Citations

ABSTRACT Sodium glucose co‐transporter 2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are nephroprotective and their use is recommended for adults with chronic kidney disease (CKD). The role of SGLT2i and GLP‐1 RAs in patients with acute kidney injury (AKI) is unknown. This systematic review aimed to estimate the effect of SGLT2i or GLP‐1 RAs on clinical outcomes in AKI. We systematically searched Embase, MEDLINE, Scopus, Web of Science Core Collection, and clinical trials registries for observational studies and clinical trials from database inception to July 3, 2025. Included studies evaluated adults (≥ 18 years) with AKI during a hospitalization and compared patients subsequently exposed to either SGLT2i or GLP‐1 RAs to a non‐exposed control group. Random effects meta‐analyses were performed. Six studies related to SGLT2i (five observational, one randomized trial) and one related to GLP‐1 RAs (one observational) met eligibility criteria ( N = 432,048 patients). SGLT2i/GLP‐1 RA exposure was associated with lower odds of major adverse kidney events (MAKE) (OR 0.63, 95% CI 0.46–0.86) and all‐cause mortality [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.21–0.62] compared to controls. The odds for kidney replacement therapy were lower with SGLT2i therapy in the three studies where it was evaluated (OR 0.61, 95% CI 0.40–0.93). Sensitivity analyses restricted to SGLT2i data were consistent with the overall findings [MAKE OR 0.63 (95% CI 0.42–0.95); Mortality OR 0.34 (95% CI 0.18, 0.65)]. Exposure to SGLT2i or GLP‐1 RAs after AKI, examined primarily in observational studies, was associated with improved clinical outcomes. These findings are promising and warrant evaluation in randomized clinical trials.

Abstract Pulmonary fibrosis (PF) involves excessive collagen accumulation, yet mechanisms shifting the balance of synthesis and degradation toward net deposition remain unclear. Myeloperoxidase (MPO) inversely correlates with survival in PF. Using the bleomycin model, we found MPO knockout (MPOko) mice were protected from fibrosis, and pharmacological MPO inhibition after peak inflammation (day 7) recapitulated this protection. MPO persisted in lung tissue 21 days post-injury despite neutrophil efflux, linking acute inflammation to sustained remodeling. Mechanistically, we identified that MPO inhibits Cathepsin K (CatK), a potent collagenolytic enzyme involved in fibrosis resolution. Notably, CatK gene expression ( CTSK ) is elevated in PF, suggesting post-translational inhibition of CatK. MPOko and inhibitor-treated mice exhibited elevated CatK activity after bleomycin; exogenous addition of pathophysiologic concentrations of MPO reduced CatK activity in mouse precision-cut lung slices and human fibroblasts. Biochemically, MPO reduced CatK activity to 33% of control. In two distinct cohorts of PF patients, we observed significantly increased MPO protein levels in platelet poor plasma and in lung tissue. In PF patients, 62% had MPO levels in platelet poor plasma exceeding healthy controls, while lung tissue from other PF patients showed significantly elevated MPO staining. Plasma levels were inversely correlated with decreased survival, FVC, and DLCO. These findings establish MPO as a post-translational inhibitor of CatK-mediated collagenolysis, revealing a mechanism linking acute inflammation to sustained fibrosis and suggest a patient subpopulation that may benefit from MPO-targeted therapy. Graphical Abstract Myeloperoxidase persists in lung tissue after injury and inhibits cathepsin K activity, impairing collagen degradation and promoting extracellular matrix accumulation during pulmonary fibrosis.

Background Psychiatric disorders are increasingly contributing to global disability. Despite advances in conservative management, the prevalence of treatment-resistant cases remains high. Meanwhile, neurosurgery for psychiatric disorders (NPD) remains underused, largely due to strict regulations and historical concerns, particularly those related to neuropsychological side effects (NPSE). Objective To address this issue, we conducted a systematic review with meta-analysis to compare NPSE associated with radiofrequency ablative NPD to those observed in neuro-oncological, neurovascular and epilepsy surgeries. Methods PubMed, Embase and LILACS databases were searched in April 2024 for articles published in English/Spanish from 1990 to 2022, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results A total of 48 articles with 2678 participants were included. The frequency of transient and permanent NPSE in the NPD group ranged from 0.94% to 11.50% and 0.94% to 2.03%, respectively, comparable to the other surgical groups (epilepsy: 0.31–11.70%; vascular: 0.52–22.90%; oncology: 0.94–17.60% for transient NPSE; epilepsy: 0.31–12%; vascular: 0.40–1.96% and oncology: 0.84–1.48% for permanent NPSE). Regarding permanent NPSE, arguably the most critical consideration, the NPD group showed better outcomes in memory, language and social cognition than the epilepsy group, but worse outcomes in executive and perceptual-motor functions. Compared with the vascular group, the NPD group had better executive function but worse complex attention. Finally, the NPD group had fewer permanent deficits than the oncology group in executive function, complex attention and perceptual-motor domains, although language performance was lower. Conclusions Contemporary NPD apparently carries a similar risk of NPSE as other conventional neurosurgical procedures, challenging misconceptions and this unjustified barrier to its broader use.

Abstract Purpose: This multicenter, multi-surgeon retrospective study aimed to identify risk factors for postoperative cerebrospinal fluid (CSF) leak following endonasal resection of craniopharyngioma, while evaluating the "perception gap" through a surgeon survey. Methods: A retrospective review was conducted on 416 patients who underwent endoscopic transsphenoidal surgery (ETS) for craniopharyngioma from 20 institutions. Factors were compared between patients with and without postoperative CSF leak, and between Early (2007-2015) and Late (2016-2025) Epochs. Complementing the clinical data, a survey of 19 neurosurgeons captured expert perspectives on risk stratification and management strategies. Results: Overall postoperative CSF leak rate was 13.5% (56/416 patients). Univariate analysis identified predominantly cystic tumors (34% vs. 21%, p = 0.034)and intraoperative lumbar drain (LD) use ( p < 0.028) as associated with postoperative CSF leak. BMI ( p = 0.587), prior surgery ( p = 0.576), and tumor size ( p = 0.363) were not significant. In the multivariable analysis, LD use was associated with a higher postoperative CSF leak rate (OR 1.91, 95% CI 1.06–3.46; p = 0.030). Between Epochs, nasoseptal flap (NSF) utilization increased from 70.7% to 87.6% ( p <0.001). NSF was protective (OR 0.28, 95% CI 0.07–0.92; p = 0.037) in the Early Epoch; no factors were significant in the Late Epoch. The surgeons’ survey identified prior surgery and intraoperative high flow leaks as primary risks; however, their LD protocols diverged from clinical data. Conclusion: Despite increased use of NSF, CSF leak persists. The study highlights a significant divergence between expert perception and clinical data regarding lumbar drains.

Background Reductions in blood pressure (BP) control among patients with hypertension were observed early in the COVID‐19 pandemic. The degree to which BP control may have returned to prepandemic levels is unknown. Methods Individuals aged 18 to 85 years with hypertension from 17 health systems participating in the National Patient‐Centered Clinical Research Network were identified using electronic health record data collected as part of routine care. BP control (percentage of patients whose most recent BP measurement was <140/<90 mm Hg) was estimated in a series of 12‐month rolling measurement periods from 2017 through 2022 (January 1, 2017 through December 31, 2017; April 1, 2017 through March 31, 2018; … January 1, 2022 through December 31, 2022). Differences in average BP control between 2022 (January 1, 2022 through December 31, 2022) and 2019 (January 1, 2019 through December 31, 2019) were estimated overall (adjusted for age, sex, and race and ethnicity) and by race and ethnicity (adjusted for age and sex). Results Our sample included 1 193 314 persons with hypertension in 2019 (48.9% aged 65–85 years, 52.9% men, 66.2% non‐Hispanic White) and 1 499 418 individuals in 2022 (50.6% aged 65–85 years, 47.1% men, 62.7% non‐Hispanic White). The weighted average BP control dropped from 65.3% in 2019 to 61.8% in 2020 and then partially recovered to 62.6% in 2022 (adjusted mean difference, −2.6 percentage points [95% CI, −5.0 to −0.2]). Non‐Hispanic Asian individuals experienced the largest temporal drop in BP control, declining from 68.4% in 2019 to 63.9% in 2022. Conclusions BP control was disrupted during the COVID‐19 pandemic and had not fully rebounded to prepandemic levels by the end of 2022. Continued surveillance is needed to determine whether the decline in BP control will persist and will result in future adverse cardiovascular events.

ABSTRACT Introduction It is controversial whether surgical correction of tethered spinal cord in non‐myelomeningocele tethered cord patients results in reversal versus stabilization of urologic (GU), gastrointestinal (GI), and musculoskeletal (MSK) symptoms. Objective To determine factors associated with clinical improvement in symptoms after spinal cord de‐tethering, and evaluate whether pre‐operative urodynamic testing predicts post‐operative clinical outcomes. Methods 213 non‐myelomeningocele children who underwent primary spinal cord de‐tethering at a quaternary children's hospital from 2012 to 2020 were retrospectively reviewed. Age at surgery, gender, and presence of GU symptoms, constipation, MSK symptoms, and urodynamic studies were collected. Pre‐operative symptoms and demographics were compared between patients with and without resolution of GU symptoms after surgery. Results Mean age at surgery was 5.36 years, 48% were female, and mean length of follow up was 1.8 years. Before surgery, 133/213 (62%) experienced a GU symptom. 105/213 (49%) patients were potty‐trained. Of 105 potty‐trained patients, 50 (48%) had daytime incontinence and 55 (52%) had nocturnal enuresis. Of 88 potty‐trained patients with urinary symptoms, 22 (25%) had resolution of and 59 (67%) had improvement following surgery. Of the 102 with constipation, 45 (44%) had improvement. Of the 116 with musculoskeletal symptoms, 60 (52%) had improvement. Patients with resolution of GU symptoms were younger (4.97 vs. 8 years, p = 0.0019). Patients with daytime urinary incontinence ( p = 0.0119) were less likely to have resolution of GU symptoms. There was no difference in urodynamic findings between patients with and without improvement or resolution of urologic symptoms. Conclusion Younger age at de‐tethering surgery is associated with improvement in genitourinary symptoms. Preoperative urodynamic studies may not be predictive of postoperative outcomes.

Homeobox (HOX) transcription factors are encoded within highly organized loci expressed along an anterior–posterior axis through embryogenesis and in a pleiotropic manner in hematopoiesis. HOX expression has been exhaustively studied in the context of oncogenesis and malignancy, but the compensatory substitution of HOX paralogs makes mechanistic annotation in steady-state hematopoiesis challenging. Despite this, HOX genes reflect numerous non-redundant roles in healthy hematopoiesis including HSC self-renewal, development, lymphopoiesis, myelopoiesis, and erythropoiesis. Here, we review historical and current insights into HOX functions in steady-state hematopoiesis and highlight unexplored avenues in their biology that could further elucidate their significance to hematopoietic homeostasis.

PURPOSE Homologous recombination deficiency (HRD) is a key determinant of sensitivity to DNA-damaging agents; however, its genomic characterization in colorectal cancer (CRC) remains limited. This study investigated whether low RNA expression of homologous recombination (HR) genes identifies patients with metastatic CRC who derive survival benefit from oxaliplatin- or irinotecan-based therapy. METHODS A total of 22,957 metastatic CRC samples were subjected to DNA and RNA sequencing (Caris Life Sciences, Dallas, TX). Patients with microsatellite instability–high or pathogenic HR gene mutations were excluded to define a HR-proficient cohort. Overall survival (OS) was compared between patients with low (bottom 25%) versus high (top 25%) RNA expression of HR genes after oxaliplatin or irinotecan exposure. Validation was performed in the PARADIGM phase III trial cohort (n = 262) of first-line modified fluorouracil, leucovorin, and oxaliplatin-treated patients with available RNAseq data. RESULTS In the discovery cohort, low expression of core HR genes correlated with significantly longer OS after oxaliplatin or irinotecan exposure, specifically RAD51 (43.0 v 36.3 months; P < .005) and BLM (42.9 v 34.2 months; P < .005). Similar associations were observed for RAD51 (28.1 v 22.9 months; P = .02) and BLM (29.1 v 23.2 months; P < .005) in irinotecan-treated patients. In the PARADIGM validation cohort, low BLM expression was associated with improved OS (41.5 v 22.4 months; HR = 0.52; P = .002), whereas RAD51 showed a favorable but nonsignificant trend. These findings remained significant after adjustment for treatment arm, tumor sidedness, and metastatic burden. CONCLUSION Low BLM RNA expression is associated with improved survival after treatment with DNA-damaging agents, whereas low RAD51 expression shows a favorable but nonsignificant trend. These findings are exploratory and suggest that RNA-based HR gene expression may warrant further investigation as a potential prognostic biomarker in metastatic CRC.

Abstract Introduction: Black prostate cancer (CaP) survivors experience unique quality-of-life (QoL) and recovery challenges after treatment compared with their White counterparts. Smartphone-delivered mobile health interventions offer promising avenues for symptom tracking and lifestyle changes; but their feasibility, user engagement, and acceptability in this population remain unclear. This study assessed the feasibility, engagement, and preliminary impact of the Survivorship App for Ethnically Diverse Black Prostate Cancer Survivors (SAFE-CaPS), designed to improve self-monitoring behaviors and health outcomes. Methods: Nine Black CaP survivors (seven U.S.-born, one African-born, and one Caribbean-born) participated in a 12-week pilot study of SAFE-CaPS. The app provided daily prompts for symptoms (pain, sleep, fatigue, sexual function, anxiety, depression) and behavior tracking (physical activity, diet), brief self-management support, and physician alerts for severe symptom reports. Mental health (GAD-7 and PHQ-9) and QoL (FACT-P) were assessed at baseline and after 12 weeks. Feasibility was evaluated based on adherence rates (i.e., ≥70% of daily diary entries). Engagement and acceptability were assessed via app analytics and qualitative interviews on usability and cultural relevance. Participants were compensated up to $125 via Greenphire ClinCard. Surveys were analyzed with SPSS v29, and interviews with Atlas.ti v23. Results: Participants’ median age at diagnosis was 56 years; six had a positive family history of CaP, and four had undergone radical prostatectomy. Four participants met the feasibility threshold, and eight completed the study. Most daily entries reflected mild pain, fatigue, bowel and urinary issues, and generally good sleep. Several participants frequently reported severe sexual dysfunction, and most diary responses indicated &lt;20 minutes of physical activity per day. Fruit/vegetable intake was low, with about half of daily responses showing 1-2 servings. At baseline, eight participants had minimal anxiety, while five had moderate depression. Overall, QoL improved from week 1 to week 12 in physical, emotional, and functional well-being, while social well-being declined over time. Interviews emphasized the app’s user-friendly design, ease of navigation, and acceptability as key strengths, with several participants highlighting its simplicity and ease of use, with recommendations to reduce repetitive items and address minor technical issues. Conclusions: SAFE-CaPS was feasible and well accepted. Sexual dysfunction, low physical activity, and moderate depression emerged as key concerns, heightening the need for integrated mental health, activity support, and stronger engagement strategies in future mHealth interventions. Citation Format: Gaurav Kumar, Parisa Ghasemi, Yan D. Zhao, Zsolt Nagykaldi, Kathleen A. Dwyer, Andrew G. McIntosh, Ernie Kaninjing, Mary E. Young, Dickey Sabrina, Daniel Morton, Opeyemi Bolajoko, Darla E. Kendzor, Motolani Ogunsanya. Feasibility of a survivorship app for black prostate cancer survivors: Results from a 12-week mHealth pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6307.