Citations

AbstractThe characterization of single extracellular vesicle (EV) has been an emerging tool for the early detection of various diseases despite there being challenges regarding how to interpret data with different protocols or instruments. In this work, standard EV particles were characterized for single CD9+, single CD81+ or double CD9+/CD81+ tetraspanin molecule positivity with two single EV analytic technologies in order to optimize their EV sample preparation after antibody labelling and analysis methods: NanoImager for direct stochastic optical reconstruction microscopy (dSTORM)‐based EV imaging and characterization, and Flow NanoAnalyzer for flow‐based EV quantification and characterization. False positives from antibody aggregates were found during dSTORM‐based NanoImager imaging. Analysis of particle radius with lognormal fittings of probability density histogram enabled the removal of antibody aggregates and corrected EV quantification. Furthermore, different machine learning models were trained to differentiate antibody aggregates from EV particles and correct EV quantification with increased double CD9+/CD81+ population. With Flow NanoAnalyzer, EV samples were prepared with different dilution or fractionation methods, which increased the detection rate of CD9+/CD81+ EV population. Comparing the EV phenotype percentages measured by two instruments, differences in double positive and single positive particles existed after percentage correction, which might be due to the different detection limit of each instrument. Our study reveals that the characterization of individual EVs for tetraspanin positivity varies between two platforms—the NanoImager and the Flow NanoAnalyzer—depending on the EV sample preparation methods used after antibody labelling. Additionally, we applied machine learning models to correct for false positive particles identified in imaging‐based results by fitting size distribution data.

The NCCN Guidelines for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer provide multidisciplinary diagnostic workup, staging, and treatment recommendations for this disease. These NCCN Guidelines Insights detail how the evolution of the use of PARP inhibitors as maintenance and single-agent regimens for the treatment of ovarian cancer informed panel recommendations in the guidelines.

INTRODUCTION: Pouchitis and Crohn's-like disease of the pouch (CLDP) are common in patients who undergo ileal pouch anal anastomosis for ulcerative colitis. We conducted separate systematic reviews to evaluate the effectiveness of available interventions to prevent and treat pouchitis and CLDP. METHODS: Through systematic literature reviews, we identified studies that evaluated the effectiveness of probiotics, antibiotics, 5-aminosalicylates, nonsystemic oral corticosteroids, and advanced therapies for prevention and treatment of pouchitis and CLDP for meta-analysis. Primary outcomes were occurrence of pouchitis for pouchitis prevention and clinical response for pouchitis and CLDP treatment. We estimated the relative effectiveness of these interventions using the existing placebo response rates or hypothetical spontaneous improvement rates derived from clinical trials of pouchitis, ulcerative colitis, and Crohn's disease. RESULTS: Probiotics were effective for primary (relative risk [RR] 0.18; 95% confidence interval [CI] 0.05–0.62) and secondary prevention (RR 0.17; 95% CI 0.09–0.34) of pouchitis. Antibiotics were effective for treatment of acute and chronic pouchitis (12 cohorts; RR 1.67; 95% CI 1.34–2.01; response rate 65%; 95% CI 52–75) with ciprofloxacin and metronidazole-based regimens being more effective than rifaximin. Advanced therapies were effective for treatment of chronic antibiotic-refractory pouchitis (31 cohorts; RR 1.71; 95% CI 1.28–2.56; response rate 50%; 95% CI 43–57) and CLDP (10 cohorts; RR 2.49; 95% CI 1.87–3.73; response rate 74%; 95% CI 68–79) without significant difference between classes. DISCUSSION: Multiple medical interventions are effective for prevention and treatment of pouchitis and CLDP. Given the overall low quality of data, further research is needed to confirm these findings.

AbstractBackgroundThere is growing interest in global health (GH) among medical trainees in the United States. However, providing GH training opportunities at the fellowship level presents several challenges. Understanding of barriers and facilitators to implementing GH training is essential for addressing these challenges.MethodsWe developed a comprehensive survey of 65 Likert‐scale multiple‐choice and open‐ended questions to assess perspectives of pediatric hematology/oncology fellowships leaders on GH training. The survey was electronically distributed to program leaders at all ACGME‐accredited pediatric hematology/oncology fellowships programs, and data were summarized using descriptive analysis.ResultsOf 73 eligible programs, we had a 45.2% response rate with 27 complete and 6 partial responses. Respondents represented programs across the United States, including 19 (57.6%) affiliated with NCI‐Designated Cancer Centers. Fourteen programs (43.8%) currently offer GH training opportunities, whereas 18 programs expressed interest in future opportunities (15, 83.3%) or plan to offer them soon (3, 16.7%). Major barriers identified include competing training priorities (23, 82.1%), lack of faculty mentors in the division (23, 82.1%), and lack of dedicated institutional funding (20, 71.4%). Key facilitators include the interest and initiative of current fellows (27, 96.4%), dedicated institutional funding (26, 92.8%), and having established international partnerships (26, 92.8%).ConclusionsThe study reveals strong interest in GH training in pediatric hematology/oncology fellowships. Despite challenges such as competing priorities and a lack of mentors, significant facilitators include current fellows’ initiatives, dedicated funding, and established international partnerships. These insights can help shape future initiatives to incorporate GH into pediatric oncology/hematology fellowship training.

ABSTRACT Background Cognitive impairment (CI) is a critical complication in peritoneal dialysis (PD) patients, associated with decreased quality of life and increased hospitalization. Despite its significant impact, the prevalence, risk factors, and consequences of CI in PD patients are not well understood. We aimed to determine the prevalence, risk factors, and outcomes of CI in PD patients. Methods We performed systematic reviews in OVID Medline, Embase, and Cochrane databases until February 2024 to identify cross-sectional and cohort studies on prevalence of CI (identified by cognitive assessment scales) in PD patients. The Newcastle–Ottawa Scale was used to assess risk of bias. A pooled meta-analysis of CI prevalence in PD and a subgroup analysis comparing the risk of CI between PD and non-PD settings were performed using a random-effects model. Results A total of 19 studies were identified, involving 2882 PD patients. The pooled prevalence of CI in PD patients was 47.7% (95%CI: 35.8–59.9%). CI in patients undergoing PD appears to be associated with older age, female gender, lower levels of education, and is linked to higher rates of hospitalization and peritonitis, compared to those without CI. However, it is not associated with increased mortality. Compared to hemodialysis, PD showed a trend toward a lower risk of CI (OR 0.64, 95%CI 0.39–1.03; P = .068). Conclusion CI is highly prevalent and associated with several adverse clinical outcomes in PD patients. These findings could contribute to facilitate the development of screening and early intervention strategies to reduce the burden of disease in this population.

AbstractObjectiveThis study aimed to evaluate the diagnostic accuracy of dried blood spot (DBS) compared with conventional serum Aquaporin‐4‐IgG (AQP4‐IgG) testing.MethodsProspective multicenter diagnostic study was conducted between April 2018 and October 2023 across medical centers in the United States, Uganda, and the Republic of Guinea. Neuromyelitis optica spectrum disorder (NMOSD) patients and controls collected blood on filter paper cards along with concurrent serum samples. These samples underwent analysis using flow cytometric live‐cell‐based assays (CBA) and enzyme‐linked immunosorbent assay (ELISA) to determine AQP4 serostatus. The accuracy of AQP4‐IgG detection between DBS and serum (gold standard) was compared.ResultsAmong 150 participants (47 cases, 103 controls), there was a strong correlation between DBS and serum samples (Spearman's correlation coefficient of 0.82). The AUC was 0.97 (95% CI: 0.92–0.99). AQP4‐IgG detection through DBS showed 87.0% sensitivity (95% CI: 0.74–0.95) and 100% specificity (95% CI: 0.96–1.00) using CBA, and 65.2% sensitivity (95% CI: 0.43–0.84) and 95.2% specificity (95% CI: 0.76–0.99) using ELISA. Serum ELISA demonstrated 69.6% sensitivity (95% CI: 0.47–0.87) and 98.4% specificity (95% CI: 0.91–0.99). The stability of DBS in detecting AQP4‐IgG persisted over 24 months for most cases.InterpretationThe DBS represents a viable alternative for detecting AQP4‐IgG in resource‐limited settings to diagnose NMOSD, offering high sensitivity and specificity comparable to serum testing. Moreover, DBS has low shipping costs, is easy to administer, and is suitable for point‐of‐care testing.

Objective: Despite excellent functional outcomes after shoulder stabilization surgery, a substantial number of patients fail to return to sports (RTS) at the preinjury level. The psychological factors affecting RTS postsurgery have been underexplored. This scoping review aimed to identify and analyze potential psychological factors influencing the decision to RTS after shoulder stabilization surgery. Data Sources: We reviewed the EBSCOhost/SPORTDiscus, PubMed/Medline, Scopus, EMBASE, and Cochrane Library databases for studies on patients with anterior glenohumeral instability who underwent stabilization surgery. We included studies that reported on RTS and considered the psychological factors influencing the decision to return. Main Results: Our analysis comprised 21 articles involving 2073 patients. Psychological factors influencing RTS after surgery were categorized within the framework of transactional stress and coping model. Primary appraisal factors, such as fear of reinjury, kinesiophobia, and anxiety, emerged as significant influencers. In addition, we explored factors related to social support, self-determination, motivation, competing interests, and advanced age. Assessment tools were used to evaluate the psychological readiness for RTS. Conclusions: This scoping review identified fear of reinjury and kinesiophobia as important psychological barriers to returning to sports after shoulder stabilization surgery. The limited use of psychological assessment tools and lack of comparative studies have restricted robust conclusions. Level of Evidence: Level IV, Scoping review.