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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 Of 15 accelerated approvals, 66.7% remained pending, 13.3% received full approval, and 20% were withdrawn.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.

We report that moderate hyperoxia during a critical window of mucociliary differentiation disrupts terminal maturation in neonatal airway epithelial cells cultured in a three-dimensional model. Hyperoxia induces mitochondrial bioenergetic dysfunction and metabolic reprogramming, with proteomic analysis identifying complex I disruption as a key driver of impaired differentiation. Overall, these findings reveal a previously underrecognized link between mitochondrial bioenergetics and airway epithelial development, positioning metabolic dysfunction as an early trigger of hyperoxia-induced neonatal airway injury.

Background: Surgical resection (SR) and liver transplantation (LT) are the main curative options for non-hepatocellular carcinoma (non-HCC) liver malignancies, including colorectal liver metastases (CRLMs), intrahepatic cholangiocarcinoma (iCCA), hilar cholangiocarcinoma (hCCA), and neuroendocrine tumor liver metastases (NETLMs). Resection aims for negative margins and adequate hepatic reserve, while LT offers treatment for unresectable disease but is limited by donor scarcity, immunosuppression, and ethical constraints. Methods: A targeted literature search (2005–2025) was conducted using PubMed and Google Scholar with predefined MeSH terms combining “liver resection,” “hepatectomy,” and “liver transplantation” across non-HCC malignancies. Relevant studies, reviews, and guidelines were included. Results: For CRLMs, SR remains standard with 5-year overall survival (OS) up to 58%, while LT offers 60–83% in highly selected unresectable cases. In iCCA, resection achieves median survival around 40 months, and LT yields OS up to 69% in very early or neoadjuvant-controlled disease. For hCCA, the Mayo protocol combining neoadjuvant therapy with LT provides 5-year OS of 65–80%. In NETLMs, LT achieves 63–97% OS under strict criteria. Conclusions: SR remains first-line for resectable non-HCC malignancies, while LT provides superior outcomes in unresectable yet biologically favorable disease, emphasizing careful selection and organ allocation.

Background: Endometriosis affects an estimated 10% of reproductive-aged women and is associated with increased ovarian cancer risk. While BRCA1/2 mutations are established risk factors for ovarian cancer, their association with endometriosis remains unclear. This study aimed to characterize the prevalence and clinical features of endometriosis within a large cohort of BRCA mutation carriers. Methods: A descriptive analysis was conducted using data from a multi-center longitudinal cohort of women with pathogenic BRCA variants. Reproductive history and related factors were collected through self-reported questionnaires and compared. Results: Among 16,950 BRCA carriers, the prevalence of endometriosis was 2.4%. Compared to BRCA carriers without endometriosis, those with endometriosis were more likely to carry a BRCA2 mutation, have post-secondary education, and experience earlier menarche. BRCA carriers with endometriosis had a lower ovarian cancer prevalence than those without (10% vs. 15%, p < 0.001). Conclusions: This is the first study of this scale to report the prevalence of endometriosis among BRCA mutation carriers, which was lower than previously reported in the general population. The association between endometriosis and ovarian cancer does not appear to be generalizable to this population. Further prospective studies are warranted to clarify this association among BRCA mutation carriers.

Key Points Health care utilization rates in elderly kidney transplant were no different between the high kidney donor profile index and low kidney donor profile index group. Number of readmissions and surgical interventions in elderly kidney transplant was no different between the high kidney donor profile index and low kidney donor profile index group. Death censored graft loss was higher in the high kidney donor profile index group, whereas the patient survival was no different between the high kidney donor profile index and low kidney donor profile index groups. Background High kidney donor profile index (KDPI) kidneys (KDPI >85%) are often associated with increased risks of post-kidney transplant (KT) complications and greater health care utilization (HCU), particularly in elderly recipients with multiple comorbidities. These concerns frequently lead to underutilization of high KDPI kidneys in older transplant candidates, thereby limiting their access to transplantation despite potential clinical benefits. The aim of this study was to compare post-KT HCU between elderly recipients of high versus low KDPI deceased donor kidneys. The primary outcome included differences in hospital readmissions, surgical interventions, and outpatient service use at multiple post-transplant time points. Secondary outcome included graft function, graft survival, and patient survival. Methods A retrospective analysis of elderly solitary KT recipients (age ≥65 years) between January 1, 2011, and December 31, 2020. Patients were stratified into high KDPI (>85%, n =160) and low KDPI (≤85%, n =453) groups. We assessed inpatient and outpatient HCU, including readmissions at 30, 90, and 365 days post-transplant, surgical interventions, and outpatient visits (emergency department, transplant clinic, endocrine clinic, and ambulatory infusion units). Results There were no statistically significant differences between high and low KDPI groups in rates of hospital readmissions, surgical interventions, or outpatient visits (all P > 0.05). Delayed graft function rates were also similar ( P = 0.61). The low KDPI group had significantly higher eGFR at 4 months, 1, 2, and 3 years post-transplant (all P < 0.001). However, days alive and out of the hospital within 90 and 365 days post-transplant were comparable between the groups (all P > 0.05). Overall patient survival was similar ( P = 0.08), although death-censored graft loss was significantly higher in the high KDPI group ( P = 0.001). Conclusions Among elderly KT recipients, high KDPI kidney recipients had comparable post-transplant HCU and overall survival with those receiving low KDPI kidneys, despite lower long-term graft function. These findings suggest that high KDPI kidneys remain a viable option for older patients, offering timely access to transplantation.

ABSTRACT Background Previous studies on the relationship between prediabetes, HbA1c and cognitive trajectories show mixed results. Therefore, we investigated the association of prediabetes, diabetes and HbA1c with change in global and domain‐specific cognitive scores in cognitively unimpaired (CU) adults, as well as the potential effect modification by sex or age. Methods This longitudinal study included 4236 CU persons aged ≥ 50 years from the population‐based Mayo Clinic Study of Aging. We ran linear mixed‐effect models with baseline prediabetes, diabetes and HbA1c predicting longitudinal global and domain‐specific (i.e., memory, language, attention/executive function, and visuospatial skills) cognitive z‐scores and raw scores. Models were adjusted for age, sex, education, medical comorbidity, repeated cognitive testing, and ApoEɛ4. We additionally ran models with sex and age interactions. Results Compared to normoglycemic individuals, individuals with prediabetes and diabetes showed poorer performance on cognitive tests, i.e., TMT‐B, category fluency, and block design subtest over time. Additionally, the presence of prediabetes, diabetes, longer diabetes duration and higher HbA1c were associated with faster global and domain‐specific cognitive decline over a median follow‐up of 6.4 years (range 1–19). Three‐way interactions showed that the effect of diabetes on decline in global cognition, attention and visuospatial domains was more pronounced in women than in men. Age did not modify the effect of diabetes or higher HbA1c on cognition. Conclusions The results suggest that prediabetes and diabetes significantly shorten the timeframe before a potentially clinically noticeable change in global and domain‐specific cognition is reached. Thus, lifestyle modification to reverse prediabetes and prevent diabetes could potentially reduce the rate of cognitive decline in aging populations. The findings differed by sex (i.e., the effect of diabetes on decline in global cognition, attention and visuospatial domains was more pronounced in women than men).