Nevin Manimala

Clin Drug Investig. 2026 Mar 15. doi: 10.1007/s40261-026-01537-z. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Vortioxetine is widely used in Switzerland for treating major depressive episodes, but systematically collected data from routine clinical practice are not available. We evaluated real-world effectiveness and tolerability of vortioxetine for treating major depressive episodes in Swiss clinical practice.

METHODS: A prospective non-interventional observational study was conducted with an observation period of approximately 8 weeks from vortioxetine initiation. Adults with a current major depressive episode for whom a decision to initiate vortioxetine had been made independent of the study were eligible for inclusion. Assessment of depressive symptoms, functioning, safety and tolerability were performed at four study visits. Pre-planned explorative descriptive statistics were applied.

RESULTS: Of 226 patients enrolled, 208 (92.0%) completed the study. At baseline, the mean (standard deviation) sum of the unanchored Montgomery-Åsberg Depression Rating Scale items was 34.3 (8.89), indicating severe depression. Depression severity tended to be underestimated when relying on clinical estimation without any scale alone. Significant reductions were observed from baseline to visit 4 in the sum of the unanchored Montgomery-Åsberg Depression Rating Scale items, in all individual items, and in the Clinical Global Impression-Severity scale (all p < 0.001). The severity of impairment of all assessed functioning domains also decreased. Adverse drug reactions were reported in 7.5% of patients. Effectiveness and tolerability of vortioxetine was rated good or very good by >88% of clinicians and patients.

CONCLUSIONS: Patients who initiated vortioxetine for treating a major depressive episode experienced improvements in depressive symptoms and functioning. Vortioxetine was well tolerated. Underestimation of depressive episode severity by clinicians reinforces the importance of using rating scales in clinical practice.

PMID:41832924 | DOI:10.1007/s40261-026-01537-z

Am J Prev Med. 2026 Mar 14:108282. doi: 10.1016/j.amepre.2026.108282. Online ahead of print.

ABSTRACT

INTRODUCTION: The U.S. Food and Drug Administration’s The Real Cost Youth E-Cigarette Prevention Campaign partnered with the National Cancer Institute to provide SmokefreeTeen cessation resources to the campaign audience. This study explored how traffic directed to the SmokefreeTeen website from campaign messages interacted with content and how engagement differed on the basis of traffic source.

METHODS: Using SmokefreeTeen web traffic data from April 2021 to December 2022 (and analyzed in 2024), the study descriptively and statistically compared page views and engagement with cessation tools (3-step Vaping Reality Check quiz; Quit Plan builder) for referrals to SmokefreeTeen from The Real Cost Youth E-Cigarette Prevention Campaign advertising, direct traffic (e.g., typed website into browser), or organic searches (e.g., search engines).

RESULTS: Campaign traffic generated higher proportions of page views for campaign-linking pages. Quit resources engagement was greater for campaign visits, with a higher proportion of Vaping Reality Check completions and Quit Plan completions and downloads than of other sources. Organic searches generated the highest proportion of overall traffic, followed by direct website and the campaign.

CONCLUSIONS: The Real Cost’s primary goal is youth tobacco prevention. Because many youth experience E-cigarette-related addiction, the campaign also shares evidence-based cessation resources. Linking to SmokefreeTeen resources from campaign assets resulted in substantial traffic to intended pages and engagement with cessation tools. The campaign’s ability to successfully link to SmokefreeTeen cessation resources demonstrates that digital media campaigns, such as The Real Cost tobacco prevention campaigns, can reach audiences at various stages of tobacco use and encourage engagement with online cessation resources.

PMID:41832902 | DOI:10.1016/j.amepre.2026.108282

Eur J Surg Oncol. 2026 Mar 6;52(5):111740. doi: 10.1016/j.ejso.2026.111740. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to identify psychosocial subtypes among gastric cancer (GC) patients and examine their associations with quality of life (QoL) and survival outcomes.

METHODS: A prospective cohort design was adopted, including 455 newly diagnosed GC patients admitted to the Union Hospital of Fujian Medical University between January 2023 and August 2024. Depressive symptoms and sleep quality were assessed using the Patient Health Questionnaire-9 (PHQ-9) and Pittsburgh Sleep Quality Index (PSQI), respectively. QoL was evaluated using the EORTC QLQ-C30 and QLQ-STO22 questionnaires. Latent class analysis (LCA) was performed based on social support, depressive symptoms, and sleep quality to identify distinct psychosocial subtypes. Between-group QoL differences at 6 months were examined with pairwise comparisons adjusted for baseline QoL (ANCOVA).

RESULTS: Three psychosocial subtypes were identified: low-risk (37.6%), moderate-risk (40.4%), and high-risk (22.0%). At 6 months postoperatively, the low-risk group showed higher physical functioning than the high-risk group (94.02 ± 8.16 vs. 89.83 ± 14.10; P = 0.011) and higher cognitive functioning than the moderate-risk group (98.56 ± 3.68 vs. 96.08 ± 8.96; P = 0.001) on the EORTC QLQ-C30. Global health status/QoL was also higher in the low-risk group than in the moderate- and high-risk groups (68.47 ± 21.39 vs. 62.57 ± 22.95 vs. 61.89 ± 21.05; P = 0.023 and 0.027, respectively). Dysphagia symptom burden on the EORTC QLQ-STO22 was greater in the moderate- and high-risk groups than in the low-risk group (10.90 ± 11.54 and 11.71 ± 11.49 vs. 6.83 ± 10.17; P = 0.001 and 0.002, respectively). In multivariable Cox regression, the high-risk group had a higher risk of death than the low-risk group (HR = 3.95, 95% CI: 1.20-13.00; P = 0.024).

CONCLUSIONS: Psychosocial subtypes identified by LCA were associated with 6-month postoperative QoL, and the high-risk subtype was an independent predictor of overall survival among GC patients. Early identification of high-risk patients may facilitate precision supportive care and inform multidimensional interventions to improve both QoL and survival.

PMID:41832888 | DOI:10.1016/j.ejso.2026.111740

Nutrition. 2026 Feb 10;147:113158. doi: 10.1016/j.nut.2026.113158. Online ahead of print.

ABSTRACT

OBJECTIVES: Metabolic syndrome (MetS) is a cluster of cardiometabolic-related conditions that occur together with obesity. Visceral adiposity specifically is an important risk factor for MetS. The visceral adiposity index (VAI) is a sex-specific estimate of visceral adiposity presence and dysfunction and while a reliable predictor of MetS, more research is needed to establish VAI cut-points across varying populations before it can be used as a clinical tool. The purpose of this secondary analysis was to assess the effectiveness of the VAI and other anthropometric indices to predict MetS and to create cut-points using a sample of older adults with obesity using data from the Calorie Restriction in Overweight SeniorS (CROSSROADS) Study.

METHODS: The CROSSROADS Study was a randomized controlled trial that investigated the effects of a 12-month diet and exercise intervention among older adults with obesity (ClinicalTrials.gov, #NCT00955903). For statistical analysis, Pearson’s chi-squared tests, Wilcoxon Signed-Rank Test, logistic regression, and receiver operative characteristic curve analyses were conducted.

RESULTS: VAI was significantly associated with MetS presence in this sample more than other anthropometric indices (P < 0.001). A previously established VAI cut-point of 2.261 had the highest Youden Index for all sub-samples except for the Black participants, where the newly established VAI cut-point of 1.58 determined in this study had the highest Youden Index.

CONCLUSIONS: Among a sample of older adults with obesity, VAI is significantly associated with MetS. However, further research is needed to evaluate population-specific VAI cut-points to assess for practical utility before being used in clinical settings.

PMID:41832848 | DOI:10.1016/j.nut.2026.113158

Nutrition. 2026 Feb 18;147:113168. doi: 10.1016/j.nut.2026.113168. Online ahead of print.

ABSTRACT

BACKGROUND: Bariatric surgery (BS), including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), effectively treats severe obesity through enhanced secretion of satiety hormones (glucagon-like peptide-1 [GLP-1], peptide-YY [PYY]). However, these hormonal elevations cannot be sustained long-term, resulting in diminished efficacy. Postoperative dietary fiber (DF) intake is critically low post-BS, yet DF may enhance short-chain fatty acid (SCFA)-producing microbiota and stimulate the secretion of GLP-1 and PYY, potentially sustaining metabolic benefits.

OBJECTIVES: The trial aimed to investigate the effect of DF supplementation (oat bran) on gut microbiota, hormones, and glycolipid metabolism in post-BS patients.

METHODS: In a 12-week RCT, 63 post-BS patients were randomized to control (standard care) or intervention (standard care+30 g/d oat bran, providing 9.0 g DF for 12 weeks). Outcomes included microbiota composition, the levels of GLP-1 and PYY, glycolipid parameters, and percentage of excess weight loss.

RESULTS: Sixty-three participants completed the trial (intervention: 30, control: 33). The intervention group achieved higher DF intake (15.28 ± 3.69 g/d vs. 7.45 ± 4.63 g/d, P < 0.05), with increased beneficial genera (Lachnospira, Parabacteroides) and reduced Streptococcus (P < 0.05). The intervention group showed significant improvements in fasting GLP-1 and PYY, FBG, and HDL-C (P < 0.05). Although the between-group difference in EWL% was not statistically significant (16.59 ± 5.87% vs 10.47 ± 3.29%, P > 0.05), both groups showed significant within-group improvements (P < 0.05). ITT analysis confirmed robustness.

CONCLUSION: DF supplementation significantly improved gut microbiota, enhanced enteroendocrine hormone secretion, and improved metabolic parameters in post-BS patients, supporting its use as an adjunctive therapy.

REGISTRATION NUMBER FOR CLINICAL TRIALS: The study protocol was registered with the Chinese Clinical Trial Registry (ChiCTR2400092481) at http://www.chictr.org.cn.

PMID:41832846 | DOI:10.1016/j.nut.2026.113168

J Hazard Mater. 2026 Mar 9;507:141727. doi: 10.1016/j.jhazmat.2026.141727. Online ahead of print.

ABSTRACT

Chronic exposure to organochlorine pesticides (OCPs) is associated with altered DNA methylation and metabolic diseases, but their specific methylation patterns and mediating role in metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We conducted an epigenome-wide association study among 2905 adults, measuring 19 serum OCPs and blood DNA methylation using the Illumina EPIC array. Differentially methylated probes (DMPs) were identified via linear regression, and mediation analyses assessed their mediating effects on MASLD. We also constructed an integrated adverse outcome pathway (AOP) network to illustrate the underlying mechanisms. Eighteen novel OCP-associated DMPs were identified, of which 11 DMPs were related to prevalent MASLD and four to incident MASLD, with three overlapping (cg17075888, cg27402362, and cg11024682). In the cross-sectional analysis, eight DMPs (e.g., ABCG1, CPT1A, SREBF1) statistically mediated 15.90% of the association between β-HCH and prevalent MASLD. Furthermore, the longitudinal analysis provided stronger evidence, suggesting that cg27402362 (RUNX3) mediated 5.22% of the β-HCH and incident MASLD association. The AOP network included six molecular initiating events and 19 key events, implicating lipid metabolism, oxidative stress, and immune and inflammatory pathways. This study provides novel population-based evidence that OCP exposure may be associated with MASLD development through DNA methylation mechanisms. The AOP framework further strengthens the mechanistic plausibility of OCP-induced hepatotoxicity and improves our understanding of OCP-associated MASLD.

PMID:41832812 | DOI:10.1016/j.jhazmat.2026.141727

Am J Hematol. 2026 Mar 15. doi: 10.1002/ajh.70283. Online ahead of print.

ABSTRACT

Concerns about the efficacy of high-dose methotrexate (HD-MTX) in preventing CNS recurrence in large B-cell lymphomas (LBCL) are based on studies with interpretation biases and incomplete information about HD-MTX dosing schedule and CNS events. We evaluated a pharmacokinetic-informed, CNS-directed HD-MTX protocol (3 g/m² over 3 h, preceded by a bolus) in 336 LBCL patients achieving CMR after RCHOP or derivatives. HD-MTX use was based on institutional risk scores. In this study, CNS risk was reassessed using updated criteria: CNS-IPI ≥ 4, ≥ 3 extranodal sites, or involvement of testis, kidney, adrenal gland, uterus, or breast. According to these criteria, risk was low in 228 (68%) patients and high in 108 (32%); HD-MTX was given to 20 (9%) and 49 (45%), respectively. HD-MTX was well tolerated: 96% completed therapy. After a median follow-up of 77 months, 13 (4%) patients experienced CNS relapse, always as isolated events. Among high-risk patients, CNS relapse occurred in 19% (11/59) without HD-MTX versus 0% (0/49) with HD-MTX (p = 0.0009); significant reductions were seen in patients with high-risk organ involvement (32% to 0%, p = 0.002) or ≥ 3 extranodal sites (18% to 0%, p = 0.04). HD-MTX was independently associated with improved PFS and OS in high-risk patients, likely due to reduced CNS relapses (0% vs. 19%; p = 0.0009), whereas rates of unrelated deaths (8% vs. 15%; p = 0.26) and systemic relapses (18% vs. 22%; p = 0.81) were similar. In conclusion, HD-MTX, administered via a pharmacokinetic-informed, CNS-directed schedule, with or without intrathecal chemotherapy, significantly reduces CNS relapses and improves outcomes in high-risk LBCL patients in CMR. Trial Registration: ClinicalTrials.gov Identifier: NCT07181785.

PMID:41832699 | DOI:10.1002/ajh.70283

Curr Pharm Des. 2026 Mar 12. doi: 10.2174/0113816128397599251204081009. Online ahead of print.

ABSTRACT

INTRODUCTION: Obesity and hypertension synergistically increase cardiovascular risk, with Monocyte Chemoattractant Protein-1 (MCP-1), Endothelin-1 (ET-1), and Pro-B-Type Natriuretic Peptide (Pro- BNP) implicated in vascular dysfunction and cardiac stress. However, their combined role in obesity-driven hypertension remains poorly understood. This study aimed to investigate the associations between MCP-1, ET-1, and Pro-BNP levels in obese hypertensive patients and evaluate their collective contribution to disease pathogenesis.

METHODS: This prospective, non-randomized clinical study enrolled 97 adult male participants, stratified into four groups: healthy controls (n = 22), overweight normotensive individuals (n = 25), class I obese hypertensive patients (n = 25), and class II obese hypertensive patients (n = 25). Blood samples were collected and analyzed for metabolic parameters (fasting glucose, insulin, lipid profile), oxidative stress markers (MDA, GSH, SOD), and inflammatory cytokines (VEGF, IL-1β, IL-9). Gene expression levels of MCP-1, ET-1, and Pro-BNP were quantified using real-time PCR, while protein expression was assessed via Western blotting. Statistical analyses included one-way ANOVA with Bonferroni correction, Pearson correlation coefficients, and multivariable linear regression models adjusted for age, BMI, metabolic, and oxidative stress parameters.

RESULTS: Class II obese hypertensive patients exhibited the highest systolic and diastolic blood pressure, body mass index, and the most severe metabolic dysregulation, including elevated fasting glucose, insulin resistance, and dyslipidemia. Oxidative stress was significantly increased, as indicated by elevated MDA levels and reduced GSH and SOD activity. Inflammatory cytokines, including VEGF, IL-1β, and IL-9, were markedly elevated in this group. Gene and protein expression levels of Pro-BNP, ET-1, and MCP-1 were significantly upregulated in a stepwise manner across the groups, with class II patients showing the highest expression. Specifically, protein levels of Pro-BNP, ET-1, and MCP-1 were increased by 204.8%, 222.2%, and 180.6%, respectively, compared with healthy controls (all p < 0.05). Strong positive correlations were observed between Pro-BNP and both ET-1 and MCP-1 (r = 0.991, p < 0.001 for both). Receiver operating characteristic (ROC) analysis demonstrated high predictive accuracy for Pro-BNP (AUC = 0.94), ET-1 (AUC = 0.89), and MCP-1 (AUC = 0.92), with a combined biomarker panel achieving an AUC of 0.97.

DISCUSSION: The robust interrelationships among MCP-1, ET-1, and Pro-BNP suggest their synergistic involvement in promoting vascular inflammation, endothelial dysfunction, and cardiac stress in obesity-related hypertension. These biomarkers may serve as diagnostic indicators and therapeutic targets. Limitations include the male-only cohort and cross-sectional design.

CONCLUSION: The robust interrelationships among MCP-1, ET-1, and Pro-BNP suggest their synergistic involvement in promoting vascular inflammation, endothelial dysfunction, and cardiac stress in obesity-related hypertension. These biomarkers may serve as valuable diagnostic indicators and potential therapeutic targets. Further interventional studies are warranted to validate their clinical utility and explore targeted treatment strategies.

PMID:41832687 | DOI:10.2174/0113816128397599251204081009

Curr Pharm Des. 2026 Mar 12. doi: 10.2174/0113816128423981251208075251. Online ahead of print.

ABSTRACT

INTRODUCTION: Skin hyperpigmentation is a common concern that can significantly impact aesthetic perception and self-esteem. Consequently, there is growing interest in identifying natural inhibitors of melanin synthesis to develop cosmetic formulations that are effective, safe, and sustainable. This study aimed to develop, characterize, and evaluate the in vitro anti-melanogenic potential of emulsions containing jaboticaba (Plynia peruviana (Poir.) Govaerts) peel extract in combination with azelaic acid (AA).

METHODS: Four distinct formulations were prepared: TAAJ (AA + jaboticaba extract, with turbo-shear mixing), AAJ (AA + jaboticaba extract, without high-shear mixing), TAAAE (AA + ellagic acid (EA), with turbo- shear mixing), and TAA (AA, with turbo-shear mixing). All formulations underwent physicochemical characterization and statistical analysis.

RESULTS: Particle sizes ranged from 295.20 to 630.50 nm, with polydispersity index (PDI) values between 0.1 and 1.0, and zeta potential from -6.82 to +2.02 mV. Jaboticaba peel extract demonstrated excellent performance in both antioxidant assays and mushroom tyrosinase inhibition, surpassing conventional agents. TAAJ exhibited the highest anti-melanogenic activity, achieving the greatest tyrosinase inhibition and the lowest IC50. TAAJ and AAJ showed the strongest copper-ion chelating activity, while jaboticaba peel extract and TAAAE also displayed chelating capacity; TAA showed none. TAA induced the most significant reduction in melanin synthesis in B16F10 melanoma cells.

DISCUSSION: Among the tested formulations, the most promising was selected based on macroscopic characteristics, presenting a homogeneous, milky appearance without phase separation. This suggests that all tested formulations exhibited some degree of anti-melanogenic activity, likely through distinct mechanisms influenced by the complex interactions among their active components.

CONCLUSION: To the best of our knowledge, no previous studies have investigated jaboticaba peel extract for skin hyperpigmentation. These findings highlight jaboticaba peel extract-an agro-industrial byproduct-as a promising and eco-friendly ingredient for hyperpigmentation treatment, supporting the development of innovative cosmetic formulations leveraging sustainable, plant-based resources.

PMID:41832683 | DOI:10.2174/0113816128423981251208075251

Curr Pharm Des. 2026 Mar 11. doi: 10.2174/0113816128431488251204105511. Online ahead of print.

ABSTRACT

BACKGROUND: Environmental exposure to volatile organic compounds (VOCs) may adversely affect liver function, particularly in adolescents; however, the evidence remains scarce.

OBJECTIVE: This study aimed to evaluate the individual and combined effects of VOCs exposure on liver function in adolescents, as well as the potential mediating role of lactate dehydrogenase (LDH) and possible intervention strategies.

METHODS: In total, 1,280 adolescents aged 12-19 years from the National Health and Nutrition Examination Survey were studied to examine the associations between 15 VOC metabolites and 4 liver function indicators. Four statistical models were employed to assess the associations, including weighted linear regression, restricted cubic splines, weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR). Mediation analysis was performed to evaluate whether LDH mediated or partially explained these associations.

RESULTS: Among the 15 individual VOC metabolites, 8 were observed to have a significant association with specific liver function indicators. The WQS and BKMR models consistently identified significant associations between VOC mixtures and elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Additionally, AMCC [parent VOC (pVOC): N, N-dimethylformamide] and HMPMA (pVOC: crotonaldehyde) were identified as major contributors to the combined effect. Mediation analysis showed the potential mediation effect of serum LDH on these associations. Moreover, the adverse effect of VOC exposure on adolescent liver function was significantly mitigated with adequate vitamin D intake.

DISCUSSION: The results indicate that VOC exposure is positively associated with elevated liver function indicators in adolescents, with AMCC and HMPMA as main contributors. The mediating role of LDH suggests that oxidative stress may serve as a key mechanistic pathway underlying VOC-induced liver injury. Additionally, adequate vitamin D intake appears to mitigate these adverse effects.

CONCLUSION: Our findings revealed a positive association between exposure to VOC and liver function in adolescents, and suggest that LDH may be a potential mechanism for VOC-induced liver injury. Supplementing with vitamin D may help protect adolescent liver function from the effects of VOC exposure.

PMID:41832679 | DOI:10.2174/0113816128431488251204105511