Citations

Background & Aims: We examined treatment patterns and clinical outcomes in a contemporary cohort of children with newly diagnosed inflammatory bowel disease (IBD) in a large, commercially insured U.S. population. Methods: Using the OptumLabs® Data Warehouse, we created an inception cohort of physician-diagnosed IBD in children aged 6–17 years between 2007–23. We examined cumulative incidence of hospitalization, surgery, safety events, and medication use in patients with Crohn's disease (CD) and ulcerative colitis (UC), overall and stratified by diagnostic era, race and ethnicity, sex, and age at diagnosis. Results: Among 787 children with newly diagnosed CD (age at diagnosis, 13.4±2.9y; 57% male; 82% White, 5% Black, 7% Hispanic) followed over mean 4.6±3.0y, 5-year risk of IBD-related hospitalization and major surgery was 30% and 10%, respectively. In children diagnosed in 2019–23, 1-year cumulative use of corticosteroids and advanced therapy was 46% and 75%, respectively; advanced therapy use increased significantly over time (aHR, 3.43 [95% CI, 2.71–4.32] for 2019–23 vs. 2007–12), while corticosteroid use declined (0.67 [0.53–0.84]). Risk of IBD-related hospitalization was lower in children diagnosed between 2019–23 (0.65 [0.43–0.97]) compared with those diagnosed between 2007-12; surgical risk did not decline significantly, with confidence intervals compatible with a clinically meaningful reduction. Among 399 children with newly diagnosed UC (age at diagnosis, 14.0±3.0y; 53% male; 78% White, 5% Black, 7% Hispanic) followed over 4.5±3.0y, 5-year risk of IBD-related hospitalization and colectomy was 36% and 8%, respectively. Advanced therapy use increased significantly over time (4.46 [2.85–6.98] for 2019–23 vs. 2007–12), with no significant change in hospitalization or surgical risk across eras. No consistent racial and ethnic, age, or sex differences in advanced therapy use or clinical outcomes were identified in either CD or UC. Conclusions: In a contemporary cohort of commercially insured children with newly diagnosed IBD, early advanced therapy use has increased markedly over time. Surgical risk did not decline significantly in either disease; however, the study was not powered to exclude a clinically meaningful reduction, and these findings are hypothesis-generating rather than conclusive.

Background/Objectives: A 12-week trial demonstrated that phenotype-tailored lifestyle intervention (PLI) was associated with greater weight loss than standard lifestyle intervention (SLI); however, differences in dietary patterns between groups were not examined. Methods: This secondary analysis evaluated caloric and macronutrient intake at 12 weeks in adults with obesity (BMI ≥ 30 kg/m2), classified into four energy-balance phenotypes (abnormal satiation, reduced postprandial satiety, low energy expenditure, emotional eating) (n = 77) who underwent PLI or SLI. Dietary intake was assessed by 24-h recalls and verified by a blinded registered dietitian. Results: Groups were compared at 12 weeks adjusting for baseline values. PLI was associated with lower total energy intake than SLI (1273 ± 182 vs. 1894 ± 176 kcal/day; p = 0.018), due to lower carbohydrate (464 ± 76 vs. 818 ± 73 kcal/day; p = 0.002) and fat intake (479 ± 76 vs. 697 ± 73 kcal/day; p = 0.036); absolute protein intake did not differ. However, protein comprised a greater proportion of energy intake in PLI (26.8 ± 1.6%) than SLI (19.8 ± 1.5%; p = 0.003), and dairy protein contributed more to total energy in PLI (6.8 ± 0.8% vs. 3.7 ± 0.7%; p = 0.004). Conclusions: PLI was associated with lower energy intake, mainly due to reduced carbohydrate and fat intake, and a higher relative contribution of protein, consistent with phenotype-based recommendations rather than macronutrient prescriptions. These findings suggest a potential role for personalized dietary approaches in obesity management. However, the non-randomized design does not allow causal inferences.

Introduction: Ureteral stones are a common cause of emergency presentations. Definitive stone removal at the index encounter can reduce delays and repeat interventions. It is unknown whether fellowship-trained endourologists are more likely to perform definitive management than general/other subspecialist urologists. This multicenter retrospective cohort study evaluated the influence of endourology subspecialty training on the choice between upfront definitive stone treatment and initial ureteral decompression at first presentation. Patients managed with medical expulsive therapy alone were not included. Methods: Adults (≥18 years) presenting at 2022 to seven North American academic centers with symptomatic, noninfected, computed tomography-confirmed ureteral stones were included. Patients with infection, sepsis, positive nitrites, or intraoperative pyelonephritis were excluded from the study. Variables included demographics, stone size and location, subspecialty of the on-call urologist, and management type (definitive [ureteroscopy or shockwave lithotripsy] vs deferred [(initial stent]). Multivariate logistic regression was used to identify the predictors of definitive treatment. Results: Among the 395 patients, 190 (48.0%) underwent definitive management and 205 (52.0%) underwent deferred treatment. Distal stones were treated definitively more often than proximal stones were (51.1% vs 36.6%). An endourologist was on call for 150 encounters (38.0%); 64.7% of these patients received definitive treatment, compared with 38.0% under general/other subspecialist urologists. On multivariate analysis, endourologist on-call remained independently associated with definitive management (odds ratio [OR] 3.46, 95% confidence interval [CI] 2.19–5.47, p < 0.0001), as did distal stone location (OR: 2.46, 95% CI: 1.21–5.00, p = 0.013). Severe complications are rare, and none of the patients developed sepsis. Conclusions: Endourologists were more than three times more likely to perform definitive interventions for symptomatic, noninfected ureteral stones at initial presentation. Subspecialty expertise and timely operative access enable safe, efficient, single-stage management.

Objective: The aim of this study was to evaluate outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) of thoracoabdominal aortic aneurysms (TAAAs) and complex abdominal aortic aneurysms (CAAAs) in patients actively smoking at the time of repair compared with previous smokers and non-smokers. Methods: Single-center retrospective review of elective FB-EVARs for TAAA and CAAAs between 2007 and 2023 was conducted. Demographics, comorbidities, aneurysm extent/ morphology, technical details, and peri-operative outcomes were collected. Patients were grouped into 1 of 3 groups: active smokers, prior smokers, and never smokers. Patients who stopped smoking within 6 weeks to surgery were considered active smokers. Rupture and symptomatic aneurysms were excluded. Endpoints included early (<30 days) mortality and major adverse events (MAEs). Results: There were 676 patients (73% male, mean age 74 ± 7.8). There were 141 (21%) active smokers, 455 (67%) prior smokers, and 80 (12%) never smokers. Active smokers were significantly younger than prior or never smokers (71 ± 6.7, 75 ± 6.9, and 76 ± 12, respectively; P < .001). Cardiovascular risk factors were similar, except active smokers were significantly more likely to have chronic obstructive pulmonary disease (60% vs 42% vs 6.2%, P < .001) and peripheral arterial disease (31% vs 24% vs 10%, P = .002) when compared to prior and never smokers, respectively. Patients who never smoked had significantly more extent II aneurysms (34%) than prior (18%) and active (15%) smokers, P = .001. Univariable and multivariable logistic regression analyses showed no statistically significant associations between smoking status and any specific peri-operative adverse events following surgery. Conclusion: Active smoking status does not appear to affect peri-operative outcomes after FB-EVAR for complex aortic aneurysms. Although smoking cessation must be strongly encouraged, repair should not be delayed due to active smoking status. Clinical Impact These data suggest that active smoking, in isolation, should not be considered a contraindication to elective FB-EVAR when anatomy is suitable and patients are otherswise optimized. This is particularly relevant for high-risk patients who may have limited alternative treatment options. Proceeding with FB-EVAR in active smokers does not appear to compromise early safety or procedural efficacy.

Abstract Background and Objectives Cryoprecipitated antihemophilic factor (cryoprecipitate), fibrinogen concentrate (FC), and pathogen‐reduced cryoprecipitated fibrinogen complex (PR cryoprecipitate) are sources of fibrinogen replacement, and each has advantages and disadvantages in terms of cost, efficacy, safety, and logistics of administration. This study examines the respective utilization frequencies of these different products at institutions in North America and the factors influencing the decision on which one(s) to adopt. Materials and Methods A survey was distributed via email to contacts for Advancement of Blood and Biotherapies (AABB)‐accredited blood banks/transfusion services. Survey questions covered topics including the availability and usage of FC, cryoprecipitate, and PR cryoprecipitate, as well as the perceived advantages of each product. Results A total of 53 responses were received from surveyed institutions (estimated 25% response rate). Over half (31/53, 58.5%) of respondents exclusively used cryoprecipitate, 30.2% (16/53) used two sources of fibrinogen replacement, and 7.5% (4/53) used all three (cryoprecipitate, FC, and PR cryoprecipitate). More than half of the institutions restricted FC to specific indications, primarily for cost containment. The most commonly cited advantages of FC over cryoprecipitate were storage convenience and rapid reconstitution. Conclusion Surveyed institutions in the United States and Canada primarily use cryoprecipitate for fibrinogen replacement, with variable usage of FC and limited usage of PR cryoprecipitate. The perception of FC being more expensive than cryoprecipitate predominated. Further studies comparing available fibrinogen replacement options would be valuable, particularly with consideration of product acquisition cost, wastage, impacts on utilization of other blood products, and patient outcomes.

Objective To assess the effect of Moses™ 2.0 (Lumenis Be Ltd., Yokneam Illit, Israel; Boston Scientific, Marlborough, MA, USA) for lithotripsy of renal stones of 8–20 mm in diameter on operative time, surgeon workload, and retropulsion. Subjects/Patients and Methods In our multicentre, randomised, double‐blind clinical trial, patients were randomised 1:1 to standard or Moses 2.0 laser lithotripsy and stratified by stone size. Patients and surgeons were blinded to laser modality. Primary outcomes were total operative time as well as surgeon workload assessed by the National Aeronautics and Space Administration‐Task Load Index (NASA‐TLX). Secondary outcomes were stone retropulsion evaluated by blinded video review and postoperative clinical outcomes. Linear regression modelling was used for analysis. Results A total of 153 patients (79 Standard, 74 Moses 2.0) with similar clinical, stone, and operative characteristics were evaluated. There was no significant difference in operative times between the Standard and Moses 2.0 groups ( P = 0.73). Moses 2.0 was associated with lower effort, frustration, mental, physical, and temporal workload, as well as higher rated overall performance compared to the standard laser. Video review demonstrated no difference in rates of retropulsion ( P = 0.13). Complication rates (Standard: 13%; Moses 2.0: 10%) and stone‐free rates (Standard: 51%; Moses: 2.0 55%) were comparable. Conclusion Our study evaluated the impact of Moses 2.0 technology on high‐powered renal stone dusting, constituting the largest double‐blind trial of its kind to date. There was insufficient evidence to suggest any difference in operative times or clinical outcomes when using Moses 2.0 compared to standard laser lithotripsy. Moses 2.0 was associated with reduced surgeon workload, which has implicit impact on surgeon wellness.

Abstract Purpose: Inhibitors of the Ataxia telangiectasia and Rad3-related (ATR) protein kinase, a critical component of the DNA damage repair response, have synergistic anti-cancer activity with platinum compounds in preclinical models. We therefore conducted a Phase 2 study of the ATR inhibitor berzosertib+carboplatin vs. docetaxel+carboplatin in metastatic castration-resistant prostate cancer. Patients and Methods: Patients previously treated with at least one androgen receptor pathway inhibitor and taxane underwent mandatory biopsy and were randomized 1:1 to receive Arm A (docetaxel 60 mg/m2+carboplatin AUC4 day 1; or carboplatin AUC5 if not a docetaxel candidate) or Arm B (berzosertib 90 mg/m2 days 2,9+carboplatin AUC5 day 1) every 21 days. The primary endpoint was overall response rate (ORR; ≥50% PSA decline or radiographic response). Results: Of 73 randomized patients, 65 received protocol treatment: 34 on Arm A (26 docetaxel+carboplatin; 8 carboplatin alone) and 31 on Arm B. Thirteen patients (38%) in Arm A and 20 (65%) in Arm B had ≥Grade 3 treatment-related adverse events (TrAEs). ORR was 15% in Arm A (5/34; 5/26[19%] with docetaxel+carboplatin) and 0% in Arm B (0/31). At interim analysis after 65 of planned 130 patients were treated, enrollment was halted due to futility. Homologous recombination repair deficiency status from tissue and blood did not correlate with clinical outcomes, but ATM-deficiency or high levels of phoshpo-KAP1 detected in tissue was associated with clinical benefit across both arms of the trial. Conclusions: Berzosertib+carboplatin demonstrated lower ORR and more frequent ≥grade 3 TrAEs compared to docetaxel+carboplatin in this heavily pre-treated, biomarker-unselected population. NCT03517969

Importance Recent case reports suggest that B antigen–containing blood products may be associated with anaphylactic transfusion reactions in recipients with preformed immunoglobulin E to galactose- α -1,3-galactose (alpha-gal). Objective To test the association of local alpha-gal syndrome (AGS) prevalence and allergic transfusion reaction (ATR) in patients with blood type O. Design, Setting, and Participants In this international, multicenter, retrospective cohort study at academic medical centers, sites were assigned to AGS high- or low-prevalence clusters based on the known geographic distribution of AGS. Data were collected on platelet or plasma transfusions and ATRs during 2020 to 2024. Consecutive patients receiving platelet or plasma transfusions were included. Exposures Patients with blood type O who received B or AB units and patients with blood type O who received O units (reference group) in AGS high- and low-prevalence clusters were compared. Main Outcomes and Measures Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. The main measure was the overall risk ratio (RR) for ATRs to B or AB plasma or platelets in AGS high- vs low-prevalence clusters. Results In total, 558 823 platelet and plasma transfusions at 40 sites in 5 countries were analyzed, of which ATRs occurred in 1744 transfusions (0.3%). In the US AGS high-prevalence cluster (9 sites), significantly more ATRs of any severity occurred among patients with blood type O who received B or AB units vs patients with blood type O who received O units (overall RR, 3.93; 95% CI, 2.96-5.21; P &amp;lt; .001). In contrast, in the primary analysis of the AGS low-prevalence cluster (15 sites), excess ATRs to B or AB units were not detected. In subgroup analyses among patients with blood type O receiving B units, the RR for moderate to severe ATRs was 9.14 (95% CI, 5.39-15.52; P &amp;lt; .001) in the AGS high-prevalence cluster vs 2.15 (95% CI, 1.34-3.47; P = .002) in the AGS low-prevalence cluster. Outside the US, a signal consistent with TRAGS was not detected. Conclusions and Relevance This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.