Category: Nevin Manimala

Ann Med. 2026 Dec;58(1):2534083. doi: 10.1080/07853890.2025.2534083. Epub 2026 Jun 19.

ABSTRACT

OBJECTIVES: This meta-analysis aimed to evaluate the association between endometriosis (EM) and cardiovascular disease (CVD) risk by synthesizing evidence from large-scale cohort studies, with emphasis on subtype-specific risks and geographic disparities.

METHODS: We systematically searched PubMed, Embase, and Cochrane Library for cohort studies published until December 2024. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses stratified CVD subtypes (e.g. ischemic heart disease, atrial fibrillation), continents, and country development levels. Heterogeneity and publication bias were assessed via I² statistics, sensitivity analyses, and Egger’s test.

RESULTS: Eleven cohort studies (n = 3,100,610 participants) were included. EM was associated with a 22% increased risk of all-cause CVD (HR = 1.22; 95% CI: 1.08-1.38; I² = 94.6%). Subgroup analyses revealed elevated risks for myocardial infarction (HR = 1.29; 95% CI: 1.10-1.50), coronary artery disease (HR = 1.47; 95% CI: 1.29-1.67), and cerebrovascular events (HR = 1.18; 95% CI: 1.12-1.25), but not heart failure. Geographic disparities were significant, with higher CVD risks in Asian (HR = 1.36; 95% CI: 1.25-1.48) and North American cohorts (HR = 1.37; 95% CI: 1.16-1.61) compared to European populations (HR = 0.93; 95% CI: 0.64-1.34).

CONCLUSIONS: EM is independently associated with an elevated risk of CVD, particularly for coronary artery disease and myocardial infarction. These findings underscore the need for targeted cardiovascular monitoring in EM patients, particularly in high-risk populations.

PMID:42322096 | DOI:10.1080/07853890.2025.2534083

Eur J Haematol. 2026 Jun 19. doi: 10.1111/ejh.70247. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of the complement C3 inhibitor pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria (PNH).

METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for studies reporting pegcetacoplan use in PNH. Outcomes included transfusion-requirement, hemoglobin normalization, mean hemoglobin levels, lactate dehydrogenase normalization, reticulocyte count normalization, and safety endpoints. Pooled proportions with 95% confidence intervals were calculated using random-effects models, and heterogeneity was assessed using the I² statistic.

RESULTS: Five studies comprising 271 patients were included. Transfusion avoidance was observed in 80.6% of patients, with a pooled transfusion-requirement rate of 19.4%. LDH normalization occurred in 68.5% of patients (I² = 0%). Hemoglobin normalization was observed in 42.9%, while reticulocyte count normalization reached 66%. Any-grade adverse events occurred in 83.5% of patients, most commonly pyrexia, headache, and dizziness. Serious adverse events occurred in 16.6%, decreasing to 12% after sensitivity analysis. Breakthrough hemolysis was reported in 14.8%, and infections in 17%.

CONCLUSION: Pegcetacoplan demonstrates consistent efficacy signals across key hematologic endpoints and an acceptable safety profile, supporting its potential role as an important therapeutic option, particularly in patients with persistent extravascular hemolysis despite C5 inhibition.

PMID:42322093 | DOI:10.1111/ejh.70247

Eur Heart J Cardiovasc Imaging. 2026 Jun 20:jeag154. doi: 10.1093/ehjci/jeag154. Online ahead of print.

ABSTRACT

AIMS: To establish normal sex- and age-specific longitudinal strain curves, to quantify their morphological variation with age, and to demonstrate their utility by deriving novel measures from them with the aim of testing prognostic value.

METHODS AND RESULTS: Age- and sex-appropriate normal strain curves were derived from healthy participants of the Copenhagen City Heart Study (CCHS). Four novel measures were constructed: early (EDS) and late (LDS) diastolic strain, primarily to assess age-related variation in strain curve morphology, and mean and diastolic strain deviation. Their prognostic value was assessed using Cox proportional hazards regression and C-statistics internally in the CCHS and externally in the LOOP study against a composite endpoint of cardiovascular death and incident heart failure or atrial fibrillation.In total, 1,641 healthy subjects (mean±SD age 45.3±15.2 years, 62.3% female) from the CCHS and 1,307 (mean±SD age 74.4±4.0 years, 47.4% female) from the LOOP study were included. EDS decreased with age while LDS increased. During a median follow-up of 4.9 [IQI: 3.0, 5.6] years, 409 (31.3%) subjects met the outcome in the LOOP study. Mean strain deviation was independently associated with the outcome (adjusted HR = 1.02 (95% CI: 1.00, 1.05), p = 0.045), while diastolic strain deviation was not.

CONCLUSION: We established normal sex- and age-specific longitudinal strain curves and furthermore demonstrated their utility by deriving novel measures from these with prognostic value beyond conventional measures. While promising, further validation in external populations is warranted. The normal curves and relevant code are publicly available.

PMID:42322083 | DOI:10.1093/ehjci/jeag154

Influenza Other Respir Viruses. 2026 Jun;20(6):e70277. doi: 10.1111/irv.70277.

ABSTRACT

OBJECTIVES: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may affect cognition, but its association with incident dementia remains inconsistent. We explored the association of SARS-CoV-2 infection and its vaccination with dementia risk in a nationwide sample of middle-aged and older adults.

METHODS: This nested case-control study used electronic healthcare data from Israel’s largest health provider. Participants were dementia-free individuals aged ≥ 50 years at baseline (March 2020), followed up until May 2022. Incident dementia cases were matched to dementia-free controls using density sampling by age, sex, and date of entry to the study, with a ratio of 1:10. SARS-CoV-2 was defined by positive polymerase chain reaction (PCR) or institutional antigen tests. Multivariable conditional logistic regression models evaluated the association of SARS-CoV-2, its severity and vaccination, and pneumonia as a comparator, with dementia risk.

RESULTS: Among the 1,145,322 eligible participants, 27,280 dementia cases were matched to 272,800 controls. SARS-CoV-2 infection was associated with increased dementia risk (OR = 1.18; 95% CI 1.12-1.24; p < 0.001). This association was confined to hospitalized individuals with mild (OR = 2.39; 95% CI 2.07-2.76) and moderate-to-severe disease (OR = 1.93; 95% CI 1.70-2.20), was comparable to pneumonia (OR = 1.89; 95% CI 1.80-1.99), and was no longer evident after 6 months (OR = 1.04; 95% CI 0.96-1.12). COVID-19 vaccination was associated with 7%, 15%, and 31% lower dementia risk after two, three, and four doses, respectively. Unvaccinated individuals with prior COVID-19 had the highest dementia risk.

CONCLUSIONS: Dementia diagnoses are increased after COVID-19, especially in hospitalized patients. Risk is comparable to other respiratory infections.

PMID:42322076 | DOI:10.1111/irv.70277

Paediatr Perinat Epidemiol. 2026 Jun 19. doi: 10.1111/ppe.70167. Online ahead of print.

ABSTRACT

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication with both short- and long-term adverse outcomes for both mothers and their offspring. CenteringPregnancy group prenatal care (CPNC) model has gained popularity due to its unique design to support pregnant individuals in managing multiple risk factors during pregnancy. However, whether participation in CPNC reduces the risk of developing GDM remains uncertain.

OBJECTIVE: To compare the GDM incidence between pregnant individuals receiving CPNC and those receiving traditional individual prenatal care (IPNC).

METHODS: This retrospective cohort study included 8313 participants (CPNC: 1832; IPNC: 6481) from South Carolina. GDM was screened and diagnosed between 24 and 30 weeks of gestation with the two-step approach. We applied inverse probability of treatment weighting (IPTW) using stabilized propensity score (PS) weights. The weighted risk ratio (RR) of CPNC relative to IPNC for GDM was estimated using weighted marginal log-binomial models.

RESULTS: In the original cohort, the incidence of GDM was 4.7% in the CPNC group and 6.8% in the IPNC group. After applying stabilized IPTW, baseline characteristics were well balanced between groups. In the weighted pseudo-cohort, CPNC was associated with a lower risk of GDM compared with IPNC (RR 0.64, 95% confidence interval [CI] 0.51, 0.81). In subgroup analyses, this inverse association was observed among non-Hispanic White (RR 0.61, 95% CI 0.43, 0.86) and non-Hispanic Black participants (RR 0.69, 95% CI 0.47, 1.00), but not among Hispanic participants (RR 1.05, 95% CI 0.62, 1.77). Results from multivariable logistic regression in the original cohort were consistent in direction but less precise. There was no evidence of additive interaction by race/ethnicity.

CONCLUSIONS: Pregnant individuals receiving CPNC had a lower risk of developing GDM than those receiving IPNC.

PMID:42322067 | DOI:10.1111/ppe.70167

J Pediatr Orthop B. 2026 Jun 23. doi: 10.1097/BPB.0000000000001368. Online ahead of print.

ABSTRACT

To systematically evaluate the accuracy, reliability, and clinical applicability of artificial intelligence and large language models (LLMs) in pediatric orthopedics, comparing their performance against established clinical guidelines and assessing their utility for patient education and clinical decision support. A search of PubMed and ScienceDirect (2020-2025) identified 2624 articles using the keywords ‘ChatGPT’, ‘Gemini’, ‘Claude’ and ‘orthopedic pediatrics’. After screening and refinement using Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, 15 studies met inclusion criteria. Studies evaluated ChatGPT, Google Gemini, Meta AI, Microsoft Copilot, and Claude across multiple pediatric orthopedic conditions across conditions like developmental dysplasia of the hip, slipped capital femoral epiphysis, and scoliosis. Heterogeneity was assessed using Cochran’s Q and I2 statistics, and publication bias was evaluated using funnel plots and Egger’s test. LLM accuracy ranged from 44.3 to 93% (pooled: 74.1%), with pooled accuracy of 74.1%. Reproducibility was moderate, with ChatGPT demonstrating a Spearman coefficient of 0.55 for complex queries. Regional expert consensus scores varied significantly (Europe: 80, North America: 65; P = 0.034; Fleisskappa = 0.113). Up to 33% of responses to guideline-based questions were rated neutral or inaccurate. Reading complexity was elevated (Flesch-Kincaid grade: 12.7), exceeding the recommended sixth-grade level. Parent surveys indicated 82% trust in artificial intelligence as supplementary tools with professional oversight. Minimal statistical heterogeneity was observed (I2 = 0.00%), though publication bias was detected (Egger’s test P = 0.0001). LLMs show potential for education and triage but lack consistency in complex scenarios, elevated reading complexity, and significant regional variability in expert assessments. These tools should be used as educational supplements under professional medical supervision rather than for independent clinical decision-making. Broader clinical application requires domain-specific tuning, standardized evaluation, and readability optimization.

LEVEL OF EVIDENCE: Level V- systematic review.

PMID:42322047 | DOI:10.1097/BPB.0000000000001368

Mov Disord Clin Pract. 2026 Jun 19. doi: 10.1002/mdc3.70712. Online ahead of print.

ABSTRACT

BACKGROUND: Orthostatic myoclonus is characterized by irregular, lower limb myoclonic bursts during stance and is a major cause of postural instability and falls. However, studies are limited, and little is known about its pathophysiology.

OBJECTIVES: We sought to define the clinical and electrophysiological features of orthostatic myoclonus in a large, single-center cohort.

METHODS: We included 42 participants (24 males, 18 females) with a mean age of 74 years (range, 46-93) from Westmead Hospital presenting with orthostatic myoclonus from 2007 to 2023. Medical records were retrospectively reviewed for demographic details, symptoms, co-morbidities, and treatment. Lower limb surface electromyography (EMG) was analyzed using a custom-designed algorithm to automatically identify myoclonic bursts and measure their duration, synchronicity, and rhythmicity. Differences in burst parameters between muscles and associations between burst parameters and clinical characteristics were statistically evaluated.

RESULTS: Mean burst durations during standing were 77 to 90 ms across lower limb muscles. Maximum burst activity and bilateral synchronicity occurred in tibialis anterior. Only 12% of participants exhibited any rhythmicity. A total of 79% of participants had a coexistent neurological disorder including 26% with parkinsonism. There was no significant association between parkinsonism and burst parameters. However, there was a significant, inverse correlation between the presence of neuropathy or radiculopathy and synchronous activity (P = 0.02).

CONCLUSIONS: We provide a computationally robust clinical and electrophysiological analysis of orthostatic myoclonus in a large cohort. Our findings support the theory of a subcortical generator arising from protean secondary causes and subject to peripheral modulation. Further work is needed to clarify treatment outcomes.

PMID:42322040 | DOI:10.1002/mdc3.70712

Int J Cancer. 2026 Jun 19. doi: 10.1002/ijc.70613. Online ahead of print.

ABSTRACT

Cancer-related fatigue (CRF) is a prevalent symptom among colorectal cancer (CRC) survivors. While inflammation is a proposed underlying mechanism, longitudinal evidence including pre-treatment assessments remains scarce. Within the population-based PROCORE study, newly diagnosed CRC patients provided blood samples and completed questionnaires at diagnosis (n = 411; 60.6% male; age = 67.0 years), 12- (n = 304), and 24-month follow-up (n = 252). Eleven inflammatory biomarkers (CRP, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, sTNFRI, and sTNFRII) were assayed; CRF was measured with the Multidimensional Fatigue Inventory. Hybrid linear mixed models disentangled between- and within-subject associations, controlling for sociodemographic (e.g., age), clinical (e.g., cancer treatment), and lifestyle covariates (e.g., BMI), sleep quality, and pain. A normative age- and sex matched sample (n = 204; 52.5% male; age = 64.3 years) was included for comparison. Soluble TNF receptors (sTNFRI/II) were most robustly and positively associated with nearly all fatigue dimensions. CRP was positively associated with mental and physical fatigue; IL-8 positively associated with multiple domains including reduced motivation; and IFN-γ positively associated with general fatigue and reduced activity. Lower IL-1α was associated with more mental fatigue. Between-subject effects mirrored overall results; within-subject effects were more selective. Associations were most consistently observed for mental fatigue. In controls, less associations were significant; CRP was the most robust marker and positively associated with general fatigue, reduced activity, and reduced motivation. CRC survivors exhibited a broader, mostly TNF-α driven inflammatory signature of fatigue than controls. Findings highlight inflammation as a potential target underlying CRF, informing survivorship care strategies.

PMID:42322026 | DOI:10.1002/ijc.70613

Cancer Med. 2026 Jun;15(6):e71973. doi: 10.1002/cam4.71973.

ABSTRACT

INTRODUCTION: Cervical cancer is the fourth leading cause of cancer deaths in women, and mortality varies significantly by region, with the highest rate in southeastern US. This study evaluated the association between comorbidity burden and cervical cancer survival and compared the prognostic performance of the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI).

METHODS: A retrospective cohort study was conducted using electronic medical records of women diagnosed with cervical cancer between 2011 and 2021 at a large academic hospital in southeastern US. CCI and ECI were estimated to assess 5-year overall survival using the Kaplan-Meier methods and multivariable Cox proportional hazard models, stratified by age at diagnosis (young < 50 vs. old ≥ 50 years) and adjusting for baseline demographics. Two-year survival analyses were also conducted. Predictive discrimination of CCI and ECI models was compared using Harrell’s C-statistic.

RESULTS: Higher comorbidity burden was associated with increased mortality across age groups. Compared with patients with no comorbidities (CCI = 0), CCI scores of 1-4 and ≥ 5 were associated with higher 5-year mortality among younger women (adjusted hazard ratio [aHR] = 2.35 (1.03-5.35); 2.80 (1.38-5.69), respectively) and older women (aHR = 2.38 (1.26-4.50); 1.43 (0.63-3.27), respectively). ECI scores ≥ 3 were also strongly associated with increased 5-year mortality in both age groups. Both indices demonstrated acceptable and comparable predictive discrimination for 5-year survival in both age groups (C-statistics ranging from 0.74-0.70). Findings were consistent in 2-year survival analyses.

CONCLUSION: Greater comorbidity burden is independently associated with worse survival among cervical cancer patients; highlighting the importance of comorbidity management in cervical cancer care.

PMID:42322013 | DOI:10.1002/cam4.71973

Cancer Rep (Hoboken). 2026 Jun;9(6):e70611. doi: 10.1002/cnr2.70611.

ABSTRACT

BACKGROUND: Post-treatment weight gain and gut dysbiosis are important concerns in breast cancer patients. However, evidence on the gut microbiota in this population, particularly in relation to physical activity, is limited.

AIM: Therefore, we compared gut microbiota in breast cancer patients with obesity with healthy controls and non-cancer controls with obesity and subsequently examined the effects of a combined dance and dietary intervention on gut microbiota, metabolic health, physical fitness, and quality of life.

METHODS AND RESULTS: The observational part compared gut microbiota in breast cancer patients with obesity (BCO, BMI 32.43 ± 4.90 kg/m²) with non-cancer controls with obesity (OC, BMI 37.78 ± 6.68 kg/m²) and healthy controls (HC, BMI 21.26 ± 1.26 kg/m²). A controlled trial was conducted in breast cancer patients with obesity, with an intervention group (INT, n = 13) receiving a 12-week combined dance and dietary intervention and non-intervention controls (CTRL, n = 10). Gut microbiota was assessed using 16S rRNA sequencing, physical fitness was evaluated by an incremental bicycle ergometer test and motor tests, and quality of life was measured using the EORTC QLQ-C30 and BR23 questionnaires. In the observational study, breast cancer patients showed significant differences in beta diversity and a lower relative abundance of health-associated bacteria (e.g., Faecalibacterium prausnitzii) compared with both controls. In the controlled trial, the intervention led to a significant improvement in body composition, physical fitness (e.g., Vo2max, handgrip strength), and several validated quality-of-life domains (e.g., fatigue, body image). A statistically significant difference in beta diversity at the post-intervention phylum level was observed (p = 0.046, R² = 0.11). Microbiota composition within INT shifted toward, increased health-associated taxa (Bifidobacterium spp.) and reduced opportunistic pathogens (Klebsiella oxytoca). However, a decrease in butyrate-producing taxa (Ruminococcus bromii, Ruminiclostridium hungatei) was also observed.

CONCLUSION: Breast cancer patients showed more negative shifts in gut microbiota compared with both controls. In addition, a 12-week combined dance and dietary intervention improved body composition, physical fitness, quality of life, and was associated with mixed but potentially beneficial changes in select gut microbiota taxa among breast cancer patients with obesity.

TRIAL REGISTRATION: Clinical trial registration number: NCT07213271.

PMID:42321999 | DOI:10.1002/cnr2.70611