Tag: nevin manimala

JAMA Netw Open. 2025 Jul 1;8(7):e2521158. doi: 10.1001/jamanetworkopen.2025.21158.

ABSTRACT

IMPORTANCE: Umbilical cord blood-derived cells (UCBCs) are increasingly being evaluated for neuroprotective properties in perinatal brain injury.

OBJECTIVE: To report early neurodevelopmental outcomes of extremely preterm infants who received autologous UCBCs in the CORD-SaFe study.

DESIGN, SETTING, AND PARTICIPANTS: This study reports early follow-up on the preplanned secondary aims of a phase 1 safety and feasibility nonrandomized clinical trial conducted between May 2021 and November 2023, with early follow-up completed in August 2024. Participants were infants born at less than 28 weeks’ completed gestation who received autologous UCBCs in the CORD-SaFe study at Monash Children’s Hospital, Australia. A contemporaneous cohort of noninfused infants born during the study period was included for comparison. Data were analyzed from October to December 2024.

INTERVENTION: Autologous UCBC administered intravenously in the second postnatal week of life.

MAIN OUTCOMES AND MEASURES: Infants underwent brain magnetic resonance imaging to assess structure and injury (Kidokoro score) at term-equivalent age. Assessments at 52 to 54 weeks postmenstrual age included General Movements Assessment, Hammersmith Infant Neurological Examination score, and clinical examination to diagnose risk of cerebral palsy.

RESULTS: A total of 23 infants (median [IQR] gestation, 26 [25-27] weeks; median [IQR] birth weight, 748 [645-981] grams; 17 [73.9%] male) were administered UCBCs at a median (IQR) dose of 42.3 (31.1-63.2) million cells/kg. The contemporaneous cohort included 93 infants (median [IQR] gestation, 26 (24-27) weeks; median [IQR] birth weight, 769 [660-1017] grams; 39 [41.9%] male). Median (IQR) Kidokoro score was 2 (1-3) for the UCBCs group and 3 (2-5) for the contemporaneous cohort, with no statistically significant difference observed between the groups (adjusted median difference, 0 [95% CI, -1.78 to 1.78]). No infants in the UCBC group were assessed as high risk for cerebral palsy compared with 6 of 87 assessed infants (6.8%) in the contemporaneous group; however, the difference was not statistically significant (adjusted log odds, 0.31 [95% CI, -0.76 to 1.38]). No differences in Hammersmith Infant Neurological Examination score (adjusted log odds, -1.50 [95% CI, -5.78 to 2.78]) and absent fidgety movements (adjusted odds ratio, 0.24 [95% CI, 0.20 to 3.04]) were observed between groups.

CONCLUSIONS AND RELEVANCE: This phase 1 nonrandomized clinical trial assessing the safety and feasibility of autologous UCBCs in extremely preterm infants did not find significant differences in brain imaging parameters and early neurodevelopmental outcomes between the cell therapy and contemporaneous untreated groups. It was encouraging to note no infants who received UCBCs were assessed as high risk for cerebral palsy at 52 to 54 weeks postmenstrual age, and the absence of high risk for CP merits further study.

TRIAL REGISTRATION: ANZCTR.org.au Identifier: ACTRN12619001637134.

PMID:40608334 | DOI:10.1001/jamanetworkopen.2025.21158

JAMA Oncol. 2025 Jul 3. doi: 10.1001/jamaoncol.2025.1891. Online ahead of print.

ABSTRACT

IMPORTANCE: Non-clear cell renal cell carcinomas (nccRCCs) present considerable challenges owing to their heterogeneity and limited clinical trial representation. Understanding the benefits of combining immunotherapy and targeted therapy for these subtypes is crucial for improving patient outcomes.

OBJECTIVE: To evaluate the efficacy of various first-line immunotherapy combinations and targeted therapy in treating metastatic nccRCC.

DATA SOURCES: A systematic literature search was conducted across PubMed, Embase, and Cochrane Library databases from inception until December 31, 2024, using relevant keywords and medical subject headings terms.

STUDY SELECTION: Studies were included if they involved patients with nccRCC, reported on immune checkpoint inhibitor (ICI)-based therapies, and provided data on objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and disease control rate (DCR).

DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data, with discrepancies resolved by a third expert. Observational study quality was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed, and heterogeneity was evaluated using the I2 statistic.

MAIN OUTCOME AND MEASURES: The primary outcomes of interest were ORR, PFS, OS, and DCR.

RESULTS: The analysis included 23 studies encompassing various subtypes of nccRCC. Pooled results indicated an ORR of 26.6% and a DCR of 57.8% for nccRCC treatments. Median PFS was 6.59 months, and the median OS was 21.11 months. ICIs demonstrated significant efficacy in nccRCC, exhibiting marked clinical activity across different subtypes. Although monotherapy with ICIs showed effectiveness, combination therapies yielded superior clinical outcomes.

CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found that ICIs, particularly when combined with targeted therapies, showed promising efficacy in treating metastatic nccRCC. These findings support their integration into treatment guidelines and emphasize the importance of personalized treatment strategies. Future research should focus on long-term outcomes, safety profiles, and the identification of biomarkers to optimize patient selection and improve outcomes.

PMID:40608318 | DOI:10.1001/jamaoncol.2025.1891

JAMA Health Forum. 2025 Jul 3;6(7):e251640. doi: 10.1001/jamahealthforum.2025.1640.

ABSTRACT

IMPORTANCE: There is a growing consensus that commercial prices vary in ways that do not reflect quality of care and are a key factor in high health care spending in the US.

OBJECTIVE: To assess the geographic variation in commercial prices relative to Medicare rates for both hospital and professional services at the state and substate levels, estimate the change in these prices and determine which characteristics are associated with higher hospital prices.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed deidentified aggregated health care claims data for 2 time frames of service, from January 1, 2020, through December 31, 2020, and from June 1, 2022, through May 31, 2023, to construct commercial-to-Medicare price ratios for hospital and professional services at the state and geozip levels (491 geozips correspond to combinations of zip codes in 50 states and the District of Columbia). Multivariable regression models were estimated to assess the association between commercial-to-Medicare relative hospital prices and various market characteristics at the geozip level. Data analysis was conducted from July through November 2024.

EXPOSURES: Exposures defined at the geozip level included hospital and insurer market concentrations, the share of hospitals beds associated with nonprofit hospitals, the share of beds associated with health systems, the presence of a major teaching hospital, mean household income, the share of the population who had public health insurance, and the share who were uninsured.

MAIN OUTCOMES AND MEASURES: Commercial prices relative to Medicare rates for inpatient, outpatient, combined hospital, and professional services.

RESULTS: This cross-sectional study of 1.2 billion claim lines in 2020 and 1.5 billion claim lines from June 2022 through May 2023 found that private insurers’ in-network allowed amounts were 246% (ratio [SD], 2.46 [0.6]) of the Medicare rates for hospital services and 124% (ratio [SD], 1.24 [0.3]) of the Medicare rates for professional services. The mean commercial-to-Medicare price ratio for professional services slightly declined from 2020 to 2022-2023, while the mean (SD) price ratio for hospital services increased by 5.5%, from 2.34 (0.5) in 2020 to 2.46 (0.6) in 2022-2023. There was substantial variation in the commercial-to-Medicare price ratios across states and geozips. Geozips with very high hospital market concentration levels (Herfindahl-Hirschman Index [HHI]>3500) were associated with a commercial-to-Medicare price ratio higher by 0.21 (95% CI, 0.02-0.39; P = .03) relative to geozips with HHI levels lower than 1500, which represents an 8.4% increase above the 2022-2023 mean. High insurer concentration was negatively associated with the commercial-to-Medicare hospital price ratios (-0.13; 95% CI, -0.26 to 0.01; P = .04), whereas having a major teaching hospital in the geozip (0.20; 95% CI, 0.06-0.34; P = .01), being in the highest household income quartile (0.35; 95% CI, 0.13-0.57; P = .002), and the share of the population who were uninsured (0.03; 95% CI, 0.01-0.05; P < .001) were positively associated with price ratios.

CONCLUSIONS AND RELEVANCE: Examination of a major claims database revealed substantial geographic variation in commercial-to-Medicare price ratios and increases in the price ratio for hospital services over time. Substate market and hospital characteristics were also associated with higher commercial-to-Medicare relative prices. These factors, including high hospital market concentration, could be used to identify and target specific areas more amenable to policies aimed at curbing hospital price growth.

PMID:40608307 | DOI:10.1001/jamahealthforum.2025.1640

JAMA Health Forum. 2025 Jul 3;6(7):e251748. doi: 10.1001/jamahealthforum.2025.1748.

ABSTRACT

IMPORTANCE: Medicare beneficiaries dually enrolled in Medicare and Medicaid have some of the highest care needs. Finding ways to support dually eligible beneficiaries in the Medicare Advantage (MA) program has become a policy goal.

OBJECTIVE: To determine if enrollment in different MA plan types is associated with differences in disenrollment.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included Medicare enrollment data from dually eligible Medicare beneficiaries in 2021. Analyses were conducted between March 2024 and February 2025. Data were analyzed from January through March 2025.

EXPOSURE: Enrollment in different MA plan types, including those that exclusively serve dual-eligible beneficiaries (coordination-only, dual-eligible special needs plans [D-SNPs] and fully integrated D-SNPs [FIDE-SNPs]), standard MA plans that serve dual-eligible and non-dual-eligible beneficiaries, and D-SNP look-alike plans, defined as standard MA plans that primarily enroll dual-eligible beneficiaries.

MAIN OUTCOMES AND MEASURES: One-year disenrollment from one plan to another or to traditional Medicare.

RESULTS: Among 2 698 434 dually eligible beneficiaries in 2021, the mean (SD) age was 66.9 (14.1) years, and 62.5% were female individuals. Of dual-eligible beneficiaries enrolled in FIDE-SNPs in 2021, 19 001 (8.1%) disenrolled by 2022. Of those enrolled in coordination-only D-SNPs, D-SNP look-alikes, and standard MA plans in 2021, disenrollment rates were 18.3%, 30.5%, and 28.2%, respectively. Disenrollment rates were higher for Black beneficiaries and those who used more health services, including inpatient stays and more days of nursing home care.

CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study suggest that FIDE-SNPs retained their members at higher rates, which could be a sign of improved care experiences. Understanding how FIDE-SNPs may be affecting patient care will be important moving forward.

PMID:40608306 | DOI:10.1001/jamahealthforum.2025.1748

Neuropsychopharmacol Hung. 2025 Jun;27(2):88-105.

ABSTRACT

AIM: The impairment of working memory is a common phenomenon after stroke and critically affects daily functioning. Transcranial direct current stimulation and computer- based cognitive training are widely used in neurorehabilitation to enhance cognitive functions. This study examined the single vs combined effect of anodal stimulation and computer-based inhibitory control training on working memory function among post-stroke patients.

METHODS: Thirty-five participants were randomly allocated to receiving either active stimulation, sham stimulation with training, or active stimulation with training. Forward/ Backward Digit Span Task, Listening Span Task, Corsi Block Tapping Task, and Trail Making Test were used to assess working memory functions at baseline and after the ten-session experimental program. For statistical analysis, we performed a Linear Mixed-effects Model.

RESULTS: A significant group-by-time interaction showed in favour of the combined group over the active stimulation group in the case of forward digit span (p=.028).

CONCLUSION: Results indicate that cognitive training and stimulation solely did not lead to significant improvements in working memory related functions among post-stroke patients. However, the combined application may be favourable. The effectiveness of cognitive training and transcranial direct current stimulation needs further examination. (Neuropsychopharmacol Hung 2025; 27(2): 88-105) Keywords: rehabilitation, stroke, transcranial direct current stimulation, cognitive training, working memory.

PMID:40608292

Ophthalmol Ther. 2025 Jul 3. doi: 10.1007/s40123-025-01192-1. Online ahead of print.

ABSTRACT

INTRODUCTION: We investigated the relationship between optical coherence tomography (OCT) angiography (OCTA)-derived vascular parameters, central visual field (10-2 VF), ganglion cell complex (GCC), and retinal nerve fiber layer (RNFL) thickness in patients with advanced glaucoma.

METHODS: This retrospective, cross-sectional study included 28 eyes of 23 patients with advanced glaucoma (VF mean deviation [MD] worse than – 12 dB on 24-2 testing). All participants underwent comprehensive ophthalmic examinations, OCT, OCTA, and 10-2 VF tests. Pearson’s correlation was used to assess relationships between structural, functional, and vascular parameters.

RESULTS: Statistically significant positive correlations were found between GCC thickness and 10-2 VF MD (r = 0.529, p = 0.005), and between parafoveal superficial capillary plexus vessel density (SCP-VD) and 10-2 VF MD (r = 0.549, p = 0.002). Macular SCP vessel area density showed a positive correlation with RNFL thickness (r = 0.429, p = 0.036). Mean vessel length in the optic nerve head layer exhibited a negative correlation with 10-2 VF MD (r = – 0.528, p = 0.003). Quadrant-wise analysis revealed positive associations between SCP-VD and both GCC (r = 0.409, p = 0.038) and RNFL thickness (r = 0.410, p = 0.047) in the superior hemifield, and between deep capillary plexus vessel density and RNFL thickness (r = 0.533, p = 0.007) in the inferior hemifield.

CONCLUSION: Parafoveal SCP-VD and GCC thickness, due to their significant correlations with 10-2 VF MD, may serve as surrogate markers for monitoring central visual function and disease progression in advanced glaucoma, particularly when reliable VF testing is not feasible.

PMID:40608266 | DOI:10.1007/s40123-025-01192-1

Appl Biochem Biotechnol. 2025 Jul 3. doi: 10.1007/s12010-025-05319-9. Online ahead of print.

ABSTRACT

Gastric cancer (GC) stands as one of the most common malignancies globally, characterized by significant incidence rates. Phosphofructokinase muscle isoform (PFKM), a critical rate-limiting enzyme in glycolysis, has its expression modulated by lactate production in tumor cells. The objective of this study is to elucidate the underlying molecular mechanisms by which PFKM contributes to the pathogenesis of GC. The viability, migration, and invasion of GC cells were analyzed by CCK-8 and transwell assays. Each condition was repeated three times. The regulation of H3K18la on transcription activity of CNTNl was evaluated by·dua-luciferase reporter assay. Animal experiment was performed using nude mice with six mice in each group, and tumor growth was evaluated. Statistical analysis was performed using GraphPad Prism software with t-test, one-way or two-way ANOVA. We found that PFKM was over-expressed in GC. Downregulated PFKM restrained the viability, migration, invasion, glucose uptake, and lactate production of GC cells. Mechanically, PFKM interacted with CNTN1 and facilitated the enrichment of H3K18la at the CNTN1 promoter region. Overexpression of CNTN1 reversed the inhibitory effects of PFKM knockdown on GC progression. Our research showed that increasing PFKM levels accelerated GC development by regulating CNTN1 expression through mechanisms involving histone lactylation, which could potentially contribute to novel approaches in diagnosing and treating GC.

PMID:40608258 | DOI:10.1007/s12010-025-05319-9

Eur J Clin Microbiol Infect Dis. 2025 Jul 3. doi: 10.1007/s10096-025-05170-0. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary tuberculosis (PTB) is a respiratory infectious disease that seriously endangers people’s health and incurs high treatment costs, which quickly leads to catastrophic expenditure for patients and their families. A centralized hospitalization treatment (CHT) strategy can be implemented to mitigate the transmission of PTB. This study evaluates the effectiveness of a CHT approach in reducing the magnitude of Mycobacterium tuberculosis (MTB) transmission in household contacts (HHCs) of confirmed PTB cases and explores potential risk factors for PTB.

METHODS: This retrospective cohort study used PTB cases from Guizhou, China, between January 2022 and October 2023. The HHCs of PTB cases diagnosed etiologically and treated with non-CHT were designated as the exposed group, and the HHCs of those treated with CHT were the non-exposed group. The ratio of the HHCs to index cases was 1:1-3. Face-to-face interviews were conducted for the participants by medical staff at home. R software was used for data analysis. Continuous variables were cut to create new categorical variables and were analyzed using the Chi-square test or Fisher test according to the nature of the data. The risk factors of PTB/LTBI and covariates were analyzed using a multivariate logistic regression model evaluated by the Akaike information criterion (AIC) and elucidated by a Directed Acyclic Graph (DAG). The alpha (α) test level of all statistical tests was 0.05.

RESULTS: 1007 participants were investigated, including 559 HHCs of PTB index cases from CHT settings and 448 HHCs of PTB index cases from non-CHT sites (treated at home). Of the two groups, 46 HHCs tested positive for PTB/LTBI (latent TB infections), with a 3.4% positive detection rate (19 cases) in the HHCs of PTB index cases treated with CHT and 6.0% (27 cases) in the HHCs of those treated with non-CHT, with positive detection of LTBI [17(3.0%) vs. 26(5.8%)] and [3(0.5%) vs. 5(1.1%)] of PTB in the former than that in the latter. A statistically significant difference was found between the two LTBI groups. In the univariate analysis, family caregivers, age, marital status, CHT, eating the same food with the patient, sleeping in the same room with the patient, and caring for the patient for more than or equal to 2 months were risk factors for PTB/LTBI among HHCs. The treatment of PTB families with non-CHT was an independent factor of PTB/LTBI in the HHCs through multivariate analysis and AIC evaluation.

CONCLUSIONS: The transmission of PTB/LTBI to HHCs is lower in the HHCs of CHT patients than in the HHCs of those treated with non-CHT after controlling for the other factors including older age, abnormal marriage, and staying with PTB patients equal to or more than two months.

PMID:40608256 | DOI:10.1007/s10096-025-05170-0

Ann Nucl Med. 2025 Jul 3. doi: 10.1007/s12149-025-02078-9. Online ahead of print.

ABSTRACT

OBJECTIVE: Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of bone-modifying agent (BMA) therapy in patients with prostate cancer and bone metastasis. This study aimed to assess the effectiveness of the temporal changes in jaw-specific bone scan index (ΔBSIJ) as quantitative markers for early prediction of MRONJ in patients with prostate cancer receiving BMA therapy.

METHODS: This retrospective study included 33 patients with prostate cancer with bone metastases who underwent bone scintigraphy before and after BMA initiation. BSIJ was measured using BONENAVI software, and the difference between pre- and post-BMA BSIJ values was considered ΔBSIJ. Statistical analyses, including paired t-test, receiver operating characteristic (ROC) curve analysis, and Kaplan-Meier survival estimate, were employed to assess the predictive value of ΔBSIJ for MRONJ.

RESULTS: Of the 33 patients, 10 developed MRONJ during a median follow-up period of 29 months. ΔBSIJ was significantly higher in the MRONJ group than in the non-MRONJ group (0.05 vs. – 0.04, p = 0.002). ROC analysis revealed the highest area under the curve (AUC = 0.823) for ΔBSIJ compared with the pre- and post-BMA BSIJ values. A ΔBSIJ cutoff of 0.039 predicted MRONJ with 60% sensitivity and 91% specificity. Patients with ΔBSIJ ≥ 0.039 exhibited significantly shorter MRONJ-free survival than those with ΔBSIJ < 0.039 (median: 18.4 months vs. not reached, p < 0.001).

CONCLUSION: ΔBSIJ is a novel and clinically useful quantitative marker for the early detection of MRONJ in patients with prostate cancer receiving BMA therapy. This study highlights the potential of leveraging functional imaging and temporal changes in BSIJ to improve MRONJ management.

PMID:40608250 | DOI:10.1007/s12149-025-02078-9

Ann Biomed Eng. 2025 Jul 3. doi: 10.1007/s10439-025-03775-2. Online ahead of print.

ABSTRACT

PURPOSE: The objective of this study was to characterize joint level morphology and alignment differences across stages of progressive collapsing foot deformity (PCFD) within the talocrural, subtalar, talonavicular, and calcaneocuboid joints using multi-bone statistical shape modeling (SSM) and joint distance measurements from weightbearing computed tomography (WBCT) scans. This was achieved by employing multi-bone SSM in conjunction with precise joint measurement analysis, utilizing WBCT scans to investigate the intricate changes within the talocrural, subtalar, talonavicular, and calcaneocuboid joints.

METHODS: A retrospective analysis was conducted on patients with PCFD who failed conservative treatment. Two groups of 20 feet each were formed for flexible PCFD and rigid PCFD, with 27 additional feet identified as asymptomatic controls. All 67 participants underwent a WBCT scan, and 3D models were created as inputs for multi-bone SSM and joint distance measures.

RESULTS: The first principal component analysis mode contained 45.8% of the variation in the population while the second mode contained 13.3% of the variation and the third mode contained 6.4% of variation accounting for 65.6% of the overall variation in the multi-bone model. Joint space distance measurement differences were observed between all three groups for all articulations. The primary difference between flexible PCFD and rigid PCFD multi-bone SSM was a statistically significant medial shift of alignment of the talar neck, resulting in worsened peritalar subluxation.

CONCLUSION: PCFD is quantifiably variable across a clinical population when evaluating joint level measurements as well as morphologic and alignment variations. Talonavicular joint malalignment severity may be a clinical key in distinguishing between stages of PCFD.

PMID:40608241 | DOI:10.1007/s10439-025-03775-2