Citations

Background Large vessel occlusion (LVO) stroke is associated with a high risk of permanent disability. There are no reliable tools providing periprocedural information on clot characteristics, such as composition and length, that may impact first pass effect, which has been shown to improve functional outcomes. In the first study of a novel technology, we evaluated whether the Clotild Smart Guidewire System (Clotild), an impedance-based device, can provide in situ information on clot characteristics during a mechanical thrombectomy procedure. Methods This is the first-in-human, international, multicentric, single-arm trial involving LVO stroke patients. Of 45 enrolled subjects, 41 constituted the safety population; 39 was the per protocol population, of which 26 subjects with complete impedance data comprised the performance population. The latter was divided into development (11 subjects) and validation (15 subjects) populations for prediction model development and assessment. The safety endpoint assessed Clotild-related intracranial vessel perforation/dissection. Performance endpoints evaluated Clotild’s ability to perform classification of impedance measurements distinguishing substantial versus negligible local content in red blood cells (RBCs) and platelets, to detect the arterial wall and the distal end of the clot. Results The safety endpoint was met in all subjects. Performance analysis comparing the agreement between Clotild’s output and impedance experts’ readings showed an area under the receiver operating characteristic curve (AUC) of 0.97 (95% CI 0.93 to 0.99) for RBC, and 0.94 (95% CI 0.89 to 0.98) for platelet clot composition. Regarding detection, Clotild’s performance showed an AUC of 0.69 (95% CI 0.59 to 0.77) for the arterial wall, and 0.83 (95% CI 0.59 to 1.00) for the distal end of the clot. Conclusions Clotild was proven safe to acquire impedance data and to provide information on in situ clot characteristics in large vessel occlusions.

Abstract Background Coccidioidomycosis is the most prevalent endemic mycosis in the United States. Diagnosis of coccidioidomycosis can be challenging due to limitations of conventional diagnostics. Detection of fungal plasma cell-free DNA (cfDNA) is a novel noninvasive testing modality for the diagnosis of invasive fungal disease. In this study, we characterized the performance of Coccidioides plasma cfDNA polymerase chain reaction (PCR). Methods A retrospective study was conducted in patients with suspected coccidioidomycosis who underwent plasma cfDNA PCR testing and conventional fungal testing for Coccidioides immitis and Coccidioides posadasii. Patients were categorized per the EORTC/MSGERC case definitions as proven or probable for sensitivity analyses and no coccidioidomycosis for specificity analyses. Results Overall, 362 plasma samples from unique patients were included in this study. The overall sensitivity, specificity, and positive- and negative-predictive values of Coccidioides plasma cfDNA PCR at 0.04% prevalence were 57.5% (27/47; 95% CI, 42.2%–71.7%), 100% (315/315; 95% CI, 98.8%–100%), 100% (95% CI, 87.2%–100%), and 100% (95% CI, 100%–100%), respectively. The sensitivity was 33.3% (2/6; 95% CI, 4.3%–77.7%) in patients with pulmonary focal disease, 66.7% (14/21; 95% CI, 43.0%–85.4%; P≥.05) in patients with pulmonary multifocal disease, and 52.6% (10/19; 95% CI, 39.6%–77.9%; P≥.05) in patients with disseminated coccidioidomycosis. In patients with concurrent antigen results, the sensitivity of cfDNA PCR was 58.3% (14/24; 95% CI, 39.6%–77.9%) compared with 37.5% (9/24; 95% CI, 18.8%–59.4%; P≥.05) for antigen. Conclusions Coccidioides plasma cfDNA PCR is modestly sensitive but highly specific, which can be useful for rapid and noninvasive diagnosis of coccidioidomycosis.

Abstract Aims Mitral valve prolapse (MVP) is a common valvular disorder associated with ventricular arrhythmias (VAs) in a subgroup of patients, known as arrhythmic MVP (AMVP). Arrhythmic MVP patients with malignant VAs typically receive an implantable cardioverter-defibrillator (ICD) for secondary prevention. However, data regarding the incidence of appropriate ICD therapy and the type of arrhythmia recurrence in this population remain scarce. This study aimed to evaluate the incidence of appropriate ICD therapies and type of arrhythmia recurrence in AMVP patients with an ICD implanted for secondary prevention. Methods and results A systematic literature search was conducted in PubMed/MEDLINE and EMBASE databases until January 2025. Studies reporting the incidence of appropriate ICD therapy in AMVP patients were included. A total of 9 studies met the inclusion criteria, resulting in 166 AMVP patients with ICDs for secondary prevention. The mean age was 41.8 years, with 55.8% of patients being female. Over a weighted mean follow-up of 4.9 ± 3.1 years, 34.9% [95% confidence interval (CI): 28.1–42.5] of the patients experienced recurrence of VA. The pooled incidence of appropriate ICD therapies during follow-up was 8.1 per 100 person-years (95% CI: 5.6–10.5, I2: 11.7%). Regarding the type of arrhythmic recurrence, the majority of arrhythmias (53.8%, 95% CI: 44.3–63.0%) were in the form of ventricular fibrillation or polymorphic ventricular tachycardia (VT), while the remaining arrhythmias were reported as monomorphic VT. Among 67 ventricular arrhythmic episodes reported in 7 studies with available data, 65 required shock therapy, corresponding to a shock proportion of 97.0% (95% CI: 89.6–99.6%). Conclusion Arrhythmic MVP patients with ICDs for secondary prevention exhibit a high risk of recurrent arrhythmias, with recurrences in the form of polymorphic VA occurring in more than half of the cases. PROSPERO registration number: CRD42024588610

Abstract Background Postoperative spinal implant infections (PSIIs) are a serious complication of instrumented spinal fusion. Although debridement with implant retention is standard for early infection, the optimal duration of antimicrobial therapy remains uncertain. Methods We conducted a multicenter retrospective cohort study across 10 US academic centers, including adults with early PSII (≤90 days after fusion surgery) from 2017 to 2021. We excluded patients who experienced treatment failure within 6 weeks of debridement. The primary outcome was treatment failure. Antibiotic therapy effect was analyzed as a time-varying exposure using adjusted Cox proportional hazards models. Secondary analyses included 12-week landmark and clone-censor-weighted models to compare durations ≤ 12 weeks versus >12 weeks. Results A total of 116 patients out of 499 (23.2%) experienced treatment failure during a median follow-up of 3.2 years. Among patients who remain failure-free 6 weeks from debridement, being on antibiotics was not associated with treatment failure (adjusted hazard ratio [aHR] 0.71; 95% CI .48–1.07; P = .10). In a 12-week landmark analysis limited to 359 patients who were not on indefinite suppressive antibiotic therapy, treatment durations > 12 weeks did not significantly reduce the risk of failure (aHR 1.01; 95% CI .62–1.64; P = .99). Results were consistent in the clone-censor-weight sensitivity analysis (aHR 0.85; 95% CI .62–1.16; P = .30). Conclusions Prolonged antibiotic therapy was not associated with improved outcomes in early PSII managed with debridement and implant retention. These results support shorter, individualized antibiotic courses in patients with adequate surgical source control.

Abstract Summary A retrospective cohort study of 113,729 IBD patients with low cardiovascular (CV) risk using the US National TriNetX database. Anti-TNF and anti-integrin therapies were linked to reduced major adverse cardiovascular events (MACE), while JAK inhibitors showed no increased risk. Background Due to underlying chronic inflammation, inflammatory bowel disease (IBD) is associated with an increased risk of major adverse cardiovascular events (MACE). There is limited data on the role of cardiovascular (CV) risk factors and IBD medications on MACE. We aim to determine the association between MACE and IBD medications in a large national cohort of IBD patients with low baseline CV risk. Methods We conducted a retrospective cohort study between January 1, 2015—November 15, 2023 using the TriNetX database. Using logistic regression analysis, IBD patients exposed to biologics and small molecules were assessed for outcomes of individual and composite MACE [myocardial infarction (MI), ischemic stroke, percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG)]. Outcomes were adjusted for demographics, non-advanced IBD therapies, statin use, CV risk factors, and prior history of coronary artery disease (CAD). Results We identified 113,729 IBD patients with an average age of 42 years and low prevalence of CV risk factors (5-6%). Anti-TNF therapy was associated with a statistically significant decreased risk of composite MACE [adjusted OR (aOR) 0.795, 95% CI 0.670-0.930, p = 0.005] and PCI/CABG [aOR 0.56, 95% CI 0.274-0.562, p = 0.002] and anti-integrin therapy was associated with a decreased risk of composite MACE [aOR 0.76, 95% CI 0.580-0.980, p = 0.035]. Anti-IL12/23 and JAK inhibitors showed no increased risk of MACE. Conclusion In a cohort of young IBD patients with low CV risk, use of anti-TNF and anti-integrins is associated with a decreased risk of MACE and there was no increased risk of MACE with JAK inhibitors.

Abstract Minimal residual disease (MRD) has been endorsed by the FDA Oncology Drugs Advisory Committee as an endpoint for accelerated approval in multiple myeloma based on individual patient data collected from randomized trials. However, emerging data from recent trials were not included. A novel artificial intelligence (AI)–assisted framework is proposed, which automates information identification and extraction, providing up-to-date analyses that confirm moderate trial-level and strong individual patient–level associations between MRD− rates at suspected complete response (MRD-CR) and survival endpoints in multiple myeloma. Specifically, this study utilized an AI-assisted framework that identifies relevant studies and filters critical information to analyze published data via 2 independent objectives. First, we examined the trial-level association using the coefficients of determination (R2) and its 95% confidence intervals (CI) based on published statistics of treatment effects on MRD and various endpoints. Next, we generated synthetic individual patient data with covariates through AI-curated tools to estimate the individual-level association. The AI tool searched for eligible randomized clinical trials (RCT). A total of 20 two-arm comparisons from 19 RCTs were analyzed. Trial-level analysis showed an R2 of 0.71 (95% CI, 0.52–0.89) pooling disease subpopulations. Furthermore, AI techniques were applied to create synthetic individual data, combining information extracted from Kaplan–Meier curves and subgroup analyses from published literatures. Using generated synthetic data, we estimated the individual-level correlation between MRD-CR rates and progression-free survival outcomes with a bivariate copula model and calculated a global odds ratio of 7.28 (95% CI, 5.60–8.95). Significance: (i) A novel AI-assisted framework is proposed, which automates information identification and extraction, providing rapid up-to-date analyses. (ii) Moderate trial-level and strong individual patient–level associations between MRD and various clinical endpoints in multiple myeloma are confirmed.

Abstract Background Osteoarthritis is a leading cause of disability worldwide, and cell‐based treatments including adipose‐derived and bone marrow aspirate have been sought by the lay and medical community as treatment options. Objective To perform a scoping review of published literature on cell‐based injections allowed by the U.S. Food and Drug Administration for the treatment of osteoarthritis to synthesize existing evidence and identify research gaps for future evaluation. Methods A comprehensive search of five databases was executed from inception through January 2, 2025. Studies that met the inclusion criteria were original research studies written in English on Food and Drug Administration‐allowed cell‐based treatments in adults with osteoarthritis of any joint. Results The database search yielded 4257 unique records. After screening, 84 studies met the inclusion criteria, encompassing 9996 patients and a total of 10,508 procedures. The primary research study designs were cohort studies ( n = 62), focused on treatment of knee osteoarthritis ( n = 63), and described bone marrow aspirate ( n = 42) and adipose‐derived ( n = 42) treatments. Postprocedure monitoring ranged from 6 weeks to 5 years, with most studies ≤1 year ( n = 59). Patient‐reported outcomes were reported in 83 of 84 studies; few provided imaging outcomes including magnetic resonance imaging ( n = 9) or radiographs ( n = 2). Conclusion This review identified limited randomized controlled trials, limited studies outside the knee, limited description of cell‐based treatments, and treatment protocols, along with inconsistent patient‐reported outcomes limited to 1 year in most studies. We propose establishing reporting guidelines in research on cell‐based therapies.

ABSTRACT Background Platelet factor 4‐polyanion enzyme‐linked immunosorbent assays (ELISAs) are considered highly sensitive for diagnosing heparin‐induced thrombocytopenia (HIT), such that current practice guidelines recommend use of ELISA‐negative results to exclude HIT. Once HIT is ruled out, alternative, non‐heparin‐based anticoagulant treatments are ceased, and heparin reintroduction frequently occurs. Methods Antigen‐based and PF4‐dependent functional testing were used to study PF4/polyvinylsulfonate ELISA‐negative platelet‐activating antibodies in HIT‐suspected patients. Results Three patients with clinical presentations consistent with HIT tested negative in an ELISA using PF4‐polyvinylsulfonate (PF4/PVS), an antigenic target very commonly used for HIT antibody screening. All three patients demonstrated PF4‐dependent platelet activation in functional testing that was sensitive to blockade of platelet FcγRIIa receptors and inhibited by high concentrations of heparin, consistent with pathogenic HIT antibodies. Functional testing‐based screening of 500 ELISA‐negative patients identified three additional patients whose sera activated platelets in a PF4‐ and FcγRIIa‐dependent manner and had clinical histories consistent with HIT. Five of the six ELISA‐negative HIT patients were re‐exposed to heparin, which precipitated a decrease in platelet counts in all re‐exposed patients, and one patient developed a new thrombus. Conclusions Recognition of ELISA‐negative HIT is critical to avoid harm due to the cessation of alternative anticoagulation therapy and re‐exposure of these patients to heparin.

Abstract Introduction Professional identity formation in healthcare professions education (HPE) is a complex and often fraught process. Physicians and trainees experience identity struggles as they navigate their personal and professional development, along with the conflicting expectations, cultural norms and systemic pressures within the healthcare environment. Despite growing attention to these challenges, conceptual clarity around identity struggle remains limited. Method To advance theoretical understanding of identity struggle, we conducted a critical narrative review of identity theories from developmental psychology, social psychology and sociology. We selected three major theoretical traditions—Neo‐Eriksonian, symbolic interactionist and social identity theories—and analysed their conceptualizations of identity, identity development and identity struggle. We examined these diverse perspectives to inform research and educational practice on professional identity formation in HPE. Results Each theoretical tradition offers distinct insights into identity struggle. Neo‐Eriksonian theories emphasize exploration and commitment as central processes, framing struggle as developmental and potentially productive. Symbolic Interactionist theories highlight the role of socialization and identity dissonance, viewing struggle as emerging from tensions between personal agency and societal norms. Social Identity theories focus on group belonging and intergroup dynamics, conceptualizing struggle at both individual and socio‐contextual levels. We provide common critiques and limitations of each theoretical tradition. These perspectives illuminate varied mechanisms through which identity struggle manifests and evolves. Discussion This review underscores the multifaceted nature of identity struggle and the value of theoretical pluralism in understanding professional identity formation. Struggle is not inherently negative; rather, it can be a catalyst for growth when appropriately framed and supported. We propose how educators and researchers might use these theoretical lenses to design interventions that foster productive identity development and address systemic contributors to identity struggles. We invite scholars drawing on critical perspectives of power and structure to challenge and deepen the conversation on identity struggle in HPE.

ABSTRACT Large symptomatic splenic pseudocysts, though rare, should be considered in patients with persistent left upper abdominal pain as we report in our case. Imaging enables diagnosis, and laparoscopic spleen‐preserving cyst decompression and deroofing provide a safe, effective treatment, relieving symptoms while maintaining splenic function and avoiding the morbidity associated with splenectomy and its long‐term complications.