Nevin Manimala

Cell Transplant. 2025 Jan-Dec;34:9636897251349377. doi: 10.1177/09636897251349377. Epub 2025 Jun 25.

ABSTRACT

Obesity is a well-known risk factor for many diseases, but the impact of baseline body mass index (BMI) on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains controversial. To elucidate the influence of pretransplant BMI on post-allo-HSCT outcomes including graft-versus-host disease (GVHD), overall survival (OS), relapse-free survival (RFS), and nonrelapse mortality (NRM), we conducted a retrospective study using registry data which comprised 1092 adult patients who underwent allo-HSCT between 2015 and 2023. Among the 1092 eligible patients (53.2% male), 56.5% were normal-weight; 24.8% were overweight and 9.1% were obese. Multivariable analyses revealed that compared with normal-weight patients, obese individuals had a higher risk of grade II-IV and III-IV acute GVHD (aGVHD), especially in the gastrointestinal system, with aHRs of 2.08 (95% CI, 1.47-2.94), 2.60 (95% CI, 1.52-4.44), and 3.71 (95% CI, 2.00-6.88), respectively. The probability of OS and RFS was significantly lower in overweight (P = 0.034, P = 0.015, respectively) and obese patients (P = 0.033, P = 0.024, respectively) as compared with normal-weight patients, with aHRs increasing by ~38% (aHR, 1.38; 95% CI, 1.03-1.86), ~40% (aHR, 1.40; 95% CI, 1.07-1.83), ~58% (aHR, 1.58; 95% CI, 1.04-2.40), and ~56% (aHR, 1.56; 95% CI, 1.06-2.29), respectively. Furthermore, the NRM of obese patients was statistically higher than normal-weight patients (P = 0.02, sHR, 2.19; 95% CI, 1.12-4.27). A subgroup analysis revealed that the adverse effects of obesity on OS, RFS, and NRM were primarily observed in the subgroup of patients aged < 40 years and patients with acute lymphoblastic leukemia. The increased risk of grade II-IV aGVHD due to obesity was observed across all subgroups. In conclusion, Obesity prior to allo-HSCT increases the risk of aGVHD and NRM, leading to poorer OS. These findings underscore the importance of closely monitoring high-risk patients and offering opportunities for early intervention.

PMID:40560651 | DOI:10.1177/09636897251349377

JAMA Cardiol. 2025 Jun 25. doi: 10.1001/jamacardio.2025.1865. Online ahead of print.

ABSTRACT

IMPORTANCE: In the original validation, the Predicting Risk of Cardiovascular Disease (CVD) Events (PREVENT) equations demonstrated good discrimination and calibration among racial and ethnic groups, but the model performance among Asian and Hispanic disaggregated subgroups has not been previously described.

OBJECTIVE: To assess the performance of the PREVENT equations by race and ethnicity, including disaggregated Asian and Hispanic subgroups.

DESIGN, SETTING, AND PARTICIPANTS: This was an electronic health record-based retrospective cohort study of primary care patients aged 30 to 79 years across Sutter Health, a large integrated health system in Northern California, from January 2010 to September 2023. Patients who had at least 2 primary care visits during the study period were eligible for the study (1 484 582). Those outside of the study age range, with prior CVD events in the washout period, missing key predictors, or having at least 1 predictor out of the allowed normal range for the American Heart Association’s PREVENT equations, were excluded, leaving a study population of 361 778.

EXPOSURE: Eligible patients had complete baseline data required for the PREVENT equations, including non-high-density lipoprotein cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, body mass index, estimated glomerular filtration rate (or creatinine), diabetes, and current smoking status, and were free from CVD at baseline.

MAIN OUTCOMES AND MEASURES: The primary outcomes were CVD events, identified using International Classification of Diseases, Ninth and Tenth Revisions, codes described in the PREVENT derivation.

RESULTS: Among 361 778 patients who met the inclusion criteria, mean (SD) age was 54.6 (12.2) years; 191 151 (53%) were female; and 81 424 (22%) were non-Hispanic Asian and 40 897 (11%) were Hispanic. Over a mean (SD) follow-up of 8.1 (3.2) years, there were 22 648 (6.3%) CVD events. The C statistic for total CVD was 0.83 (95% CI, 0.82-0.84) for the Asian population and 0.80 (95% CI, 0.79-0.81) for the Hispanic population. The calibration slopes were 0.84 (95% CI, 0.78-0.90) and 1.02 (95% CI, 0.94-1.10) for Asian and Hispanic patients, respectively. Within the Asian population, C statistics for total CVD among disaggregated Asian subgroups ranged from 0.79 (95% CI, 0.77-0.81) in Filipino patients to 0.85 (95% CI, 0.83-0.87) in Asian Indian patients. The calibration slope for total CVD was less than 1 for all Asian subgroups except Asian Indian. Among disaggregated Hispanic subgroups, the C statistics were similar and between 0.80 and 0.82 for total CVD, and the calibration slope for total CVD included 1 for all subgroups. There were small differences in the performance of atherosclerotic CVD and heart failure PREVENT equations among racial and ethnic groups and subgroups.

CONCLUSIONS AND RELEVANCE: The PREVENT equations appropriately predicted risk in contemporary diverse Asian and Hispanic subgroups with modest variation in performance across disaggregated subgroups.

PMID:40560603 | DOI:10.1001/jamacardio.2025.1865

JAMA Netw Open. 2025 Jun 2;8(6):e2517291. doi: 10.1001/jamanetworkopen.2025.17291.

ABSTRACT

IMPORTANCE: While epinephrine is commonly administered in children with out-of-hospital cardiac arrest (OHCA) via an intraosseous (IO) or intravenous (IV) route, the optimal route of epinephrine delivery is unclear.

OBJECTIVE: To evaluate the association between the route of epinephrine administration (IO or IV) and patient outcomes after pediatric OHCA.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of pediatric patients (aged <18 years) with nontraumatic OHCA treated by emergency medical services who received prehospital epinephrine either via an IO or IV route. Patients were included in the Resuscitation Outcomes Consortium Epidemiologic Registry, a prospective OHCA registry at 10 sites in the US and Canada from April 2011 to June 2015. Data analysis was performed from May 2024 to April 2025.

EXPOSURE: Epinephrine administration route: IO or IV route.

MAIN OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge. The secondary outcome was return of spontaneous circulation (ROSC) before hospital arrival. Propensity scores were calculated and inverse probability of treatment weighting (IPTW) was performed with stabilized weights to control imbalances in measured patient demographics, cardiac arrest characteristics, and bystander and prehospital interventions.

RESULTS: Of 739 eligible patients (median [IQR] age, 1 [0-11] years), 449 (60.8%) were male. Epinephrine was administered via an IO route for 535 (72.4%) and via an IV route for 204 (27.6%) patients. In the IPTW pseudopopulation (740 weighted cases), there was no significant difference in survival to hospital discharge (IO epinephrine: 28 of 528 patients [5.3%] vs IV epinephrine: 12 of 212 patients [5.7%]; risk ratio [RR], 0.92; 95% CI, 0.41-2.07) or prehospital ROSC (IO epinephrine: 76 of 528 patients [14.4%] vs IV epinephrine: 46 of 212 patients [21.7%]; RR, 0.66; 95% CI, 0.42-1.03) between the IO and IV epinephrine groups.

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of pediatric patients with OHCA in the US and Canada, the route of epinephrine administration was not associated with survival to hospital discharge or prehospital ROSC. This may support the practice of administering epinephrine via IO or IV route.

PMID:40560587 | DOI:10.1001/jamanetworkopen.2025.17291

JAMA Netw Open. 2025 Jun 2;8(6):e2517402. doi: 10.1001/jamanetworkopen.2025.17402.

ABSTRACT

IMPORTANCE: SARS-CoV-2 continues to evolve, population immunity changes, and COVID-19 vaccine formulas have been updated, necessitating ongoing COVID-19 vaccine effectiveness (VE) monitoring.

OBJECTIVES: To evaluate the VE of 2023-2024 COVID-19 vaccines against COVID-19-associated emergency department (ED) and urgent care (UC) encounters, hospitalizations, and critical illness, including during XBB- and JN.1-predominant periods.

DESIGN, SETTING, AND PARTICIPANTS: This test-negative design VE case-control study was conducted using data from September 21, 2023, to August 22, 2024, from EDs, UC centers, and hospitals in 6 US health care systems. Eligible adults 18 years or older with COVID-19-like illness and molecular or antigen testing for SARS-CoV-2 were studied. Case patients were those with a positive molecular or antigen test result; control patients were those with a negative molecular test result.

EXPOSURE: Receipt of 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination with products approved or authorized for use in the US.

MAIN OUTCOMES AND MEASURES: Main outcomes were COVID-19-associated ED and UC encounters, hospitalizations, and critical illness (admission to the intensive care unit or in-hospital death). VE was estimated comparing the odds of receipt of the 2023-2024 COVID-19 vaccine with no receipt among case and control patients.

RESULTS: Among 345 639 eligible ED and UC encounters in immunocompetent adults 18 years or older with COVID-19-like illness and available test results (median [IQR] age, 53 [34-71] years; 209 087 [60%] female), 37 096 (11%) had a positive SARS-CoV-2 test result. VE against COVID-19-associated ED and UC encounters was 24% (95% CI, 21%-26%) during 7 to 299 days after vaccination. Among 111 931 eligible hospitalizations in immunocompetent adults 18 years or older with COVID-19-like illness and available test results (median [IQR] age, 71 [58-81] years), 10 380 (9%) had a positive SARS-CoV-2 test result. During 7 to 299 days after vaccination, VE was 29% (95% CI, 25%-33%) against COVID-19-associated hospitalization and 48% (95% CI, 40%-55%) against COVID-19-associated critical illness. VE was highest 7 to 59 days after vaccination (VE against ED and UC encounters 49%; 95% CI, 46%-52%; hospitalization, 51%; 95% CI, 46%-56%; critical illness, 68%; 95% CI, 56%-76%) and then waned (VE 180-299 days after vaccination against ED and UC encounters, -7% [95% CI, -13% to -2%]; hospitalization, -4% [95% CI, -14% to 5%]; and critical illness, 16% [95% CI, -6 to 34%]).

CONCLUSIONS AND RELEVANCE: In this case-control study of VE, 2023-2024 COVID-19 vaccines were estimated to provide additional effectiveness against medically attended COVID-19, with the highest and most sustained estimates against critical illness. These results highlight the importance of receiving recommended COVID-19 vaccination for adults 18 years or older.

PMID:40560584 | DOI:10.1001/jamanetworkopen.2025.17402

JAMA Netw Open. 2025 Jun 2;8(6):e2517718. doi: 10.1001/jamanetworkopen.2025.17718.

ABSTRACT

IMPORTANCE: Medicare is the primary health insurance payer for 1.5 million reproductive-aged women with disabilities, yet it is the only major form of US health insurance that is not required to cover contraceptives for pregnancy prevention.

OBJECTIVE: To evaluate whether Medicare’s contraceptive coverage gaps were associated with reduced use of contraceptives by enrollees with disabilities.

DESIGN, SETTING, AND PARTICIPANTS: In this national, cross-sectional study, traditional Medicare (TM), Medicare Advantage (MA), and Medicaid claims from female enrollees aged 20 to 49 years receiving Social Security Disability Insurance or Supplemental Security Income from January 1, 2016, to December 31, 2020, were linked. The propensity score-weighted probability of contraceptive use by public insurance type was estimated, then the association between gaining contraceptive coverage through a transition from Medicare to dual Medicare-Medicaid enrollment and contraceptive use was evaluated using a staggered-entry difference-in-differences design. Data were analyzed from December 3, 2024, to April 5, 2025.

EXPOSURES: Public insurance enrollment in TM, MA, dual TM-Medicaid, dual MA-Medicaid, or Medicaid.

MAIN OUTCOMES AND MEASURES: Monthly use of permanent contraceptives, long-acting reversible contraceptives (intrauterine device and implant), and short-acting contraceptives (injectable and oral contraceptives, patch, and ring).

RESULTS: A total of 51 501 303 monthly observations from 1 606 129 women were included in the analysis. Mean (SD) age was 35.93 (8.58) years; 1.8% of monthly observations were from Asian women, 30.7% from Black women, 13.0% from Hispanic women, 52.6% from White women, and 1.9% from multiracial women or women identifying as another race and ethnicity not reported on previously. Those enrolled in TM and MA were more often older and non-Hispanic White compared with those dual enrolled or enrolled in Medicaid. The estimated monthly probability of use of any contraceptive method was lowest among TM (4.9%; 95% CI, 4.9%-4.9%) and MA (6.6%; 95% CI, 6.5%-6.6%) enrollees, followed by Medicaid (11.0%; 95% CI, 11.0%-11.0%), dual MA-Medicaid (11.3%; 95% CI, 11.3%-11.4%), and dual TM-Medicaid (13.1%; 95% CI, 13.0%-13.1%) enrollees. Gaining contraceptive coverage through dual enrollment was associated with an increase of 3.9 (95% CI, 3.5-4.3) percentage points (35%) in use of any contraceptive method, with the largest increase in use of short-acting methods at 2.6 (95% CI, 2.3-3.0) percentage points (45%).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of contraceptive use in the Medicare program, gaining contraceptive coverage through dual Medicare-Medicaid enrollment was associated with increased contraceptive use among disabled Medicare enrollees, suggesting that Medicare’s coverage gaps pose a financial barrier to desired contraceptive use. Given these findings, Medicare should be required to cover all US Food and Drug Administration-approved contraceptive methods without cost-sharing. Doing so would align Medicare’s coverage requirements with those of Medicaid, private insurance plans, and TRICARE.

PMID:40560583 | DOI:10.1001/jamanetworkopen.2025.17718

Rheumatology (Oxford). 2025 Jun 25:keaf311. doi: 10.1093/rheumatology/keaf311. Online ahead of print.

ABSTRACT

OBJECTIVES: Sex-related differences exist in the clinical presentation and treatment outcomes of patients with psoriatic arthritis (PsA). The biological pathways driving these differences remain unknown. We conducted an untargeted proteomic study to identify sex-specific serum proteins and biological pathways in males and females with PsA.

METHODS: We used an aptamer-based panel to measure 6402 serum proteins in 50 male and 50 female patients with active PsA and 50 age- and sex-matched non-psoriatic controls. Differential expression and pathway enrichment analysis identified differentially expressed proteins (DEPs) and enriched pathways between male and female PsA patients. Machine learning classifiers were used to develop sex-specific multi-biomarker models to distinguish PsA patients from controls. Proteins with the highest predictive performances were highlighted from random forest models.

RESULTS: The differential analysis revealed over 20 times more sex-specific DEPs in PsA males vs controls (n = 741) than in PsA females vs controls (n = 31). The enriched pathways among DEPs in PsA males vs PsA females were related to intracellular signalling, vascular function, cytokine signalling, and immune cell functions. All models discriminated PsA from controls for both sexes with an area under the curve of 0.85-0.99. Variable importance analysis identified leukotriene A-4 hydrolase as a significant predictor in PsA females vs controls, whereas interleukin-36 alpha, NEK7, and PIK3CA/PIK3R1 were significant in PsA males vs controls.

CONCLUSION: Significantly more dysregulated proteins and biological pathways were found in males than in females with PsA. The identified proteins and pathways offer potential new targets for sex-based research in PsA.

PMID:40560578 | DOI:10.1093/rheumatology/keaf311

Br J Radiol. 2025 Jun 25:tqaf139. doi: 10.1093/bjr/tqaf139. Online ahead of print.

ABSTRACT

OBJECTIVES: Approximately 10% of breast and 20% of ovarian cancers are hereditary in nature. The most commonly implicated genes are the BRCA genes, and the current gold standard for testing is by direct DNA sequencing. This process is expensive, time-consuming, and has a turnaround time of several weeks. Radiogenomics involves extracting quantitative data from medical imaging and using mathematical models to predict the underlying genetic makeup of tissues.

AIM: To perform a systematic review and meta-analysis evaluating the accuracy of radiogenomics in determining BRCA alteration status.

METHODS: A systematic review was performed in accordance with PRISMA guidelines. Diagnostic test accuracy analyses (ie pooled sensitivity and specificity) were performed. Statistical analyses were performed using RevMan V5.4.

RESULTS: 13 studies compromising 2835 patients were included. Of these, 857 were BRCA alteration carriers. The mean age of patients was 46 years. Radiogenomic methods correctly identified BRCA alteration with a strong diagnostic test accuracy (pooled sensitivity: 0.82, 95% confidence interval (CI): 0.79-0.84, pooled specificity: 0.81, 95% CI: 0.78-0.83).

CONCLUSION: Radiogenomics may be an accurate method to predict BRCA alterations. However, these findings should be validated in larger, prospective studies to determine their utility in clinical practice. Until further refinement of these methods, DNA sequencing should remain the gold standard.

ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first systematic review and meta-analysis that has been carried out on this topic. We believe that our results demonstrate the potential clinical utility radiogenomics could have in the BRCA alteration testing process.

PMID:40560570 | DOI:10.1093/bjr/tqaf139

JAMA Surg. 2025 Jun 25. doi: 10.1001/jamasurg.2025.1999. Online ahead of print.

ABSTRACT

IMPORTANCE: Although tumor-infiltrating lymphocytes (TILs) have been implicated as prognostic biomarkers across various malignancies, the clinical application remains challenging. This study evaluated the applicability of artificial intelligence (AI)-powered spatial mapping of TIL density for prognostic assessment in resected pancreatic ductal adenocarcinoma (PDAC).

OBJECTIVE: To evaluate the prognostic significance of AI-powered spatial TIL analysis in resected PDAC and its clinical applicability.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with PDAC who underwent up-front R0 resection at a tertiary referral center between January 2017 and December 2020. Whole-slide images of retrospectively enrolled patients with PDAC and up-front R0 resection were analyzed. An AI-powered whole-slide image analyzer was used for spatial TIL quantification, segmentation of tumor and stroma, and immune phenotype classification as immune-inflamed phenotype, immune-excluded phenotype, or immune-desert phenotype. Study data were analyzed from January 2017 to August 2023.

EXPOSURE: Use of AI-powered spatial analysis of the tumor microenvironment in resected PDACs.

MAIN OUTCOMES AND MEASURES: Tumor microenvironment-related risk factors and their associations with overall survival (OS) and recurrence-free survival (RFS) outcomes were identified.

RESULTS: Among 304 patients, the mean (SD) age was 66.8 (9.4) years with 171 male patients (56.3%), and preoperative clinical stages I and II were represented by 54.3% patients (165 of 304) and 45.7% patients (139 of 304), respectively. The TILs in the tumor microenvironment were predominantly concentrated in the stroma, and the median intratumoral TIL and stromal TIL densities were 100.64/mm2 (IQR, 53.25-121.39/mm2) and 734.88/mm2 (IQR, 443.10-911.16/mm2), respectively. Overall, 9.9% of tumors (30 of 304) were immune inflamed, 85.2% (259 of 304) were immune excluded, and 4.9% (15 of 304) were immune desert. The immune-inflamed phenotype was associated with the most prolonged OS (median not reached; P < .001) and RFS (median not reached; P = .001), followed by immune-excluded phenotype and immune-desert phenotype. High intratumoral TIL density was associated with longer OS (median, 52.47 months; 95% CI, 41.98-62.96; P = .004) and RFS (median, 21.67 months; 95% CI, 14.43-28.91; P = .02). A combined analysis of the pathologic stage with immune phenotype predicted better survival of stage II PDAC stratified as immune-inflamed phenotype than stage I PDAC stratified as non-immune-inflamed phenotype.

CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that the use of AI has markedly condensed the labor-intensive process of TIL assessment, potentially rendering the process more feasible and practical in clinical application. Importantly, the IP may be one of the most important prognostic biomarkers in resected PDACs.

PMID:40560550 | DOI:10.1001/jamasurg.2025.1999

Int Urol Nephrol. 2025 Jun 25. doi: 10.1007/s11255-025-04624-w. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop a standardized evidence-based practice plan for exercise during dialysis in maintenance hemodialysis patients based on the best evidence.

METHODS: Based on the Johns Hopkins evidence-based nursing practice model as theoretical guidance, the evidence of exercise during dialysis in maintenance hemodialysis patients was systematically retrieved, evaluated and summarized, and an evidence-based practice plan was formed and applied in clinical practice. 35 patients and 19 nurses were reviewed before and after the application of evidence, and the obstacle factors and improvement measures were discussed and analyzed. The effect and significance of the evidence application were analyzed by comparing the patients’ grip strength, 30-s sit-to-stand test, quality of life score, self-efficacy, and dialysis adequacy.

RESULTS: Extracted 28 pieces of evidence from 35 best evidence sources and 8 review indicators were formulated. Following the implementation of evidence-based practices, the adherence rates for the eight indicators showed significant improvement (P < 0.05). The analysis identified 12 barriers and 12 facilitators, leading to the development of 16 change strategies. Before and 1 month, 2 months and 3 months after the application of evidence, the patients’ grip strength, 30-s sit-to-stand test and quality of life score were compared, and the differences were statistically significant (P < 0.05). There was no significant difference in self-efficacy and dialysis adequacy (P > 0.05).

CONCLUSIONS: Evidence-based practice of intradialytic exercise in maintenance hemodialysis patients can standardize intradialytic exercise rehabilitation. It can improve the muscle strength of upper and lower limbs and the quality of life of patients. However, its effect on self-efficacy and dialysis adequacy is limited.

PMID:40560523 | DOI:10.1007/s11255-025-04624-w

Int Urol Nephrol. 2025 Jun 25. doi: 10.1007/s11255-025-04619-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Ductal adenocarcinoma (DAC) is the second most common subtype of prostate cancer and is believed to have more aggressive biology compared to acinar adenocarcinoma (AAC). This study aimed to compare pathological and oncological outcomes between DAC and AAC in patients undergoing robotic-assisted radical prostatectomy (RARP).

METHODS: This was a single-center, retrospective cohort study of consecutive patients who underwent RARP between 2008 and 2023. Patients with DAC or AAC on final pathology were included. A 1:1 propensity score matching was performed based on key clinicopathologic variables. Primary outcomes included adverse pathological features, biochemical persistence, and biochemical recurrence (BCR). Statistical analyses included logistic regression and Cox proportional hazards models.

KEY FINDINGS AND LIMITATIONS: Among 844 DAC and 14,357 AAC patients (median follow-up: 4.1 years), DAC was associated with higher extracapsular extension (48.2% vs. 35.4%, difference = 12.8%, 95% CI: 9.4-16.3, p < 0.001), biochemical persistence (8.3% vs. 4.4%, OR = 1.97, 95% CI: 1.52-2.56, p < 0.001), and BCR (20.1% vs. 12.5%, HR = 1.70, 95% CI: 1.44-2.01, p < 0.001). In the matched cohort, DAC had higher biochemical persistence (8.4% vs. 5.5%, OR = 1.58, 95% CI: 1.07-2.33, p = 0.03) but no differences in BCR or overall survival. Limitations include retrospective design and residual confounding.

CONCLUSIONS AND CLINICAL IMPLICATIONS: DAC exhibits more aggressive pathological features and higher biochemical persistence after RARP. These findings may warrant closer surveillance and further prospective studies to guide DAC-specific management strategies. In this report, we compared outcomes after prostate cancer surgery in men with two types of prostate cancer: the common acinar type and the less common, more aggressive ductal type. We found that men with ductal prostate cancer had worse outcomes after surgery, including a higher chance of the cancer not being fully removed. These findings suggest that men with ductal prostate cancer may need closer monitoring and specialized treatment plans.

PMID:40560522 | DOI:10.1007/s11255-025-04619-7