Publications by Year: 2026

BACKGROUND: The effects of small, realistic changes in physical activity and sedentary behaviour on population-level mortality are unclear. We aimed to estimate the proportion of deaths preventable by 5-min and 10-min incremental increases in moderate-to-vigorous intensity physical activity (MVPA) and 30-min and 60-min reductions in daily sedentary time.

METHODS: We did an individual participant data meta-analysis of prospective cohort studies. We included studies with device-measured physical activity and sedentary time. We estimated the proportion of deaths prevented (potential impact fractions; PIFs) by changes in (1) the approximately 20% least active participants (high-risk approach) and (2) all participants except the approximately 20% most active (population-based approach). We calculated PIFs from adjusted hazard ratios estimated for 5-min and 10-min increases in MVPA and 30-min and 60-min reductions in sedentary time from observed levels across the activity distribution.

FINDINGS: We included seven cohorts from Norway, Sweden, and the USA (n=40 327; 4895 deaths). Data from the UK Biobank (n=94 719; 3487 deaths) were analysed separately. A 5-min/day increase in MVPA in the least active participants might prevent 6·0% (95% CI 4·3-7·4) of all deaths. A similar increase in MVPA in all participants except the most active might prevent 10·0% (6·3-13·4) of all deaths. Reducing sedentary time by 30 min/day might prevent 3·0% (2·0-4·1) of all deaths in the high-risk approach and 7·3% (4·8-9·6) in the population-based approach. Results from the UK Biobank were of a smaller magnitude but still substantial-eg, reducing sedentary time by 30 min/day in all except the most active participants was associated with preventing 4·5% (2·8-6·1) of total deaths.

INTERPRETATION: Small and realistic increases in MVPA of 5 min/day might prevent up to 6% of all deaths in a high-risk approach and 10% of all deaths in population-based approach. Reducing sedentary time by 30 min/day might prevent a smaller, but still meaningful, proportion of deaths in the two risk scenarios.

FUNDING: None.

BACKGROUND: Approved IL-23p19 subunit inhibitors, including guselkumab, require intravenous induction dosing in patients with ulcerative colitis. We aimed to evaluate the efficacy and safety of subcutaneous guselkumab induction in adults with moderately to severely active ulcerative colitis.

METHODS: The ASTRO double-blind, treat-through, randomised, placebo-controlled, phase 3 trial enrolled adults (≥18 years) at 153 sites (community centres or hospitals) in 25 countries with moderately to severely active ulcerative colitis (modified Mayo score 5-9 with a Mayo endoscopic subscore [MES] ≥2 and a Mayo rectal bleeding subscore [RBS] ≥1) and current or history of inadequate response or intolerance to corticosteroids, azathioprine, 6-mercaptopurine, biologics, JAK inhibitors, or sphingosine 1-phosphate receptor (S1P) inhibitors or a history of corticosteroid dependence. By permuted blocks and stratified by inadequate response or intolerance to biologics, JAK inhibitors, or S1P inhibitors (yes/no) and baseline MES (2 or 3), eligible participants were randomly assigned (1:1:1) to receive either subcutaneous guselkumab 400 mg at weeks 0, 4, and 8 followed by 100 mg every 8 weeks (400/100 mg group), subcutaneous guselkumab 400 mg at weeks 0, 4, and 8 followed by 200 mg every 4 weeks (400/200 mg group), or matched subcutaneous placebo. Investigators, study-site personnel, and participants were masked to treatment assignment. Participants who met rescue criteria at week 16 received subcutaneous guselkumab 400 mg at weeks 16, 20, and 24 followed by 100 mg every 8 weeks (placebo group) or continued their assigned guselkumab treatment (sham rescue). The primary outcome of clinical remission at week 12 (defined as Mayo stool frequency subscore of 0 or 1 and not increased from baseline, Mayo RBS of 0, and MES of 0, or 1 with no friability) was assessed among all participants who were randomly assigned and received at least one dose of study drug according to the treatment group to which they were assigned. Safety was assessed until week 24 among all participants who were randomly assigned and received at least one dose of study drug according to the treatment they received. This trial is registered with ClinicalTrials.gov, NCT05528510, and is ongoing.

FINDINGS: Between Sept 13, 2022, and April 2, 2024, 651 participants were screened for eligibility and 418 participants were randomly assigned to the guselkumab 400/100 mg group (n=139), the guselkumab 400/200 mg group (n=140), and the placebo group (n=139). Mean age was 41·7 years (SD 14·2), 256 (61%) of 418 participants were male, and 162 (39%) were female. Mean ulcerative colitis duration was 7·6 years (SD 6·7) and mean modified Mayo score was 6·7 (1·2). A significantly greater proportion of participants receiving guselkumab 400 mg induction versus placebo had clinical remission at week 12 (77 [28%] of 279 vs nine [6%] of 139; adjusted treatment difference 21 percentage points, 95% CI 14-28; p<0·0001). At week 24, 49 (35%) participants in the guselkumab 400/100 mg group, 51 (36%) in the guselkumab 400/200 mg group, and 13 (9%) in the placebo group were in clinical remission (the difference between both guselkumab groups and placebo was statistically significant). The frequencies of adverse events in the guselkumab groups (74 [53%] of 139 for 400/100 mg and 85 [61%] of 140 for 400/200 mg) were similar to that in the placebo group (91 [65%] of 139). There were no treatment-related deaths, and no new safety concerns were identified. The most frequently reported adverse events were worsening of ulcerative colitis (14 [10%] in the 400/100 mg group, nine [6%] in the 400/200 mg group, and 29 [21%] in the placebo group), arthralgia (11 [8%], seven [5%], and three [2%]), and upper respiratory tract infection (ten [7%], five [4%], and nine [6%]). Serious adverse events occurred in five (4%) participants in the 400/100 mg group, six (4%) in the 400/200 mg group, and 17 (12%) in the placebo group.

INTERPRETATION: Subcutaneous guselkumab induction and maintenance was safe and efficacious for 24 weeks in participants with moderately to severely active ulcerative colitis, establishing a fully subcutaneous guselkumab regimen as a treatment option in this patient population.

FUNDING: Johnson & Johnson.

IMPORTANCE: A previous study showed a high prevalence of central sensitization syndrome (CSS) in patients with autonomic symptoms. The prevalence of CSS in postural tachycardia syndrome (POTS), a form of dysautonomia, is unknown.

OBJECTIVES: To analyze the prevalence of CSS in POTS.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study included patients with a POTS diagnosis confirmed by autonomic testing at Brigham and Women's Faulkner Hospital between 2022 and 2025. Data were analyzed from April to August 2025.

EXPOSURE: POTS with and without CSS.

MAIN OUTCOMES AND MEASURES: Central Sensitization Inventory (to assess central sensitization syndrome [CSS]), COMPASS-31 (autonomic symptoms), Neuropathy Total Symptom Score-6 (NTSS-6, sensory symptoms), PROMIS (global health), and autonomic testing (Valsalva maneuver, deep breathing, sudomotor function, and head-up tilt) with skin biopsies. Primary outcome was the central sensitization inventory score with secondary outcomes individual test performances.

RESULTS: This study included 305 patients with POTS, of whom 264 (86.6%) met criteria for CSS (mean [SD] age, 33.21 [10.75] years; 30 males [11.4%]; 234 females [88.6%]). Patients with CSS compared with those without CSS had longer duration of symptoms, were more frequently female, exhibited higher rates of anxiety (195 [73.9%] vs 20 [48.8%]; P = .002), depression (168 [63.6% vs 14 [34.1%]; P = .001), fibromyalgia (46 [17.4%] vs 0 [0%]; P = .008), irritable bowel syndrome (IBS, 90 [34.1%] vs 7 [17.1%]; P = .046), headaches (176 [66.7%] vs 12 [29.3 %]; P < .001), treatment with antihistamine medication (136 [51.5%] vs 13 [31.7%]; P = .03), psychiatric medication (163 [61.7%] vs 17 [41.5 %]; P = .02), pain medication (127 [48.1%] vs 8 [19.5%]; P = .001), and gastrointestinal medication (82 [31.1%] vs 5 [12.2 %]; P = .02), and had higher COMPASS-31 scores (51.93 [13.23] vs 31.18 [10.49]; P < .001), NTSS-6 scores (11.32 [4.86] vs 4.44 [3.32]; P < .001), NRS scores (3.26 [2.73] vs 0.54 [1.21]; P < .001), and worse PROMIS scores (20.36 [5.45] vs 27.96 [4.73]; P < .001). Autonomic tests showed lower orthostatic end-tidal carbon dioxide (27.59 [6.39] mm HG vs 29.46 [4.68] mm HG; P = .002) and a greater orthostatic decline in cerebral blood flow velocity (17.08 [8.72] cm/sec vs 13.68 [5.04] cm/sec; P < .001) in the CSS group. Both groups had similar prevalence of autonomic failure (223 [84.5%] vs. 33 [80.5%]; P = .67, mostly mild intensity), and abnormal skin biopsy (43% in both groups).

CONCLUSIONS AND RELEVANCE: These findings suggest that CSS was common in patients with POTS and may represent a higher-order sequela of cerebrovascular, respiratory, and autonomic dysregulation. This heightened central processing may amplify symptom perception through altered interoceptive signaling. Central sensitization and autonomic impairment may coexist, and management should focus on both conditions.

PURPOSE OF REVIEW: This review examines sex- and gender- specific differences in the pathophysiology, presentation, and clinical complications of atherosclerosis. We explore both traditional and emerging risk factors and identify diagnostic and treatment gaps that disproportionately affect women.

RECENT FINDINGS: Traditional risk factors such as diabetes and smoking confer greater cardiovascular risk in women than men. Women also experience unique risk factors, including adverse pregnancy outcomes, polycystic ovary syndrome, early menopause, and higher prevalence of autoimmune diseases, that further elevate their risk. Women are more likely to experience ischemia and myocardial infarction in the setting of non-obstructive coronary disease (INOCA/MINOCA). Despite having less plaque than men at any given age, high risk features on cardiac computed tomography angiography carry greater risk. Women are also less likely to receive lipid-lowering agents and other preventive therapies. Recognizing sex-based differences in atherosclerosis is critical to advancing more nuanced, equitable, and personalized cardiovascular disease prevention and care.

PURPOSE OF REVIEW: Point-of-care ultrasound (POCUS) has become an indispensable diagnostic and procedural tool across many medical specialties. However, formalized ultrasound training within urology residency programs remains limited. This review aims to outline a practical framework for designing and implementing a structured POCUS curriculum tailored specifically to urology training.

RECENT FINDINGS: Various programs have implemented POCUS curricula, often with longitudinal instruction, modular content, hands-on training, and competency-based assessments. While urology has historically relied on sporadic exposure, often limited to prostate biopsies or intraoperative imaging, recent integration into the residency training demonstrates the utility of ultrasound amongst all urologic organs. National surveys of residents and practicing urologists reveal persistent deficiencies in both confidence and formal training opportunities, despite high interest and perceived clinical value. A review of emerging urology-specific curricula shows that programs adopting structured, multimodal approaches, combining didactics, video-based learning, supervised training, and simulation report improvements in user confidence, technical proficiency, and clinical utilization. Early data suggest that when implemented longitudinally, these frameworks can help to broaden ultrasound use in clinical settings. However, published experiences remain limited to a small number of institutions, underscoring the need for broader utilization and interventional studies. Current literature supports a structured POCUS curriculum for urology trainees, yet widespread adoption remains at an early stage. A unified framework could help standardize expectations, ensure equitable training experiences, and better prepare residents for modern practice. Multi-institutional collaboration, increased research on educational outcomes, and potential guidance from accrediting bodies will be critical to advancing ultrasound education and establishing national standards for urologic POCUS training.

PURPOSE: Repeat transurethral resection (re-TURBT) is recommended for all patients with high-risk bladder cancer to improve staging and oncologic outcomes. However, contemporary evidence on the role of re-TURBT is lacking. We therefore examined the contemporary rates of upstaging at re-TURBT and the association of re-TURBT with disease recurrence and progression.

MATERIALS AND METHODS: We identified patients with an incident diagnosis of high-grade Ta, low-grade T1 and high-grade T1 urothelial carcinoma of the bladder between 2010 and 2022. The association of re-TURBT with disease recurrence and progression was evaluated using Cox regression. Rates and predictors of residual tumor and upstaging at re-TURBT were evaluated using univariable logistic regression.

RESULTS: A total of 328 patients were included, of whom 88 (27%) underwent re-TURBT. Among those who underwent re-TURBT, 9 (10%) were upstaged to ≥ T2, while 39 (44%) were found to have residual non-muscle invasive disease. Median follow-up time was 13 and 24 months for RFS and PFS, respectively. In a multivariable analysis, re-TURBT was not associated with a significant difference in disease recurrence or progression compared with no re-TURBT. In unadjusted analysis, a higher Charlson index was associated with an increased risk of upstaging and residual tumors. A greater number of tumors was associated with increased risks of residual tumor at re-TURBT.

CONCLUSIONS: In a contemporary cohort of patients with bladder cancer, the rate of upstaging at re-TURBT was 10%, lower than historical studies. The rate of residual non-muscle invasive disease remains high at 44%. Re-TURBT was not associated with a statistically significant difference in disease recurrence or progression.

BACKGROUND: Prehospital transfusion of whole blood (WB) is being adopted in civilian Emergency Medical Services (EMS) systems, but the characteristics of patients receiving WB may differ by region. We aimed to compare prehospital WB transfusion programs in Sweden and in the Northeastern United States, focusing on patient demographics and transfusion details.

METHODS: We conducted a retrospective observational study of EMS-initiated WB transfusions in three regions in Sweden (2020-2024) and in multiple EMS programs in the Northeastern United States (2024). We compared patient age, sex (with female patients categorized as of childbearing potential (FCP) if ≤ 50 years), indication for transfusion (trauma vs. non-trauma), and prehospital WB transfusion practice (number of units initiated/completed and RhD type).

RESULTS: A total of 196 patients received prehospital WB (85 in Sweden, 111 in U.S.). Sweden's WB recipients were younger (median age   41 vs. 59 years) and more often trauma patients (90.6% vs. 72.1%) compared to the U.S.

COHORT: The proportion of female patients was similar, but Sweden had a higher percentage of FCPs among WB recipients (24% vs. 8%). Swedish EMS were more likely to transfuse multiple units before hospital arrival. Practice differed in RhD type: 97% of U.S. patients received RhD-positive WB, whereas 91% of Swedish patients received RhD-negative WB. Consequently, all 9 FCPs in the U.S. group received at least one Rh-positive unit, compared to 1 of 18 FCPs in Sweden.

CONCLUSION: Significant differences exist between Sweden and the Northeastern U.S. in prehospital WB transfusion demographics and practices. These findings highlight that one should not assume similar patient profiles or transfusion strategies across different countries' EMS WB programs.

This study investigates how socioeconomic status, insurance type, and geography shape access to inpatient synthetic facial implant surgery in the United States. Using HCUP-NIS data from 2016 to 2020 (n=68), the authors show that lower-income patients are more likely to be publicly insured, experience significantly longer hospital stays, and are underrepresented in cosmetic and gender dysphoria-related procedures, while higher-income, urban patients more often self-pay for elective implants clustered in large metropolitan and Pacific regions. Despite low overall complication rates, inpatient admissions are associated with high costs, and rural and low-income patients face pronounced barriers to care, particularly for facial feminization surgery. This work highlights the need for broader outpatient data capture, qualitative research among marginalized groups, and standardized insurance coverage policies to promote equitable, cost-effective access to functional and aesthetic facial implant procedures.