Nevin Manimala

J Urol. 2026 May 20:101097JU0000000000005127. doi: 10.1097/JU.0000000000005127. Online ahead of print.

ABSTRACT

PURPOSE: MRI membranous urethral length is associated with post-prostatectomy continence. Nevertheless, it is not routinely used for patient counseling because predictive models haven’t been externally validated. The objective of this study was to assess the performance of membranous urethral length continence model on an external cohort.

METHODS: A continence prediction model was applied to a prospective cohort of patients with a pre-prostatectomy MRI and validated assessment of post-operative continence between 2015-2023. Patients from multiple surgeons underwent open or robotic prostatectomy. Membranous urethral length was retrospectively measured by two reviewers. The model included: age, nerve spare plan, prostate volume, surgical approach, and membranous urethral length. Continence definitions were: 0 pads/24hours and 0-1 pad/24 hours. Model performance was assessed using c-statistics, calibration curves, and decision curve analyses.

RESULTS: Among 500 patients, median membranous urethral length was 11 mm (IQR 8.1, 14). One-year post-prostatectomy continence (defined as 0 pads/24h) occurred in 312 (62%) patients. The c-statistic was 0.64 (95% CI 0.59, 0.69). The calibration was poor. The decision curve analysis showed no net-benefit of using the model. Continence defined as 0-1 pad/24h was achieved in 450 (90%) patients. The c-statistic was 0.69 (95%CI 0.61, 0.76) and the calibration was moderate. Decision curves showed a net-benefit of using the model over a range of clinically relevant continence risk thresholds.

CONCLUSION: This recalibrated prediction model incorporating MRI derived membranous urethral length provides net-benefit for predicting continence defined as 0-1 pad/24h. However, the model was not useful for predicting 0 pad use.

PMID:42160664 | DOI:10.1097/JU.0000000000005127

Lab Med. 2026 Apr 3;57(3):lmag025. doi: 10.1093/labmed/lmag025.

ABSTRACT

INTRODUCTION: ATP2B1 and STK39 loci influence blood pressure in genome-wide association studies. We tested whether ATP2B1 rs2681472 and STK39 rs35929607 are associated with essential hypertension and blood pressure.

METHODS: We studied 194 untreated hypertensive adults and 191 normotensive control individuals. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Logistic regression evaluated hypertension risk, and linear regression assessed systolic and diastolic blood pressure (BP) under genotypic, dominant, and additive models, with adjustment for clinical covariates; the false discovery rate was controlled.

RESULTS: The STK39 rs35929607 G allele was associated with hypertension (adjusted odds ratio [OR], 1.97 [95% CI, 1.21-3.21]; P = .007) and higher systolic BP (+8.02 mm Hg per G allele, 95% CI, 2.18-13.87; P = .007). Effects on diastolic BP were weaker (additive P = .10; dominant P = .06). ATP2B1 rs2681472 showed no statistically significant associations (hypertension per T allele OR, 1.18 [95% CI, 0.74-1.87]; P = .49). In sex-stratified analyses, STK39 associations were evident in men (hypertension OR, 3.22 [95% CI, 1.42-7.31]; P = .005; systolic BP, +15.88 mm Hg [95% CI, 5.95-25.80]; P = .002) but not in women.

DISCUSSION: In our study cohort, STK39 rs35929607 is associated with essential hypertension and higher systolic BP, with possible sex-specific effects. ATP2B1 rs2681472 is not associated with hypertension or BP traits.

PMID:42160625 | DOI:10.1093/labmed/lmag025

J Pak Med Assoc. 2026 Apr;76(4):567-570. doi: 10.47391/JPMA.20901.

ABSTRACT

OBJECTIVE: To evaluate adherence to the guidelines for the management of gallstones in a tertiary care setting.

METHODS: The clinical audit was conducted at the General Surgical Unit VI, Civil Hospital, Karachi, and comprised data of laparoscopic cholecystectomy from October 1 to November 1, 2023. Management practices were assessed using the guidelines published by the National Institute of Health and Care Excellence. The audit conformed to the Standards for Quality Improvement Reporting Excellence 2.0 guidelines for quality improvement projects. Data was analysed using SPSS 20.

RESULTS: Of the 62 patients, 49(79%) were females, 12(21%) were males, 18(29%) were aged 40-50 years and 17(27.4%) were aged 30-49 years. All the 62(100%) patients underwent liver function tests and an ultrasound of the abdomen. There were 26(41.9%) patients with acute cholecystitis, and 6(23%) underwent surgery within a week of diagnosis as recommended. There were 48(77.4%) symptomatic patients, and the recommended day-care admission was employed for 15(31,3%).

CONCLUSION: The delay in surgical intervention for acute cholecystitis warranted attention. Balancing this with resource limitations underscored the need for effective adaptive strategies to optimise patient care.

PMID:42160558 | DOI:10.47391/JPMA.20901

J Neuropathol Exp Neurol. 2026 May 20:nlag032. doi: 10.1093/jnen/nlag032. Online ahead of print.

ABSTRACT

Astrocytes play essential roles in various functions including ionic homeostasis, energy metabolism, neurotransmission, and regulation of the blood-brain barrier. Researchers have reported that hyperphosphorylated tau in astrocytes can be identified in postmortem, particularly in individuals over the age of 60 years. Astrocytic p-tau has also been reported in association with chronic traumatic encephalopathy neuropathologic change (CTE-NC). This study investigates possible association between subpial aging-related tau astrogliopathy (ARTAG) and a history of playing high school American-style football. Postmortem brain tissue samples were obtained from 176 men (median age at death = 65 years; range = 50-96) from the Lieber Institute for Brain Development. There were 128 with no known history of participating in contact or collision sports and 48 (27.3%) who participated in football. Subpial ARTAG was identified in 23 cases (13.1%). Those who participated in football had a higher percentage with subpial ARTAG than those who did not participate in football (20.8% vs 10.2%), although this difference was not statistically significant (P =.061). The 2 groups did not differ in the percentages who had subpial ARTAG in a sulcal depth (10.4% of former football players and 7.8% of controls). More research is needed to understand possible associations between subpial ARTAG, aging, and CTE-NC.

PMID:42160102 | DOI:10.1093/jnen/nlag032

G3 (Bethesda). 2026 May 20:jkag076. doi: 10.1093/g3journal/jkag076. Online ahead of print.

ABSTRACT

Coccolithophores, such as Gephyrocapsa huxleyi (formerly Emiliania huxleyi) play a key role in oceanic carbon cycling through calcification. However, the molecular mechanisms regulating coccolith formation remain unclear. In this study, we performed an integrative analysis of whole-genome bisulfite sequencing (WGBS) and RNA-Seq data on two closely related strains of G. huxleyi: the calcifying M217 and the non-calcifying CCMP1516. We identified over 17,000 differentially methylated regions (DMRs) and more than 12,000 differentially expressed genes (DEGs) between the two strains. Our findings reveal statistical associations between DNA methylation patterns-particularly in CpG contexts-and changes in gene expression, implicating epigenetic regulation of calcification. Functional enrichment analyses highlighted genes involved in dynein complex activity, phosphate transport, carbonic anhydrase function, and calcium signaling as key contributors to biomineralization. Statistical modeling confirmed that hypo-methylation in promoter and gene regions is positively associated with gene expression, especially in calcification-related genes. However, the expression differences between the strains are complex and cannot be fully explained by methylation changes alone. This work provides new molecular insights into epigenetic regulation of biomineralization in coccolithophores, with implications for understanding environmental adaptation and biogeochemical cycling.

PMID:42160072 | DOI:10.1093/g3journal/jkag076

JAMA Psychiatry. 2026 May 20. doi: 10.1001/jamapsychiatry.2026.1053. Online ahead of print.

ABSTRACT

IMPORTANCE: Interleukin 6 (IL-6), a keystone inflammatory cytokine, is a credible mechanistic candidate for causing depression. However, randomized clinical trials testing its treatment potential remain scarce.

OBJECTIVE: To identify likely treatment-sensitive outcomes and effect size for systemic IL-6 inhibition in patients with difficult-to-treat depression.

DESIGN, SETTING, AND PARTICIPANTS: This 4-week, proof-of-concept, double-blind, parallel-arm, placebo-controlled randomized clinical trial recruited adults with moderate-to-severe International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) depression, poor antidepressant response, low-grade systemic inflammation (high-sensitivity C-reactive protein [hs-CRP] level ≥0.3 mg/dL on 2 tests), and depression somatic symptoms (Beck Depression Inventory II somatic symptoms score ≥7) from primary and secondary care and self-referral from 2018 to 2022. Participants were randomized into minimization balanced groups on depression severity and sex. Assessments were conducted at baseline and 7, 14, and 28 days after infusion. Data were analyzed from 2023 to 2025.

INTERVENTION: Single intravenous infusion of IL-6R antagonist tocilizumab (8 mg/kg, maximum 800 mg/patient) or normal saline.

MAIN OUTCOMES AND MEASURES: The primary outcome was depression somatic symptoms at 14 days after infusion. The secondary outcome was total depression severity. Exploratory outcomes included fatigue, anxiety, anhedonia, quality of life, and cognition. Outcomes were assessed using validated scales and interpreted against clinically meaningful thresholds.

RESULTS: A total of 30 participants (mean [SD] age, 41.1 [12.3] years; 24 [80.0%] female) were randomized, including 14 in the tocilizumab group and 16 in the placebo group. Of these, 29 participants received the assigned infusion and completed follow-up. As expected for a small proof-of-concept study, no results reached statistical significance, including little improvement in depression somatic symptoms at day 14 (adjusted mean difference: -0.12; 95% CI, -2.51 to 2.28). However, a pattern of greater stepwise improvement over time was observed with tocilizumab in somatic symptoms, depression severity, fatigue, psychological symptoms, state anxiety, and quality of life, with the largest effects observed at the final follow-up (day 28). Tocilizumab may also improve more individual depressive symptoms. Treatment effects were within ranges considered clinically meaningful for depression severity, fatigue, anxiety, and quality of life. At the final follow-up, remission (7 participants [53.9%] vs 5 participants [31.3%]; number needed to treat [NNT] = 5) and response (6 participants [46.2%] vs 3 participants [18.8%]; NNT = 4) rates favored tocilizumab compared with placebo. Baseline hs-CRP level, but not IL-6 level, tracked depression improvement, suggesting hs-CRP may better predict immunotherapy response in depression than drug-specific biomarkers. Tocilizumab was well tolerated, with no serious adverse events or withdrawals.

CONCLUSIONS AND RELEVANCE: These findings highlight treatment-sensitive outcomes, effect sizes, and patient selection methods for testing systemic IL-6 inhibition in patients with difficult-to-treat depression, and call for a large-scale efficacy trial of anti-IL-6 treatment in depression.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16942542.

PMID:42160062 | DOI:10.1001/jamapsychiatry.2026.1053

JAMA Netw Open. 2026 May 1;9(5):e2613689. doi: 10.1001/jamanetworkopen.2026.13689.

ABSTRACT

IMPORTANCE: Judicious use of radiology imaging is an important quality measure in emergency care for children. Prior studies have shown differences in imaging utilization by insurance status and race and ethnicity.

OBJECTIVE: To examine if measures of hospital and emergency department (ED) pediatric capabilities modify the association between insurance, race and ethnicity, and imaging utilization.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study combined data from the 2019 State Emergency Department and State Inpatient Databases of 8 states with the 2019 National Emergency Department Inventory-USA and the 2021 National Pediatric Readiness Project (NPRP) Survey on patients 18 years of age or younger. There were 857 034 total ED visits across 3 cohorts, encompassing patients with asthma, head trauma, or abdominal trauma. Statistical analysis was performed from May 2024 to January 2026.

EXPOSURE: Pediatric capability, as measured by presence of a pediatric emergency care coordinator, readiness according to NPRP data, and hospital functional capability (inpatient and intensive care unit bed status).

MAIN OUTCOMES AND MEASURES: The association of insurance and race and ethnicity (separate models) with imaging utilization was examined across the 3 cohorts. Chest radiography was evaluated for patients with asthma, head computed tomography (CT) was evaluated for patients with head trauma, and abdominal CT was evaluated for patients with abdominal trauma. Separate mixed-effects logistic regression models were constructed, adjusting for age, sex, presence of a complex chronic condition, diagnostic grouping system severity score, hospital pediatric ED visit volume, and complexity of the hospital patient mix (percentage of patients with complex chronic conditions and mean severity clinical score) with random intercept for hospital. As a sensitivity analysis, these associations were examined separately for discharged patients.

RESULTS: There were 857 034 total ED visits in the 3 cohorts, encompassing patients with asthma (380 719 ED visits; mean [SD] age, 9.6 [5.0] years; 210 598 male [55%]), head trauma (435 644 ED visits; mean [SD] age, 7.2 [5.7] years; 264 004 male [61%]), and abdominal trauma (40 671 ED visits; mean [SD] age, 11.0 [5.4] years; 21 632 male [53%]). Children with public insurance were less likely to have undergone imaging across all measures compared with those with private insurance (asthma: adjusted odds ratio [AOR], 0.85 [95% CI, 0.83-0.86]; head trauma: AOR, 0.77 [95% CI, 0.75-0.78]; abdominal trauma: AOR, 0.59 [95% CI, 0.55-0.63]). In the adjusted model, compared with non-Hispanic White patients, non-Hispanic Black and Hispanic patients were less likely to have undergone imaging across all measures (non-Hispanic Black, asthma: AOR, 0.83 [95% CI, 0.81-0.85]; non-Hispanic Black, head trauma: AOR, 0.77 [95% CI, 0.74-0.79]; non-Hispanic Black, abdominal trauma: AOR, 0.60 [95% CI, 0.55-0.65]; Hispanic, asthma: AOR, 0.91 [95% CI, 0.89-0.93]; Hispanic, head trauma: AOR, 0.85 [95% CI, 0.82-0.87]; Hispanic, abdominal trauma: AOR, 0.72 [95% CI, 0.66-0.80]). The presence of pediatric capability was associated with differences in imaging utilization, but not with changes in the pattern of association between either insurance or race and ethnicity and imaging utilization. Similar results were observed among those who were discharged.

CONCLUSIONS AND RELEVANCE: In this cohort study of pediatric ED visits, increased pediatric capability was not associated with differences in the patterns of imaging utilization by insurance status or race and ethnicity. Additional efforts are needed to ensure that pediatric capability improves quality and equity of care.

PMID:42160054 | DOI:10.1001/jamanetworkopen.2026.13689

JAMA Netw Open. 2026 May 1;9(5):e2613808. doi: 10.1001/jamanetworkopen.2026.13808.

ABSTRACT

IMPORTANCE: Low-risk pancreatic cystic lesions (PCLs) represent common incidental findings with potential for malignant transformation, warranting long-term surveillance. However, data on their long-term cancer risk are limited, leading to inconsistency in current surveillance strategies.

OBJECTIVE: To determine the long-term incidence of pancreatic cancer among patients with low-risk PCLs, and to identify baseline clinical and imaging factors associated with cancer development.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among adults (aged ≥18 years) who underwent contrast-enhanced abdominal computed tomography (CT) or magnetic resonance imaging (MRI) between January 1, 2009, and December 31, 2021, at a large, multisite health care system in Massachusetts. MRI or CT scans were screened for PCLs without high-risk stigmata, worrisome features, or coexisting pancreatic mass. Eligible patients with low-risk PCLs were longitudinally followed up. Data analysis was performed from February 2024 to May 2025.

EXPOSURES: Baseline demographic, clinical, and imaging characteristics of patients with low-risk PCLs.

MAIN OUTCOMES AND MEASURES: The outcome was incidence of pancreatic cancer (defined as pathologically confirmed adenocarcinoma, invasive mucinous neoplasms, or high-grade dysplasia). Censoring was defined as absence of pancreatic cancer on imaging follow-up for more than 1 year after the initial examination documenting the PCL. Multivariable cause-specific Cox proportional hazards regression models assessed the associations between baseline factors and incident pancreatic cancer, accounting for death as a competing risk. Associations were reported as hazard ratios (HRs). Risk stratification performance was assessed using Harrell C-statistic and net reclassification index (NRI).

RESULTS: Among 499 631 patients reviewed, 6064 with low-risk PCLs were identified and included in the analytic sample, contributing 20 145 person-years of follow-up. Patients had a mean (SD) age at diagnosis of 65.9 (12.3) years and included 3612 females (59.6%). Of the 6064 patients, 38 (0.6%) developed pancreatic cancer, with an incidence rate of 1.89 (95% CI, 1.29-2.49) cases per 1000 person-years, which was higher than the previously reported general population rate of 0.14 cases per 1000 person-years. Twenty-six of 38 patients (68.4%) had cancer that arose from the cyst site, while 12 (31.6%) developed cancer from a different region of the pancreas. Ten patients (26.3%) were diagnosed more than 5 years after initial PCL detection. In multivariable analysis, larger cyst size (HR, 2.24; 95% CI, 1.45-3.48), main pancreatic duct ectasia (HR, 2.84; 95% CI, 1.18-6.84), and older age (HR, 1.04; 95% CI, 1.01-1.07) were associated with cancer. Adding age to a cyst size-based risk stratification model improved estimation of pancreatic cancer risk (NRI, 0.20 [95% CI, 0.03-0.37]; change in C-statistic, 0.14 [95% CI, 0.07-0.22]).

CONCLUSIONS AND RELEVANCE: This cohort study found that low-risk PCLs were associated with a sustained long-term pancreatic cancer risk and were best stratified by combining clinical and imaging factors. Longer than a 5-year follow-up of low-risk PCLs may be warranted to reduce missed or delayed diagnosis of pancreatic cancer.

PMID:42160052 | DOI:10.1001/jamanetworkopen.2026.13808

JAMA Netw Open. 2026 May 1;9(5):e2613904. doi: 10.1001/jamanetworkopen.2026.13904.

ABSTRACT

IMPORTANCE: Mental health services fail to provide culturally safe care for Aboriginal peoples, contributing to persistent health disparities. Understanding how psychiatric care is organized, alongside lived experiences of care, may identify leverage points for service redesign.

OBJECTIVE: To examine Aboriginal mental health care pathways using integrated qualitative and quantitative analysis.

DESIGN, SETTING, AND PARTICIPANTS: This mixed-methods study was conducted from June 2022 to December 2023 at the Great Southern Mental Health Service in Western Australia. Twenty Aboriginal adults were recruited; the quantitative component included 19 patients with 1108 documented clinical interactions, and 7 participated in in-depth yarning interviews. Novel analytical methods included a community-preserving surrogate network algorithm and transition-matrix trajectory clustering.

MAIN OUTCOMES AND MEASURES: Centrality metrics identifying key agents in the clinical interaction network; patient trajectory clustering based on clinical action sequences; qualitative themes from yarning interviews using reflexive thematic analysis.

RESULTS: A total of 20 Aboriginal adults were recruited; the quantitative analysis included 19 patients (mean [SD] age, 38.4 [15.9] years; 10 women and 9 men) with 1108 documented interactions, with 7 patients (mean [SD] age, 44.0 [17.8] years; 4 women and 3 men) participating in qualitative yarning interviews. The clinical interaction network had a core-periphery structure in which patients often served as the main link between external agents and hospital staff. Aboriginal mental health workers had closeness centrality above the 99th percentile in surrogate networks, indicating a structurally distinctive central position within the network. Trajectory analysis identified 3 care pathways: predominantly internal care, prolonged internal engagement, and complex external referral with repeated readmissions. Qualitative themes emphasized cultural safety, kinship, and ongoing trauma and showed inconsistent Aboriginal mental health worker presence during crises, while integrated analyses highlighted their pivotal yet vulnerable role within fragmented care pathways, underscoring the need for trauma-informed, culturally safe redesign.

CONCLUSIONS AND RELEVANCE: In this mixed-methods study, Aboriginal mental health workers occupied central bridging positions, and patients were intermediaries between disconnected parts of the system. Strengthening culturally grounded roles and redesigning care pathways based on operational information flow may improve care coordination and cultural safety in multisetting mental health systems.

PMID:42160050 | DOI:10.1001/jamanetworkopen.2026.13904

J Biopharm Stat. 2026 May 20:1-15. doi: 10.1080/10543406.2026.2670521. Online ahead of print.

ABSTRACT

The hERG safety assay is crucial for assessing the risk of delayed repolarization and QT interval prolongation in investigational drugs, yet a lack of consensus exists on classifying drugs into appropriate risk categories based on assay results. We propose a two-stage statistical framework for quantitative assessment of hERG safety assay classification for investigational products adhering to ICH E14 S7b Q&A Best Practice protocols. Our framework employs a fixed margin equivalence testing approach to evaluate concurrent positive controls against the positive control reference in Stage 1, followed by a logistic regression model based on a T-score to classify the investigational product into two risk categories (QT effect ≥ 10 msec or < 10 msec) in Stage 2. Applied to real-world data, our method demonstrates the ability to classify investigational products with an AUROC of at least 0.9, using a pre-specified probability margin. Additionally, our approach addresses lab-to-lab variability in hERG safety assay assessment, providing a standardized, quantitative method for evaluating hERG assay results that could improve consistency in drug risk assessment across the pharmaceutical industry.

PMID:42160048 | DOI:10.1080/10543406.2026.2670521