Citations

Abstract In phase 3 oncology clinical trials, identifying and understanding potential sources of differential censoring (DC), which describes censoring imbalance between treatment arms, in overall survival (OS) endpoints is vital to reduce bias and misinterpretation of OS benefit. Among 322 trials, 34 (11%) trials exhibited DC overrepresented in the control arm (DCC). Compared to trials without DC or those with DC overrepresented in the experimental arm (DCE), trials with DCC showed higher rates of OS benefit (56% vs. 32%; odds ratio [OR] = 2.26, 95% CI = 1.04 to 4.90; P = .04) and were associated with patient withdrawal (median 8.0% vs. 3.8%; P = .0002), lack of double blinding (15% vs. 48%, OR = 0.19, 95% CI = 0.06 to 0.56; P = .003), and better global quality of life in the experimental arm (32% vs. 13%, OR = 3.01, 95% CI = 1.26 to 7.19; P = .01). OS DCC is a prominent challenge that requires rigorous trial design and comprehensive patient and mortality follow-up to reduce bias in interpreting OS benefit.

Background and Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by multisystem involvement, including renal cysts, hepatic cysts, intracranial aneurysms, and aortic root dilatation and dissection. Though exceedingly rare, cervical artery dissections (CeAD) have been reported in association with ADPKD. The aim of this retrospective observational study is to investigate clinical features in patients with ADPKD that increase the probability of an associated CeAD diagnosis. Materials and Methods: The National Inpatient Sample from 2016 to 2020 was utilized to compare clinical features for patients with an ICD-10 code diagnosis of ADPKD, CeAD, and both ADPKD and CeAD. The Cochran–Armitage test and Chi-square test were utilized to assess clinical features or trends in ADPKD patients associated with a concurrent CeAD diagnosis. Results: Between 2016 and 2020, there were 224,065 people with ADPKD, 86,135 with CeAD and 155 with both (0.05%). The total cohort had a mean age of 56.74 years, with 47.26% female participants (p = 0.70), and was predominantly white (66.15%, p < 0.001). In patients with ADPKD, comorbid acute ischemic stroke (p < 0.001), transient ischemic attack (p < 0.001), aortic dissection (p < 0.001), coronary artery dissection (p < 0.001), subarachnoid hemorrhage (p < 0.001), coagulation defects (p = 0.002), and hypertension (p < 0.001) are risk factors associated with an increased probability of concomitant CeAD. Conclusions: CeAD in ADPKD patients is rare. In ADPKD patients, acute ischemic stroke, transient ischemic attack, aortic dissection, coronary artery dissection, subarachnoid hemorrhage, coagulation defects, and hypertension are risk factors of concomitant CeAD. Recognizing these factors can aid in the decision to screen for concomitant CeAD in patients with ADPKD.

Traumatic brain injury (TBI) is one of the leading causes of death and neurological disability worldwide. The search for biomarkers that indicate TBI severity and prognosis with greater accuracy is ongoing. This study aimed to evaluate the significance of several neuroinflammatory cytokines and chemokines, assessing their potential as biomarkers in pediatric TBI (pTBI). This was an exploratory analysis of inflammatory cytokines and chemokines measured in a subset of 26 children aged 0–18 years with TBI and 21 controls. TBI severity was determined by GCS. The functional outcome was measured via the GOS-E score at 6 weeks and 3, 6, 9, and 12 months post-injury. Serum samples were analyzed for ICAM-1, VCAM-1, SAA, CRP, IFN-g, IL-10, IL-12p70, IL-13, IL-1b, IL-2, IL-4, IL-6, IL-8, TNF-a, TNF-b, eotaxin, eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1a, MIP-1b and TARC. Levels of IL-6, IL-10, IL-13, IL-16, MDC, and GM-CSF were increased, and IFN-γ, IL-5, IL-8, and eotaxin-3 were decreased at enrollment when compared with controls. Elevated IL-6 and IL-10 at enrollment were associated with severe TBI (AUC of 1, p = 0.0002 and p = <0.0001, respectively). IL-6, IL-10, IL-16, and TNF-β at enrollment and IL-5 at 24 h were elevated in children with unfavorable outcomes, with an AUC > 0.8, suggesting biomarker potential. Our data indicate that several cytokines and chemokines measured after TBI may aid in the assessment of pTBI severity and prognosis. IL-6, IL-10, and IL-16 may show potential as biomarkers for pTBI severity and outcomes.

Background: Adeno-associated viruses (AAVs) are widely used vectors for in vivo gene therapy, but their standard storage at −80 °C limits deployment in regions lacking ultracold infrastructure. Strategies enabling stable AAV storage at higher temperatures are needed to support global distribution. Methods: Nine AAV serotypes were lyophilized in simple sucrose-based buffers. Post-lyophilization vector integrity was assessed by measuring in vitro transduction efficiency using a luciferase reporter in cell-based assays. Stability of selected serotypes (AAV2.5 and AAV6) was further evaluated over 8 weeks under varying storage temperatures. Results: Lyophilization in sucrose preserved transduction activity for all tested serotypes (AAV1, AAV2, AAV2.5, AAV3, AAV4, AAV5, AAV6, AAV8, AAV9, and AAVrh10). Notably, AAV2, AAV2.5, and AAV6 exhibited 3- to 6-fold increases in transduction, an effect attributable to the sucrose excipient rather than the lyophilization process itself. Long-term stability of lyophilized vectors varied by serotype, temperature, and vial-seal integrity. AAV6 retained full activity for at least 8 weeks when stored at 4 °C or −20 °C. Conclusions: AAV vectors can be effectively lyophilized in simple sucrose solutions, enabling storage at standard −20 °C freezer temperatures while maintaining functional activity. Optimization of lyophilization buffers and excipients may further extend AAV stability at higher temperatures, improving feasibility for global gene therapy deployment.

Background Artificial intelligence (AI)-generated text to video is emerging in medical education, but its effectiveness, accuracy and safety remain uncertain. We aimed to synthesise empirical studies evaluating these tools in learner or patient education. Methods A comprehensive search was conducted in MEDLINE/PubMed, Google Scholar, Scopus, Cochrane Review and Web of Science for studies published up to January 2025. Eligible studies evaluated AI-generated text to video for medical or patient education, reporting both quantitative and qualitative outcomes. Two reviewers screened and extracted data. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Out of 103 identified studies, five studies met the inclusion criteria: four evaluated patient education and one evaluated physician training. Clinical areas were ophthalmology (2/5), plastic surgery (1/5), dysphagia rehabilitation (1/5) and neurosurgical training (1/5). In ophthalmology, control materials outperformed AI-generated videos on image/script accuracy (p<0.005), with similar script-image alignment. In dysphagia rehabilitation, a randomised trial reported improvements in swallowing function and related outcomes with an AI-assisted video game intervention (p<0.001). A plastic surgery study reported greater user preference for a video avatar tool compared with a text chatbot (63.5% vs 28.1%). Across the reviewed studies, samples were small and CIs were rarely reported. Outcome measures were heterogeneous, and meta-analysis was not feasible. Conclusion AI-generated videos can enhance engagement or selected outcomes in certain contexts, yet concerns about accuracy and inconsistent measurement persist. Current evidence is sparse and mixed. Currently, these tools can complement, rather than replace, standard resources until non-inferiority is demonstrated for the prespecified primary outcomes. PROSPERO registration number CRD42025640042.

Background Bowel obstruction in the setting of peritoneal metastases is a complex clinical situation. Evidence for operative intervention in this setting remains unclear. This study aimed to compare outcomes between patients with bowel obstruction and peritoneal metastases who underwent operative intervention vs those who underwent conservative management. Methods This was a retrospective single center study of all patients that were consulted on by the Division of Colon and Rectal Surgery in the 6-year period between January 1st 2019 and December 31st 2024 for the management of bowel obstruction in the setting of peritoneal metastases. The study compared patients who underwent operative intervention vs those who underwent conservative management. The primary outcome measures were ability to tolerate solid food at discharge, median obstruction free survival, and median overall survival. Results A total of 100 patients were diagnosed with bowel obstruction in the setting of peritoneal carcinomatosis. 47 patients underwent operative intervention and 53 underwent non-operative management. Those who underwent operative intervention were more likely to tolerate solid food at discharge (78.72% vs 47.17%, P < 0.01) and had a longer median obstruction free survival (593 days vs 147 days, P = 0.01). No difference was identified in overall survival (133 days vs 99 days, P = 0.49). Conclusions Bowel obstruction in the setting of peritoneal metastases is a complex situation that requires a personalized and pragmatic approach for each patient. Selecting those who may benefit from operative intervention can be challenging, however, there are subsets of patients for whom surgical management may be offered with acceptable outcomes.

Background While it is clear that abnormal tau structures contribute to the clinical symptoms of Alzheimer's disease (AD), which of the many structural entities found in the AD brain underlie templated misfolding and progression of disease remains uncertain. However, their identification is crucial to target for more effective diagnostics and therapeutics. Objective To identify the most pathogenic tau species driving Alzheimer's disease progression. Methods We compared the biochemical and templated seeding properties of tau isolated from post-mortem brain tissue of patients with varying rates of clinical progression, categorized as rapid, slow, or typical, based on longitudinal decline in cognitive performance assessed by Clinical Dementia Rating Sum of Boxes scores. Sarkosyl-insoluble filamentous preparations were compared to aqueous-soluble preparations. Focusing on the aqueous-soluble proteins, we further characterized the most efficient seeding species using size-exclusion chromatography and quantifying oligomers using dot blot under both native and denaturing conditions. Results A rapidly progressive course corresponded to enhanced tau seeding behavior, with the strongest correlations observed in the aqueous-soluble fraction. Using size-exclusion chromatography, we demonstrated that the seeding activity of fractions containing oligomers, correlated most strongly with disease aggressiveness. Moreover, quantifying oligomers using dot blot under both native and denaturing conditions, we found that rapid progressors had higher levels of oligomeric tau, which was also more stable. Conclusions Aqueous-soluble oligomeric tau species may be an important driver of AD progression. Substantial heterogeneity was observed even in purified samples, suggesting that variations in tau conformers among patients may contribute to differences in clinical disease progression.

Abstract The comparative value of liposomal cytarabine/daunorubicin (CPX-351) versus venetoclax plus a hypomethylating agent (Ven-HMA) in the frontline treatment of older adults with primary ( de novo ) or secondary acute myeloid leukemia (AML) remains uncertain. In the current study, we retrospectively examined outcomes of 600 patients with newly diagnosed AML treated with CPX-351 (N = 112) or Ven-HMA (N = 488). AML subtypes included de novo (46%), post-myelodysplastic syndrome (MDS) (19%), post-myeloproliferative neoplasm (MPN) (12%), post-MDS/MPN (6%), therapy-related (17%) and AML with myelodysplasia-related genetic abnormalities (AML-MR; 46%). Patients receiving CPX-351 were younger (median 65 vs. 73 years; p < 0.01), predominantly female (50% vs. 38%; p = 0.02), more likely to have secondary AML (68% vs. 51%; p < 0.01), and less likely to harbor NPM1 MUT (5% vs. 12%; p = 0.02). Rates of complete response with or without count recovery (CR/CRi) were comparable between CPX-351 and Ven-HMA (55% vs. 60%; p = 0.30), including in AML-MR (60% vs. 63%; p = 0.70). Ven-HMA use was associated with fewer infectious complications (62% vs. 83%; p < 0.01) and yielded higher CR/CRi rates in males (60% vs. 45%; p = 0.04), de novo AML (68% vs. 50%; p = 0.03), and in the presence of STAG2 MUT (86% vs. 44%; p = 0.02), or CEBPA MUT (88% vs. 50%; p = 0.03). Overall survival censored for transplant, was similar (median 10 vs. 13 months; p = 0.90), with Ven-HMA being superior in post-MDS AML (median 12 vs. 7 months; p = 0.02) and CPX-351 in the presence of SF3B1 MUT (not reached vs. 14 months; p < 0.01). Our findings suggest that Ven-HMA is as effective and less toxic than CPX-351 in newly diagnosed AML, including AML-MR, despite selection of younger, fitter patients for CPX-351.

Background/Objective: The COVID-19 pandemic led to a widespread transition to online learning. Yet, it is unclear how this shift in learning format impacted school attendance in adolescents with chronic pain, a group that struggles with school absenteeism. This study compared school attendance and format (e.g., in-person, online) in patients with chronic pain attending an Intensive Interdisciplinary Pain Treatment Program (IIPT) before the pandemic to an age- and gender-matched sample of youth attending the program after the pandemic. Methods: Participants were 226 school aged adolescents (13–18 years; M age = 15.89, SD = 1.46) enrolled in an IIPT before and after the COVID-19 pandemic. Patients admitted before March 2020 (pre-pandemic group; n = 113) were compared to an age- and gender-matched group of patients who were admitted to the IIPT from November 2021 to November 2023 (post-pandemic group = 113). Upon admission to the program, participants completed validated measures of internalizing symptoms and functional disability. They also completed structured questions related to pain and school history. Results: Significantly more patients in the post-pandemic group were attending school through online and home-schooling options (p < 0.01). Youth who attended the IIPT after the pandemic missed fewer school days (p < 0.05) than those who attended before the pandemic. The groups did not differ in functional disability or internalizing symptoms. However, participants in the post-pandemic group who attended online school missed more school days (p < 0.01) and experienced greater functional disability (p < 0.05) than those who attended in person. Conclusions: The findings highlight how the COVID-19 pandemic may lead to sustained changes in the way adolescents with chronic pain attend school, with implications for increased functional disability and school dropout among this vulnerable population.