Search Results (20,362)

Toxoplasma gondii is a globally prevalent zoonotic parasite with major public health and veterinary impacts. In Egypt, One Health data on its distribution among blood donors and livestock are limited. This multicentric cross-sectional study aimed to determine the seroprevalence of Toxoplasma gondii among asymptomatic blood donors and livestock across six different Egyptian governorates and to identify the associated risk factors. Serum samples of 2000 asymptomatic blood donors and 500 animals (cattle and buffaloes) were tested for anti-Toxoplasma gondii IgG and IgM antibodies using ELISA. Sociodemographic and behavioral data were collected using a structured questionnaire. Overall IgG seroprevalence in blood donors was 41.8%, with IgM seropositivity at 2.1%. Significant regional variation was observed (p < 0.001), ranging from 66.5% in Alexandria to 16% in Cairo. The most significant risk factors were consumption of undercooked meat, contact with cats, and engagement in agricultural activities (p < 0.001). Among livestock, IgG and IgM seroprevalence were 7.2% and 5.2%, respectively, indicating active parasite circulation. The presence of seropositivity among apparently healthy donors raises concerns regarding transfusion safety. These findings highlight substantial and regionally heterogeneous Toxoplasma gondii exposure in Egypt. A One Health approach integrating public health education, food safety measures, and targeted screening of high-risk populations and animals is essential to reduce disease burden. Full article

Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease frequently accompanied by obesity and cardiometabolic disturbances. This study evaluated metabolic, inflammatory, and genetic correlates of overweight/obesity in ethnic Kazakh patients with psoriasis and explored potential multilocus genetic interactions. Materials and Methods: This study included 150 patients with clinically confirmed psoriasis, comprising 75 patients with overweight/obesity and 75 non-overweight/obese individuals frequency-matched by age and sex; because group sizes were fixed by design rather than sampled in proportion to prevalence, the reported odds ratios reflect within-sample associations rather than population-level risk estimates. Clinical, anthropometric, biochemical, inflammatory, and genetic data were collected using standardized protocols. Multivariable logistic regression was used to assess clinical, metabolic, and inflammatory correlates of overweight/obesity. Associations between three candidate polymorphisms, rs1558902 in FTO, rs696574 in CALCRL, and rs10968110 in ZTV, were evaluated. Results: In the multivariable model adjusted for age and sex, higher triglyceride levels (adjusted OR 4.73, 95% CI 1.36–18.57), higher HbA1c (adjusted OR 1.71, 95% CI 1.09–2.91), and lower HDL-C levels (adjusted OR 0.36, 95% CI 0.18–0.66) were independently associated with overweight/obesity. In genetic analyses, rs10968110 in ZTV showed significant associations with overweight/obesity in genotype, additive trend, allelic, and dominant models, while the recessive model was not significant. The FTO rs1558902 variant was also significantly associated with overweight/obesity, with the strongest support observed under additive, allelic, and dominant assumptions. In contrast, rs696574 in CALCRL was not significantly associated with overweight/obesity. Exploratory MDR analysis identified rs10968110 as the most stable single-locus model, whereas higher-order models showed only limited additional discriminatory value and lower cross-validation consistency. Conclusions: Among ethnic Kazakh patients with psoriasis, overweight/obesity was associated with an adverse cardiometabolic profile characterized by elevated triglycerides, higher HbA1c, and reduced HDL-C. Candidate genetic findings suggest that ZTV rs10968110 and FTO rs1558902 may be associated with overweight/obesity susceptibility, although these results should be considered exploratory pending validation in larger independent cohorts. These findings support integrated cardiometabolic assessment in psoriasis care and further investigation of genetic susceptibility to obesity in this population. Full article

Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive lysosomal storage disorder caused by mutations in the SMPD1 gene, resulting in sphingomyelin accumulation. With a birth prevalence of 0.25–0.6 per 100,000, it is more prevalent in Ashkenazi Jewish and Middle Eastern populations. The disease features a clinical spectrum ranging from severe, early-onset neurodegeneration (infantile neurovisceral ASMD) to chronic, non-neurological visceral involvement (chronic visceral ASMD) and intermediate forms (chronic neurovisceral ASMD). The chronic visceral form is characterized by liver dysfunction, respiratory symptoms, and hepatosplenomegaly, which can lead to secondary thrombocytopenia. The majority of patients exhibit thrombocytopenia and/or mild bleeding manifestations, most commonly easy bruising and epistaxis, whereas clinically significant bleeding events, including gastrointestinal or variceal hemorrhage, occur less frequently. Systematic platelet-function studies in patients with ASMD are currently lacking. Evidence retrieved from biological models indicates that ASMD contributes to platelet dysfunction, including impaired secretion and thrombin generation, mediated by complex pathological mechanisms. These findings underscore the importance of hematological monitoring and further research in patients with this condition and could potentially offer new therapeutic possibilities. Full article

Progressive Familial Intrahepatic Cholestasis (PFIC) is a rare liver disorder that, although typically present in childhood, can also occur in adulthood. Early diagnosis is crucial for appropriate clinical management, prognostic assessment, and therapeutic decision-making; however, it remains challenging due to phenotypic variability and the frequent identification of genetic variants of uncertain significance (VUS). Advances in next-generation sequencing (NGS) and whole-exome sequencing (WES) have improved the detection of disease-associated variants, revealing that the same genetic variants—often in a heterozygous state—may lead to adult-onset cholestatic disease, with milder or atypical presentations, while still conferring a significant risk of progressive liver injury and related complications. To assess the diagnostic yield and clinical utility of NGS panels and WES in adults with suspected PFIC or unexplained cholestatic liver disease, focusing on variant interpretation, emerging disease-associated genes, and clinical significance of VUS. A literature review was conducted to assess molecular diagnostics in adult cryptogenic cholestasis, with a focus on studies employing targeted NGS panels and WES. Selected studies were examined for diagnostic yield, variant classification, interpretive challenges, including VUS, and integration with clinical data. Data on patient demographics, sequencing techniques, and variant interpretation strategies were extracted to evaluate the current capabilities and limitations of genomic testing. From an initial search of 211 publications, 15 studies met the inclusion criteria, comprising five large adult cohorts and ten single-patient or trio-based reports. Across 72 patients, sequencing technologies identified 75 pathogenic or likely pathogenic variants, predominantly missense mutations, demonstrating high genetic heterogeneity. The most implicated genes included ABCB4, ABCB11, ATP8B1, TJP2, and USP53, with diagnostic yields ranging from 13.2% in large heterogeneous cohorts to substantially higher rates in carefully selected individual cases. VUS were identified in up to 67% of cases, highlighting the need for multidisciplinary interpretation integrating clinical, biochemical, and genetic data. Emerging evidence also implicated ciliopathy-associated genes such as DCDC2, NPHP3, PKHD1, TULP3, and TTC21B, expanding the genetic spectrum of adult cholestasis. Clinically, presentations ranged from mild biochemical abnormalities to progressive cholestasis, with pruritus being a common feature across studies. Comprehensive genetic testing significantly enhances diagnostic accuracy, informs prognosis, and guides individualized management in adults with cryptogenic cholestasis. Emerging evidence suggests that ciliopathy-associated genes may contribute to the genetic architecture of adult cholestatic disorders, further expanding the spectrum of disease-associated genes. However, the high prevalence of VUS remains a major challenge, highlighting the need for functional studies, longitudinal follow-up, and improved variant interpretation frameworks. As genomic technologies and analytical approaches continue to evolve, genetic testing is expected to play an increasingly central role in precision hepatology. Full article

Background and Objectives: Sarcopenia is highly prevalent among older adults with chronic kidney disease (CKD) and is associated with adverse clinical outcomes. The finger-ring (Yubi-wakka) test is a simple anthropometric screening tool based on calf circumference; however, its performance in older adults with CKD remains unclear. This study aimed to investigate the association of the finger-ring test with low muscle mass, sarcopenia, and comprehensive geriatric assessment parameters and to evaluate its diagnostic performance for identifying low muscle mass in older adults with CKD. Materials and Methods: This cross-sectional study included 115 patients aged ≥65 years with CKD who were evaluated in geriatric and nephrology inpatient services. After excluding two participants with missing finger-ring measurements, 113 individuals were analyzed. Muscle mass was assessed using bioelectrical impedance analysis and low muscle mass was defined according to EWGSOP2-based Turkish cut-off values. Demographic characteristics, anthropometric measurements, laboratory findings, and comprehensive geriatric assessment parameters were recorded. Correlation analyses, logistic regression models, receiver operating characteristic (ROC) analyses, and likelihood-ratio tests were performed. Results: Among 113 participants, 62 were classified as finger-ring positive (FR = 0) and 51 as finger-ring negative (FR = 1). Low muscle mass was significantly more frequent in the FR = 0 group than in the FR = 1 group (51.6% vs. 24.0%, p = 0.005). Finger-ring test results showed strong correlations with calf circumference (rho = 0.689, p < 0.001) and body mass index (BMI) (rho = 0.631, p < 0.001), whereas the correlation with muscle mass was modest (rho = 0.250, p = 0.008). For detecting low muscle mass, the finger-ring test demonstrated an area under the curve (AUC) of 0.643 (95% CI 0.554–0.732), sensitivity of 72.7%, specificity of 55.9%, positive predictive value of 51.6%, and negative predictive value of 76.0%. In multivariable analyses, BMI remained the strongest independent determinant of finger-ring test results, whereas the association with muscle mass lost statistical significance after BMI adjustment. Adding age and sex significantly improved discrimination, while the contribution of nutritional status was limited. Conclusions: The finger-ring test is associated with low muscle mass in older adults with CKD; however, its diagnostic performance is modest and appears to be substantially influenced by body size and calf circumference. Therefore, the finger-ring test should be considered a simple adjunctive screening tool rather than a stand-alone method for identifying low muscle mass in this population. Full article

Gynecological malignancies and breast cancer impose substantial health and economic burdens. This review examines how local and systemic microbiota may affect epithelial integrity, inflammation, estrogen metabolism, and immunity. The vaginal ecosystem is the most extensively studied female microbial niche. Cervical cancer serves as the most illustrative clinical example: loss of stable Lactobacillus crispatus dominance and increased prevalence of anaerobic bacteria (anaerobic dysbiosis) are associated with persistent HPV infection, which directly elevates the risk of cervical precancerous lesions. The estrobolome is particularly relevant in endometrial cancer, where intestinal bacterial beta-glucuronidase activity may increase estrogen reabsorption, particularly in obesity and metabolic disease. In ovarian cancer, microbiota is being studied as a possible risk modifier in BRCA1 carriers, but the evidence remains exploratory. In breast cancer, intratumoral bacteria may shape the immune microenvironment, particularly in triple-negative disease. The primary limitation of current research is methodological heterogeneity. Low-biomass samples, such as those from the ovary or endometrium, are highly susceptible to technical contamination. Most studies are cross-sectional and cannot establish causality. Current evidence supports microbiota as a modifier, not a standalone marker or a substitute for standard diagnosis and treatment. Its most plausible near-term role is in multiparameter risk or response models, pending standardized prospective validation. Full article

Pathogenic Vibrio species are a major cause of disease outbreaks in aquaculture, leading to substantial economic losses and posing risks to food safety. The increasing prevalence of antibiotic resistance among these pathogens has created an urgent need for alternative antimicrobial strategies. Phage-derived endolysins, which specifically degrade bacterial peptidoglycan, have emerged as promising candidates to replace or supplement conventional antibiotics. In this study, we systematically characterized the endolysin LysV039C from the Vibrio alginolyticus phage phiV039C. Whole-genome analysis identified a 462 bp endolysin gene, which was cloned into the pET-28a vector, expressed in E. coli BL21, and purified. The lytic activity of the recombinant enzyme was evaluated using a turbidity reduction assay. LysV039C showed the strongest activity (58.9%) against host bacteria in the logarithmic phase, with peak activity (60.7–64.1%) achieved at 53 μg/mL, 35 °C, and neutral pH. The addition of 2.5 mM EDTA enhanced activity to 63.8%, whereas 10 mM divalent metal ions strongly inhibited the enzyme (<6.5%). Lytic spectrum analysis demonstrated that LysV039C exhibited a broader lytic spectrum against six Vibrio species than its parent phage phiV039C. Overall, LysV039C combines high environmental adaptability (alkaline tolerance, suitability for aquaculture temperature ranges) with efficient and broadened lytic activity against multiple Vibrio species. These findings provide a foundation for developing eco-friendly agents for the prevention and control of pathogenic Vibrio and offer a valuable reference for the mining of other phage-derived antibacterials against aquatic pathogens. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is characterized by excessive hepatic lipid accumulation and metabolic dysfunction. Although microRNA-34a (miR-34a) has been implicated in hepatic lipid metabolism, the molecular mechanisms underlying its contribution to MASLD remain incompletely understood. Here, we investigated the role of miR-34a in FFA-induced hepatic steatosis using HepG2 cells and explored RXR-associated signaling as a potential therapeutic strategy. RT-qPCR quantified miR-34a expression; direct target interactions were validated using dual-luciferase reporter assays; proteomic alterations were characterized by iTRAQ-based proteomics followed by Ingenuity Pathway Analysis (IPA); and transcriptomic responses to 9-cis-retinoic acid (9-cis-RA) were analyzed by RNA sequencing. FFA treatment significantly increased miR-34a expression, and dual-luciferase assays confirmed that miR-34a directly targets the 3′-UTRs of RXRα, PPARα, and SIRT1. Integrated proteomic and transcriptomic analyses consistently identified LXR/RXR signaling as one of the principal pathways associated with miR-34a dysregulation and 9-cis-RA treatment. Pharmacological activation of RXR-associated signaling with the pan-RXR agonist 9-cis-RA attenuated intracellular lipid accumulation and reduced the expression of key regulators of lipogenesis and fatty acid uptake, including FASN, SCD1, FABP4, and CD36. Collectively, these findings support the miR-34a–RXRα axis as one regulatory component within a broader nuclear receptor network associated with hepatic lipid homeostasis and support further investigation of RXR-associated signaling as a potential therapeutic strategy for MASLD. Nevertheless, confirmation of receptor-specific mechanisms and validation in more physiologically relevant experimental models will be required. Full article

Background/Objectives: Congenital anomalies and neurodevelopmental disorders frequently co-occur and exhibit substantial genetic and phenotypic heterogeneity, posing a persistent diagnostic challenge. Exome sequencing has become an important first- or second-tier diagnostic tool for these conditions, yet diagnostic yields vary considerably depending on phenotype, ancestry, sequencing strategy, and interpretation, with over half of referrals remaining without a definitive genetic diagnosis. Methods: We analyzed data from 692 patients referred to the Department of Cytogenetics and Genomics at the Cyprus Institute of Neurology and Genetics between January 2021 and December 2025 for clinical exome sequencing or whole-exome sequencing as part of the diagnostic work-up for congenital disorders and/or syndromic or non-syndromic neurodevelopmental disorders. Results: A total of 134 distinct variants were identified, corresponding to an overall diagnostic yield of 17.9% out of which 52 (38.8%) were novel, and 50 variants (37.3%) were de novo, as expected from the high proportion of severe neurodevelopmental presentations. Missense variants were the most prevalent within our cohort, while chromatin and transcriptional regulator genes constituted the largest functional gene category, followed by variants in collagen-encoding genes. Conclusions: This study provides the first systematic, mutational-level characterization of a Cypriot Mendelian disease cohort, establishing a local baseline diagnostic yield and revealing a high proportion of novel variants that reflect the underrepresentation of Eastern Mediterranean populations in global databases. These findings underscore the value of submitting population-specific variants to public repositories and of phenotype-driven reanalysis targeting recurrent gene families, supporting more efficient diagnostics and future precision medicine initiatives in Cyprus. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic disorder associated with an elevated risk of cardiovascular disease. Mac-2 binding protein glycosylation isomer (M2BPGi), a noninvasive serum biomarker of hepatic fibrosis, has also been linked to adverse metabolic and cardiovascular outcomes. However, the association between serum M2BPGi levels and subclinical coronary atherosclerosis in individuals with MASLD remains unclear. We investigated the association between serum M2BPGi levels and coronary artery calcium score (CACS), an established imaging marker of subclinical atherosclerosis, in individuals with MASLD. Methods: This retrospective cross-sectional study included 6514 adults with MASLD who underwent health screening examinations between 2020 and 2025. Participants were categorized into quartiles according to serum M2BPGi levels: Q1 (<0.48), Q2 (0.48–0.61), Q3 (0.62–0.80), and Q4 (≥0.81). Coronary artery calcification (CAC) was defined as CACS > 0. Multivariable logistic regression analysis was performed after adjustment for age, sex, smoking status, liver enzymes, adiposity, dysglycemia, blood pressure, and lipid profile. Multivariable ordinal logistic regression analysis was additionally performed to evaluate the association between M2BPGi levels and CAC severity. Results: The prevalence of CAC increased progressively across M2BPGi quartiles (39.4%, 45.3%, 48.5%, and 57.4% for Q1–Q4, respectively; p < 0.001). In multivariable logistic regression analysis, participants in the highest M2BPGi quartile had significantly higher odds of CAC presence than those in the lowest quartile (OR, 1.32; 95% CI, 1.10–1.58; p = 0.0035). Higher M2BPGi quartiles were also independently associated with greater CAC severity in multivariable ordinal logistic regression analysis (OR, 1.33; 95% CI, 1.13–1.57; p = 0.0007 for Q4 vs. Q1). Conclusions: Higher serum M2BPGi levels were independently associated with both the presence and severity of CAC in individuals with MASLD. These findings suggest that M2BPGi may serve as a potential biomarker for identifying individuals with MASLD at increased risk of subclinical atherosclerosis and may complement conventional cardiovascular risk assessment. Full article

Background: Hearing health in Kazakhstan is documented through parallel administrative systems whose indicators are often conflated. We examined three administrative layers of hearing health during 2020–2025: dispensary registration of ear and hearing-loss diagnoses, disability certification as a severe administrative endpoint, and cochlear implantation (CI) as the specialised treatment response, with reference to Global Burden of Disease (GBD) 2021 estimates. Methods: We conducted a national ecological, region-year, multi-source administrative registry study across all 20 regions of Kazakhstan from 2020 to 2025. The dataset included 114 region-year observations and integrated Dispensary Report Form No. 12, the State Register of Persons with Disabilities, and the Electronic Register of Inpatient Patients. Dispensary indicators were interpreted as registered healthcare-utilisation measures, not population prevalence or incidence. Trends were assessed using Mann–Kendall tests with Benjamini–Hochberg false-discovery-rate correction. Regional patterns were examined using Spearman correlation, inequality metrics, and exploratory clustering. Results: Among adults, registered H60–H95 annual morbidity increased from 231,209 to 278,897 cases (CAGR +3.8%; FDR p = 0.016), and first-time registrations rose from 126,513 to 167,674 (CAGR +5.8%; FDR p = 0.016). Active dispensary observation declined modestly from 21,840 to 19,881. H65–H66 chronic otitis first-time registration remained stable, while active observation declined sharply. Paediatric H90–H91 registration was stable. In 2025, 31,560 persons were registered with hearing impairment-related disability, including 26,522 adults. CI procedures increased from 285 to 523. Adult CI activity was intermittent between 2012 and 2018 (peak 140 in 2013), ceased in 2019–2020, and was re-established from 2021 (14 → 129 procedures in 2025), reaching 24.7% of all CI. Most procedures were concentrated in Almaty and Astana. Compared with the GBD-2021 estimate of 17,212 per 100,000, administrative indicators captured much narrower service-utilisation and severe-certification layers. Conclusions: Kazakhstan’s administrative data describe distinct hearing-health layers rather than competing prevalence estimates. Adult screening, regional audiology capacity, post-CI rehabilitation, and longitudinal outcome registries are priority areas. Full article

Background: We aimed to investigate the prevalence of HSD17B13 polymorphisms while evaluating the correlation between HSD17B13 gene variants and NASH prevalence in the Taiwanese population. Furthermore, we tried to identify the diagnostic value of liver enzymes as non-invasive biomarkers for NASH in morbidly obese patients. Methods: Severely obese patients with non-alcoholic fatty liver disease (NAFLD) who received liver biopsy during bariatric surgery and controls of liver donors who underwent donor hepatectomy were enrolled from 2016 to 2021. Genotyping was utilized in TaqMan PCR assays. For comparison of NAFLD severity, patients were divided into no NASH (NAFLD activity score, NAS 0–2), borderline NASH (NAS 3–4), and NASH (NAS 5–8). Results: The proportion of HSD17B13 rs72613567 TA allele carriers (T/TA and TA/TA genotypes) was 96% in both groups, corresponding to an estimated TA allele frequency of approximately 50% based on a standard allele-counting method. Among morbidly obese patients, T/TA and TA/TA genotypes were associated with lower odds of NASH prevalence compared with T/T genotype. For the non-invasive predictive factors of NASH, NASH group had significantly higher level of liver enzymes compared to “no NASH” and “borderline NASH” groups. Receiver operating characteristic curve analysis revealed there were moderate predictive values for NASH in AST (AUC = 0.71, p = 0.014) and ALT (AUC = 0.73, p = 0.007). Conclusions: Our study revealed a relatively high prevalence of the loss-of-function TA variant of HSD17B13 in this southern Taiwanese cohort, irrespective of body weight. This variant may contribute to the comparatively lower prevalence of NASH in the region. Additionally, AST and ALT may have potential predictive value for NASH prevalence. Given the single-center design, further larger, population-representative studies are warranted. Full article

Background: Concurrent use of acetylcholinesterase inhibitors (AChEIs) and medicines with anticholinergic activity is a clinically important medication safety concern in dementia care because these medicines may pharmacologically oppose dementia treatment and increase the risk of avoidable harm. This review systematically synthesised evidence on the prevalence, patterns, predictors and clinical consequences of concurrent use of anticholinergic and anti-dementia drugs (ADDs) in older adults with dementia. Methods: A PRISMA-informed systematic review was conducted employing Ovid MEDLINE, Embase and PsycINFO from January 2010 to April 2026. Observational studies were eligible if they included older adults with dementia and reported concurrent exposure to at least one anticholinergic medicine and an ADD, defined as AChEIs and/or memantine. Study quality was appraised using the Newcastle–Ottawa Scale. Results: Twenty-eight studies were included, spanning community, outpatient memory-clinic, acute hospital, long-term care and population-based settings. Two distinct exposure constructs were identified: (1) temporal co-prescribing and (2) cumulative anticholinergic burden among ADD users. Reported prevalence varied markedly according to the exposure definition and setting. Concurrent use was lowest in studies limited to bladder antimuscarinic overlap, generally around 5–13%,but increased to 20–45% when broader anticholinergic definitions were used. In long-term care and institutional cohorts, concurrent exposure reached 61–67%. Recurring predictors included polypharmacy, fragmented care or multiple prescribers, urinary symptoms, behavioural and psychological symptoms of dementia, Parkinson’s disease and non-geriatric prescribing. One large population-based study reported that high anticholinergic burden was associated with treatment modification of AChEIs (aHR 1.12), delirium (aHR 1.52), and two-year mortality (aHR 1.23). Additional studies reported associations with longer hospital stays or readmission. Conclusions: Concurrent use of anticholinergic medicines and ADDs is a common, clinically important and potentially modifiable medication-safety problem in dementia care. Full article

Background: Atopic dermatitis (AD) and asthma are common type 2 inflammatory diseases linked by the atopic march. In adults with AD, the prevalence of comorbid asthma and the strength of the AD–asthma association remain uncertain, with marked heterogeneity across studies. Moreover, the role of modern systemic therapies in this comorbidity is increasingly debated. Objective: To estimate the global pooled prevalence of asthma in adults with AD, quantify the AD–asthma association, and discuss the potential impact of targeted therapies (dupilumab, abrocitinib, omalizumab) on asthma comorbidity. Methods: Systematic review and random-effects meta-analysis (ID CRD420261304804) of observational studies from PubMed, EMBASE, and Cochrane Library (inception to 19 January 2026). Pooled prevalence and odds ratios (ORs) were calculated, with subgroup analyses by region, ethnicity, and disease definition. Results: Seventy-five studies were included. The global pooled prevalence of asthma in adults with AD was 25.9% (95% CI 22.1–30.0%; I² = 99.9%). AD was significantly associated with asthma (OR 3.64, 95% CI 2.89–4.57; I² = 98.6%). Prevalence varied from 9.3% in Asia to 63.2% in South America. Although dupilumab and other targeted agents are effective in both diseases, isolated reports of new-onset asthma after treatment were identified; these cases more likely reflect the natural progression of AD or unmasking of pre-existing asthma than a direct adverse drug reaction. Conclusions: Asthma is highly prevalent in adults with AD and is strongly associated with AD. Geographic and ethnic disparities call for stratified screening. Clinicians should be aware that new-onset respiratory symptoms during targeted therapy may represent AD-related comorbidity rather than drug-induced asthma. Full article

Background: Autoimmune diseases (AIDs) are associated with increased cardiovascular risk. However, specific protein mediators linking AIDs to major adverse cardiovascular events (MACE) and cardiovascular death (CV death) remain unexplored. This study identifies proteomic mediators linking AIDs to MACE via high-dimensional mediation analysis in the UK Biobank. Methods: We used UK Biobank data with proteomic profiling by Olink platform. Participants with prevalent myocardial infarction (MI), stroke, and heart failure at baseline were excluded. AIDs were categorized into musculoskeletal (MSK), vasculitis, gastrointestinal (GI), neurologic, and rheumatic fever subsets. Fine–Gray models assessed associations between AIDs and MACE and CV death. Proteome-wide association studies identified proteins associated with both AIDs and cardiovascular outcomes. High-dimensional mediation analysis (HIMA) explored protein-mediated pathways. All models adjusted for age, sex, lipids, BMI, smoking, hypertension, diabetes, chronic kidney disease, atrial fibrillation, and coronary artery disease. Results: Among 400,633 participants (median follow-up 14.5 years, 44.8% male), AIDs were present in 28,754 (7.2%). All AID categories were associated with increased MACE (sHR: MSK 1.34, vasculitis 1.67, GI 1.20, neurologic 1.33, rheumatic fever 1.38; all p < 0.001). For CV death, MSK, vasculitis, and rheumatic fever showed increased risk (sHR 1.34, 1.78, 1.51; all p ≤ 0.004), but not GI or neurologic AIDs. In 43,599 participants with proteomic data, HIMA identified 66 and 32 unique potential mediators linking AIDs to MACE and CV death, respectively. Four proteins (Growth Differentiation Factor 15, Interleukin-15, urokinase plasminogen activator receptor, and Tenascin C) mediated the AID-MACE relationship across multiple AID categories. Growth Differentiation Factor 15 and Interleukin-15 were shared mediators for CV death. Conclusions: This proteomic analysis identifies specific proteins that may mediate the association between AIDs and adverse cardiovascular outcomes, offering mechanistic insights into immune-related cardiovascular risk. These findings are hypothesis-generating and require replication and validation before the identified proteins can be considered causal mediators or adopted for clinical risk stratification. Full article