Nevin Manimala

Scand J Gastroenterol. 2026 Feb 28:1-10. doi: 10.1080/00365521.2026.2636062. Online ahead of print.

ABSTRACT

BACKGROUND: Neurological and psychiatric morbidity has been associated with celiac disease but has been scarcely studied in dermatitis herpetiformis (DH), a cutaneous manifestation of celiac disease. Hence, this cohort study aimed to investigate neurological and psychiatric morbidity in patients with DH and celiac disease.

METHODS: The study comprised 368 DH patients and 1,072 celiac disease patients without DH and their 1,099 and 3,197 refences, matched 1:3 on age, sex, calendar period and place of residence. Their neurological and psychiatric morbidity was studied using the Care Register for Health Care and international classification of diseases codes. Hazard ratios (HR) were calculated using Cox proportional hazard model.

RESULTS: In DH the risk for any neurological disease was not statistically significantly increased (HR 1.27; 95% CI 0.94-1.71), but Alzheimer’s disease and extrapyramidal diseases were found to be more common in DH when compared with their references. In contrast, in celiac disease excess risks for any neurological disease (HR 1.31; 95% CI 1.09-1.56) and particularly for migraine and headaches were detected. The risk for any psychiatric disease was found to be decreased in DH (HR 0.65; 95% CI 0.47-0.90), as were the risks for anxiety and substance abuse. In celiac disease, increased risks for any psychiatric disease (HR 1.20; 95% CI 1.01-1.42), depression, and anxiety disorders were noted.

CONCLUSIONS: The neurological and psychiatric morbidity of patients with DH and celiac disease patients without DH seems to differ, but the reasons for this varying disease burden remain yet unidentified.

PMID:41761874 | DOI:10.1080/00365521.2026.2636062

J Intern Med. 2026 Feb 28. doi: 10.1111/joim.70079. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the efficacy and safety of extended interval (Q3-4W) enzyme replacement therapy (ERT) versus standard biweekly (Q2W) ERT in clinically stable type 1 Gaucher disease (GD) patients.

METHODS: We emulated a target trial with a sequential trial design, using data from the French Gaucher Disease Registry. Eligible patients were treated for ≥2 years biweekly without clinical events. Every 3 months, switchers to Q3-4W were matched to Q2W patients by age, sex, referral center follow-up, disease history (bone events, anemia, thrombocytopenia, splenectomy, and hepatosplenomegaly), and dose of ERT. The primary outcome was a composite of GD-related events (bone events, anemia, and thrombocytopenia). A 10% non-inferiority margin was prespecified. Secondary outcomes were biomarker changes and economic analyses.

RESULTS: Among 280 eligible GD patients, 63 switched to Q3-4W and were matched to a total of 215 Q2W patients, followed for an average of 6.3 years. No significant difference in the risk of clinical events was observed between groups (hazard ratio: 0.98 [95% confidence intervals (CI): 0.54-1.51]). During follow-up, absolute risk difference remained below the 10% non-inferiority threshold at all timepoints. Biomarkers remained stable or slightly decreased in the Q3-4W group. The dosing interval extension led to an average reduction of 55 infusions per patient, corresponding to approximately €450,000 saved per patient over 6 years.

CONCLUSION: In stable GD1 patients, extending ERT administration to every 3-4 weeks was non-inferior to the standard biweekly regimen, supporting personalized spacing strategies that may improve quality of life and reduce healthcare costs.

PMID:41761869 | DOI:10.1111/joim.70079

Eur Eat Disord Rev. 2026 Feb 28. doi: 10.1002/erv.70094. Online ahead of print.

ABSTRACT

OBJECTIVE: The early response effect, defined as a reliable symptomatic improvement during the initial phase of treatment, is the most robust predictor of recovery following eating disorder treatment. This study aimed to investigate which symptom domains mostly influence the early response effect.

METHODS: Data from N = 232 adult patients (90.8% females; mean age = 29.97, SD = 10.67) treated in an outpatient eating disorder psychotherapy service were randomly partitioned into training (N = 161) and test (N = 71) samples. A Bayesian network model was developed in the training sample, modelling early changes (sessions 1-4) and interactions among symptoms measured by the Eating Disorder Examination Questionnaire (EDE-Q). A variable selection approach was applied to include only the most important variables in the model (i.e., reliable predictors of recovery). The trained model was externally validated by applying it to predict post-treatment recovery status in the test sample. Prediction accuracy was evaluated using the AUC statistic.

RESULTS: The model identified a network of six interrelated eating disorder symptoms which were the most important predictors of recovery. The model was reliable in predicting recovery status and showed good generalisability to a test sample (training AUC = 0.81 vs. test AUC = 0.77). Early changes in six areas (ranked by importance) reliably predict recovery after therapy: [1] avoidance of body exposure; [2] feelings of ‘fatness’; [3] preoccupation with food, eating or calories; [4] fear of losing control over eating; [5] dissatisfaction with body shape; [6] dietary rules.

DISCUSSION: The identification of early response domains associated with eventual recovery could help to inform targeted interventions strategies for patients with eating disorders. Future replication is warranted in more diverse and larger samples, including the applicability of these findings to different diagnostic groups.

PMID:41761864 | DOI:10.1002/erv.70094

J Neurotrauma. 2026 Feb 28:8977151261424705. doi: 10.1177/08977151261424705. Online ahead of print.

ABSTRACT

Cavum septum pellucidum (CSP) is a common neuroimaging finding linked to repetitive head trauma, yet its relationship to blast exposure among the military population remains elusive. Here, we investigated whether lifetime exposure to different types of blast is associated with CSP morphology among Special Operations Forces (SOF) personnel. We retrospectively analyzed 323 SOF members from the Comprehensive Brain Health and Trauma Program at Home Base who completed high-resolution 3T MRI and the Blast Exposure Threshold Survey (BETS), which quantifies lifetime exposure to explosive weapons across five blast exposure count categories (BEC1-BEC5). CSP grade and length were assessed using validated criteria on coronal 3D T1-weighted Magnetization Prepared Rapid Gradient Echo scans. A CSP length-to-septum length ratio (CSP ratio) was calculated to adjust for anatomical variation. BEC1-BEC5 were log-transformed to correct skewness and are referred to as log-BEC1-5.Variance inflation factor analysis indicated low multicollinearity among predictors (log-BEC1-5 and age), and variable selection using Least Absolute Shrinkage and Selection Operator regression identified log-BEC5 (exposure to large explosives) as the only retained predictor. In fully adjusted models, only log-BEC5 remained significantly associated with CSP measures and was therefore the focus of subsequent analyses.Participants were stratified by BEC5 = 0 vs. BEC5 > 0, and associations with CSP measures were assessed using group comparisons, multivariable regression, and dose-response models.Among 323 participants (mean age 42.7 ± 8.8 years), 273 (84%) reported any BEC5 exposure. SOF members with BEC5 > 0 had significantly greater CSP presence (42.1% vs. 22.0%, p = 0.007) and longer CSP length (median 3 mm vs. 2 mm, p = 0.002). In age-adjusted models, BEC5 > 0 was associated with greater odds of CSP presence (OR = 2.58, 95% CI 1.26-5.25, p = 0.009) and a 1.45 mm increase in CSP length (p = 0.004). In continuous models, each one-unit increase in log-BEC5 was associated with a 0.31 mm increase in CSP length (p = 0.008) and a 0.0059 increase in CSP ratio (p = 0.008).These findings indicate a statistically significant association between cumulative exposure to heavy explosives and CSP enlargement, suggesting that CSP may serve as a potential imaging marker of blast-related neurotrauma.

PMID:41761850 | DOI:10.1177/08977151261424705

Brain Inj. 2026 Feb 28:1-19. doi: 10.1080/02699052.2026.2636708. Online ahead of print.

ABSTRACT

AIM: This systematic review and meta-analysis critically evaluates preclinical evidence on leptin’s efficacy and mechanistic actions in rodent models of focal cerebral ischemia.

METHOD: Comprehensive searches of PubMed, EMBASE, Scopus, and Google Scholar (1995-2024) identified 17 eligible studies (n = 1,383 animals), following PRISMA 2020 guidelines and PROSPERO registration (CRD42023461569). Data extraction and risk of bias assessment (SYRCLE tool) were conducted independently by dual reviewers. Pooled standardized mean differences (SMD) were calculated using a random-effects model.

RESULTS: Leptin administration significantly reduced infarct volume (SMD = -2.76; 95% CI: -3.65 to -1.86; p < 0.001) and ameliorated neurological deficits (SMD = -4.37; 95% CI: -5.80 to -2.95; p < 0.001), with pronounced effects in murine models. Mechanistically, leptin mitigated apoptosis – indicated by lowered cleaved Caspase-3 and TUNEL-positive cells – and promoted the upregulation of proteins involved in neuroprotection, including BCL-2, p-STAT, TRPV1, and the leptin receptor.

CONCLUSION: Although this meta-analysis demonstrates the promising neuroprotective properties of leptin, the substantial heterogeneity among studies and the resulting lower certainty of evidence highlight the critical need for future research employing standardized methodologies, rigorous study designs, and sufficient statistical power to validate these findings and support their translation into clinical settings.

PMID:41761843 | DOI:10.1080/02699052.2026.2636708

J Periodontol. 2026 Feb 28. doi: 10.1002/jper.70080. Online ahead of print.

ABSTRACT

BACKGROUND: Periodontitis, a chronic inflammatory disease, is linked to systemic conditions such as cardiovascular and kidney disease. Serum α-Klotho, an anti-aging protein with anti-inflammatory properties, has been associated with systemic diseases, but its role in periodontitis is unclear. This study evaluated the relationship between serum α-Klotho levels and periodontitis severity while accounting for confounders.

METHODS: In this cross-sectional study, data from 961 participants in the National Health and Nutrition Examination Survey (NHANES) database were analyzed. Periodontitis was classified into stages (I-IV) and grades (A-C) using the ACES (Application of the 2018 periodontal status Classification to Epidemiological Survey data) guidelines. Serum α-Klotho levels were measured via enzyme-linked immunosorbent assay (ELISA). Ordinal logistic regression assessed associations between α-Klotho levels and periodontitis, adjusting for confounders such as age, smoking, comorbidities, and oral hygiene. The number of lost teeth was analyzed as a secondary outcome.

RESULTS: In both adjusted and unadjusted regression models, no significant association was found between α-Klotho levels and periodontitis. Particularly, adjusted models revealed no significant association between α-Klotho levels and periodontitis stage (OR = 1.0001, p = 0.547, 95% CI: 0.9997-1.0006) or grade (OR = 0.9996, p = 0.144, 95% CI: 0.9991-1.0001). Age, smoking, and comorbidities significantly predicted severity. Despite a weak negative correlation between α-Klotho and tooth loss (r = -0.07, p = 0.023), this association was no longer significant after adjustment.

CONCLUSION: No significant association was found between serum α-Klotho levels and periodontitis severity. Age, smoking, and comorbidities were key predictors, highlighting the multifactorial nature of periodontitis. Further longitudinal and mechanistic studies are needed to clarify whether α-Klotho has a value as a biomarker of periodontal inflammation or disease progression.

PMID:41761827 | DOI:10.1002/jper.70080

Pak J Pharm Sci. 2026 Apr;39(4):1167-1174. doi: 10.36721/PJPS.2026.39.4.REG.15419.1.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) represents the most common type of persistent arrhythmia in older adults. This research assesses the impact of integrating sodium-glucose cotransporter 2 inhibitors (SGLT2i), specifically dapagliflozin, into standard care on atrial remodeling and the recurrence of AF in elderly patients with multiple co-existing conditions.

OBJECTIVE: The findings aim to inform improved treatment strategies for this patient population.

METHOD: The study enrolled 174 elderly persistent AF (PAF) patients, comparing 88 (research group) who received dapagliflozin plus standard care against 86 controls on standard care only. The primary endpoints were the incidence of AF recurrence and the magnitude of change in left atrial diameter (LAD) at the 12-month mark. Secondary outcomes included levels of myocardial fibrosis biomarkers (PIIINP, PICP, TGF-β1), inflammation markers (hs-CRP, IL-6), cardiac function tests (NT-proBNP, LVEF), quality of life (6MWT, ADL) and safety monitoring.

RESULTS: The research group showed a lower rate of AF recurrence at 12 months than the control group (P<0.05); this benefit was even greater in patients with diabetes (P<0.05). LAD decreased after treatment in both groups and the decrease was greater in the research group (P<0.001). The research group also achieved greater reductions in serum PIIINP, PICP, TGF-β1, hs-CRP and IL-6 compared to the control group (P<0.05). Furthermore, a more substantial drop in NT-proBNP was observed (P<0.05). LVEF remained stable in the research group but declined slightly in the control group (P<0.05). Quality of life metrics also favored the research group, which showed superior gains in both 6MWT distance and ADL scores (P<0.05). The safety profile was similar between groups, with no statistically significant difference in adverse effects (P<0.05).

CONCLUSION: These results indicate that adding dapagliflozin to standard care is a promising treatment option for PAF.

PMID:41761812 | DOI:10.36721/PJPS.2026.39.4.REG.15419.1

Pak J Pharm Sci. 2026 Apr;39(4):1112-1120. doi: 10.36721/PJPS.2026.39.4.REG.14929.1.

ABSTRACT

BACKGROUND: Acute pancreatitis (AP) is a common gastrointestinal emergency characterized by unpredictable severity. Early identification of patients at risk for severe disease is essential for timely intervention and improved outcomes, yet reliable prognostic markers remain limited, particularly in Central Asian clinical settings.

OBJECTIVE: To identify early clinical, laboratory, and demographic predictors of acute pancreatitis (AP) severity using statistical and machine learning approaches, to improve early risk stratification and guide prompt clinical management.

METHODS: This retrospective case series analysed 40 patients diagnosed with AP between 2022 and 2024 at tertiary hospitals in Bishkek, Kyrgyzstan. Admission data, including demographic characteristics, clinical symptoms, and laboratory values, were collected and evaluated using the revised Atlanta criteria. Statistical analyses included correlation testing, subgroup comparisons, and logistic regression, while a machine-learning-based feature importance analysis was used to identify key predictors of severe AP.

RESULTS: Several variables were significantly associated with severe AP. Serum amylase >500 U/L (OR = 5.2, p 7lt; 0.001), WBC count >15×10⁹/L (OR = 4.7, p <0.001), and BMI ≥30 (OR = 3.4, p = 0.003) emerged as strong predictors of severity. A strong correlation was observed between total bilirubin and jaundice (r = 0.62, p < 0.001). Obese patients had longer hospital stays compared with non-obese patients (median 12 vs. 7 days; p = 0.021). Machine learning analysis confirmed serum amylase, WBC count, and BMI as the most influential predictors.

CONCLUSION: Serum amylase, WBC count and BMI are practical, easily accessible markers that can support early prediction of AP severity. Incorporating these indicators into initial assessment protocols may enhance risk stratification and optimize clinical decision-making. Prospective multicentre studies are needed to validate these findings and refine AP severity prediction models.

PMID:41761807 | DOI:10.36721/PJPS.2026.39.4.REG.14929.1

Pak J Pharm Sci. 2026 Apr;39(4):990-998. doi: 10.36721/PJPS.2026.39.4.REG.13681.1.

ABSTRACT

BACKGROUND: Depression is a common mental disorder. Patients with treatment-resistant depression (TRD) often experience sleep disorders (SD), which interact with each other and aggravate the deterioration of the disease.

OBJECTIVE: In this study, we analyzed the effect of paroxetine combined with low-dose quetiapine on patients with treatment-resistant depression complicated by sleep disorders.

METHODS: We divided treatment-resistant depression + sleep disorders 120 patients into a control group treated with paroxetine and a research group treated with paroxetine + low-dose-quetiapine. Hamilton Depression Scale (HAMD-17), Self-rating Anxiety and Depression Scale (SAS/SDS), Pittsburgh Sleep Quality Index (PSQI) and serum indexes (cortisol, epinephrine, thyroid hormone, etc.) were used to analyze the data.

RESULTS: In terms of clinical efficacy, the research group demonstrated superior efficacy. Besides, the research group showed lower self-rating anxiety/depression scale scores than the control group after treatment (P<0.05). In terms of sleep quality, the Pittsburgh Sleep Quality Index of the research group also decreased more significantly compared with the control group (P<0.05). Moreover, better stress injury alleviation and endocrine function improvement were determined in the research group (P<0.05). The two groups were not statistically different in treatment compliance and adverse reactions (P>0.05).

CONCLUSION: Paroxetine combined with a low dose of quetiapine is a clinically effective approach for treatment-resistant depression with sleep disorders and is recommended for clinical use.

PMID:41761797 | DOI:10.36721/PJPS.2026.39.4.REG.13681.1

Pak J Pharm Sci. 2026 Apr;39(4):970-978. doi: 10.36721/PJPS.2026.39.4.REG.15414.1.

ABSTRACT

BACKGROUND: Hepatocarcinogenesis arising from liver cirrhosis is a major contributor to hepatocellular carcinoma (HCC), but effective interventions remain limited Objective: This study aimed to elucidate the molecular mechanism by which icariin suppresses cirrhosis-to-cancer progression through the ROS/NLRP3/miR-145 axis.

METHODS: Fifty Sprague-Dawley rats were randomly assigned to five groups: control, model, low-dose icariin (ICA-L), high-dose icariin (ICA-H), and positive control. In vitro, SMMC-7721 and HepG2 cells were treated with TGF-β1 and various concentrations of icariin to assess their effects on hepatocellular carcinoma cell activity.

RESULTS: Compared with the model group, icariin significantly reduced the liver index, serum AFP levels, Ki-67 positivity, and hepatic ROS levels in rats, suppressed NLRP3 expression, upregulated miR-145, and effectively ameliorated liver fibrosis and dysplasia (P<0.05). In SMMC-7721 cells, icariin inhibited TGF-β1-induced proliferation, migration and invasion, promoted apoptosis and G0/G1 phase arrest, while concurrently increasing exosomal miR-145 levels (P<0.05). Further mechanism verification confirmed that miR-145 directly targets and inhibits NLRP3 expression.

CONCLUSION: Icariin effectively inhibits cirrhosis-associated carcinogenesis by suppressing the ROS-NLRP3 pathway and upregulating miR-145, providing a theoretical basis for the prevention and treatment of cirrhosis and hepatocellular carcinoma.

PMID:41761795 | DOI:10.36721/PJPS.2026.39.4.REG.15414.1