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Background Randomized clinical trials (RCTs) are considered the gold standard for evaluating the efficacy of healthcare interventions. However, conflicts of interest (COIs) can compromise the scientific integrity in these trials. This study characterized COIs in RCTs on spinal cord stimulation for chronic pain, focusing on the prevalence, disclosure, and monetary value of COIs. Methods This cross-sectional study analyzed RCTs published from January 1, 2013 to July 27, 2023. Primary outcomes included the presence, disclosure, and monetary value of COIs, while secondary outcomes assessed the presence of direct/indirect COIs, sponsor access to data, and associations between COIs and select variables, including journal impact factor, publication year, and study outcomes. Results Of 38 RCTs, 30 (78.9%) reported COIs. On average, 35.6% of authors per RCT had at least one COI, with a mean of 0.7 COIs per author. The mean annual monetary value of COIs was US$41,157.83 per author per RCT. 29 RCTs (76.3%) had undisclosed COIs, with an average of 24.2% of authors per RCT having undisclosed COIs. Sponsor access to data was reported in 67.6% of RCTs. No associations were observed between the mean percentage of authors with COIs and the monetary value of COIs and select dependent variables (impact factor, publication year, and study outcomes). Conclusions A substantial majority of RCTs reported COIs with many authors having undisclosed conflicts, highlighting the need for stringent COI disclosure guidelines to maintain research integrity. Expanding COI registry systems globally and increasing non-industry funding are crucial steps toward enhancing transparency and reducing biases in medical research.

PURPOSE International medical graduates (IMGs) are an essential component of the oncology workforce in the United States, comprising a third of all practicing oncologists and almost half of hematology/oncology fellows. In this article, we discuss the contributions of IMGs in the US oncology workforce, review unique challenges faced by IMGs, and propose potential solutions to overcome these challenges. METHODS ASCO's IMG Community of Practice was established with the mission to connect, mentor, guide, raise awareness, and overcome the challenges unique to IMGs interested in pursuing medical oncology in the United States. The content of this article is based on discussions at the IMG Community of Practice meetings at ASCO's 2023 and 2024 Annual Meetings. RESULTS IMGs bring an inherent diversity of thought and experience to the oncology workforce. They provide high-quality, culture- and language-concordant care to a diverse population of patients with cancer. However, IMGs in oncology face significant hardships throughout their careers, including visa-related restrictions, psychosocial and cultural struggles, as well as differential treatment while applying for residency and fellowship training, and early career positions. Greater awareness of these challenges among the members of the hematology/oncology community, along with institutional and individual efforts to support IMGs, is warranted. CONCLUSION We encourage oncology professionals and institutions to join our efforts in recognizing the unique paths of IMGs and providing support and advocacy to maximize the potential of IMGs in the US oncology workforce.

Abstract Historically, treatment options for blastic plasmacytoid dendritic cell neoplasm (BPDCN) were limited to conventional chemotherapy, adopted from regimens used to treat acute myeloid or acute lymphoblastic leukemias, or lymphomas. Nowadays, a novel therapy targeting CD123 is available to treat BPDCN. Yet, regardless of treatment choice, achieving a first complete remission represents the main goal of therapy, because it represents the best opportunity to prolong survival in BPDCN, if offered an allogeneic hematopoietic cell transplant (allo-HCT) as consolidative therapy. Although no specific conditioning regimen is considered standard of care in allo-HCT–eligible patients, recent data from 2 large registries reported a survival advantage when offering total body irradiation–based myeloablative conditioning (MAC) regimens. Unfortunately, applicability of MAC regimens is not feasible in patients who are older/unfit, which represents a considerable proportion of patients presenting worldwide. In such cases, reduced intensity conditioning regimens represent the next best option. Autologous HCT could be considered in patients who are older/unfit who did not have bone marrow involvement at initial presentation and at time of the procedure, albeit data supporting this option are less abundant. Future research is needed to decipher the interplay between clinical, genetic, and molecular features of the disease to personalize treatment accordingly, by enhancing efficacy and avoiding unnecessary toxicities.

AbstractCellular senescence is an established cause of cell and tissue aging. Senescent cells have been shown to increase in multiple organs during aging, including the skin. Here we hypothesized that senescent cells residing in the skin can spread senescence to distant organs, thereby accelerating systemic aging processes. To explore this hypothesis, we initially observed an increase in several markers of senescence in the skin of aging mice. Subsequently, we conducted experiments wherein senescent fibroblasts were transplanted into the dermis of young mice and assessed various age‐associated parameters. Our findings reveal that the presence of senescent cells in the dermal layer of young mice leads to increased senescence in both proximal and distal host tissues, alongside increased frailty, and impaired musculoskeletal function. Additionally, there was a significant decline in cognitive function, concomitant with increased expression of senescence‐associated markers within the hippocampus brain area. These results support the concept that the accumulation of senescent cells in the skin can exert remote effects on other organs including the brain, potentially explaining links between skin and brain disorders and diseases and, contributing to physical and cognitive decline associated with aging.

Abstract The grey matter of the brain develops and declines in coordinated patterns during the lifespan. Such covariation patterns of grey matter structure can be quantified as grey matter networks, which can be measured with magnetic resonance imaging. In Alzheimer’s disease, the global organization of grey matter networks becomes more random, which is captured by a decline in the small-world coefficient. Such decline in the small-world value has been robustly associated with cognitive decline across clinical stages of Alzheimer’s disease. The biological mechanisms causing this decline in small-world values remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and small-world coefficient in mutation carriers (N = 219) and non-carriers (N = 136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Amyloid beta, Tau, synaptic (Synaptosome associated protein-25, Neurogranin) and neuronal calcium-sensor protein (Visinin-like protein-1) preceded loss of small-world coefficient by several years, while increased levels in CSF markers for inflammation (Chitinase-3-like protein 1) and axonal injury (Neurofilament light) co-occurred with decreasing small-world values. This suggests that axonal loss and inflammation play a role in structural grey matter network changes.

Abstract Obstructive sleep apnoea (OSA) is associated with an increased risk for cognitive impairment and dementia, which likely involves Alzheimer’s disease pathology. Non-rapid eye movement slow-wave activity (SWA) has been implicated in amyloid clearance, but it has not been studied in the context of longitudinal amyloid accumulation in OSA. This longitudinal retrospective study aims to investigate the relationship between polysomnographic and electrophysiological SWA features and amyloid accumulation. From the Mayo Clinic Study of Aging cohort, we identified 71 participants ≥60 years old with OSA (mean baseline age = 72.9 ± 7.5 years, 60.6% male, 93% cognitively unimpaired) who had at least 2 consecutive Amyloid Pittsburgh Compound B (PiB)-PET scans and a polysomnographic study within 5 years of the baseline scan and before the second scan. Annualized PiB-PET accumulation [global ΔPiB(log)/year] was estimated by the difference between the second and first log-transformed global PiB-PET uptake estimations divided by the interval between scans (years). Sixty-four participants were included in SWA analysis. SWA was characterized by the mean relative spectral power density (%) in slow oscillation (SO: 0.5–0.9 Hz) and delta (1–3.9 Hz) frequency bands and by their downslopes (SO-slope and delta-slope, respectively) during the diagnostic portion of polysomnography. We fit linear regression models to test for associations among global ΔPiB(log)/year, SWA features (mean SO% and delta% or mean SO-slope and delta-slope), and OSA severity markers, after adjusting for age at baseline PiB-PET, APOE ɛ4 and baseline amyloid positivity. For 1 SD increase in SO% and SO-slope, global ΔPiB(log)/year increased by 0.0033 (95% CI: 0.0001; 0.0064, P = 0.042) and 0.0069 (95% CI: 0.0009; 0.0129, P = 0.026), which were comparable to 32% and 59% of the effect size associated with baseline amyloid positivity, respectively. Delta-slope was associated with a reduction in global ΔPiB(log)/year by −0.0082 (95% CI: −0.0143; −0.0021, P = 0.009). Sleep apnoea severity was not associated with amyloid accumulation. Regional associations were stronger in the pre-frontal region. Both slow-wave slopes had more significant and widespread regional associations. Annualized PiB-PET accumulation was positively associated with SO and SO-slope, which may reflect altered sleep homeostasis due to increased homeostatic pressure in the setting of unmet sleep needs, increased synaptic strength, and/or hyper-excitability in OSA. Delta-slope was inversely associated with PiB-PET accumulation, suggesting it may represent residual physiological activity. Further investigation of SWA dynamics in the presence of sleep disorders before and after treatment is necessary for understanding the relationship between amyloid accumulation and SWA physiology.

As anti-diversity, equity, and inclusion (DEI) legislation continues to gain traction, it is essential for those in science, technology, engineering, mathematics, and medicine (STEMM) to grasp its implications and explore ways to preserve inclusive environments. Anti-DEI measures can result in the dismantling of support structures, such as DEI centers and peer counseling groups, leading to a decline in vital support programs on college campuses and beyond. In this Voices article, we examine these emerging challenges and underscore the critical need to reframe DEI as a tool for fostering inclusion and benefits all individuals.

Abstract With the increasing opportunities for medical management of von Hippel–Lindau (VHL)-related lesions, fundamental questions are arising regarding the possibilities of the FDA-approved medication (Belzutifan) to delay the progression of other non-VHL-related tumors that are not requiring urgent surgical interventions. We present a follow-up report on a VHL patient, with a co-morbid history of pulmonary mucosa-associated lymphoid tissue lymphoma, who was initially described in the clinical scientific literature ~10 years ago. This patient’s case highlights some of the challenges for some VHL patients with comorbid non-VHL-related tumors and potential opportunities for targeted support.

BACKGROUND AND OBJECTIVE There is limited research on screening for social determinants of health (SDOH) in hospitalized pediatric patients. In this article, we describe patient characteristics related to SDOH screening in the hospital setting and examine relationships with acute care metrics. METHODS This is a retrospective cohort study. From July 2020 to October 2021, a 14-question SDOH screener was administered to families of patients admitted or transferred to the hospital medicine service. Information was collected regarding screen results, demographics, patient comorbidities, patient complexity, and acute care metrics. Unadjusted and multivariable analyses were performed using generalized estimation equation logistic regression models. RESULTS Families in 2454 (65%) patient encounters completed SDOH screening, with ≥1 need identified in 662 (27%) encounters. Families with significant odds for positive screening results in a multivariable analysis included primary language other than English (odds ratio [OR] 4.269, confidence interval [CI] 1.731–10.533) or Spanish (OR 1.419, CI 1.050–1.918), families identifying as “Black” (OR 1.675, CI 1.237–2.266) or Hispanic (OR 1.347, CI 1.057–1.717) or having a child on the complex care registry (OR 1.466, CI 1.120–1.918). A positive screening result was not associated with increased length of stay, readmission, or 2-year emergency department or acute care utilization. CONCLUSIONS In hospitalized pediatric patients, populations at the greatest odds for positive needs include families with primary languages other than English or Spanish, those that identified as certain races or ethnicities, or those having a child on the complex care registry. A positive SDOH screening result in this study was not associated with an increase in length of stay, readmission, or acute care utilization.