Citations

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of heterogenous hematologic malignancies characterized by the proliferation of blood cells and consist of myelofibrosis, polycythemia vera, and essential thrombocythemia. The NCCN Guidelines for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the aim of providing recommendations for the comprehensive care of adults with these diseases. The panel of experts convenes at least once a year to discuss requested changes to the Guidelines and to evaluate emerging data. These Guideline Insights focus on some of the recent updates for myelofibrosis.

Abstract Genetic studies have significantly advanced our understanding of tauopathies, yet the genetic aetiology of Pick’s disease, a rare 3-Repeat tauopathy, remains unclear. The MAPT p.A152T variant has been identified as a risk factor for Alzheimer’s disease and progressive supranuclear palsy, but its role in Pick’s disease is unknown. In this study, we examined the prevalence of MAPT p.A152T in the largest series of neuropathologically confirmed Pick’s disease cases to date (n = 401). Through genotyping, we identified a single mutation carrier in the Pick’s disease cohort (minor allele frequency = 0.12%). We previously reported MAPT p.A152T at a 0.20% frequency in healthy controls (n = 2456), suggesting that it does not associate with 3-Repeat tauopathy risk. To further investigate the effect of the variant on MAPT transcript expression, we used bulk RNA sequencing in Alzheimer’s disease and progressive supranuclear palsy A152T mutation carriers. We did not detect significant differences in 4-Repeat tau levels, though preliminary trends may indicate more nuanced effects that need to be examined with long-read sequencing in a larger series. Overall, our study suggests that MAPT p.A152T does not increase Pick’s disease risk and may instead be linked to 4-Repeat or mixed tau pathologies, warranting further functional investigation.

Exercise and physical activity are recognized as essential tools to optimize fitness and longevity, improve overall health, and reduce the risk of cardiovascular disease and other major comorbidities. However, there are inherent risks associated with participation in sports and exercise, regardless of the level of competition or skill required. As such, there is a need for cardiologists to understand the unique aspects of competitive and recreational athletics, as well as sport and exercise science, as it relates to overall heart health and cardiovascular risk. In this article, we provide an overview of the essential aspects of sports and exercise cardiology. We describe the roles and responsibilities of a sports and exercise cardiologist as a member of a comprehensive team of experts who provide care of athletes at all levels of sport, emphasize the importance of risk stratification and prevention of sudden cardiac arrest, the role of exercise for maintaining and optimizing overall health in the general population, describe the growing field of sports electrophysiology and also discuss unique aspects of sports cardiology applied to environmental health and care of the tactical athlete. Knowledge gaps and directions for future clinical and research investigation are reviewed.

Importance There is no consensus on staging and surveillance imaging for cutaneous squamous cell carcinoma (CSCC). Although imaging has been shown to affect management, broad recommendations from the National Comprehensive Cancer Network have led to variability in clinical practice. Objective To develop multidisciplinary consensus recommendations on the use of staging and surveillance imaging of localized CSCC. Evidence Review A multidisciplinary expert panel across academic and clinical practice settings convened a Delphi consensus, with 3 iterative survey rounds from January to June 2025. Data were analyzed from February 2025 to January 2026. Eligibility defined by at least 1 to 2 CSCC publications during the previous 5 years, involvement in a relevant clinical trial, experience treating at least 3 patients monthly with CSCC, and/or 5 years or longer of clinical practice. Fifty-four experts were invited and 45 (83%) completed all 3 rounds and were included in the final analysis. Structured Delphi surveys evaluated clinical scenarios, imaging modalities, and surveillance strategies for CSCC. Consensus and near-consensus recommendations were generated, defined as 80% or greater and 70% to 79% agreement, respectively. Findings The 45 participants (21 female individuals [47%] and 24 male individuals [53%]; 14 Asian individuals [31%], 1 multiracial individual [2%], and 30 White individuals [67%]) consisted of dermatology (15 [33%]), medical oncology (7 [16%]), radiation oncology (9 [20%]), radiology (9 [20%]), surgery (3 [7%]), and otolaryngology specialists (2 [4%]). The Delphi panel recommended staging and surveillance for CSCCs with at least a 15% risk of metastasis. Consensus or near consensus was reached to recommend staging and surveillance imaging for tumors with a concern for metastasis, bone invasion, invasion beyond subcutaneous fat, large-caliber nerve invasion, or a diameter of 4 cm or larger or the combination of tumors with poorly differentiated histology and any of the following: diameter of 2 cm or larger, lymphovascular invasion and subcutaneous fat invasion, or lymphovascular invasion and small-caliber perineural invasion. Computed tomography imaging was the preferred modality for nodal staging (38 [84%]) and surveillance (35 [78%]). For surveillance duration, consensus was reached to provide imaging for at least 2 years, and near consensus was reached for at least 3 years. Conclusions and Relevance This study provides an expert consensus–based framework to standardize imaging in localized CSCC that may inform future guidelines.

TAF7, a core subunit of the general transcription factor TFIID, regulates transcription and additionally functions as an RNA chaperone that directs nascent nuclear RNAs to cytoplasmic polysomes, thereby influencing protein synthesis. Here, we identify a set of novel cytoplasmic interactors and a previously unappreciated cytoplasmic role for TAF7 in oncogenesis. BioID-mediated proximity labeling identified STAT3 and the CCT and WASH complexes as prominent cytoplasmic interactors of TAF7. These interactions were validated by co-immunoprecipitation and proximity ligation assays. We further showed that cytoplasmic TAF7 levels increased during oncogenesis in proportion to cancer cell pathogenicity. Notably, TAF7 engagement with STAT3, CCT and WASH complexes is markedly enhanced during cellular transformation, consistent with their functions in cancer progression. Together, these findings reveal a cytoplasmic TAF7 interactome and implicate elevated cytoplasmic TAF7 as associated with oncogenesis.

Abstract Background Hospitalists work in complex clinical environments with rising patient acuity and competing demands. Uncertainty is an inescapable part of this work, yet little is known about how hospitalists experience and manage clinical uncertainty. Objectives To explore how hospitalists experience and manage uncertainty in clinical practice. Methods We conducted a single‐center qualitative study using reflexive thematic analysis within a constructivist paradigm. We interviewed hospitalist attending physicians during and/or after their work week and analyzed data inductively, drawing on literature about uncertainty in other clinical contexts. To strengthen rigor and trustworthiness, we held return‐of‐findings feedback sessions with participants. Results We interviewed 12 hospitalists between April 2023 and September 2024. Across diverse clinical situations, participants framed uncertainty through the lens of hospital discharge, using it as an anchor for decision‐making. Managing uncertainty required cognitive and emotional resources and was influenced by participants’ “bandwidth,” or perceived capacity to manage competing professional and personal demands. Perceived bandwidth shaped participants’ responses to uncertainty. Adequate bandwidth encouraged uncertainty engagement, while limited bandwidth prompted deferral or offloading. Participants described how they attempted to ease the burden of uncertainty for their oncoming colleagues by adjusting their documentation and care plans during handoffs. Conclusions Hospitalists experience uncertainty as a routine part of clinical practice and manage it pragmatically to advance patients toward discharge. Their approaches are shaped by their perceived bandwidth. The influences of uncertainty should be considered when assessing workload, organizing clinical service, and planning handoffs.

Importance Risk-reducing salpingo-oophorectomy (RRSO) is an effective option to prevent ovarian cancer in high-risk individuals, but adverse effects from premature menopause are a barrier to uptake. Interval salpingectomy with delayed oophorectomy (ISDO) may be an effective alternative. Objective To evaluate the association of ISDO vs RRSO and sexual function and menopausal symptoms. Design, Setting, and Participants This prospective, multicenter, nonrandomized (patient preference) clinical trial was performed among Women Choosing Surgical Prevention participants with a pathogenic or likely pathogenic germline variant conferring an increased risk for ovarian cancer. Patients from 9 US centers were enrolled from June 2, 2016, to October 28, 2020; chose ISDO or RRSO; and were followed up for 24 months. The analysis was performed on November 13, 2024. Interventions Participant-selected RRSO or ISDO. Main Outcomes and Measures Changes in sexual function and menopausal symptoms from baseline to 6, 12, and 24 months. Inverse probability weighting was applied to achieve covariate balance across groups. Results The analytic sample included 334 female participants (mean [95% CI] age at consent, 39.2 [38.7-.9.7] years) who underwent RRSO (n = 165) or ISDO (n = 169) and completed 6-month questionnaires. Significantly more participants experienced clinically meaningful worsening of sexual function at 6 months compared with baseline after RRSO vs ISDO (33.1% [39 of 118] vs 16.8% [17 of 101], respectively; odds ratio, 2.00 [95% CI, 1.20-3.35]) and at 12 months (39.2% [38 of 97] vs 18.3% [17 of 93], respectively; odds ratio, 1.69 [95% CI, 1.09-2.63]). This finding was no longer significant at 24 months. When restricted to the RRSO group who took hormone replacement therapy, there was no significant worsening of total sexual function scores or menopausal symptoms compared with baseline. No interval ovarian cancers were reported. Conclusions and Relevance This nonrandomized clinical trial comparing RRSO with ISDO found that ISDO was less likely to impair sexual function, which addresses an important barrier to surgical prevention in high-risk patients in premenopause. After RRSO, use of hormone replacement therapy mitigated menopausal symptoms and prevented decline in sexual function. More information is needed about the safety of ISDO. Trial Registration ClinicalTrials.gov Identifier: NCT02760849

Black race and Hispanic ethnicity are associated with higher mortality in severe combined immunodeficiency (SCID) following hematopoietic cell transplantation (HCT), though mechanisms remain unclear. We evaluated 796 children with SCID who received nonsibling HCT between 1982 and 2020 using data from the Primary Immune Deficiency Treatment Consortium. Overall survival for Black (aHR 2.47, 95%CI 1.64, 3.71) and Asian/Pacific Islander patients (aHR 1.82, 95%CI 1.00, 3.30) was significantly lower compared with non-Hispanic White patients, while Hispanic patients had lower event-free survival (aHR 1.83, 95%CI 1.27, 2.63) compared with non-Hispanic White patients. Even after adjusting for age and infection, Black patients with SCID had more than twofold hazard of death compared with non-Hispanic White patients. NBS was associated with earlier diagnosis, reduced infection at HCT, and elimination of survival disparities between Black and non-Hispanic White patients. These findings suggest that universal, system-level interventions such as NBS can mitigate disparities in outcomes for children with SCID.

Importance Transvaginal pelvic imaging is an integral and sensitive aspect of gynecologic care that individuals find both invasive and burdensome. At-home transvaginal imaging provides an opportunity to navigate these barriers to care. Objective To evaluate the use of at-home transvaginal ultrasonography for gynecologic assessment, as measured by diagnostic imaging quality and participant satisfaction, in a broad sampling of women aged 22 to 50 years. Design, Setting, and Participants Prospective, interventional, single group nonrandomized clinical trial with blinded review of collected images from premenopausal women aged 22 to 50 from Florida, Massachusetts, Maryland, Maine, Minnesota, New Hampshire, Texas, Utah, Virginia, Vermont, and Washington, DC. Images were gathered between July 2022 and July 2023, and data were analyzed from April to September 2025. Intervention At-home pelvic ultrasonography guided by verbal communication with a fully trained remote sonographer who had real-time access to study images. Cine clips were used to capture standard views of the uterus, ovaries, cervix, and posterior cul-de-sac. Main Outcomes and Measures Primary outcomes were image quality and participant net promoter score (NPS), reflecting participants' likelihood of recommending the procedure, with higher scores indicating greater likelihood. Secondary outcomes included minor pain or discomfort, sonographer reported experience and/or pain, and all other adverse events. Results A total of 265 participants (mean [SD] age, 32 [6.7] years; mean [SD] body mass index, 27.0 [5.6]) enrolled in the trial, and 263 ultrasonographic scans were completed. Image quality showed that 253 at-home ultrasonographic scans (96.2%) met diagnostic quality while 10 (3.8%) did not. NPS was significantly higher with use of the at-home ultrasonography (59) compared with in-clinic scans (24), with an adjusted difference of 33.7 (95% CI, 23.3-44.0; z = 6.35; P < .001). No adverse events were reported. Conclusions and Relevance This nonrandomized clinical trial of at-home pelvic ultrasonography in premenopausal women demonstrated that broad use of at-home gynecologic ultrasonography technology is feasible, safe, and preferred by participants and sonographers compared with in-clinic ultrasonography. At-home ultrasonographic imaging presented an innovative and clinically acceptable alternative to in-clinic care, providing opportunities for improved access to and decreased burden of gynecologic and reproductive care. Registration ClinicalTrials.gov NCT05443698