Search Results (39,197)

Autoimmune and immune-mediated inflammatory diseases (IMIDs) develop when genetically and environmentally susceptible hosts lose stable immune tolerance. The gut ecosystem is increasingly recognized as a biologically active interface in this process. Its bacterial, fungal, and viral components may shape mucosal and systemic immunity through antigenic stimulation, barrier regulation, and metabolite-dependent signaling, although the strength of evidence is uneven: bacteriome data are currently the most mature, whereas mycobiome, virome, and phageome findings remain more disease-specific and emerging. Dysbiosis may influence autoimmunity through overlapping routes, including epithelial barrier failure, altered short-chain fatty acid, bile acid, and tryptophan metabolism, molecular mimicry, and cross-kingdom microbial interactions. Nutrition is central to this network because dietary substrates determine microbial growth, metabolic output, epithelial integrity, and immune-cell differentiation. In this narrative review, we integrate evidence on disease-associated bacteriome, mycobiome, and virome patterns in systemic autoimmune diseases, with emphasis on rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, spondyloarthritis, vasculitides, and idiopathic inflammatory myopathies. COVID-19 is considered not as a proven causal driver of autoimmunity, but as an example of an environmental and infectious insult capable of perturbing microbiome–barrier–immune communication. Finally, we discuss diet-based and microbiome-targeted approaches, including probiotics, prebiotics, synbiotics, and postbiotics, as adjunctive strategies that may help restore microbial resilience and immune balance. A better understanding of the diet–microbiome–host immunity axis may support more personalized preventive and therapeutic concepts in autoimmune disease. Full article

Background and Clinical Significance: Carcinoid heart disease (CHD) is an uncommon valvular manifestation of neuroendocrine tumours, usually affecting right-sided cardiac valves. Left-sided involvement is rare and is generally associated with bronchopulmonary carcinoid, right-to-left shunting, or markedly elevated circulating vasoactive substances. Therapeutic decision-making is particularly challenging in advanced disease when severe tricuspid regurgitation occurs in patients at prohibitive surgical risk. Case Presentation: We report the case of a 61-year-old male patient with progressive dyspnoea, abdominal distension, lower-limb oedema, facial flushing, and 15 kg of unintentional weight loss. Transthoracic and transoesophageal echocardiography demonstrated torrential tricuspid regurgitation caused by thickened, retracted, and immobile leaflets, with additional mitral and aortic valve involvement, raising strong suspicion of CHD. An agitated-saline contrast study demonstrated delayed right-to-left shunting without patent foramen ovale, suggesting an extracardiac, likely intrapulmonary, shunt. Somatostatin receptor PET/CT identified a pancreatic lesion with metastatic disease, and bone marrow biopsy confirmed neuroendocrine tumour infiltration. Owing to prohibitive surgical risk, as reflected by a Tricuspid Regurgitation Impact Score (TRI-SCORE) with an estimated in-hospital mortality of 65%, unfavourable tricuspid anatomy for repair, and refractory venous congestion, heterotopic bicaval valve implantation was performed (TricValve system -P&F). Discussion: This case highlights the role of echocardiography in recognising the characteristic phenotype of CHD, detecting occult right-to-left shunting, and supporting selection of a palliative transcatheter intervention. It also illustrates the value of a multimodality diagnostic strategy integrating echocardiography, functional oncological imaging, and histopathology in tumour-related cardiac disease. Conclusions: In selected inoperable patients with advanced carcinoid-related tricuspid regurgitation, heterotopic bicaval valve implantation may represent a feasible strategy for reducing venous congestion and improving functional status. Full article

Background: The diagnostic value of surface electromyography (sEMG) for identifying muscles affected by myofascial trigger points (TrPs) remains controversial. However, advances in pain neurophysiology and discussions regarding TrPs within the International Classification of Diseases (ICD-11) have renewed interest in objective diagnostic approaches. Objective: To synthesize current evidence on the diagnostic utility of sEMG for detecting TrP-related muscle alterations across different electromyographic signal analysis domains. Methods: A scoping review was conducted following JBI guidance and PRISMA-ScR guidelines. PubMed, Scopus, Web of Science, CINAHL and Cochrane were searched for studies involving adults with symptomatic or asymptomatic TrPs, myofascial pain syndrome, or TrP-related referred pain. Fifteen studies met the inclusion criteria. Analyses included amplitude-, frequency-, time–frequency-, and spatial-domain sEMG parameters. Results: Muscles affected by TrPs showed increased resting electromyographic activity and reduced activation during maximal voluntary contraction in several studies. Frequency domain analyses indicated changes in median frequency and muscle fatigue index, whereas time–frequency analyses suggested redistribution of sEMG signal energy toward lower-frequency components or altered spectral power during experimentally provoked referred pain. Spatial analyses revealed altered activation patterns, although these findings did not consistently correspond with TrP anatomical locations. Overall, the limited number of studies assessing diagnostic sensitivity and specificity prevents firm conclusions. Conclusions: sEMG may be useful as a non-invasive complementary tool for functional assessment and monitoring of TrP-related muscle dysfunction. However, current evidence does not support its use as a standalone diagnostic method. Time–frequency, machine learning-supported and spatial analyses appear promising for future clinical research, but standardized protocols and external validation are required before clinical diagnostic criteria can be proposed. Full article

Background: Immune mechanisms are increasingly implicated in the heterogeneity of schizophrenia spectrum disorders. Cytomegalovirus (CMV), a latent immunomodulatory herpesvirus, is linked to cognitive and immunological alterations, but its electrophysiological correlates remain largely unexplored. This study investigates the relationships among CMV serostatus, EEG features, inflammatory markers, and clinical–cognitive variables. Methods: In this prospective cross-sectional study, 123 patients with schizophrenia spectrum disorders underwent integrated clinical, cognitive, laboratory, and qualitative visual EEG assessments. CMV exposure was determined via IgG serology. Results: Global electroencephalographic EEG organization did not differ by CMV serostatus. However, a descriptive increase in resting-state sharp-wave discharges was observed in CMV-seronegative patients, independent of baseline cortical rhythms. Immunologically, CMV-seropositive individuals exhibited significantly higher total leukocyte counts, consistent with latent viral immune remodeling rather than overt systemic inflammation. Clinically, CMV-seropositive patients demonstrated descriptively higher scores on the disorganization dimension derived from the PANSS (Positive and Negative Syndrome Scale) five-factor consensus model. While these variations did not retain statistical significance after multiple testing correction, separate dimensional analyses revealed that patients exhibiting sharp waves demonstrated better overall cognitive functioning and superior performance within a memory-related item grouping. Notably, the presence of sharp-wave activity was independent of both peripheral inflammatory profiles and treatment-resistant status, underscoring a distinct electrophysiological phenotype. Conclusions: CMV exposure represents a modulating biological background associated with corrected leukocyte elevations and subtle electrophysiological variability, rather than a direct determinant of global clinical severity. The nominal EEG variations and their independent link to better-preserved memory performance highlight non-linear neuroimmune interactions. Given the cross-sectional design, these exploratory patterns warrant a non-causal interpretation but outline a foundation for future longitudinal investigations. Full article

The oncocytic variant of adrenocortical carcinoma (OACC) represents an exceptional type of adrenal malignancy, with heterogenous presentation. Currently, the genetic and molecular spectrum remains an open matter. A 20-year-old adult was accidentally found with a 7.2 cm adrenal tumor and underwent an open right adrenalectomy with OACC confirmation. Post-adrenalectomy positron emission tomography/computed tomography was negative. Immunohistochemistry was positive for calretin, inhibin, steroidogenic factor 1; Ki67 of 20%. Microsatellite instability was 7.61. Lin–Weiss–Bisceglia score showed 2 major criteria [mitoses 6/50 HPF + positive atypical mitoses], the reticuline algorithm (disrupted reticuline network + mitoses 6/50 HPF) was consistent for a malignant behavior, the Helsinki score was of 48. Next generation sequencing identified a likely pathogenic variant of CEL gene (heterozygote, c.539-2A>G) in peripheral blood and two pathogenic variants in the tumor: exon 48, NF1 gene [c.7159_7164del p.(N2387_F2388del)] and exon 6, TP53 gene [c.596delG p.(G199Efs*48)]. Polycystic ovary syndrome type A has been diagnosed as teenager with no phenotype change before the tumor detection. After surgery, oocyte retrieval and cryopreservation upon ovarian stimulation protocol (OSP) was performed before starting mitotane therapy. To the best of our knowledge, this is a novel genetic configuration in OACC with an impact on prognosis to be determined. Hyperandrogenemia stands on a dual source (potential CEL-driven insulin resistance for the ovary and OACC-originating for the adrenal glands). Also, this is the first case to receive OSP in OACC, noting that a tailored multidisciplinary management is mandatory. Full article

Objective: Hemispherotomy is an effective treatment for select forms of drug-resistant hemispheric epilepsy, including perinatal stroke, Rasmussen’s encephalitis, and Sturge–Weber syndrome. Post-traumatic epilepsy (PTE) has been reported to occur in ~10% of children following traumatic brain injury (TBI). TBI has not been extensively evaluated as an indication for hemispherotomy, as its effects are rarely unilateral. Here, we report the results from five pediatric cases of hemispherotomy for drug-resistant hemispheric PTE. Methods: A retrospective review was performed of all pediatric patients with drug-resistant PTE secondary to TBI who underwent hemispherotomy between 2018 and 2022 at the Children’s Hospital of Philadelphia (n = 5). All patients initially underwent craniectomy and subsequent cranioplasty due to TBI; criteria for hemispherotomy were met in the following years, leading to a recommendation for hemispherotomy at the epilepsy surgery conference. Clinical characteristics, seizure and functional outcomes, and postoperative complications were reviewed. Seizure outcomes were classified according to the Engel criteria. Results: Five children (median age: 8.3 years, range: 5.0–10.3 years) with drug-resistant PTE underwent lateral trans-sylvian hemispherotomy. TBI etiology included non-accidental trauma (n = 3) and motor vehicle accidents (n = 2). All patients exhibited Engel Class Ia seizure outcomes (median follow-up: 15 months, range: 5–39 months), with a reduction in anti-seizure medications from a median of five preoperatively to one postoperatively. No patient experienced re-operation. Neuropsychological outcomes were patient-specific, with most exhibiting a mix of gains and challenges after surgery. Conclusion: We demonstrate the use of hemispherotomy to treat drug-resistant, hemispheric PTE in five children, with excellent reduction in seizure frequency and mixed or improved neuropsychological outcomes. Full article

Fatigue and muscle wasting are common clinical manifestations of inherited and acquired neuromuscular disorders, including peripheral neuropathies, neuromuscular junction disorders, and myopathies. These conditions encompass a wide disease spectrum with variable prognoses, making accurate diagnosis essential for appropriate management. Congenital myasthenic syndromes (CMSs) are rare, inherited disorders characterized by impaired neuromuscular transmission. Although symptoms often begin in infancy or early childhood, later onset during adolescence or adulthood is increasingly recognized. Clinical phenotypes vary according to the underlying molecular defect, but fatigable weakness predominantly affecting axial and proximal limb muscles is a hallmark feature. We report an adolescent male who developed progressive proximal muscle weakness and wasting over several years, resulting in significant functional impairment. Initial evaluation suggested limb–girdle muscular dystrophy. However, comprehensive investigations, including whole-exome sequencing, identified a heterozygous CHRNB1 mutation consistent with postsynaptic CMS. Targeted pharmacological therapy led to clinical improvement. This case highlights the importance of considering CMS in patients presenting with limb–girdle weakness and underscores the value of genetic testing in establishing an accurate diagnosis and guiding treatment. Full article

Chatuphalatika is a traditional Thai polyherbal formulation whose metabolically active fraction has not been identified. This study fractionated the aqueous extract (CPT) by sequential liquid–liquid partitioning to obtain solvent fractions. The ethyl acetate fraction (CPTX) had the highest total phenolic content and was enriched in hydrolyzable tannins, particularly chebulagic acid. CPTX showed the strongest inhibitory activity against HMG-CoA reductase in vitro. In vivo, C57BL/6 mice were fed a high-fat diet for 12 weeks, then treated with CPT, CPTX, or silymarin for 8 weeks while high-fat diet feeding continued. Both CPT and CPTX improved serum lipid profiles. High-dose CPTX (500 mg/kg) additionally reduced fasting blood glucose, serum ALT, and relative liver weight, without affecting body weight or adipose tissue weights. These findings indicate that phenolic enrichment concentrates the hepatic and lipid-lowering activity of Chatuphalatika. HMG-CoA reductase inhibition was used as a screening criterion to identify CPTX as the active fraction; the in vivo hepatometabolic improvements are consistent with, but do not directly confirm, modulation of cholesterol biosynthesis and hepatic lipid metabolism. Full article

Background/Objectives: Therapeutic plasma exchange (TPE) is an extracorporeal treatment used in thrombotic microangiopathies (TMAs) and various autoimmune and neurological disorders. However, data regarding its use during early pregnancy remain limited. This study aimed to evaluate maternal laboratory response and perinatal outcomes in pregnant women who underwent TPE before 26 weeks of gestation. Methods: This retrospective case series included 10 pregnant women diagnosed before 26 weeks of gestation who underwent TPE between 2010 and 2023. Clinical and laboratory parameters before and after TPE were compared. Results: Indications for TPE included HELLP syndrome (n = 4), thrombotic thrombocytopenic purpura (n = 3), presumed atypical haemolytic uremic syndrome (n = 1), neuromyelitis optica (n = 1), and Guillain–Barré syndrome (n = 1). The mean gestational age at diagnosis was 22.1 ± 3.1 weeks, and the mean gestational age at delivery was 27.1 ± 6.9 weeks. Five fetuses (50%) died and five (50%) survived to discharge. In patients with TMAs, TPE was associated with significant decreases in LDH, INR, APTT, ALT, AST, and total bilirubin levels, along with a significant increase in platelet count and ADAMTS13 activity (p < 0.01). No maternal complications occurred in neurological cases, all of which resulted in term deliveries with healthy neonates. Conclusions: In this uncontrolled case series, TPE was associated with rapid maternal clinical and laboratory improvement in selected pregnant women with TMAs, although a causal effect cannot be established from these data. However, perinatal outcomes were primarily determined by gestational age at delivery: all fetal losses occurred before 26 weeks, whereas all infants survived when delivery occurred after 26 weeks. Larger studies are needed to confirm these findings. Full article

Chronic overlapping pain conditions (COPCs) refer to a set of chronic pain disorders that frequently co-occur and may involve partially overlapping mechanisms. The U.S. National Institutes of Health currently recognizes ten COPCs: fibromyalgia, painful temporomandibular disorders, chronic low back pain, chronic migraine headache, chronic tension-type headache, irritable bowel syndrome, endometriosis, interstitial cystitis/bladder pain syndrome, vulvodynia, and myalgic encephalomyelitis/chronic fatigue syndrome. When multiple COPCs coexist, they are associated with a disproportionate multimorbidity burden, including greater pain, poorer psychological well-being, functional limitations, disability, fatigue, sleep disturbances, diminished quality of life, and increased healthcare utilization. Despite their impact, COPCs remain under-recognized, underdiagnosed, and undertreated. Combining structured literature searches and citation tracking with narrative syntheses, this review examines comorbid relationships, the burden of multimorbidity, and potentially overlapping nociplastic mechanisms. By adopting a multimorbidity-based perspective rather than a one-disease, one-treatment approach, it highlights barriers to care—including limited clinical awareness, under-recognition of additional COPCs, limited mechanistic understanding, and fragmented care—and proposes integrated strategies emphasizing prevention, systematic screening, mechanism-informed assessment, and coordinated, patient-centered multimodal management. Full article

Background: Wearable cardioverter-defibrillators (WCDs) are equipped with the TRENDS remote-monitoring system, enabling continuous assessment of arrhythmias, physiological parameters, and patient-reported outcomes. This study evaluated the clinical utility of TRENDS-integrated WCD management and compared it with a historical control. Methods: We prospectively analyzed 36 consecutive patients who received a WCD with TRENDS between 2019 and 2024 and compared them with 30 historical controls treated before the implementation of TRENDS. Results: The WCD indications were heart failure as primary prevention (64%) and acute coronary syndrome with ventricular arrhythmias (28%). Among 18 patients who met the criteria for an implantable cardioverter-defibrillator (ICD), including 1 patient with WCD shock, 9 ultimately underwent ICD implantation. The mean daily WCD wear-time was 21.3 h and did not differ significantly from that of the historical control. The response rate to health-related questionnaires was 89%. TRENDS detected symptom exacerbation in 31% of patients, weight gain in 19% of patients, and missed medication in 19% of patients. Daily step-count was significantly lower in patients with ICD indications than in those without (5012 ± 2980 steps vs. 7977 ± 3584 steps, p = 0.01). TRENDS data also aided in initiating anticoagulation therapy and optimizing beta-blocker therapy. Conclusions: TRENDS provided clinically actionable physiologic and patient-reported information that supported individualized cardiovascular management. Full article

Objectives: Borrelia burgdorferi sensu lato, a spirochete bacterium responsible for Lyme borreliosis—the most common tick-borne infection in North America and Europe—can trigger the production of antiphospholipid antibodies. These antibodies target host lipids such as cardiolipin (CL), phosphatidic acid (PA), phosphatidylcholine (PC), and phosphatidylserine (PS), which the spirochete incorporates into its membrane from the surrounding environment. Although antiphospholipid antibodies are typically associated with antiphospholipid syndrome (APS), they may also arise during infections, including Lyme borreliosis. This study aimed to develop and optimize several enzyme-linked immunosorbent assays (ELISAs) for measuring various antiphospholipid antibodies in patients with Lyme borreliosis. Methods: Thirty patients diagnosed with Lyme borreliosis were enrolled: ten with solitary erythema migrans (EM), ten with multiple EM (MEM), and ten with late manifestations known as acrodermatitis chronica atrophicans (ACA). Forty healthy blood donors served as controls. Four distinct antiphospholipid antibody ELISAs were developed, each using a different phospholipid coating: CL, PA, PC, and PS. Serum of APS patient was used as a positive control and for standard curve generation. Results: All four ELISAs were successfully established and demonstrated good measurement precision. Significant differences in antiphospholipid antibody levels and positivity rates were observed between Lyme borreliosis patients and healthy blood donors. Notably, levels of antibodies directed against PA (aPA), PC (aPC), and PS (aPS), both IgG and IgM, were significantly higher in patients with late Lyme borreliosis, manifested as ACA, compared to healthy blood donors. In contrast, anti-CL (aCL) levels did not differ significantly between groups. Patients with ACA also showed the highest frequency of multiple antiphospholipid antibody positivity, with 7 out of 10 patients testing positive for three or more antiphospholipid antibodies. Conclusions: Accurate and precise in-house ELISAs for the detection of aCL, aPA, aPC, and aPS using APS sera as standard material were developed and validated for the analysis of samples of patients with Lyme borreliosis. Our data suggest that antiphospholipid antibody levels—specifically aPA, aPC, and aPS—differ across clinical manifestations of Lyme borreliosis, with the greatest increases observed in patients with ACA. Full article

Background and Objectives: Ticagrelor reduces ischemic events in acute coronary syndrome (ACS) but increases bleeding risk. Clinical predictors of bleeding are well established; the contribution of cytochrome P450 polymorphisms involved in ticagrelor metabolism remains uncertain, with conflicting reports in the literature. We examined the association of CYP3A4* 22 (rs 35599367), CYP3A5* 3 (rs 776746), and CYP4F2 (rs3093135) with bleeding in a Serbian ACS cohort. Materials and Methods: This prospective, single- center observational study enrolled 105 consecutive ACS patients undergoing percutaneous coronary intervention (PCI) or medical management after coronary angiography and receiving dual antiplatelet therapy (DAPT) with acetylsalicylic acid and ticagrelor at the University Clinical Center Niš between January 2024 and the end of May 2025. Bleeding events occurring during the index hospitalization and the six-month follow-up were classified according to the Bleeding Academic Research Consortium (BARC) criteria. Genotyping used TaqMan assays. Associations with bleeding were assessed using Firth’s penalized logistic regression, with multivariable adjustment for age and renal function. Severity-stratified analyses and gradient-boosted machine learning (XGBoost with SHAP) were performed as exploratory analyses. Results: Thirteen patients (12.4%) experienced bleeding (nine minor [BARC 1/2], four major [BARC 3/5]). Age ≥ 75 years (univariable OR 7.62, p = 0.001) and eGFR < 60 mL/min/1. 73 m ² (OR 3.68, p = 0.006) were the strongest predictors. CYP3A5 *1 carrier status was univariably associated with bleeding (OR 4.16, p = 0.043) but did not remain significant after adjustment for age and renal function, and *1 carriers were significantly older and more likely to have impaired renal function. No genotype was associated with major (BARC 3/5) bleeding. The apparent effect was concentrated in minor bleeding (BARC 1/2 rate: 30.8% versus 5.5%), with no major events among *1 carriers. CYP 3 A 4* 22 (OR 1.37, p = 0.109) and CYP 4 F 2 (OR 1.17, p = 0.111) showed no association. Machine-learning analyses confirmed eGFR and age as the dominant predictors. Conclusions: In this Serbian ACS cohort, clinical factors—particularly advanced age and impaired renal function—dominated the prediction of bleeding risk. The CYP3A5 signal was largely explained by baseline imbalances in age and renal function. CYP 3 A 4* 22 and CYP 4 F 2 polymorphisms did not contribute additional predictive information. Preemptive genotyping for these variants is unlikely to materially improve bleeding-risk assessment beyond standard clinical evaluation in patients of this type. Full article

Pulmonary hypertension (PH) is a progressive, multifactorial syndrome characterized by elevated pulmonary arterial pressure and right heart dysfunction, associated with significant morbidity, impaired quality of life, and poor prognosis. Advances in classification, hemodynamic definitions, and targeted pharmacotherapies have improved understanding and management, yet therapeutic challenges persist across the five World Health Organization groups of PH. Historically, exercise was discouraged due to concerns about adverse hemodynamic effects, but growing evidence has suggested that structured, supervised training is safe and beneficial. Randomized trials and meta-analyses show improvements in six-minute walk distance, peak oxygen uptake, right ventricular function, ventilatory efficiency, and health-related quality of life, with a low incidence of adverse events. Physiological adaptations include favorable cardiac remodeling, enhanced endothelial function, improved skeletal and respiratory muscle performance, and improved neurohormonal activity. Despite this evidence, barriers such as patient fears, limited clinical expertise, and restricted access to specialized rehabilitation programs hinder widespread implementation. Current guidelines recommend supervised exercise as part of pulmonary rehabilitation for patients with stable PH, supporting its role as an adjunct to pharmacotherapy. This descriptive review briefly summarizes the pathophysiology of PH, phenotype-related differences and current therapeutic approaches, and the beneficial adaptations to exercise training, with the aim of informing exercise specialists and supporting safer, more effective integration of exercise-based rehabilitation into patient care. Full article

Dimensional and transdiagnostic models have become central to contemporary efforts to move psychiatric nosology beyond DSM/ICD categories. This shift reflects persistent limitations of categorical syndromes as final biological targets, including within-diagnosis heterogeneity, cross-diagnostic comorbidity, developmental instability, and incomplete alignment with underlying mechanisms. This article examines a central unresolved problem in this transition: when, if ever, a descriptive or predictive psychiatric dimension can be interpreted as a candidate disease axis. We conducted a conceptual synthesis of major dimensional and transdiagnostic frameworks, including Research Domain Criteria (RDoC), Hierarchical Taxonomy of Psychopathology (HiTOP), the general psychopathology factor, cross-disorder genomic models, clinical staging approaches, and data-driven subtyping. The analysis separates three levels of inference that are often conflated in psychiatric research: descriptive structure, predictive utility, and disease-level biological validity. The synthesis identifies a recurrent inferential error in which reproducible factors, clusters, or classifiers are prematurely treated as evidence of disease architecture. Such constructs may describe real covariance patterns or improve prognostic prediction without establishing biological validity. We propose an eight-domain hierarchical framework for promotion to candidate disease-axis status, organized into four core gatekeepers—replication across cohorts, ascertainment, and methods, developmental coherence, incremental prognostic value beyond diagnosis and nonspecific severity, and discriminability from nonspecific severity—and four supporting/disciplining domains: cross-level convergence, mechanistic constraint, clinical leverage, and explicit falsifiability/boundary conditions. On this basis, middle-level transdiagnostic spectra and selected cross-disorder genomic liabilities appear more defensible as candidate disease axes than highly global or weakly specified constructs. Psychiatry was justified in turning toward dimensional models, but dimensionality alone does not confer biological validity. The key task is not to choose between categories and dimensions, but to define the evidential thresholds under which dimensional constructs warrant ontological promotion. Full article