Tag: nevin manimala

JAMA Psychiatry. 2025 Jun 4. doi: 10.1001/jamapsychiatry.2025.0801. Online ahead of print.

ABSTRACT

IMPORTANCE: Major depressive disorder (MDD) and obesity are common noncommunicable disorders associated with substantial disease burden, which frequently occur comorbidly. Intriguingly, converging lines of evidence from animal models and genetic and observational studies have suggested a biological link between obesity, metabolic syndrome, and depression. Several small randomized clinical trials (RCTs) have suggested the antidepressive potential of statins.

OBJECTIVE: To examine whether simvastatin added to escitalopram is efficacious in improving depressive symptoms compared with add-on placebo.

DESIGN, SETTING, AND PARTICIPANTS: This was a confirmatory, double-blind, placebo-controlled, multicenter RCT. Adults with MDD and comorbid obesity from 9 tertiary care settings in Germany were enrolled in this analysis. Data were analyzed from July to October 2024.

INTERVENTIONS: Simvastatin (40 mg per day) or placebo as add-on to escitalopram (10 mg for the first 2 weeks, then increased to 20 mg until the end of study) in a double-blind fashion for 12 weeks.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline (week 0) to week 12.

RESULTS: From August 21, 2020, to June 06, 2024, a total of 161 patients were enrolled at 9 sites in Germany, of which 160 patients were included in the intention-to-treat analysis (placebo: n = 79, simvastatin: n = 81; mean [SD] age, 39.0 [11.0] years; 126 female [79%]). Retention in the trial was excellent (95.6%), and blinding was effectively maintained. There were 4 serious adverse events with no difference between the groups. Primary end point analysis in the intention-to-treat sample showed no significant treatment effect of add-on simvastatin in MADRS scores (mixed models for repeated measures least squares mean difference, 0.47 points; 95% CI, -2.08 to 3.02; P = .71). No effects of simvastatin treatment were observed in any of the mental health-related secondary end points. However, simvastatin treatment significantly reduced low-density lipoprotein cholesterol (simvastatin, -40.37 mg/dL; 95% CI, -47.41 to -33.33 mg/dL; placebo, -3.78 mg/dL; 95% CI, -11.18 to 3.62 mg/dL; P < .001), total cholesterol (simvastatin, -39.07 mg/dL; 95% CI, -49.42 to -28.73 mg/dL; placebo, -4.89 mg/dL; 95% CI, -15.64 to 5.87 mg/dL; P < .001), and C-reactive protein (simvastatin, -1.04 mg/L; 95% CI, -1.89 to -0.20 mg/L; placebo, 0.57 mg/L; 95% CI, -0.28 to 1.42 mg/L; P = .003) compared with placebo.

CONCLUSIONS AND RELEVANCE: The study failed to meet its primary end point. This demonstrates that simvastatin did not exert additional antidepressive effects when added to escitalopram in patients with comorbid MDD and obesity, despite improving the cardiovascular risk profile.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04301271.

PMID:40465256 | DOI:10.1001/jamapsychiatry.2025.0801

Chaos. 2025 Jun 1;35(6):063115. doi: 10.1063/5.0270132.

ABSTRACT

Time-series analysis plays a crucial role in understanding the dynamics of real-world systems across various scientific and engineering disciplines. We in this paper propose a novel approach to identifying chaotic dynamics by a geometric method based on deep learning. Specifically, we construct a map from the observed time-series data and seek the existence of a topological horseshoe in the map, which indicates chaotic behavior. We demonstrate the effectiveness of our method by numerical experiments on the Hénon map, the Lorenz system, and the Duffing system. The results show that the topological horseshoe theory combined with deep neural works provides a valuable tool for detection of chaos in complex nonlinear systems from time series.

PMID:40465250 | DOI:10.1063/5.0270132

Melanoma Res. 2025 May 27. doi: 10.1097/CMR.0000000000001046. Online ahead of print.

ABSTRACT

Wide local excision (WLE) is the standing surgical choice for acral lentiginous melanoma (ALM), yet research is scarce in evaluating other surgical options for ALM and its recurrence rates remain two to five times more likely than other melanoma subtypes. This study evaluates the overall survival outcomes associated with different surgical modalities in patients with stage 0-II ALM. This retrospective cohort study surveyed the National Cancer Database from 2004 to 2021 for International Classification of Diseases-10 codes specific for all skin structures with histologically confirmed ALM for stage 0-II patients. Using IBM SPSS, statistical analyses were conducted via variable frequency with crosstabulations and Chi-squared tests, Kaplan-Meier survival curves with log-rank pairwise comparisons, and Cox proportional hazards regression models. Data for 6737 patients showed significantly greater overall survival for biopsy followed by gross excision (BFGE) than WLE [median overall survival = 204.8 months (P < 0.001); hazard ratio = 0.77 (95% confidence interval, 0.68-0.87)]. Median overall survival for WLE was 181.6 months. Cross analysis of Breslow depth (BD) with surgical procedures revealed the majority (21.8%) of WLEs were completed for lesions with a BD of 0.1-5 mm followed by 16.8% for lesions greater than 3 cm (P < 0.001). Crossanalysis of surgical margins of the primary site with surgical procedures, showed no residual tumor in 92.1% of all BFGE patients, which is 3.7% and 3.3% less patients than major amputation and WLE. This study highlights significant differences across ALM surgery options, suggesting each modality has their own niche and BFGE should be investigated further.

PMID:40465243 | DOI:10.1097/CMR.0000000000001046

Oncologist. 2025 Jun 4;30(6):oyaf104. doi: 10.1093/oncolo/oyaf104.

ABSTRACT

BACKGROUND: The efficacy and safety of chemotherapy combined with programmed cell death protein-1 (PD-1) inhibitors in postoperative adjuvant therapy of pancreatobiliary subtype ampullary adenocarcinoma (AAC) are uncertain. This study aims to evaluate the effect of such treatment on the survival of this patient population.

METHODS: We retrospectively collected patients with pancreatobiliary subtype AAC who underwent surgical treatment at the Sun Yat-sen Memorial Hospital from January 2018 to December 2022. Patients with high-risk recurrence factors after surgery were divided into surgery alone group, adjuvant chemotherapy group, and adjuvant chemoimmunotherapy group. The Kaplan-Meier method was used to plot survival curves, and the Log-Rank method was used to compare the differences in overall survival (OS) and recurrence-free survival (RFS) between groups.

RESULTS: A total of 71 people were enrolled, including 24 patients received surgery alone, 31 patients received adjuvant chemotherapy, and 16 patients received adjuvant chemoimmunotherapy. The median time of clinical follow-up was 17.8 [IQR 8.3-28.4] months. The 1-year OS rates of the surgery alone group, adjuvant chemotherapy group, and adjuvant chemoimmunotherapy were 41.7%, 71.0%, and 93.3%, respectively. The 2-year OS rates were 28.6%, 47.7%, and 84.0%, respectively. The median OS was 6.8 months and 22.1 months, but the adjuvant chemoimmunotherapy group did not reach (P = .0002). The median RFS was 4.7 months, 15.7 months, and 14.8 months, respectively, but the differences were not statistically significant (P = .0613). Univariate and multivariate Cox analysis results showed that tumor size >2.3 cm (HR = 2.06, 95% CI, 1.06-4.04; P = .034) and the treatment regimen were independent factors affecting prognosis, compared to surgery alone and adjuvant chemotherapy (HR = 0.521, 95% CI, 0.26-1.04; P = .065), adjuvant chemoimmunotherapy (HR = 0.106, 95% CI, 0.02-0.47; P = .003) significantly improves patient survival. There was no statistically significant difference in any complications between the 3 groups (P > .05). Compared with the adjuvant chemotherapy group, patients in the adjuvant chemoimmunotherapy group are more likely to experience hypothyroidism (P = .044) and pruritus (P = .022). There is no statistically significant difference in other AEs between the 2 groups (P > .05).

CONCLUSION: Compared with surgery alone or adjuvant chemotherapy, patients with pancreatobiliary subtype AAC who received adjuvant chemoimmunotherapy showed better OS, and the drug-related toxicity was acceptable.

PMID:40465242 | DOI:10.1093/oncolo/oyaf104

Updates Surg. 2025 Jun 4. doi: 10.1007/s13304-025-02263-5. Online ahead of print.

ABSTRACT

Laparoscopic right hemicolectomy (Lap-RHC) presents technical challenges due to the complex vascular anatomy of the mesentery, which increases the risk of intraoperative bleeding and complicates surgical navigation. Accurate identification of the superior mesenteric vein (SMV) is crucial for maintaining surgical safety and achieving optimal oncological outcomes. To address these challenges, this study proposes the terminal ileal vein (TIV) approach, a novel technique designed to facilitate precise SMV identification and enable en bloc resection of the ileal mesentery while preserving mesenteric integrity. This retrospective cohort study evaluated a novel TIV approach compared to the traditional ileocolic vascular pedicle (IVP) approach for SMV identification and en bloc mesentery resection in patients with right-sided colon cancer. A total of 196 patients underwent Lap-RHC between 2022 and 2023, with 67 patients matched by propensity score included in both groups. The TIV approach involves initiating dissection at the TIV to accurately locate the SMV and facilitate en bloc resection of the ileal mesentery. In the balanced cohort, statistically significant differences were observed between groups regarding operation times (186 [120-299] vs. 210 [146-375] minutes, p = 0.001) and intraoperative blood loss (50 [20-400] vs. 70 [20-600] mL, p = 0.033). Differences were also found for time to urinary catheter removal (1 [1-3] vs. 2 [1-5] days, p = 0.012) and postoperative hospital stays (6 [5-12] vs. 7 [5-15] days, p = 0.006). The calculated importance proportion of the TIV approach related to these perioperative variables was between 15 and 25%. In this retrospective cohort, the TIV approach demonstrated reproducible entry into the mesenteric dissection plane and was accompanied by perioperative outcome differences that may reflect technical simplification. Further prospective investigation is needed to determine its clinical utility.

PMID:40465205 | DOI:10.1007/s13304-025-02263-5

Adv Ther. 2025 Jun 4. doi: 10.1007/s12325-025-03211-w. Online ahead of print.

ABSTRACT

INTRODUCTION: A combination of olanzapine and samidorphan (OLZ/SAM), approved by the US Food and Drug Administration (2021) for the treatment of adults with schizophrenia (SZ) or bipolar I disorder (BD-I), mitigates weight gain associated with olanzapine treatment. This study examined changes in healthcare resource utilization (HCRU) among patients with SZ or BD-I after initiating OLZ/SAM.

METHODS: This retrospective analysis utilized USA-based administrative claims data from April 19, 2021 to December 31, 2022. Adults aged ≥ 18 years with SZ or BD-I who had continuous enrollment ≥ 6 months before (baseline) and after (follow-up) OLZ/SAM initiation (index) were eligible. HCRU comparisons included inpatient admissions, average number of inpatient days, emergency department (ED) visits, and outpatient visits between 6-month baseline and follow-up periods.

RESULTS: In total, 1546 patients initiated OLZ/SAM (SZ: n = 855, mean age 39.4 years, 52.6% male; BD-I: n = 691, 38.4 years, 31.0% male). Overall, 446 (52.2%) patients with SZ and 302 (43.7%) patients with BD-I remained on OLZ/SAM during the full 6-month follow-up (median days persistent 182 and 106, respectively). In the SZ and BD-I cohorts, proportions of patients with all-cause and mental health (MH)-related inpatient admissions and ED visits significantly decreased between baseline and follow-up (all-cause: all P ≤ 0.026; MH-related: all P < 0.001). Findings were similar for disease-specific outcomes with the exception that reductions in BD-I-related ED visits were not significant. Average number of inpatient days decreased after OLZ/SAM initiation in both cohorts; in patients with BD-I, those reductions were statistically significant (all P ≤ 0.022). The proportions of patients with outpatient visits were similar between baseline and follow-up for both cohorts.

CONCLUSIONS: Results from this first real-world study assessing HCRU after OLZ/SAM initiation suggest that OLZ/SAM results in reductions in burden for patients, providers, and the healthcare system, as evidenced by reductions in acute all-cause, MH-related, and disease-specific HCRU among SZ and BD-I cohorts.

PMID:40465200 | DOI:10.1007/s12325-025-03211-w

Epilepsia. 2025 Jun 4. doi: 10.1111/epi.18488. Online ahead of print.

ABSTRACT

OBJECTIVE: Widespread structural pathology in the limbic system is a hallmark of temporal lobe epilepsy (TLE). In this work, we sought to describe a comprehensive readout of limbic abnormalities in TLE using neurite orientation distribution and density imaging (NODDI).

METHODS: This is a retrospective study of patients with drug-resistant TLE and healthy controls who underwent research magnetic resonance imaging. We estimated the degree of deviation of the NODDI parameters neurite density index (NDI) and orientation dispersion index (ODI) from healthy controls in limbic regions in the form of univariate z-scores. We calculated a multivariate deviation score combining both NDI and ODI (Mahalanobis distance). A summary score representing the overall level of deviation across limbic regions was then computed using the sum of regional deviation scores. We next assessed the diagnostic performance of summary scores in lateralizing TLE as well as associations with neuropsychological deficits and 12-month surgical outcome.

RESULTS: The Mahalanobis distance revealed unique patterns of abnormalities between TLE participants (n = 74) and controls (n = 42), with only four of 18 (22%) areas displaying overlapping univariate and multivariate deviations. The multivariate summary score achieved the highest diagnostic accuracy in clinical lateralization of nonlesional TLE (area under the curve [AUC] = .95, 95% confidence interval [CI] = .77-1). Among surgical patients (n = 30), summary scores corresponding to the hemisphere ipsilateral and contralateral to surgery were predictive of seizure freedom at 12 months (AUC = .84, 95% CI = .76-.93).

SIGNIFICANCE: We demonstrate unique patterns of abnormalities in neurite density and coherence in limbic microstructure in TLE. A summary score accounting for deviations in both neurite density and coherence achieved high diagnostic accuracy in clinical lateralization of TLE and was associated with surgical outcomes, warranting further study as a putative biomarker in TLE to be used alongside clinical data.

PMID:40465169 | DOI:10.1111/epi.18488

Int J Comput Assist Radiol Surg. 2025 Jun 4. doi: 10.1007/s11548-025-03409-x. Online ahead of print.

NO ABSTRACT

PMID:40465168 | DOI:10.1007/s11548-025-03409-x

Trop Anim Health Prod. 2025 Jun 4;57(5):242. doi: 10.1007/s11250-025-04486-5.

ABSTRACT

Dromedary camels thrive in arid regions and play a crucial role in meat, milk, and labor production. The transition period around parturition impacts maternal and neonatal health by altering antioxidant capacity and increasing oxidative stress. This study investigated the relationship between the transition period and antioxidant capacity in dromedary camels to enhance management practices and welfare. Ten multiparous pregnant camels were monitored from 60 days AP to 60 days PP under ethical guidelines with proper feeding and management. Blood samples and liver biopsies were collected to assess antioxidant enzymes (CAT, SOD, GPx), oxidized product (MDA), and hepatic gene expression via ELISA and qPCR. Statistical analyses in SAS determined time effects, with significance set at P < 0.05. Parturition significantly affected CAT, MDA, and GPx concentrations (P < 0.01). CAT peaked three days AP before declining PP, while MDA spiked at parturition. SOD decreased AP but returned to baseline PP, whereas GPx dropped significantly by seven days PP. Antioxidant-related gene expression increased significantly around parturition, while TNF-α and IL-6 remained stable. PP, some genes returned to AP levels, while others exhibited delayed recovery. This study highlights the liver’s key role in regulating oxidative stress during the transition period and provides insights into improving camel health and productivity in harsh environments. These findings pave the way for future research on nutritional and management strategies to strengthen antioxidant defenses in livestock.

PMID:40465156 | DOI:10.1007/s11250-025-04486-5

Eur Geriatr Med. 2025 Jun 4. doi: 10.1007/s41999-025-01249-1. Online ahead of print.

NO ABSTRACT

PMID:40465142 | DOI:10.1007/s41999-025-01249-1