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Background Right ventricular (RV) maladaptation to elevated pulmonary afterload is the primary determinant of outcomes in pulmonary artery (PA) hypertension; however, the pathobiological mechanisms underlying RV decompensation remain poorly understood. Methods We performed global untargeted metabolomics on plasma from 55 patients who underwent gold‐standard RV‐PA coupling measurements using multibeat pressure volume loop assessment in a single‐center cohort and from 1027 patients with coupling surrogate measurements in a larger multicenter cohort, the PVDOMICS (Pulmonary Vascular Disease Phenomics) study. Age and sex‐adjusted linear regression was performed to identify associations between metabolites and coupling metrics. Additionally, we performed a metabolic flux analysis using gene expression data from RV tissue in an independent cohort of 32 patients. Partial least squares–discriminant analysis was used to identify metabolites and reactions characteristic of the decompensated RV. Results RV‐PA coupling was negatively associated with tricarboxylic acid (TCA) cycle intermediate levels. Specifically, plasma α‐ketoglutarate and fumarate were significantly associated with all coupling metrics in both cohorts. Metabolic flux analysis indicated that decompensated RVs exhibited aberrant TCA cycle activity, including reduced acetyl coenzyme A entry and increased lactate elimination, suggesting a shift from the TCA cycle toward glycolysis at the RV tissue level. Conclusions We identify an association between circulating TCA cycle intermediate levels and RV‐PA uncoupling in 2 independent cohorts, and dysregulated TCA cycle metabolism in decompensated PA hypertension RVs, suggesting that aberrant TCA cycle metabolism could represent a hallmark of RV maladaptation in PA hypertension. Further study of this pathway is warranted to develop novel biomarkers of RV function or RV‐targeted therapies.

Objectives Generative artificial intelligence (GAI) tools can enhance the quality and efficiency of medical research, but their improper use may result in plagiarism, academic fraud and unreliable findings. Transparent reporting of GAI use is essential, yet existing guidelines from journals and institutions are inconsistent, with no standardised principles. Design and setting International online Delphi study. Participants International experts in medicine and artificial intelligence. Main outcome measures The primary outcome measure is the consensus level of the Delphi expert panel on the items of inclusion criteria for GAMER (Rreporting guideline for the use of Generative Artificial intelligence tools in MEdical Research). Results The development process included a scoping review, two Delphi rounds and virtual meetings. 51 experts from 26 countries participated in the process (44 in the Delphi survey). The final checklist comprises nine reporting items: general declaration, GAI tool specifications, prompting techniques, tool’s role in the study, declaration of new GAI model(s) developed, artificial intelligence-assisted sections in the manuscript, content verification, data privacy and impact on conclusions. Conclusion GAMER provides universal and standardised guideline for GAI use in medical research, ensuring transparency, integrity and quality.

Abstract Introduction: Hemolytic uremic syndrome (HUS) is especially uncommon in adults and can manifest as devasting complications including severe acute kidney injury (AKI) and microangiopathic hemolytic anemia (MAHA). Transfusion-related acute lung injury (TRALI) is a rare complication of blood product transfusion that is characterized by the rapid development of noncardiogenic pulmonary edema. We present a rare case of HUS complicated by TRALI requiring mechanical ventilation. Case Description: A 41-year-old female farmer, who occasionally drank raw cow's milk, was admitted with abdominal pain and distension, bloody diarrhea, poor appetite, decreased urine output and fatigue. She was found to have MAHA and stage 3 AKI. Imaging demonstrated pancolitis and workup revealed Shiga toxin-producing E. coli, O157:H7 serotype which was consistent with a diagnosis of HUS. Tests for DIC, TTP and atypical HUS were negative. She was not a candidate for dialysis, plasma exchange or eculizumab. With supportive measures including 3 units of packed red blood cell (pRBC), her symptoms, renal function, and bicytopenia improved and she was discharged. Two days post-discharge, she presented to the ED for unilateral vision changes, left hemiparesis, and lower extremity tremor. After negative neurological evaluation, this was attributed to encephalopathy secondary to HUS. She received 1 unit of pRBCs for a hemoglobin of 6.8. Within 3 hours of transfusion, she developed acute respiratory distress requiring intubation and ICU transfer. CT chest angiogram was negative for pulmonary embolism but demonstrated diffuse bilateral lower lobe dependent consolidations concerning for TRALI (Figure 1). After diuresis, she was able to be extubated within 48 hours with return to her respiratory and neurologic baselines soon after. Discussion: The pathophysiology of TRALI involves neutrophil sequestration and priming in the pulmonary vasculature with subsequent neutrophil activation by donor blood product factors where active infection is a known risk factor. Active HUS likely contributed to neutrophil priming through endothelial damage and systemic inflammation, predisposing this patient to TRALI. There are few reports of similar cases in the literature. TRALI can be subdivided into type I and type II; type I has no risk factors for acute respiratory distress syndrome (ARDS) while type II does. TRALI must also be distinguished from ARDS and transfusion-associated circulatory overload; these distinctions are predominantly made based on timing of respiratory symptom onset. This case highlights the importance of keeping TRALI in the differential for all patients with active or recent infection, including HUS, who develop acute-onset respiratory decompensation after transfusion.

Gastric cancer is the fifth leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improve survival, and enhance the quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing has had a significant impact on clinical practice and patient care. Targeted therapies have demonstrated encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. This selection from the NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer highlights recommendations for biomarker testing and discusses updates for the treatment of advanced disease, including peritoneal carcinoma as only disease and unresectable locally advanced, recurrent, or metastatic disease.

Abstract Motion of the visual field can alter postural sway and cause illusions of self-motion. The relative perceptual sensitivity of self-motion versus visual field motion induced by virtual reality (VR) stimulation and whether observable sway differs based on perceptual task is unknown. Methods to quantify sway perception while concurrently measuring sway do not exist. We measured head sway and motion perception (self or world) in healthy adults who stood with feet together wearing a VR headset while experiencing adaptive staircases of virtual sinusoidal pitch rotation about the ankle axis. In separate conditions of randomly ordered blocks, subjects were asked to indicate (yes/no) if the room moved (regardless of perceived postural sway) or if their postural sway increased (regardless of perceived room motion). Head sway area was measured by tracking movement of the VR headset. Yes/No responses were fit with psychometric curves to determine points of subjective equality (PSEs) for room motion and postural sway. PSEs were compared between conditions. Effects of motion perception (binary responses) on head sway area before, during, and after visual stimulation were examined. The mean PSE for room motion (0.42 degrees) was significantly lower than for postural sway (2.02 degrees) [t(1,18) = 4.4714, p = 0.00029]. Head sway area was significantly larger during (z = 11.53, p < 0.001) and after (z = 5.09, p < 0.001) visual stimulation only when participants perceived increased postural sway. Nearly 5-fold greater amplitudes of oscillating VR visual stimuli were required to induce perceptions of altered self-versus visual field motion. Observed head sway during visual motion was only linked to perceptual responses when participants focused internally on self-motion, not externally on room motion.

Abstract This multisociety infection prevention guidance document was developed for individuals and organizations that engage in sterilization or high-level disinfection (HLD). It was endorsed by SHEA, APIC, ASGE, IDSA, and SGNA. This guidance is based on a synthesis of published scientific evidence, theoretical rationale, current practices, practical considerations, writing group consensus, and consideration of potential harm when applicable. The supplementary material includes a summary of recommendations. The guidance provides an overview of the Spaulding Classification and considerations around manufacturers’ instructions for use (MIFUs). Its recommendations address: point-of-use treatment prior to sterilization or HLD, preparation of reusable medical devices at the location of processing, sterilization, and immediate use steam sterilization (IUSS), HLD of lumened and non-lumened devices, processing of reusable medical devices used with lubricating or defoaming agents, monitoring for effectiveness of processing, handling of devices after HLD, augments and alternatives to HLD, processing of investigational devices, tracking of reusable medical devices, and approaches to implementation.

PURPOSE Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We analyze the role of germline DICER1 status in outcomes of ovarian SLCT. METHODS Patients with SLCT were enrolled in the International Pleuropulmonary Blastoma/ DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and those with known germline DICER1 status were selected for analysis. RESULTS Of 162 patients with SLCT, 60% had a germline DICER1 pathogenic or likely pathogenic (P/LP) variant. The adjusted 3-year recurrence-free survival (RFS) was 87.2% (95% CI, 79.4 to 95.8) for patients with a germline DICER1 P/LP variant compared with 78.1% (95% CI, 66.4 to 91.9) for those without a germline DICER1 P/LP variant ( P = .043). The adjusted 3-year and 5-year overall survival (OS) was 93.9% (95% CI, 87.3 to 100.0) for those with a germline DICER1 P/LP variant compared with the 3-year OS of 91.3% (95% CI, 83.4 to 100.0) and the 5-year OS of 78.2% (95% CI, 63.8 to 95.9) for those without a germline DICER1 P/LP variant ( P = .021). Among patients with a germline DICER1 P/LP variant, the risk of a subsequent, nonrecurrent event was 36.2% (95% CI, 21.4 to 48.1) within 10 years. Previous/concurrent and subsequent neoplasms were rare among those without a germline DICER1 P/LP variant. CONCLUSION This cohort study of patients with SLCT demonstrated that those with germline DICER1 P/LP variants had superior RFS and OS even when adjusting for other prognostic factors. Beyond prognostic implications of a germline DICER1 P/LP variant, germline testing helps identify patients at risk of subsequent neoplasms, including metachronous SLCT.

AbstractBackgroundOvarian juvenile granulosa cell tumors (juvGCT) are rare sex cord‐stromal tumors that occur primarily in children and adolescents. This study summarizes the clinical presentation and outcomes of patients with juvGCT.MethodsPatients were enrolled in the International Ovarian and Testicular Stromal Tumor and/or International Pleuropulmonary Blastoma/DICER1 Registries. Available medical records were abstracted, and pathology was centrally reviewed. Surgical staging was classified using the 2014 International Federation of Gynecology and Obstetrics (FIGO) criteria.ResultsIn total, 70 patients with juvGCT enrolled and were diagnosed between 2001 and 2024; most patients (81%, 57 of 70) presented with FIGO stage I disease. Adjuvant chemotherapy was given in 30% (21 of 70); all regimens were platinum‐based. Three‐year event‐free survival among patients with stage IA tumors was 80.2% (95% confidence interval [CI], 62.4%–100.0%), IC1 was 87.4 (95% CI, 72.4%–100.0%), IC2‐IC3 was 63.6% (95% CI, 40.7%–99.5%), and II‐IV was 48% (95% CI, 24.6%–93.8%). Of the patients with recurrent juvGCT with known mitotic index (MI), all had MI greater than 19 mitoses per 10 high power fields (HPF) at diagnosis.ConclusionOutcomes were worse for patients with FIGO stage ≥IC2 disease and for tumors with >19 mitoses per 10 HPF. Given the prognostic significance of MI, the authors strongly recommend the assessment of MI for all juvGCTs. More information about tumor biology is critical to identify which patients may benefit from adjuvant chemotherapy and to facilitate the development of novel therapies.

Abstract The range of Babesia microti (Franca, 1910)-infected ticks is expanding, resulting in locally acquired human babesiosis cases occurring in new areas: Maryland (2009), the District of Columbia (2013), Virginia (2016), and West Virginia (2017). We collected host-seeking ticks from old fields, ecotones, forested habitats and animal hosts in Delaware, Maryland, and Virginia, 2010 to 2024. Ixodes scapularis Say, the tick vector of babesiosis, was captured in all 3 states. PCR revealed B. microti in 2.7% (36/1310) of I. scapularis, with site prevalence ranging from &lt;1% to 12.5% infected. The first B. microti-positive I. scapularis was collected in Northampton County, Virginia, 2012. Of the B. microti-infected ticks, 50% (18/36) were coinfected with Borrelia burgdorferi and one was triple-infected with B. microti, B. burgdorferi, and Anaplasma phagocytophilum. We collected Ixodes keiransi Beati, Nava, Venzal, and Guglielmone ticks from Delaware and Virginia. We found B. microti and B. burgdorferi in those from Virginia, and B. burgdorferi in ticks from a shrew in Delaware. To our knowledge, this is the first report of B. microti and B. burgdorferi-positive I. keiransi from Virginia, and the first report of B. burgdorferi-positive I. keiransi from Delaware. Ixodes keiransi ticks rarely bite humans but are involved in the maintenance and spread of pathogens when sympatric with I. scapularis. We tested a subset of both tick species for Babesia duncani; none were positive. Jurisdictions in the southern mid-Atlantic region should expect babesiosis cases, and Lyme disease and anaplasmosis coinfections, and healthcare providers should consider these tick-borne infections as part of the differential diagnosis.