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Unpredictable Mechanical Mitral Valve Leaflet Motion in a Patient With Continuous-Flow LVAD
No full textBackground: Patients with a pre-existing mechanical mitral valve (MV) who undergo left ventricular assist device (LVAD) implantation pose unique challenges owing to interactions between the device and valve.
Case summary: A 56-year-old man with a history of mechanical MV replacement and multiple interventions underwent LVAD implantation. After LVAD, the mechanical MV exhibited dynamic changes of leaflet mobility, from both stuck open to both moving freely. Despite these abnormalities, there was no clinically significant mitral regurgitation or hemodynamic impact. The patient was managed without surgery or thrombolytics and experienced no adverse clinical consequences related to mechanical MV dysfunction.
Discussion: This case highlights the dynamic behavior of a mechanical MV after LVAD implantation, with variable leaflet positioning without significant mitral regurgitation or thromboembolic complications.
Take-home messages: The interaction between LVADs and mechanical valves can result in unexpected alterations in valve function and intracardiac hemodynamics, underscoring the need for individualized care. In select cases, conservative management may be appropriate
Artificial intelligence in pancreatic intraductal papillary mucinous neoplasm imaging: A systematic review
No full textBased on the Fukuoka and Kyoto international consensus guidelines, the current clinical management of intraductal papillary mucinous neoplasm (IPMN) largely depends on imaging features. While these criteria are highly sensitive in detecting high-risk IPMN, they lack specificity, resulting in surgical overtreatment. Artificial Intelligence (AI)-based medical image analysis has the potential to augment the clinical management of IPMNs by improving diagnostic accuracy. Based on a systematic review of the academic literature on AI in IPMN imaging, 1041 publications were identified of which 25 published studies were included in the analysis. The studies were stratified based on prediction target, underlying data type and imaging modality, patient cohort size, and stage of clinical translation and were subsequently analyzed to identify trends and gaps in the field. Research on AI in IPMN imaging has been increasing in recent years. The majority of studies utilized CT imaging to train computational models. Most studies presented computational models developed on single-center datasets (n = 11,44%) and included less than 250 patients (n = 18,72%). Methodologically, convolutional neural network (CNN)-based algorithms were most commonly used. Thematically, most studies reported models augmenting differential diagnosis (n = 9,36%) or risk stratification (n = 10,40%) rather than IPMN detection (n = 5,20%) or IPMN segmentation (n = 2,8%). This systematic review provides a comprehensive overview of the research landscape of AI in IPMN imaging. Computational models have potential to enhance the accurate and precise stratification of patients with IPMN. Multicenter collaboration and datasets comprising various modalities are necessary to fully utilize this potential, alongside concerted efforts towards clinical translation
Higher intensity walking training in individuals with chronic motor incomplete spinal cord injury: A randomized clinical trial
No full textBackground:
The amount of walking practice may influence locomotor recovery in individuals with motor incomplete spinal cord injury (iSCI), although the contributions of exercise intensity are not well established.
Objective:
The purpose of this blinded-assessor randomized trial was to determine the contributions of exercise intensity on locomotor outcomes in individuals > 6 months following iSCI.
Methods:
Ambulatory individuals post-iSCI with walking speeds 70% heart rate [HR] reserve or ratings of perceived exertion [RPE]≥15) or low-intensity training (LIT; <40% HR reserve; RPE≤13). Assessments were performed at baseline, post-training and at 3-month follow-up evaluation, with primary outcomes of fastest walking speeds over 10 m and during graded treadmill exercise tests, and secondary clinical and metabolic outcomes.
Results:
Of 65 participants screened, 53 were randomized to HIT (n=28) or LIT (n=25) and completed 1489/1590 (94%) planned training sessions. Peak HRs and RPEs were greater during HIT (both p<0.001). Changes in fastest gait speeds overground were not significantly different between HIT and LIT when using Bonferroni corrections [α=0.025; mean post-training differences: 0.11 m/s (95% CI: 0.04–0.17 m/s), p=0.031], although gains in peak treadmill speed were significant [mean differences: 0.25 m/s (0.15 to 0.34 m/s), p-<0.001]. Secondary outcomes of 6-minute walk test (p=0.002) and combined measures of peak metabolic capacity and efficiency (p<0.001) were also greater with HIT.
Conclusion:
Greater gains in peak treadmill speed, 6-min walk, and selected metabolic outcomes were observed with HIT vs LIT in individuals with iSCI
Cannabis Laws and Opioid Use Among Commercially Insured Patients With Cancer Diagnoses
No full textImportance: Pain is a prevalent cancer-related symptom, but limited research investigates whether cannabis is an effective analgesic for cancer pain.
Objective: To examine the association of medical and recreational cannabis dispensary availability on prescription opioid dispensing among commercially insured patients with cancer.
Design, setting, and participants: This cross-sectional study used synthetic control to investigate the association of cannabis dispensary openings with pain medication dispensing among patients with cancer. Data were extracted from Optum's deidentified Clinformatics Data Mart database from January 1, 2007, to December 31, 2020. The study population included patients aged 18 to 64 years with a cancer diagnosis and at least 6 months of continuous enrollment. Associations were estimated by age, race and ethnicity, and sex. Data were analyzed between December 2024 and February 2025.
Exposures: Exposures included indicators for whether a medical or recreational cannabis dispensary was open in each state-quarter.
Main outcomes and measures: The outcome measures for opioids prescriptions were (1) the rate of patients with a prescription per 10 000 patients, (2) the quarterly mean days' supply per prescription, and (3) the quarterly mean number of prescriptions per patient.
Results: The study included a mean (SD) of 3.05 (0.86) million patients annually across the US (mean [SD] age, 43.7 [9.6] years; mean [SD] 59.0% [0.32%] female). Medical cannabis dispensary openings were associated with significant reductions in all opioid outcomes. The rate of patients with cancer with opioid prescriptions changed by -41.07 per 10 000 (95% CI, -54.78 to -27.36 per 10 000; P < .001), the quarterly mean days' supply by -2.54 days (95% CI, -3.16 to -1.92 days; P < .001), and the mean number of prescriptions per patient by -0.099 (95% CI, -0.121 to -0.077; P < .001). Recreational dispensary openings were also associated with reductions in opioid outcomes, though estimated treatment effects were smaller. The rate of prescriptions changed by -20.63 per 10 000 (95% CI, -35.35 to -5.91 per 10 000; P = .049), the mean daily supply by -1.09 days supplied per prescription (95% CI, -1.72 to -0.46 days; P = .04), and the mean number of prescriptions per patient by -0.097 (95% CI, -0.134 to -0.060; P = .01).
Conclusions and relevance: This study's findings indicate cannabis may be a substitute for opioids in the management of cancer-related pain. However, further research directly observing cannabis use is needed to evaluate the efficacy of cannabis as a treatment for cancer-related pain
Ketamine’s Therapeutic Role in Substance Use Disorders: A Narrative Review
No full textInterest in ketamine as a novel treatment for substance use disorders (SUDs) has been increasing due to its N-methyl-D-aspartate (NMDA) glutamate receptor antagonism and mounting evidence that glutamate neurotransmission is involved in the pathogenesis of both depression and addictions. This narrative review provides an outline of clinical evidence reported in the literature from the 1970s to 2025 that examines the efficacy of ketamine for the treatment of SUDs, focusing primarily on randomized blinded controlled trials (RBCTs). Key cohort studies, retrospective studies, secondary analyses, case reports, and relevant basic neuroscience studies are reviewed to complement the more rigorous human controlled trial data. Thus far, ketamine has been tested in nine RBCTs targeting cocaine (three studies), alcohol (three studies), opioid use disorder (two studies), and nicotine (one study), suggesting efficacy for addiction in combination with psychotherapies, and often when doses produce subjectively reported mystical or psychedelic experiences. This review highlights promising preliminary evidence, and the need for more rigorous studies to elucidate the scope of drug addictions ketamine may target, its optimal dosing or route of administration, the importance of concurrent psychotherapies, professional supervision and safety monitoring, and which psychiatric comorbidities or contexts may contraindicate its use for SUDs
The intrinsic expression of NLRP3 in Th17 cells promotes their protumor activity and conversion into Tregs
No full textTh17 cells can perform either regulatory or inflammatory functions depending on the cytokine microenvironment. These plastic cells can transdifferentiate into Tregs during inflammation resolution, in allogenic heart transplantation models, or in cancer through mechanisms that remain poorly understood. Here, we demonstrated that NLRP3 expression in Th17 cells is essential for maintaining their immunosuppressive functions through an inflammasome-independent mechanism. In the absence of NLRP3, Th17 cells produce more inflammatory cytokines (IFNγ, Granzyme B, TNFα) and exhibit reduced immunosuppressive activity toward CD8+ cells. Moreover, the capacity of NLRP3-deficient Th17 cells to transdifferentiate into Treg-like cells is lost. Mechanistically, NLRP3 in Th17 cells interacts with the TGF-β receptor, enabling SMAD3 phosphorylation and thereby facilitating the acquisition of immunosuppressive functions. Consequently, the absence of NLRP3 expression in Th17 cells from tumor-bearing mice enhances CD8 + T-cell effectiveness, ultimately inhibiting tumor growth
Cognitive Trajectories in Parkinson's Disease and Lewy Body Disease
No full textBackground:
Parkinson's disease (PD) is the second most common neurodegenerative illness after Alzheimer's disease. Dementia with Lewy bodies (DLB) shares clinical and neuropathological features with PD and requires cognitive impairment to meet clinical criteria. Although cognitive impairment is common in both PD and DLB, rates of cognitive decline can vary markedly, and associated predictors are poorly understood. This study aimed to characterize the effects of risk factors‐ particularly APOE and sex‐ on the trajectories of cognitive factor scores for memory, executive function, and language in persons with PD and DLB.
Methods:
Using National Alzheimer's Coordinating Center data, we identified participants with PD or DLB with a cognitively normal neuropsychological baseline and at least two total cognitive assessments. Factor scores were previously derived for language, memory and executive function. We fit three linear mixed effects models, one each for memory, executive function, and language factor scores. Predictors in these models included sex, race, baseline age, APOE genotype (1‐2 vs. 0 ε4 alleles), education, time from baseline, and interactions between sex and time and APOE and time. We also included a linear spline at the first diagnosis of mild cognitive impairment (MCI) or dementia (some participants remained cognitively normal throughout).
Results:
494 participants with PD or DLB [193 (39.1%) female, mean baseline age: 71 (8.7 SD), 118 (23.9%) with 1‐2 ε4 alleles] were included. In the memory model, there was a faster rate of cognitive decline post‐MCI diagnosis (0.04 SD/yr; p = 0.001). This post‐MCI effect was significantly modified by APOE genotype (p = 0.01) but not by sex (p = 0.07). Post‐MCI diagnosis, people with 1‐2 APOE ε4 alleles declined 0.05 SD/year faster than people with 0 ε4 alleles. In the executive function and language models there was a faster rate of cognitive decline post‐MCI diagnosis (0.03 SD/yr, p = 0.02; 0.05 SD/yr, p <0.001) but these effects were not modified by APOE.
Conclusions:
APOE genotype was associated with an increased rate of memory decline, but not executive function or language decline in participants with PD/DLB after an MCI diagnosis. This factor may be useful for prognostication and aid in a personalized medicine approach to PD/DLB
Do Donor-Advised Funds Respond to Nonprofit Financial Distress? Insights from the 2022 Economic Slowdown
No full textCCS Fundraisin
Analysis of benign neoplasms of the rete testis formerly termed “Sertoliform cystadenomas” demonstrates that they are not Sertoli cell tumours with intra‐rete growth
No full textAims: Benign tumours of the rete testis include mostly cystadenomas and adenomas. A subset with tubular or tubulopapillary architecture shows morphological similarities to Sertoli cell tumours; these neoplasms were previously termed "Sertoliform cystadenomas of the rete testis". In the most recent WHO classification, they have been interpreted as Sertoli cell tumours, not otherwise specified (NOS), with pure intra-rete growth, and therefore excluded as an entity. The remaining cystadenomas of the rete testis vaguely resemble tumours of Mullerian origin arising in the ovaries. In this study we analyse benign tumours of the rete testis, including a subset with Sertoliform features.
Methods and results: Benign neoplasms of the rete testis were identified through query of consultation and institutional files. Clinicopathologic data were collected, and available slides were reviewed. Cases were assessed using IHC and three separate DNA sequencing panels. Eleven tumours from patients 32-78 years old were evaluated. Four were classified as Sertoliform adenomas/cystadenomas, displaying tubulo-papillary or tubular/trabecular architecture; all of them were PAX8-positive and lacked nuclear beta-catenin expression. The remaining seven tumours were benign cystadenomas NOS. Genomic analysis was performed successfully in 10/11 tumours (including all Sertoliform adenomas/cystadenomas) and revealed no pathogenic variants in CTNNB1, KRAS, or BRAF.
Conclusion: Sertoliform cystadenomas of the rete testis differ from Sertoli cell tumours NOS, as evidenced by the absence of molecular markers characteristic of Sertoli cell tumours. The remaining benign cystadenomas lack molecular alterations seen in Mullerian tumors of the ovaries
Adoption of Health Information Technologies by Area Socioeconomic Deprivation Among US Hospitals
No full textImportance: Access to and quality of care vary substantially by area socioeconomic status. Expanding hospital health information technology (HIT) adoption may help reduce these disparities, given hospitals' central role in serving underserved populations.
Objective: To examine variations in US hospital adoption of telehealth and health information exchange (HIE) functionalities by hospital service area (HSA) socioeconomic deprivation.
Design, setting, and participants: This cross-sectional study links data from the 2018-2023 American Hospital Association Annual Survey and Information Technology Survey with HSA-level area deprivation index. Nonfederal acute care hospitals with complete data on HIT outcomes, comprising 16 646 observations for the telehealth outcomes and 9218 observations for the HIE outcomes across 6 years, were included. Data were analyzed from February 2024 to February 2025.
Exposures: HSA-level area deprivation index in quartiles.
Main outcomes and measures: Hospital adoption of treatment-stage telehealth and postdischarge telehealth services and HIE infrastructure supporting electronic data query and availability. Descriptive, regression, and Blinder-Oaxaca decomposition analyses and visualized time trends in hospital HIT adoption were used in analyses.
Results: This study included 16 646 hospital-level observations and 9218 observations for health information exchange functionalities. Hospitals in the most socioeconomically deprived HSAs were significantly less likely to adopt HIT compared with those in the least deprived areas (treatment-stage telehealth: marginal effect [ME], -0.03; 95% CI, -0.06 to -0.01; postdischarge telehealth: ME, -0.03; 95% CI, -0.07 to 0.01; electronic data query capability: ME, -0.03; 95% CI, -0.06 to -0.01; electronic data availability: ME, -0.06; 95% CI, -0.11 to -0.01). Year fixed effects indicated significant increases in HIT adoption from 2018 to 2023, regardless of HSA deprivation level. Decomposition analyses showed that differences in hospital bed size, urban/rural location, and accountable care organization participation explained a substantial portion of the disparities by HSA deprivation.
Conclusions and relevance: In this study, hospitals in more socioeconomically disadvantaged HSAs remained likely to adopt telehealth and HIE functionalities. Nevertheless, HIT adoption has grown steadily over time. Accountable care organization participation may support HIT infrastructure and help reduce geographic disparities in adoption and access to care