, and Recursion Pharma. Min Tang and Prabu Rajagopalan are consultants to MEI Pharma. Sandy E. Wiley and Richard G. Ghalie are employed by and hold equity in MEI Pharma. Howard S. Hochster is consultant to GSK, AstraZeneca, Processa and Compass Therapeutics, and is expert witness for Guardant. Heinz-Josef Lenz, Michael Cusnir, Dierdre Cohen, and Jessie Y. Guo have no conflicts to disclose., (© 2024. The Author(s).)

The COVID-19 pandemic caused unprecedented disruption in all activities, especially those related to group gatherings. During the lockdown period, faith-based organizations, which are resources for both religious and health promotion activities, had to develop alternative strategies to meet those goals. The purpose of this paper is to describe the sustainability of M.I.C.A.H. Project HEAL, a partnership between an academic medical center and faith-based organizations in underserved communities in New York City, during the initial pandemic lockdown period. The use of virtual platforms facilitated Community Health Advisors (CHAs) in 13 organizations to conduct 47 health education workshops, reaching over 800 participants. Reliance on virtual platforms continued after in person gatherings were permitted. These data further support the benefits of academic partnerships with faith-based organizations to provide timely health information during a public health crisis., Competing Interests: Declarations. Ethics Approval and Consent to Participate: This project was previously considered exempt by Institutional IRB. Competing interests: The authors declare that they do not have financial interests that are directly or indirectly related to the work submitted for publication., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used to manage type 2 diabetes (T2D) and obesity. Despite their recognized benefits in glycemic control and weight management, their impact on broader systemic has been less explored., Objective: This study aimed to evaluate the impact of GLP-1RAs on a variety of systemic diseases in people with T2D or obesity., Methods: We conducted a retrospective cohort study using data from the Global Collaborative Network, accessed through the TriNetX analytics platform. The study comprised two primary groups: individuals with T2D and those with obesity. Each group was further divided into subgroups based on whether they received GLP-1RA treatment or not. Data were analyzed over more than a 5-year follow-up period, comparing incidences of systemic diseases; systemic lupus erythematosus (SLE), systemic sclerosis (SS), rheumatoid arthritis (RA), ulcerative colitis (UC), crohn's disease (CD), alzheimer's disease (AD), parkinson's disease (PD), dementia, bronchial asthma (BA), osteoporosis, and several cancers., Results: In the T2D cohorts, GLP-1RA treatment was associated with significantly lower incidences of several systemic and metabolic conditions as compared to those without GLP-1RA, specifically, dementia (Risk Difference (RD): -0.010, p < 0.001), AD (RD: -0.003, p < 0.001), PD (RD: -0.002, p < 0.001), and pancreatic cancer (RD: -0.003, p < 0.001). SLE and SS also saw statistically significant reductions, though the differences were minor in magnitude (RD: -0.001 and - 0.000 respectively, p < 0.001 for both). Conversely, BA a showed a slight increase in risk (RD: 0.002, p < 0.001)., Conclusions: GLP-1RAs demonstrate potential benefits in reducing the risk of several systemic conditions in people with T2D or obesity. Further prospective studies are needed to confirm these effects fully and understand the mechanisms., Competing Interests: Declarations. Conflict of Interest Statement: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Computed tomography (CT)-derived Epicardial Adipose Tissue (EAT) is linked to cardiovascular disease outcomes. However, its role in patients undergoing Transcatheter Aortic Valve Replacement (TAVR) and the interplay with aortic stenosis (AS) cardiac damage (CD) remains unexplored. We aim to investigate the relationship between EAT characteristics, AS CD, and all-cause mortality. We retrospectively included consecutive patients who underwent CT-TAVR followed by TAVR. EAT volume and density were estimated using a deep-learning platform and CD was assessed using echocardiography. Patients were classified according to low/high EAT volume and density. All-cause mortality at 4 years was compared using Kaplan-Meier and Cox regression analyses. A total of 666 patients (median age 81 [74-86] years; 54% female) were included. After a median follow-up of 1.28 (IQR 0.53-2.57) years, 11.7% (n = 77) of patients died. The EAT volume (p = 0.017) decreased, and density increased (p < 0.001) with worsening AS CD. Patients with low EAT volume (< 49cm 3 ) and high density (≥-86 HU) had higher all-cause mortality (log-rank p = 0.02 and p = 0.01, respectively), even when adjusted for age, sex, and clinical characteristics (HR 1.71, p = 0.02 and HR 1.73, p = 0.03, respectively). When CD was added to the model, low EAT volume (HR 1.67 p = 0.03) and CD stages 3 and 4 (HR 3.14, p = 0.03) remained associated with all-cause mortality. In patients with AS undergoing TAVR, CT-derived low EAT volume, and high density were independently associated with increased 4-year mortality and worse CD stage. Only EAT volume remained associated when adjusted for CD., Competing Interests: Declarations. Ethical approval: This is an observational study. The study protocol followed the ethical guidelines of the 1975 Declaration of Helsinki as reflected in the a priori approval by the Institution’s Human Research Committee. The study was approved by our Office of Human Research Affairs at Albert Einstein College of Medicine and consent was waived due to study design. Disclosures: Annalisa Filtz, Daniel Lorenzatti, and Leandro Slipczuk are supported by institutional grants from Amgen and Philips. Damini Dey received grant support from the National Heart, Lung, and Blood Institute, software royalties from Cedars-Sinai Medical Center, and holds a patent (US8885905B2 in USA and WO patent WO2011069120A1, Method and System for Plaque Characterization). Others have nothing to declare. Competing interests: Damini Dey received grant support from the National Heart, Lung, and Blood Institute, software royalties from Cedars-Sinai Medical Center, and holds a patent (US8885905B2 in USA and WO patent WO2011069120A1, Method and System for Plaque Characterization). Others have nothing to declare., (© 2024. The Author(s).)

Background: Anaplastic thyroid cancer (ATC) is a highly lethal disease, often diagnosed with advanced locoregional and distant metastases, resulting in a median survival of just 3-5 months. This study determines the stratified effectiveness of baseline treatments in all combinations, enabling precise prognoses prediction and establishing benchmarks for advanced therapeutic options., Methods: The study extracted a cohort of pathologically confirmed ATC patients from the Surveillance, Epidemiology, and End Results program. Overall, 1879 patients from 2000 to 2018 were identified from the database. Kaplan-Meier survival curve estimation and Cox proportional hazard regression were applied., Results: Overall, compared with no treatment, surgery raised 1-year overall survival (OS) from 0.6% to 30% and median survival from <1 month to 3 months in ATC patients. For stage IVa, surgery increased 1-year OS from 21.5% to 71.8% and median survival from 2 to 23.5 months, and in stage IVb, surgery increased 1-year OS from 9.4% to 41.3% and median survival from 2 to 7 months; however, in stage IVc, the benefits of surgery were not markedly different from non-surgical approaches. When combined with surgery, other effective non-surgical ATC treatments demonstrated a surgery-dominant synergistic effect, particularly for stages IVa and IVb ATC, but not for stage IVc ATC., Conclusions: Our study provides insights into stratified baseline treatments for patients with ATC in all stages, emphasizing surgery's vital role in a multimodal approach., Competing Interests: Disclosures: Kun Zhang, Xinyi Wang, Jianyong Lei, Anping Su, Tao Wei, Zhihui Li, and Ya-Wen Chen have no conflicts of interest to declare that may be relevant to the contents of this study., (© 2025. The Author(s).)

Cyclic GMP-AMP synthase (cGAS) is a DNA sensing cellular receptor that induces IFN-I transcription in response to pathogen and host derived cytosolic DNA and can limit the replication of some RNA viruses. Some viruses have nonetheless evolved mechanisms to antagonize cGAS sensing. In this study, we evaluated the interaction between Bluetongue virus (BTV), the prototypical dsRNA virus of the Orbivirus genus and the Sedoreoviridae family, and cGAS. We found mitochondrial damage and DNA accumulation in the cytoplasm of infected cells. In addition, we show that BTV infection blocks DNA-induced IFN-I transcription and that virus infection prevents DNA sensing by inducing cGAS and STING degradation. We identify BTV-NS3 as the viral protein responsible for cGAS degradation, showing that NS3 physically interacts with cGAS and induces its degradation through an autophagy-dependent mechanism. Taken together, these findings identify for the first time a mechanism by which a dsRNA virus interferes with a DNA sensing pathway to evade the innate immune response., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Conflict of interest: The authors have no relevant financial or non-financial interest to disclose., (© 2025. The Author(s).)

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may occur after infection. How often people develop ME/CFS after SARS-CoV-2 infection is unknown., Objective: To determine the incidence and prevalence of post-COVID-19 ME/CFS among adults enrolled in the Researching COVID to Enhance Recovery (RECOVER-Adult) study., Design, Setting, and Participants: RECOVER-Adult is a longitudinal observational cohort study conducted across the U.S. We included participants who had a study visit at least 6 months after infection and had no pre-existing ME/CFS, grouped as (1) acute infected, enrolled within 30 days of infection or enrolled as uninfected who became infected (n=4515); (2) post-acute infected, enrolled greater than 30 days after infection (n=7270); and (3) uninfected (1439)., Measurements: Incidence rate and prevalence of post-COVID-19 ME/CFS based on the 2015 Institute of Medicine ME/CFS clinical diagnostic criteria., Results: The incidence rate of ME/CFS in participants followed from time of SARS-CoV-2 infection was 2.66 (95% CI 2.63-2.70) per 100 person-years while the rate in matched uninfected participants was 0.93 (95% CI 0.91-10.95) per 100 person-years: a hazard ratio of 4.93 (95% CI 3.62-6.71). The proportion of all RECOVER-Adult participants that met criteria for ME/CFS following SARS-CoV-2 infection was 4.5% (531 of 11,785) compared to 0.6% (9 of 1439) in uninfected participants. Post-exertional malaise was the most common ME/CFS symptom in infected participants (24.0%, 2830 of 11,785). Most participants with post-COVID-19 ME/CFS also met RECOVER criteria for long COVID (88.7%, 471 of 531)., Limitations: The ME/CFS clinical diagnostic criteria uses self-reported symptoms. Symptoms can wax and wane., Conclusion: ME/CFS is a diagnosable sequela that develops at an increased rate following SARS-CoV-2 infection. RECOVER provides an unprecedented opportunity to study post-COVID-19 ME/CFS., Competing Interests: Declarations:. Conflict of Interest:: Dr. Horwitz reported receiving grants from the NIH and serving on an ad hoc committee for the National Academy of Medicine. Dr. Marconi reported receiving grants from the Centers for Disease Control and Prevention, Veteran Affairs, and the NIH; grants, personal fees, nonfinancial support, and other from Eli Lilly, Merck, and Gilead; grants and personal fees from ViiV; and nonfinancial support from Bayer. Dr. Singer reported receiving grants from Case Western Reserve University and MetroHealth. Dr. Sherif reported receiving research grants from NIH and American Cancer Society. Dr. Mullington reported receiving grants from the NIH and Open Medicine Foundation and speaker and book chapter contribution for Idorsia Pharmaceuticals. Dr Laiyemo reported receiving grants from the NIH. Dr. Peluso reported receiving personal fees from Gilead Sciences and AstraZeneca. Dr. Hess reported receiving grants from the NIH and being a member of a data and safety monitoring board for Astellas Pharmaceuticals. Disclaimer:: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the RECOVER Program, the NIH or other funders., (© 2025. The Author(s).)

Purpose: While surgeons agree that perioperative field blocks should be performed for open inguinal hernia surgery, there lacks consensus in the minimally invasive context. Prior small-scale randomized trials study pain scores only up to 24 h postoperatively. Thus, we sought to investigate the analgesic benefits of a bupivacaine transversus abdominis plane (TAP) block in the first 4 postoperative days., Methods: This is a prospective single-institution randomized control trial involving patients undergoing elective totally extraperitoneal inguinal hernia repairs, who received either a TAP block with bupivacaine 0.25% or saline placebo. Postoperatively, patients completed a pain survey (based on a 0-10 visual analog score) and an opioid/non-opioid pain medication log. Differences were detected using a Wilcoxon rank sum test for continuous variables, and a Fisher's exact test or chi-squared for categorical variables., Results: A total n = 90 patients were included in the per-protocol analysis, of which n = 46 received TAP blocks with bupivacaine versus n = 44 placebo. Patient characteristics were similar between the groups, including recurrent hernias and number of tacks placed (p > 0.05). All cases were bilateral. Postoperatively, pain scores (at rest and with movement) and pain medication use were similar for all postoperative days 1-4., Conclusion: Our study shows no significant difference in pain or opioid requirement within the first 4 days postoperatively, suggesting that the analgesic benefits of plain bupivacaine TAP blocks in totally extraperitoneal inguinal hernia repairs do not exist beyond the recovery unit. This will help inform anesthesiologists and patients in discussing risks and benefits of a TAP block in their surgical context., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest to disclose. Ethical standard: This study was approved by our institutional review board and registered with Clinicaltrials.gov (NCT05672680). Consent to participate: Informed consent was obtained from all individual participants included in the study., (© 2025. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Small bowel obstructions (SBOs) are a common complication following staged IPAA. Our goal was to compare early post-operative SBO outcomes between different staged ileal pouch-anal anastomosis (IPAA) and to further analyze the type of procedures required in patients who needed operative management of SBO., Methods: In this retrospective cohort study, we selected all patients who presented to our tertiary care center between 2008 and 2017, with ulcerative colitis or IBD-Unspecified colitis and who underwent a primary total proctocolectomy with IPAA for medically refractory disease or dysplasia (n = 623). Patients were divided into 4 groups based on staged IPAA received (1 stage vs 2 stage vs modified 2 stage vs 3 stage). Primary outcomes were compared between both groups using univariate analysis and included SBO within 6 months post-operatively of one of the IPAA stages or 18 months since the first surgery for patients who underwent 1 or 2 stage IPAAs, and need for readmission and reoperation. Risk factors for SBO, reoperation and readmission due to SBO were evaluated using multivariate logistic regression., Results: Stage 2 and 3 patients had the highest rates of SBO post-operatively. There was a significant difference in the rate of readmission between groups, with 2 and 3 stage groups having the highest rates (p < 0.05) but the rate of SBO and reoperations was not significantly different between groups. Of all patients with an SBO, 34% required operative intervention. Of these, 65% underwent diagnostic laparoscopy with lysis of adhesions and 27% required an open procedure., Conclusion: Small bowel obstructions are a common complication of staged IPAA procedures. Patients who underwent 2 and 3 stage IPAA had the highest rates of SBO, although not statistically significant. A third of patients with an SBO required surgical intervention, with diagnostic laparoscopy and lysis of adhesions being the most common procedure., Competing Interests: Declarations. Disclosures: Marine Coste, MD: no conflict of interest. Sarah Cao, MD: no conflict of interest. Maia Kayal MD: participation on a data safety monitoring or advisory board at Janssen, Bristol Myers Squib, Pfizer, Fresenius; communications chair at iUSCAN; payment or honoraria for multiple lectures and presentations including at Crohn’s and colitis Congress and IBD Horizons; consultant at Abbvie. Yun Hwa Walter Wang MD: no conflict of interest. Sue J Hahn MD: no conflicts of interest. Sergey Khaitov MD: no conflict of interest. Patricia A. Sylla MD: consultant at Ethicon, Exero Medical, RedDress, Safeheal, Stryker. Marla C. Dubinsky MD: no conflict of interest. Michael C. Plietz MD: no conflict of interest. Alexander J. Greenstein MD: no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cross-sectional imaging plays a crucial role in the detection, diagnosis, staging, and resectability assessment of intra- and extrahepatic cholangiocarcinoma. Despite this vital function, there is a lack of standardized CT and MRI protocol recommendations for imaging cholangiocarcinoma, with substantial differences in image acquisition across institutions and vendor platforms. In this review, we present standardized strategies for the optimal imaging assessment of cholangiocarcinoma including contrast media considerations, patient preparation recommendations, optimal contrast timing, and representative CT and MRI protocols with individual sequence optimization recommendations. Our recommendations are supported by expert opinion from members of the Society of Abdominal Radiology's Disease-Focused Panel (DFP) on Cholangiocarcinoma, encompassing a broad array of institutions and practice patterns., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Our primary objective was to determine the frequency and type of substance use in youth presenting to our pediatric ED (PED). Our secondary objective was to identify characteristics associated with higher-risk substance use., Methods: We conducted a tablet-based, anonymous, self-administered screening for substance use using a modified version of the Screening to Brief Intervention (S2BI) tool among a convenience sample of 383 patients 12-21 years presenting to an urban, academic PED from February to July 2023. Patients' attitudes toward ED screening and interventions for substance use also were collected. The frequency and type of substance use was analyzed by age group. Ordinal logistic regression was used to identify characteristics associated with higher-risk use (monthly or more substance use) and lower-risk use (past year use), as compared to no past year use., Results: Among 14-17-year-olds (n = 144), 38% reported substance use in the past year; 25% had higher-risk use. Among 18-21-year-olds (n = 172), 67% reported substance use in the past year; 48% had higher-risk use. Alcohol, cannabis, and tobacco were most commonly used. Substance use was rare for 12-13-year-olds. Compared to youth 14-17 years, youth 18-21 years were more likely to have either higher-risk use (aOR 3.81, 95% CI (2.24-6.47)) or lower-risk use (aOR 2.74 (1.41-5.35)), rather than no use. Compared to Asian patients, Non-Hispanic White patients (aOR 5.23 (1.07-25.66)) and Hispanic patients (aOR 3.18 (1.06-9.58)) were more likely to have higher-risk use than no use. Most patients reported that it was important for youth to be asked about substance use in the ED and to be offered help for substance use., Conclusion: Youth substance use was common in this urban, academic PED, and many patients reported higher-risk use. These findings support future research to determine the best practices for ED substance use screening and ED-based interventions for youth., Competing Interests: Declarations. Conflict of interest: All authors declare that they have no conflict of interest., (© 2024. American College of Medical Toxicology.)

Background and Aims: To investigate gender, racial, ethnic, and regional disparities in first and senior authorship positions in gastroenterology/hepatology-related randomised controlled trials (RCT)., Method: Retrospective bibliometric analysis of PubMed-indexed RCTs published between January 2000 to December 2022 in leading journals with an impact factor of at least five., Results: 943 RCTs met our inclusion criteria, providing a participant pool of 301 female (15.96%) and 1,585 male (84.04%) authors from 37 countries (70% high-income countries). Despite a significant increase in the proportion of female authors in first and senior authorship positions between 2000 and 2022 (p<0.001), females were grossly underrepresented in both authorship positions, with a male-to-female ratio of 4.45 and 6.37, respectively. The male-to-female ratio was highest among Asian authors (7.79) than among White (4.22), Hispanic (1.44), and Black (1) authors in the first authorship position. In contrast, the male-to-female ratio was similar for Asian (6.2) and White (6.67) authors in the senior authorship position, with a low underlying frequency of Hispanic and Black female authors., Conclusion: Despite significant improvements in gender, racial and ethnic representation in first and senior authorship of gastroenterology/hepatology-related RCTs published in high-impact journals, progress toward parity remains slow. Targeted interventions to improve author diversity are warranted., Competing Interests: Declarations. Ethics Approval: Since this bibliometric study involves publicly available data, approval from the institutional review board was not sought. Conflicts of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Children and adolescents are experiencing a mental health crisis. Neurodiverse patients have high rates of mental health conditions and worse outcomes. To address this disparity, the Autism Spectrum Disorder Care Pathway was applied to a pediatric emergency department (PED) and Observation Unit (OU) in order to decrease agitation experienced by these patients., Methods: This prospective cohort study was in a community-based PED and OU from June 2023 to February 2024. A medical education curriculum consisting of a multidisciplinary champion training and toolkit rollout was completed. Agitation was measured by the Behavioral Activity Rating Scale. The primary aim was to decrease frequency of agitation experienced by neurodiverse patients at any point in the PED/OU. The secondary outcome was to decrease pharmacologic intervention and physical restraint use., Results: We captured data from a total of 45 patients, with 19 baseline patients and 26 patients in the intervention group. At baseline, 9 out of 19 (47%) patients experienced agitation at some point in their PED/OU stay. After implementation of the curriculum, agitation levels decreased to 6 out of 26 (23%) patients (p = 0.04). Inter-rater reliability was 0.95. There were 3 incidences of pharmacologic intervention and no physical restraint use., Conclusions: This pilot medical education curriculum for PED and OU staff members decreased agitation in neurodiverse patients who presented for mental health complaints. This study is the foundation for expansion of the curriculum for use in general emergency departments., Competing Interests: Declarations. Ethics Approval: This project was approved by the Departmental QI Committee as well as by Institutional Review Board (IRB) at Icahn School of Medicine at Mount Sinai. Consent to Participate: This study applied an Autism Spectrum Disorder Clinical Pathway to the Pediatric Emergency Department and was a part of standard of care. Consent for medical care was obtained from at least one legal guardian or parent. Clinical Trial Registration: None. Conflict of Interest: All authors have no conflicts of interest to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Loss-of-function variants in ATP6V0A2, encoding the trans Golgi V-ATPase subunit V0a2, cause wrinkly skin syndrome (WSS), a connective tissue disorder with glycosylation defects and aberrant cortical neuron migration. We used knock-out (Atp6v0a2 -/- ) and knock-in (Atp6v0a2 RQ/RQ ) mice harboring the R755Q missense mutation selectively abolishing V0a2-mediated proton transport to investigate the WSS pathomechanism. Homozygous mutants from both strains displayed a reduction of growth, dermis thickness, and elastic fiber formation compatible with WSS. A hitherto unrecognized male infertility due to globozoospermia was evident in both mouse lines with impaired Golgi-derived acrosome formation and abolished mucin-type O-glycosylation in spermatids. Atp6v0a2 -/- mutants showed enhanced fucosylation and glycosaminoglycan modification, but reduced levels of glycanated decorin and sialylation in skin and/or fibroblasts, which were absent or milder in Atp6v0a2 RQ/RQ . Atp6v0a2 RQ/RQ mutants displayed more abnormal migration of cortical neurons, correlating with seizures and a reduced O-mannosylation of α-dystroglycan. While anterograde transport within the secretory pathway was similarly delayed in both mutants the brefeldin A-induced retrograde fusion of Golgi membranes with the endoplasmic reticulum was less impaired in Atp6v0a2 RQ/RQ . Measurement of the pH in the trans Golgi compartment revealed a shift from 5.80 in wildtype to 6.52 in Atp6v0a2 -/- and 6.25 in Atp6v0a2 RQ/RQ . Our findings suggest that altered O-glycosylation is more relevant for the WSS pathomechanism than N-glycosylation and leads to a secondary dystroglycanopathy. Most phenotypic and cellular properties correlate with the different degrees of trans Golgi pH elevation in both mutants underlining the fundamental relevance of pH regulation in the secretory pathway., Competing Interests: Declaration. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: Permissions for animal breeding and experiments were obtained from the Landesamt für Gesundheit und Soziales (LAGeSo) in Berlin, Germany (No. G0346/13, G0176/19), and the Landesamt für Verbraucherschutz und Lebensmittelsicherheit (LAVES) in Oldenburg, Germany (No. 20/3483). Consent to publish: This study does not contain any human materials or data., (© 2024. The Author(s).)

G6PC3 deficiency is a monogenic immunometabolic disorder that causes severe congenital neutropenia type 4. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis. Here, we investigated the origin and functional consequence of the G6PC3 c.210delC variant found in patients of Mexican descent. Based on the shared haplotypes amongst mutation carriers, we estimated that this variant originated from a founder effect in a common ancestor. Furthermore, by ancestry analysis, we concluded that it appeared in the indigenous Mexican population. At the protein level, we showed that this frameshift mutation leads to an aberrant protein expression in overexpression and patient-derived Epstein-Barr Virus-immortalized B (EBV-B) cells. The neutropenia observed in G6PC3-deficient patients is driven by the intracellular accumulation of the metabolite 1,5-anhydroglucitol-6-phosphate (1,5-AG6P) that inhibits glycolysis. We characterized how the c.210delC variant impacts glycolysis by performing extracellular flux assays on patient-derived EBV-B cells. When treated with 1,5-anhydroglucitol (1,5-AG), the precursor to 1,5-AG6P, patient cells exhibited markedly reduced engagement of glycolysis. Finally, we compared the clinical presentation of patients with the mutation c.210delC and all other G6PC3-deficient patients reported in the literature, and we found that the c.210delC carriers display all prominent clinical features observed in prior patients. In conclusion, G6PC3 c.210delC is a loss-of-function mutation that arose from a founder effect in the indigenous Mexican population. These findings may facilitate the diagnosis of additional patients in this geographical area. Moreover, the in vitro 1,5-AG-dependent functional assay used in our study could be employed to assess the pathogenicity of additional G6PC3 variants., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Substantial evidence suggests a downstream impact of maternal mental health on birth outcomes. The roles of comorbid maternal physical health and familial confounding underlying this association remain unclear., Methods: This cohort study included a random sample of children born 1997-2008 within a health maintenance organization (HMO) in Israel, their parents, and siblings. Outcomes were ICD-9 diagnoses of neonatal adversities (birth complications and congenital anomalies) and exposures were maternal diagnoses of mental health disorders. Odds ratios (ORs) and their 95% confidence intervals for the associations between maternal mental health diagnoses and measures of neonatal adversity were calculated using logistic regression, adjusting for maternal age, child's year of birth, socioeconomic status, and maternal physical morbidity burden. We examined potential familial confounding using a negative control approach based on paternal exposure., Results: In our sample of 74,533 children, 6,674 (9.1%) were born after birth complications and 14,569 (19.9%) with a congenital anomaly. Maternal mental health diagnosis around pregnancy was significantly associated with these measures of neonatal adversity after adjustment for potential confounders (birth complications: OR = 1.3 (1.2-1.4), p < 0.001; congenital anomalies: OR = 1.2 (1.1-1.3), p < 0.001). These associations became attenuated and non-significant after further adjustment for maternal physical morbidity burden. In a joint model, maternal and paternal diagnosis of a mental health disorder were independently associated with neonatal adversity (birth complications: OR mat =1.3 (1.1-1.4), p < 0.001; OR pat =1.2 (1.1-1.3), p = 0.004; congenital anomalies: OR mat =1.2 (1.1-1.3), p < 0.001; OR pat =1.1 (1.0-1.2), p = 0.01)., Conclusion: Physical health and familial factors play a role in the associations between maternal mental health and neonatal adversity., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the institutional review board of the University of Haifa and the Helsinki Ethics Committee. Those bodies waived the need for informed consent because the study data were fully deidentified. Consent for publication: Not applicable. Competing interests: The authors did not declare any competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Cancer screenings aid in the early detection of cancer and can help reduce cancer-related mortality. The current model of care for cancer screening is often siloed, based on the targeted cancer site. We tested the acceptability of a new model of care, called the One-Stop-Shop Cancer Screening Clinic, that centralizes cancer screenings and offers patients the option to complete all their recommended cancer screenings within one to two visits. We administered surveys to 59 community members and 26 healthcare providers to gather feedback about the One-Stop-Shop model of care. Both community members and providers identified potential benefits (e.g., decreased patient burden, increased completion of cancer screenings) and also potential challenges (e.g., challenges with workflow and timing of care) of the model of care. The results of the study support the acceptability of the model of care. Of the community members surveyed, 89.5% said, if offered, they would be interested in participating in the One-Stop-Shop Cancer Screening Clinic. Future studies are needed to formally evaluate the impact and cost effectiveness of the One-Stop-Shop Cancer Screening Clinic., Competing Interests: Declarations Ethics Approval The study was reviewed and deemed exempt human research by the Institutional Review Board of the Icahn School of Medicine at Mount Sinai (protocol code STUDY-21-01593). Competing Interests The authors declare no competing interests., (© 2024. The Author(s) under exclusive licence to American Association for Cancer Education.)

Post-traumatic stress disorder (PTSD) is a debilitating mental health condition characterized by recurrent re-experiencing of traumatic events. Despite increasing evidence suggesting that the cerebellum is involved in PTSD pathophysiology, it remains unclear whether this involvement is related to symptoms directly resulting from previous trauma exposure, such as involuntary re-experiencing of the traumatic events, or reflects a broader cerebellar engagement in negative affective states. In this study, we investigated the specific role of the cerebellum in PTSD by employing a script reactivation paradigm with personalized traumatic and sad autobiographical memories in 28 individuals diagnosed with chronic PTSD. Functional magnetic resonance imaging (fMRI) data were collected while participants listened to their own autobiographical narratives recounted by a third person. Activation in the right cerebellar lobule VI was uniquely associated with traumatic autobiographical recall and was parametrically modulated by the severity of re-experiencing symptoms. In contrast, cerebellar Crus II showed increased activation during both traumatic and sad autobiographical recall, suggesting a broader involvement in processing negative emotions. Our findings highlight the unique contribution of the right cerebellar lobule VI in the processing of traumatic autobiographical memories, potentially through its engagement in low-level representation of sensory and emotional aspects of traumatic events., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Multitarget stool DNA (mt-sDNA) is an increasingly utilized noninvasive option for colorectal cancer screening; however, its impact is limited by imperfect test adherence. Tailored patient navigation (TPN) improves adherence for other cancer screening tests, but its role in mt-sDNA is not known., Aim: Determine whether TPN improves mt-sDNA completion and reduces sample could not be processed (SCNBP) result rates., Setting: A large, urban, academic primary care clinic serving a medically vulnerable population., Participants: All patients who received mt-sDNA order in 2022 and 2023., Program Description: A patient navigator outreached all patients ordered mt-sDNA to support test completion during the 12-month intervention period in 2023., Program Evaluation: Rates of mt-sDNA completion within 90 days and SCNBP results were compared between the 12-month intervention and pre-intervention periods using generalized estimating equations. A total of 2694 patients received 3297 orders during the study. TPN was significantly associated with improved rates of 90-day mt-sDNA completion (51% vs. 39%, OR 1.67, p < .001) and SCNBP results (4% vs. 5%, OR 0.55, p < .001)., Discussion: Tailored patient navigation was associated with improved rates of mt-sDNA completion and SCNBP results despite built-in navigation services provided by the manufacturer. TPN for mt-sDNA is a promising strategy for enhancing colorectal cancer screening uptake., Competing Interests: Declarations Conflict of Interests The authors disclose the following relevant conflicts of interest: E.C., Z.S., K.J., N.B., M.F., L.J., P.W. report no conflicts; C.W. is funded by the National Cancer Institute and American Cancer Society; J.P.W. has received funding and consulting fees from the American Medical Association, Axella, Banook, BionTech, Pharmaceutical Product Development Inc., Regeneron, and Sanofi; S.H.I. has received funding from Exact Sciences and consulting fees from Exact Sciences and Geneoscopy; K.M.K. has received consulting fees from DeciBio Consulting and travel support to present this work from Exact Sciences., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: Narratives of mental illness and well-being are difficult to communicate in medical education. The arts convey these narratives and may strengthen medical student capabilities., Methods: This study evaluated the efficacy of a 2021 6-week seminar-style course for medical students focused on five mental states through the lens of visual arts, film, and literature to impact student capabilities. Pre- and post-course administration of standardized rating scales, including the Jefferson Scale of Empathy Medical Students (JSE-S), the Groningen Reflection Ability Scale (GRAS), and the Connor-Davidson Resilience Scale (CD-RISC), measured course impact on medical student empathy, reflective functioning, and resiliency, respectively. Administration of these scales on a matched control group of students not enrolled in the course served for comparison., Results: Pre- and post-course survey data demonstrates that the course improves at levels of statistical significance medical students' empathy (JSE-S score 77.50 SD = 15.76 improving to 93.80 SD 20.92, p = 0.0068, t = 4.19, df = 4) and resilience (CD-RISC score 65.83 SD = 14.36 improving to 78.60 SD = 10.92, p = 0.0137, t = 4.19, df = 4), but not reflective functioning (GRAS score 91 SD = 9.14 improving to 95.20 SD = 10.06, p = 0.1444, t = 1.81, df = 4). The control group showed no statistically significant differences pre- and post-course., Conclusions: Limitations notwithstanding, this study suggests that the analysis of film, literature, and visual art may improve medical students' empathy and resilience. Future studies may explore reproducibility among larger sample sizes at differing institutions and curricula as well as downstream effects on patient care and well-being., Competing Interests: Declarations Conflict of Interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024. The Author(s), under exclusive licence to Academic Psychiatry, LLC.)

Background: Stroke is a leading cause of death and disability worldwide. Approximately one-third of patients with stroke experienced a second stroke. This study investigates the predictive value of machine learning (ML) algorithms for recurrent stroke., Method: This study was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, Scopus, Embase, and Web of Science (WOS) were searched until January 1, 2024. The quality assessment of studies was conducted using the QUADAS-2 tool. The diagnostic meta-analysis was conducted to calculate the pooled sensitivity, specificity, diagnostic accuracy, positive and negative diagnostic likelihood ratio (DLR), diagnostic accuracy, diagnostic odds ratio (DOR), and area under of the curve (AUC) by the MIDAS package in STATA V.17., Results: Twelve studies, comprising 24,350 individuals, were included. The meta-analysis revealed a sensitivity of 71% (95% CI 0.64-0.78) and a specificity of 88% (95% confidence interval (CI) 0.76-0.95). Positive and negative DLR were 5.93 (95% CI 3.05-11.55) and 0.33 (95% CI 0.28-0.39), respectively. The diagnostic accuracy and DOR was 2.89 (95% CI 2.32-3.46) and 18.04 (95% CI 10.21-31.87), respectively. The summary ROC curve indicated an AUC of 0.82 (95% CI 0.78-0.85)., Conclusion: ML demonstrates promise in predicting recurrent strokes, with moderate to high sensitivity and specificity. However, the high heterogeneity observed underscores the need for standardized approaches and further research to enhance the reliability and generalizability of these models. ML-based recurrent stroke prediction can potentially augment clinical decision-making and improve patient outcomes by identifying high-risk patients., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background: Artificial intelligence (AI) algorithms are increasingly used to target patients with elevated mortality risk scores for goals-of-care (GOC) conversations., Objective: To evaluate the association between the presence or absence of AI-generated mortality risk scores with GOC documentation., Design: Retrospective cross-sectional study at one large academic medical center between July 2021 and December 2022., Participants: Hospitalized adult patients with AI-defined Serious Illness Risk Indicator (SIRI) scores indicating > 30% 90-day mortality risk (defined as "elevated" SIRI) or no SIRI scores due to insufficient data., Intervention: A targeted intervention to increase GOC documentation for patients with AI-generated scores predicting elevated risk of mortality., Main Measures: Odds ratios comparing GOC documentation for patients with elevated or no SIRI scores with similar severity of illness using propensity score matching and risk-adjusted mixed-effects logistic regression., Key Results: Among 13,710 patients with elevated (n = 3643, 27%) or no (n = 10,067, 73%) SIRI scores, the median age was 64 years (SD 18). Twenty-five percent were non-White, 18% had Medicaid, 43% were admitted to an intensive care unit, and 11% died during admission. Patients lacking SIRI scores were more likely to be younger (median 60 vs. 72 years, p < 0.0001), be non-White (29% vs. 13%, p < 0.0001), and have Medicaid (22% vs. 9%, p < 0.0001). Patients with elevated versus no SIRI scores were more likely to have GOC documentation in the unmatched (aOR 2.5, p < 0.0001) and propensity-matched cohorts (aOR 2.1, p < 0.0001)., Conclusions: Using AI predictions of mortality to target GOC documentation may create differences in documentation prevalence between patients with and without AI mortality prediction scores with similar severity of illness. These finding suggest using AI to target GOC documentation may have the unintended consequence of disadvantaging severely ill patients lacking AI-generated scores from receiving targeted GOC documentation, including patients who are more likely to be non-White and have Medicaid insurance., Competing Interests: Declarations: Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: The Veterans Health Administration (VHA) implemented the Clinical Resource Hub (CRH) program to fill staffing gaps in primary care (PC) clinics via telemedicine and maintain veterans' healthcare access., Objective: To evaluate PC wait times before and after CRH implementation., Design: Comparative interrupted time series analysis among a retrospective observational cohort of PC clinics who did and did not use CRH during pre-implementation (October 2018-September 2019) and post-implementation (October 2019-February 2020) periods., Participants: Clinics completing ≥10 CRH visits per month for 2 consecutive months and propensity matched control clinics., Main Measures: Two measures of patient access (i.e., established, and new patient wait times) and one measure of clinic capacity (i.e., third next available appointment) were assessed. Clinics using CRH were 1:1 propensity score matched across clinical and demographic characteristics. Comparative interrupted time series models used linear mixed effects regression with random clinic-level intercepts and triple interaction (i.e., CRH use, pre- vs. post-implementation, and time) for trend and point estimations., Key Results: PC clinics using CRH (N = 79) were matched to clinics not using CRH (N = 79). In the 12-month pre-implementation, third next available time increased in CRH clinics (0.16 days/month; 95% CI = [0.07, 0.25]), and decreased in the 5 months post-implementation (-0.58 days/month; 95% CI = [-0.90, -0.27]). Post-implementation third next available time also decreased in control clinics (-0.48 days/month; 95% CI = [-0.81, -0.17]). Comparative differences remained non-significant. There were no statistical differences in established or new patient wait times by CRH user status, CRH implementation, or over time., Conclusions: In a national VHA telemedicine program developed to provide gap coverage for PC clinics, no wait time differences were observed between clinics using and not using CRH services. This hub-and-spoke telemedicine service is an effective model to provide gap coverage while maintaining access. Further investigation of quality and long-term access remains necessary., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: To evaluate the value of pre-treatment MRI-based radiomics in patients with hepatocellular carcinoma (HCC) for the prediction of response to Yttrium 90 radiation segmentectomy., Methods: This retrospective study included 154 patients (38 female; mean age 66.8 years) who underwent contrast-enhanced MRI prior to radiation segmentectomy. Radiomics features were manually extracted on volumes of interest on post-contrast T1-weighted images at the portal venous phase (PVP). Tumor-based response assessment was evaluated 6 months post-treatment using mRECIST. A logistic regression model was used to predict binary response outcome [complete response at 6 months with no-re-treatment (response group) against the rest (non-response group, including partial response, progressive disease, stable disease and complete response after re-treatment within 6 months after radiation segmentectomy) using baseline clinical parameters and radiomics features. We accessed the value of different sets of predictors using cross-validation technique. AUCs were compared using DeLong tests., Results: A total 168 HCCs (mean size 2.9 ± 1.7 cm) were analyzed in 154 patients. The response group consisted of 113 HCCs and the non-response group of 55 HCCs. Baseline clinical parameters (AUC 0.531; sensitivity, 0.781; specificity, 0.279; positive predictive value (PPV), 0.345; negative predictive value (NPV), 0.724) and AFP (AUC 0.632; sensitivity, 0.833; specificity, 0.466; PPV, 0.432; NPV, 0.851) showed poor performance for response prediction. The model using a combination of radiomics features and clinical parameters/AFP showed the best performance (AUC 0.736; sensitivity, 0.706; specificity, 0.662; PPV 0.504; NPV, 0.822), significantly better than the clinical model (p < 0.001) or AFP alone (p < 0.001)., Conclusion: The combination of radiomics features from pre-treatment MRI with clinical parameters and AFP showed fair performance for predicting HCC response to radiation segmentectomy, better than that of AFP. These results need further validation., (© 2024. The Author(s).)

Introduction: Cardiac implantable electronic device (CIED) functions are susceptible to electromagnetic interference (EMI) from electromagnetic fields (EMF). Data on EMI risks from new-generation electronic appliances (EA) are limited., Objective: We performed a systematic literature review on the mechanisms of EMI, current evidence, and recently published trials evaluating the effect of EMF on CIEDs from electric vehicles (EV), smartphone, and smartwatch technology and summarize its safety data., Methods: Electronic databases, including PubMed and EMBASE, were searched for in vivo studies evaluating EMF strength and incidence between CIEDs and commercial EVs, new-generation smartphones, and new-generation smartwatches., Results: A total of ten studies (three on EVs, five on smartphones, one on smartphones, one on smartphones and smartwatches) were included in our systematic review. There was no report of EMI incidence associated with EVs or smartwatches. Magnet-containing smartphones (iPhone 12) can cause EMI when placed directly over CIEDs - thereby triggering the magnet mode; otherwise, no report of EMI was observed with other positions or smartphone models., Conclusion: Current evidence suggests CIED recipients are safe from general interaction with EVs/HEVs, smartphones, and smartwatches. Strictly, results may only be applied to commercial brands or models tested in the published studies. There is limited data on EMI risk from EVs wireless charging and smartphones with MagSafe technology., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Indeterminate renal masses are increasingly incidentally found on cross-sectional imaging. 99m Tc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) scans can be used to identify oncocytomas and oncocytic renal neoplasms, including a subset of chromophobe renal cell carcinomas (chRCCs), which are viewed as false-positive., Procedure: Patients imaged with renal sestamibi scans between 2014 and 2023 were reviewed. Those patients with solitary tumors that were originally classified as chRCC were included in the analysis. Imaging with SPECT/CT from the liver dome down had been carried out 75 min after the administration of 925 MBq of 99m Tc-sestamibi. All available H&E and immunostained slides were re-reviewed and classified according to WHO 2022 criteria. Confirmatory immunohistochemical stains were performed in tumors considered morphologically suspicious for non-chRCC entities., Result: A total of 18 patients with solitary tumors were included in the final analysis. 13/18 (72.2%) tumors in this cohort remained classified as chRCC, with 4/18 (22.2%) being eosinophilic-variant chRCC. The reclassified tumors (5/18 [27.8%]) included 2/18 (11.1%) low-grade oncocytic tumor (LOT), 1/18 (5.5%) eosinophilic vacuolated tumor (EVT), and 2/18 (11.1%) unclassified low-grade oncocytic neoplasms. As such, only 2/9 (22.2%) qualitatively "hot" tumors were chRCC other than eosinophilic-variant and only 1/9 (11.1%) "cold" tumors was a histology other than chRCC., Conclusion: Based on current histopathologic classification methods, it is likely that the "false-positive" rate of uptake on renal sestamibi scans with chRCC has been over-stated. Further study is warranted to better refine the optimal utility of renal sestamibi scans for non-invasive risk stratification of indeterminate renal masses., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Rapid adaptation to sudden changes in the environment is a hallmark of flexible human behaviour. Many computational, neuroimaging, and even clinical investigations studying this cognitive process have relied on a behavioural paradigm known as the predictive-inference task. However, the psychometric quality of this task has never been examined, leaving unanswered whether it is indeed suited to capture behavioural variation on a within- and between-subject level. Using a large-scale test-retest design (T1: N = 330; T2: N = 219), we assessed the internal (internal consistency) and temporal (test-retest reliability) stability of the task's most used measures. We show that the main measures capturing flexible belief and behavioural adaptation yield good internal consistency and overall satisfying test-retest reliability. However, some more complex markers of flexible behaviour show lower psychometric quality. Our findings have implications for the large corpus of previous studies using this task and provide clear guidance as to which measures should and should not be used in future studies., (© 2024. The Author(s).)

Background: Secondary adrenal insufficiency (SAI) may occur in patients after unilateral adrenalectomy for adrenal-dependent hypercortisolism (HC) or primary aldosteronism (PA). This study aimed to assess whether postoperative day (POD) 1 basal cortisol was predictive of an abnormal cosyntropin stimulation test (CST) result and the need for glucocorticoid replacement (GR)., Methods: A retrospective review of consecutive patients who underwent unilateral adrenalectomy for HC, PA, or both between September 2014 and September 2022 was performed. On POD1, CST was performed for all the patients with HC, and before 2021 for all the patients with PA. The patients with an abnormal CST result were deemed at risk of SAI and discharged with GR. Receiver operating characteristic (ROC) curves were generated to evaluate the sensitivity (SN) and specificity (SP) of basal cortisol thresholds to predict an abnormal CST result., Results: The patients underwent unilateral adrenalectomy for overt hypercortisolism (OH; n = 42), mild autonomous cortisol excess (MACE; n = 70), mixed PA/HC (n = 22), or PA (n = 73). On POD1, CST was performed for 152 patients (93% OH, 96% MACE,73% PA/HC, 41% PA), and 80 patients (53%) had SAI (67% OH, 55% MACE, 44% PA/HC, 33% PA). The SN and SP of a basal cortisol level of 10 µg/dL or lower to predict an abnormal CST were respectively 92% and 77% for OH, 94% and 73% for MACE, 100% and 85% for PA, and 100% and 67% for PA/HC. The optimal basal cortisol level for predicting an abnormal CST for patients with PA or PA/HC was 5 µg/dL or lower (SN/SP, 100%)., Conclusions: After unilateral adrenalectomy for HC, PA, or mixed PA/HC, POD1 CST improved identification of patients at risk for SAI compared with basal cortisol levels alone. The authors recommend that POD1 CST be performed to determine the risk for SAI and the need for postoperative GR after unilateral adrenalectomy for patients with HC., (© 2024. Society of Surgical Oncology.)

Background: Roughly one in six patients receiving conventional transvenous pacemaker systems experience significant complications within 1 year of implant, mainly due to the transvenous lead and subcutaneous pocket. A new helix-fixation single-chamber ventricular leadless pacemaker (LP) system capable of pre-deployment exploratory electrical mapping is commercially available. Such an LP may mitigate complications while streamlining the implantation. In this study, the initial real-world implant experience of the helix-fixation LP was evaluated following its commercial release., Methods: In patients indicated for single-chamber right ventricular pacing, helix-fixation Aveir VR LPs (Abbott, Abbott Park, IL) were implanted using the dedicated loading tool, introducer, and delivery catheter. Implant procedural characteristics, electrical parameters, and any 30-day procedure-related adverse events of consecutive implant attempts were retrospectively evaluated., Results: A total of 167 patients with Class I indication for permanent pacing received implants in four North American centers (57% male, 70 years old). Pre-fixation electrical mapping of potential sites allowed repositioning to be avoided in 95.7% of patients. Median [interquartile range] LP procedure and fluoroscopy durations were 25.5 min [20.0, 35.0] and 5.7 min [4.0, 9.2], respectively. Pacing capture threshold, sensed R-wave amplitude, and impedance were 0.8 V [0.5, 1.3], 9.0 mV [6.0, 12.0], and 705 Ω [550, 910], respectively. Implantation was successful in 98.8% of patients, with 98.2% free from acute adverse events., Conclusions: The initial, real-world experience of the helix-fixation ventricular leadless pacemaker demonstrated safe and efficient implantation with minimal repositioning, viable electrical metrics, and limited acute complications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Large Language Models (LLMs) provide clinical guidance with inconsistent accuracy due to limitations with their training dataset. LLMs are "teachable" through customization. We compared the ability of the generic ChatGPT-4 model and a customized version of ChatGPT-4 to provide recommendations for the surgical management of gastroesophageal reflux disease (GERD) to both surgeons and patients., Methods: Sixty patient cases were developed using eligibility criteria from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) & United European Gastroenterology (UEG)-European Association of Endoscopic. Surgery (EAES) guidelines for the surgical management of GERD. Standardized prompts were engineered for physicians as the end-user, with separate layperson prompts for patients. A customized GPT was developed to generate recommendations based on guidelines, called the GERD Tool for Surgery (GTS). Both the GTS and generic ChatGPT-4 were queried July 21st, 2024. Model performance was evaluated by comparing responses to SAGES & UEG-EAES guideline recommendations. Outcome data was presented using descriptive statistics including counts and percentages., Results: The GTS provided accurate recommendations for the surgical management of GERD for 60/60 (100.0%) surgeon inquiries and 40/40 (100.0%) patient inquiries based on guideline recommendations. The Generic ChatGPT-4 model generated accurate guidance for 40/60 (66.7%) surgeon inquiries and 19/40 (47.5%) patient inquiries. The GTS produced recommendations based on the 2021 SAGES & UEG-EAES guidelines on the surgical management of GERD, while the generic ChatGPT-4 model generated guidance without citing evidence to support its recommendations., Conclusion: ChatGPT-4 can be customized to overcome limitations with its training dataset to provide recommendations for the surgical management of GERD with reliable accuracy and consistency. The training of LLM models can be used to help integrate this efficient technology into the creation of robust and accurate information for both surgeons and patients. Prospective data is needed to assess its effectiveness in a pragmatic clinical environment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To evaluate radiomics features' reproducibility using inter-package/inter-observer measurement analysis in renal masses (RMs) based on MRI and to employ machine learning (ML) models for RM characterization., Methods: 32 Patients (23M/9F; age 61.8 ± 10.6 years) with RMs (25 renal cell carcinomas (RCC)/7 benign masses; mean size, 3.43 ± 1.73 cm) undergoing resection were prospectively recruited. All patients underwent 1.5 T MRI with T2-weighted (T2-WI), diffusion-weighted (DWI)/apparent diffusion coefficient (ADC), and pre-/post-contrast-enhanced T1-weighted imaging (T1-WI). RMs were manually segmented using volume of interest (VOI) on T2-WI, DWI/ADC, and T1-WI pre-/post-contrast imaging (1-min, 3-min post-injection) by two independent observers using two radiomics software packages for inter-package and inter-observer assessments of shape/histogram/texture features common to both packages (104 features; n = 26 patients). Intra-class correlation coefficients (ICCs) were calculated to assess inter-observer and inter-package reproducibility of radiomics measurements [good (ICC ≥ 0.8)/moderate (ICC = 0.5-0.8)/poor (ICC < 0.5)]. ML models were employed using reproducible features (between observers and packages, ICC > 0.8) to distinguish RCC from benign RM., Results: Inter-package comparisons demonstrated that radiomics features from T1-WI-post-contrast had the highest proportion of good/moderate ICCs (54.8-58.6% for T1-WI-1 min), while most features extracted from T2-WI, T1-WI-pre-contrast, and ADC exhibited poor ICCs. Inter-observer comparisons found that radiomics measurements from T1-WI pre/post-contrast and T2-WI had the greatest proportion of features with good/moderate ICCs (95.3-99.1% T1-WI-post-contrast 1-min), while ADC measurements yielded mostly poor ICCs. ML models generated an AUC of 0.71 [95% confidence interval = 0.67-0.75] for diagnosis of RCC vs. benign RM., Conclusion: Radiomics features extracted from T1-WI-post-contrast demonstrated greater inter-package and inter-observer reproducibility compared to ADC, with fair accuracy for distinguishing RCC from benign RM., Clinical Relevance: Knowledge of reproducibility of MRI radiomics features obtained on renal masses will aid in future study design and may enhance the diagnostic utility of radiomics models for renal mass characterization., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The safety and efficacy of CA for AF and left-sided atrial arrhythmias (AA) in patients with left atrial appendage occlusion (LAAO) devices are lacking., Methods: This is a single-center retrospective registry that included all patients with prior LAAO who underwent catheter ablation for AF or left-sided atrial arrhythmia from January 2020-January 2023. The primary outcomes were procedure-related complications, device-related complications, AA recurrence, and stroke., Results: A total of 30 patients with prior LAAO were included in the analysis (mean age 75.1 ± 7.1 years old, 50% male, mean CHA 2 DS 2 -VASc score 4 ± 1.6, 46.7% paroxysmal AF, 73.3% had prior AF ablation, mean time to ablation 475 ± 365 days). 93.3% (n = 28) and 6.6% (n = 2) patients had ablation for AF (46.7% paroxysmal, 36.7% persistent, 10% long-standing persistent) and left-sided atrial tachycardia, respectively. 16.7% (n = 5) patients underwent ablation along the left atrial appendage ostium, and 3.3% (n = 1) underwent Vein of Marshall alcohol ablation. There were 3 (10%) peri-procedural complications (1 access hematoma and two pericardial effusions requiring intervention-none related to left atrial appendage ostium or alcohol ablation). During the mean follow-up of 440 ± 379 days, 40% (n = 12) patients had AA recurrence (91.6% AF, 8.3% atrial tachycardia), of which five patients needed repeat ablation, and two patients were readmitted for heart failure. There was no stroke or any device-related complications, including new peri-device leaks or device-related thrombosis in patients who had follow-up imaging studies (n = 11, 36.7%)., Conclusion: Catheter ablation for AF (including VoM alcohol ablation) in patients with prior LAAO devices is feasible and safe with favorable outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

While robotic and laparoscopic surgeries are both minimally invasive in nature, they are intrinsically different approaches and it is critical to understand outcome differences between the two. Studies evaluating pain outcomes and opioid requirement differences between the robotic and laparoscopic colorectal resections are conflicting and often underpowered. In this retrospective, cohort study, we compare postoperative opioid requirements, reported as morphine milligram equivalents (MME), postoperative average and highest pain scores across postoperative days (POD) 0-5, and return to work in patients who underwent robotic versus laparoscopic colorectal resections. The sample size was selected based on power calculations. Daily pain scores and MME were used as outcomes in linear mixed effect models with unstructured covariance between time points. Propensity score weighting was used to adjust for imbalances. Patients in the robotic group required significantly less opioids as measured by MME on all postoperative days (p = 0.004), as well as lower average and highest daily pain scores for POD 0-5 (p = 0.02, and p = 0.006, respectively). In a linear mixed-effects model, robotic resections were associated with a decrease in average pain scores by 0.36 over time (p = 0.03) and 35 fewer MME requirements than the laparoscopic group (p = 0.0004). Patients in the robotic arm had earlier return to work (2.1 vs 3.8 days, p = 0.036). The robotic approach to colorectal resections is associated with significantly less postoperative pain, decreased opioid requirements, and earlier return to work when compared to laparoscopy, suggesting that the robotic platform provides important clinical advantages over the laparoscopic approach., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined., Objective: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population., Methods: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics., Results: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05)., Conclusions: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin., (© 2024. Society of Surgical Oncology.)