Citations

PURPOSE Outcomes in systemic light chain (AL) amyloidosis have improved with modern therapy limiting utility of existing risk stratification models. We validate a new staging system, incorporating longitudinal strain (LS) to the biomarker-based (NT-proBNP and Troponin-T) staging system in the contemporary treatment era (2015-2024). METHODS AL International Staging System (AL-ISS) was derived from a cohort of patients with AL amyloidosis from the UK National Amyloidosis Centre (2015-2019). The model was validated in patient cohorts from Europe (Greece, Italy, the Netherlands, and Switzerland), the United States (2015-2024), and the United Kingdom (2020-2024). RESULTS In total, 2,493 patients were included (derivation, n = 573; validation n = 1,920). In a multivariable model for the derivation cohort, LS ≥ –9% and cardiac biomarkers at previously validated thresholds (NT-proBNP 332 ng/L and 8,500 ng/L and high-sensitivity troponin T ≥ 50 ng/L) were independent poor prognostic factors stratifying patients into stages I, II, IIIA, IIIB, and IIIC. In the validation cohort, the patient stages were stage I: 317 (17%), II: 782 (41%), IIIA: 551 (29%), IIIB: 174 (9%), and IIIC: 96 (5%), respectively (first-line daratumumab treated: 826; 43%). With a median follow-up of 34 months, median overall survival (OS) was not reached (NR); estimated 1-year, 2-year, and 3-year OS was 82%, 74%, and 70% respectively. The median survival for stages I to II, IIIA, IIIB, and IIIC were NR, 67, 26, and 7 months (1-year OS IIIC 53% v 68% for IIIB in the daratumumab-treated patients), respectively ( P < .001). External validation exhibited good predictive performance: 12-month calibration slope was 1.09, Harrell C 0.69, Royston D 1.19, and R 2 D 0.25. Stage IIIC independently discriminated the poorest outcome across all cohorts. CONCLUSION This defines and validates a new staging system from systemic AL amyloidosis with robust identification of an ultra-poor risk stage (IIIC) in contemporarily treated patients.

ABSTRACT Purpose There is limited evidence regarding the optimal timing of urosymphyseal fistula (USF) repair. Our aim was to conduct a comparative analysis evaluating the postoperative complications and surgical outcomes among patients undergoing surgery for USF, comparing those treated in an early versus delayed fashion. Methods Fifty‐eight patients with diagnosis of USF and who underwent fistula decompression, pubic bone resection, and urinary tract reconstruction were included. Patients who underwent USF repair within 100 days of diagnosis were classified as having early repair, while those treated after 100 days were considered to have delayed repair. Results Thirty‐one underwent delayed USF repair (53.4%), while 27 underwent early repair (46.6%). Most patients were male (96.8%). The median age (72 years vs . 69 years, p = 0.13) and mean BMI (28.7 vs . 28.6, p = 0.97) were comparable between groups. The rate of overall 90‐day complications following USF repair was comparable between groups (77.4% vs . 63%, p = 0.228). We did not find a difference between the rates early complications among groups. The rates of long‐term recurrent pain (46.7% vs . 11.1%, p = 0.004), recurrent osteomyelitis (20% vs . 0%, p = 0.014), and fistula (23.3% vs . 3.7%, p = 0.033) were higher in the delayed USF repair group compared to the early USF repair group. The follow up time was similar between groups too (25.43‐months vs . 32.8‐months, p = 0.257). Conclusion While early USF repair might not affect the incidence of early complications within 90 days post‐surgery, it is associated with reduced rates of long‐term recurrent pain, recurrent osteomyelitis, and fistula recurrence compared to delayed USF repair.

Abstract Background Outcomes of patients with acute pyelonephritis (AP) treated in a hospital-at-home setting have not been comprehensively evaluated in the United States. Methods We performed a multicenter, retrospective cohort study of adults diagnosed with and managed for AP in Mayo Clinic's Advanced Care at Home (ACH) program between July 2020 and January 2025. Collected data included demographics, Charlson Comorbidity Index (CCI), genitourinary comorbidities, severity of illness (SOI), and risk of mortality (ROM) scores, as well as pyelonephritis-related complications. Outcomes included length of stay (LOS), escalation of care, and 30-day postdischarge emergency department (ED) visits, readmissions, and mortality. Results A total of 165 patients met inclusion criteria. Median age was 67 years; SOI scores were moderate in 33.3%, major in 52.1%, and extreme in 8.5%. ROM scores were moderate in 30.3%, major in 38.2%, and extreme in 6.7%. Median CCI score was 5, and all patients had preexisting genitourinary conditions. On admission, 30.9% met sepsis criteria, acute kidney injury was present in 47.3%, and bacteremia developed in 33.3%. Median LOS in the ACH program was 3.1 days. Only 4.8% required escalation to a brick-and-mortar hospital. Readmission occurred in 17.0%, and 4.8% had ED visits. No in-program deaths occurred. Conclusions This multicenter retrospective study shows that AP, including cases with high illness severity and complex comorbidities, can be managed safely and effectively in a hospital-at-home setting with careful patient selection and robust infrastructure to support timely escalation when needed.

Abstract Background The increasing reliance on accelerated approvals and surrogate endpoints for Food and Drug Administration (FDA) approvals of gastrointestinal (GI) cancer therapies raises concerns about their clinical benefit and long-term patient outcomes. The shift toward single-arm trials in regulatory decisions further complicates treatment evaluation. Material and Methods This retrospective observational study evaluated all FDA approvals for GI cancer therapies from January 2006 through January 2025. Data were extracted from FDA archives, ClinicalTrials.gov, and PubMed. Approvals were categorized by regulatory pathway (accelerated vs regular), trial design (single-arm vs randomized), and primary endpoint (surrogate vs overall survival [OS]). Clinical benefit was assessed based on OS improvement and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). The primary outcome was the proportion of approvals based on surrogate versus OS endpoints. Secondary outcomes included use of single-arm designs, frequency of accelerated approvals, OS gain, and the proportion meeting ESMO-MCBS substantial benefit (score ≥ 4). Results The FDA granted 60 GI cancer drug approvals from 67 trials. Approvals rose from 15 (25%) in 2006-2014 to 45 (75%) in 2015-2025. Single-arm trials increased to 24%, and surrogate endpoints were used in 41.8% (ORR 20.9%, PFS 19.4%). Median OS improvement was 2.1 months (IQR: 1.6-2.65). Only 24.3% of trials met ESMO-MCBS substantial benefit. Of 15 accelerated approvals, 66.7% remained pending, 13.3% received full approval, and 20% were withdrawn. Conclusion Expedited approvals have improved drug access in GI oncology, but modest benefits highlight the need to balance speed with outcomes that truly matter to patients.

ABSTRACT Objectives To critically evaluate clinical and voice‐related outcomes of in‐office serial intralesional steroid injection (SILSI) in adults diagnosed with idiopathic subglottic stenosis (iSGS). Data Sources MEDLINE, Embase, CINAHL Ultimate, CENTRAL, ClinicalTrials.gov . Review Methods A systematic search of databases was conducted from inception through April 5, 2025. Studies eligible for inclusion must have reported on adult SILSI recipients undergoing management of iSGS. Articles were independently screened and reviewed by two authors for treatment variables including steroid protocol, clinical outcomes, respiratory function, vocal outcomes, and complications. Results Of 383 studies identified, 14 met inclusion criteria ( n = 371). Triamcinolone was the most commonly used agent in 10 studies. Steroid dosage, number of treatment sessions, and injection interval varied widely across studies. Improvements in surgery‐free interval, peak expiratory flow, dyspnea index, degree of stenosis, and voice‐related outcomes were observed in several studies. No major complications were reported in the included studies. Conclusion Current evidence suggests SILSI represents a promising adjunctive therapy in the treatment of iSGS, with improvement noted across several measures. However, significant variability in steroid treatment regimens and inconsistent reporting of outcomes complicate interpretations of efficacy.

ABSTRACT Radiology education is critical for medical students' anatomical competence and clinical readiness. However, it remains insufficiently integrated in medical curricula as residency program directors describe interns' basic image interpretation as unsatisfactory. This review aims to assess the efficacy of ultrasound, CT, MRI, and X‐ray in facilitating the learning of anatomy among medical students. Following PRISMA guidelines, 983 articles were screened, and 52 studies published between 2000 and 2025 met the inclusion criteria by comparing radiology‐integrated anatomy education with traditional methods such as cadaver and atlas use. Data extraction covered study design, radiology modalities, and effect sizes. Both integrated and traditional methods consisted of medical student cohorts assessed on objective knowledge and skills with recorded quantitative outcomes. Included studies showed knowledge gains on multiple choice assessments (pooled Cohen's d = 0.99, 95% CI: 0.34–1.65) but with high heterogeneity among studies ( I 2 = 99.5%). Controlled designs were used in 21% of studies. Other investigations (68% of studies) used attitudinal surveys that revealed strong student preference for radiology‐integrated learning. Of the modalities present, ultrasound was predominant (85% of studies), with other modalities (CT: 15%; MRI/X‐ray: < 5%) substantially underrepresented despite clinical relevance. Radiology integration was shown to enhance anatomy education and clinical preparedness. The incorporation of radiology, specifically ultrasound, into anatomical education leads to a significant and substantial improvement in student learning outcomes. Future investigations can standardize assessments, expand multimodal research, and address global curricular disparities.

PURPOSE Previous studies suggest that SPOP mutations result in increased sensitivity to androgen receptor pathway inhibitors (ARPIs) but are limited by lack of granular data. We hypothesize that SPOP mutations are associated with improved outcomes across the spectrum of advanced prostate cancer (PC). METHODS Using the real-world clinicogenomic Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort database, we analyzed outcomes based on SPOP mutation status. The primary end point was overall survival (OS) from the diagnosis of metastatic disease. Secondary end points included real-world progression-free survival (PFS) and PSA90 response. RESULTS Among 2,097 patients with metastatic PC, 5.5% (N = 115) had SPOP -mutated tumors. Compared with SPOP wild-type, patients with SPOP mutations were older at diagnosis (median 65 v 63 years; P = .001) and had higher (≥8) Gleason sum (68% v 54%; P = .02), higher incidence of lung metastasis (17% v 6%; P = .001), and increased frequency of intraductal features (13% v 5%; P < .001). SPOP mutations were associated with improved PSA90 response with first ARPI exposure in the castrate-resistant setting (60% v 40.6%; OR, 2.20 [95% CI, 1.15 to 4.19]; P = .02) but not in the castrate-sensitive setting (78.9% v 71.5%; OR, 1.49 [95% CI, 0.66 to 3.37]; P = .43). Median PFS with first ARPI did not differ in SPOP- mutated versus wild-type group in both the castrate-sensitive (24.2 v 19.2 months; hazard ratio [HR], 0.80 [95% CI, 0.49 to 1.32]; P = .39) and castrate-resistant settings (15.0 v 12.4 months; HR, 0.81 [95% CI, 0.58 to 1.12]; P = .20). In multivariable analysis, SPOP mutations were associated with improved OS (HR, 0.65, P = .02). CONCLUSION SPOP mutations were associated with longer OS despite the presence of aggressive clinical features. The distinct clinical and molecular features of SPOP -mutated PC support its consideration as a unique molecular subtype with prognostic implications.

Abstract Systems-based hematology (SBH) is an emerging discipline focused on optimizing care delivery for patients with hematologic disorders within complex health care systems. Despite its growing importance, the field lacks a formal definition, standardized curriculum, and clear career pathway, hindering widespread adoption and training of future SBH experts. We sought to define core principles, competencies, challenges, and future directions of SBH to identify foundational components for a potential educational curriculum. Semistructured interviews were conducted with 8 SBH experts. Expert participants were identified through their committee involvement with the American Society of Hematology. Five overarching themes emerged: (1) The accidental expert: SBH careers have developed organically and reactively in response to pressing institutional needs, not through formal training; (2) Defining the unseen: experts define the field pragmatically by its function and roles; (3) The SBH toolkit: success requires a hybrid skillset combining clinical hematology expertise with health systems science (HSS) principles; (4) The architect's dilemma: the field's growth is hindered by interdependent challenges of building a curriculum, awareness, and securing resources; and (5) Charting the future: the discipline is poised for growth, driven by increasing health care complexity and specialization. SBH represents the nexus of HSS principles and hematology care. Formalizing SBH requires a multipronged approach, including developing a standardized curriculum that equips learners with a hybrid skillset, creating clear value for health systems and patients, and fostering a community of practice through professional societies. These findings provide a foundational framework for developing educational resources and institutional support necessary to continue advancing SBH.