Search Results (372)

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Although the aetiology of IBD remains largely unknown, several studies suggest that an individual’s genetic susceptibility, external environmental factors, intestinal microbial flora, and immune responses are all factors involved in and functionally linked to the pathogenesis of IBD. Beyond the gastrointestinal manifestations, IBD patients frequently suffer from psychiatric comorbidities, particularly depression and anxiety. It remains unclear whether these disorders arise solely from reduced quality of life or whether they share overlapping biological mechanisms with IBD. This review aims to explore the bidirectional relationship between IBD and depressive disorders (DDs), with a focus on four key shared mechanisms: immune dysregulation, genetic susceptibility, alterations in gut microbiota composition, and dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. By examining recent literature, we highlight how these interconnected systems may contribute to both intestinal inflammation and mood disturbances. Furthermore, we discuss the reciprocal pharmacologic interactions between IBD and DDs: treatments for IBD, such as TNF-alpha and integrin inhibitors, have demonstrated effects on mood and anxiety symptoms, while certain antidepressants appear to exert independent anti-inflammatory properties, potentially reducing the risk or severity of IBD. Overall, this review underscores the need for a multidisciplinary approach to the care of IBD patients, integrating psychological and gastroenterological assessment. A better understanding of the shared pathophysiology may help refine therapeutic strategies and support the development of personalized, gut–brain-targeted interventions. Full article

Background: Human metapneumovirus (hMPV) is a respiratory pathogen that causes illness ranging from mild upper respiratory tract infections to severe pneumonia, particularly in individuals with comorbidities. Fatal cases of hMPV-induced hemorrhagic pneumonia are rare and likely under-reported. Diagnosis is often delayed due to overlapping symptoms with other respiratory viruses and the rapid progression of the disease. Case presentation: We report the case of a 55-year-old man with a complex medical history, including liver cirrhosis and diabetes mellitus, who developed acute viral pneumonia. Initial symptoms appeared three days before a sudden clinical deterioration marked by shortness of breath, hemoptysis, and respiratory failure. A nasopharyngeal swab taken on the third day of illness tested positive for hMPV by qRT-PCR. The patient died the following day. Postmortem molecular testing confirmed hMPV in lung tissue and alveolar contents. Autopsy revealed bilateral hemorrhagic pneumonia with regional lymphadenopathy. Histopathological examination showed alveolar hemorrhage, multinucleated cells, neutrophilic infiltration, activated autophagy in macrophages, and numerous cytoplasmic eosinophilic viral inclusions. Conclusions: This is the first documented case of fatal hMPV pneumonia in Armenia. It highlights the potential severity of hMPV in adults with chronic health conditions and emphasizes the need for timely molecular diagnostics. Postmortem identification of characteristic viral inclusions may serve as a cost-effective histopathological marker of hMPV-associated lung pathology. Full article

Chronic inflammatory response syndrome (CIRS) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are debilitating multisystem illnesses that share overlapping symptoms and molecular patterns, including immune dysregulation, mitochondrial impairment, and vascular dysfunction. This review provides a chronological synthesis of biomarker development in CIRS, tracing its evolution from early functional tests such as visual contrast sensitivity (VCS) to advanced transcriptomic profiling. Drawing on peer-reviewed studies spanning two decades, we examine the layered integration of neuroendocrine, immunologic, metabolic, and genomic markers that collectively support a multisystem model of innate immune activation specific to environmentally acquired illness. Particular focus is given to the Gene Expression: Inflammation Explained (GENIE) platform’s use of transcriptomics to classify disease stages and distinguish CIRS from other fatiguing conditions. While ME/CFS research continues to explore overlapping pathophysiologic features, it has yet to establish a unified diagnostic model with validated biomarkers or exposure-linked mechanisms. As a result, many patients labeled with ME/CFS may, in fact, represent unrecognized CIRS cases. This review underscores the importance of structured biomarker timelines in improving differential diagnosis and guiding treatment in complex chronic illness and highlights the reproducibility of the CIRS framework in contrast to the diagnostic ambiguity surrounding ME/CFS. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, CTEPH remains underdiagnosed due to nonspecific symptoms and overlapping features with other forms of pulmonary hypertension. Basic Methodology: This review synthesizes data from large international registries, epidemiologic studies, translational research, and multicenter clinical trials. Key methodologies include analysis of registry data to assess incidence and risk factors, histopathological examination of lung specimens, and molecular studies investigating endothelial dysfunction and inflammatory pathways. Diagnostic modalities and treatment outcomes are evaluated through observational studies and randomized controlled trials. Recent Advances and Affected Population: Research has elucidated that CTEPH arises from incomplete resolution of pulmonary emboli, with subsequent fibrotic transformation mediated by dysregulated TGF-β/TGFBI signaling, endothelial dysfunction, and chronic inflammation. Affected populations are typically older adults, often with prior venous thromboembolism, splenectomy, or prothrombotic conditions, though up to 25% have no history of acute PE. The disease burden is substantial, with delayed diagnosis contributing to worse outcomes and higher societal costs. Microvascular arteriopathy and PAH-like lesions in non-occluded vessels further complicate the clinical picture. Conclusions: CTEPH is now recognized as a treatable disease, with multimodal therapies—surgical endarterectomy, balloon pulmonary angioplasty, and targeted pharmacotherapy—significantly improving survival and quality of life. Ongoing research into molecular mechanisms and biomarker-driven diagnostics promises earlier identification and more personalized management. Multidisciplinary care and continued translational investigation are essential to further reduce mortality and optimize outcomes for this complex patient population. Full article

Sickle cell disease (SCD) is a prevalent genetic disorder caused by a mutation in the beta-globin gene. Hyperhemolysis (HS) is a severe complication involving the rapid destruction of both transfused and endogenous red blood cells, commonly found in SCD. This literature review explores the clinical presentation, diagnosis, pathogenesis, and management of HS in SCD. HS can manifest acutely or in a delayed manner, complicating diagnosis due to overlapping symptoms and varying reticulocyte responses. Immunohematological assessments often reveal delayed positivity in direct antiglobulin tests and antibody screens. HS typically presents severe anemia, jaundice, hemoglobinuria, and hemodynamic instability. Diagnostic markers include elevated bilirubin and lactate dehydrogenase levels alongside a reduced reticulocyte count. The management of HS is primarily empirical, with no clinical trials to support standardized treatment protocols. First-line treatments involve steroids and intravenous immunoglobulins (IVIG), which modulate immune responses and mitigate hemolysis. Refractory cases may require additional agents such as rituximab, eculizumab, tocilizumab, and, in some instances, plasma exchange or erythropoietin-stimulating agents. Novel therapeutic approaches, including bortezomib and Hemopure, have shown promise but require further investigation. Current management strategies are empirical, underscoring the need for robust clinical trials to establish effective treatment protocols that ultimately improve outcomes for SCD patients experiencing HS. Full article

Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases. Full article

Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, often arising in the absence of structural brain damage. Yet, both conditions exhibit considerable clinical overlap—particularly in the domains of cognitive dysfunction, emotional dysregulation, and symptom persistence despite negative investigations. Objective: This review critically examines the shared and divergent features of PCS and FND/FCD. We explore their respective epidemiology, diagnostic criteria, and risk factors—including personality traits and trauma exposure—as well as emerging insights from neuroimaging and biomarkers. We propose the “Functional Overlay Model” as a clinical tool for navigating diagnostic ambiguity in patients with persistent post-injury symptoms. Results: PCS and FND/FCD frequently share features such as subjective cognitive complaints, fatigue, anxiety, and heightened somatic vigilance. High neuroticism, maladaptive coping, prior psychiatric history, and trauma exposure emerge as common risk factors. Neuroimaging studies show persistent network dysfunction in both PCS and FND, with overlapping disruption in fronto-limbic and default mode systems. The Functional Overlay Model helps to identify cases where functional symptomatology coexists with or replaces an initial organic insult—particularly in patients with incongruent symptoms and normal objective testing. Conclusions: PCS and FND/FCD should be conceptualized along a continuum of brain dysfunction, shaped by injury, psychology, and contextual factors. Early recognition of functional overlays and stratified psychological interventions may improve outcomes for patients with persistent, medically unexplained symptoms after head trauma. This review introduces the Functional Overlay Model as a novel framework to enhance diagnostic clarity and therapeutic planning in patients presenting with persistent post-injury symptoms. Full article

Background/Objectives: Multiple sclerosis (MS) is a complex neurological disease that is associated with a broad spectrum of physical and psychological symptoms. Psychosocial adjustment (PSA) refers to the ability to cope with these challenges, which influence quality of life (QoL) and depressiveness in ways not yet fully understood. This study explores the relationship of PSA and disease-specific symptoms in MS, including fatigue, a prominent MS symptom. Additionally, PSA was compared to Amyotrophic Lateral Sclerosis (ALS) to disentangle the impact of disease trajectory on PSA. Methods: We interviewed 77 MS patients using patient-reported outcome measures on QoL and depression and compared them to 30 ALS patients. Confirmatory factor analysis and regression analysis were used to identify PSA indicators and predictors in MS, while t-tests assessed PSA differences across diseases. Results: Key PSA indicators in MS included physical (PQoL), mental (MQoL), and subjective (SQoL) quality of life, as well as depressiveness, with cognitive and motor fatigue emerging as significant predictors. MS patients had higher PQoL and SQoL and lower levels of depression compared to ALS patients, while both groups were comparable with regard to MQoL. Conclusions: PSA in MS is supported by high QoL and low depression levels, with fatigue being a significant predictor. Despite different disease trajectories, patients with MS and ALS showed comparable MQoL, indicating that both diseases similarly impact mental QoL, reflecting a partial overlap in psychosocial adjustment. Overall, psychosocial adjustment was more favorable in MS, likely due to its slower disease progression compared to ALS. Full article

Autistic traits—such as social communication deficits, cognitive rigidity, and repetitive behaviors—are increasingly recognized in individuals with schizophrenia, particularly in early-onset cases and subtypes with predominant negative symptoms. This overlap has prompted investigations into shared pathophysiological mechanisms. One emerging area of focus is the role of neuroinflammation in schizophrenia, which may contribute to the manifestation of autistic features. Immunological research indicates the presence of chronic low-grade inflammation, microglial activation, and disruption of the blood–brain barrier in schizophrenia. In particular, an imbalance in T-helper (Th) cell responses—specifically a shift toward Th2 dominance or concurrent Th1/Th2 activation—may lead to dysregulated cytokine production and disturbances in neural function. These findings highlight the importance of exploring immunological pathways as a basis for specific symptom profiles. Additionally, current efforts aim to identify reliable inflammatory biomarkers in schizophrenia that could support diagnosis, predict disease course, and guide treatment. Evaluating neuroinflammatory markers in patients with autistic features may provide novel insight into schizophrenia subtypes and help tailor immunomodulatory therapies. This review explores the expression of autistic traits in schizophrenia and examines the role of neuroinflammation and Th1/Th2 imbalance as potential mechanisms and biomarkers. Full article

Ginseng rusty root symptoms (GRSs) compromise the yield and quality of Panax ginseng. While transcriptomic analyses have demonstrated extensive remodeling of stress signaling networks, the post-transcriptional defense circuitry remains obscure. We profiled alternative splicing (AS) in three phloem tissues, the healthy phloem (AG), the non-reddened phloem neighboring lesions (BG), and the reddened lesion core (CG), to delineate AS reprogramming during GRS progression. The frequency of AS was sharply elevated in CG, with intron retention predominating. Extensive gains and losses of splice events indicate large-scale rewiring of the splice network. Overlapping differentially alternative spliced genes (DAGs) identified in both CG vs AG and CG vs BG contrasts were significantly enriched for RNA–spliceosome assembly and stress–response pathways, revealing a conserved post-transcriptional response associated with lesion formation. Integrative analysis of differentially expressed genes uncovered 671 loci under dual regulation; functional classification categorized these genes in receptor-like kinase signaling and chromatin-remodeling modules, underscoring the synergy between AS and transcriptional control. Moreover, the B subgenome disproportionately contributed stress-responsive transcripts in diseased tissue, suggesting an adaptive, subgenome-biased strategy. These findings demonstrate that dynamic AS remodeling and subgenome expression bias jointly orchestrate ginseng defense against GRS and provide a framework for breeding disease-resilient crops. Full article

The coexistence of heart failure (HF) and chronic obstructive pulmonary disease (COPD) presents a significant clinical challenge due to the common risk factors, overlapping symptoms, and complex pathophysiological interactions and mechanisms. This comprehensive review explores the bidirectional relationship between HF and COPD, emphasizing their combined impact on morbidity, mortality, and quality of life. Epidemiological data reveal that up to one-third of patients with HF also have COPD, complicating diagnosis and leading to suboptimal treatment strategies. We discuss the pathways through which each disease exacerbates the other, the limitations of the current staging systems, the diagnostic tools needed to differentiate cardiac from pulmonary symptoms, and the treatment choices. Therapeutic management requires careful integration of pharmacologic and non-pharmacologic strategies, with attention paid to potential drug interactions. Evidence from clinical trials confirms that beta-blockers can be safely used in patients with COPD and highlights the importance of multidisciplinary, patient-centered care models. Prevention strategies, including smoking cessation, vaccination, and patient education, play a critical role in improving outcomes. Finally, we identify key research gaps and calls for more inclusive clinical guidelines to address the needs of patients with this overlapping syndrome. A coordinated, evidence-based approach is essential for optimizing care and improving the quality of life of patients facing the dual burden of HF and COPD. Full article

Asthma is a highly heterogeneous respiratory disease that, in its severe forms, is characterized by persistent symptoms, frequent exacerbations, and a significant impact on patients’ quality of life. Despite high-dose inhaled corticosteroids and long-acting bronchodilators, a subset of patients remains uncontrolled, necessitating advanced therapeutic strategies. The advent of biologic therapies has revolutionized the management of severe asthma, offering targeted interventions based on the underlying inflammatory endotypes, primarily T2-high and T2-low. However, selecting the most appropriate biologic remains challenging due to overlapping phenotypic features and the limited availability of validated biomarkers. This narrative review explores the clinical utility of key biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), periostin, and total and specific IgE, in guiding biologic therapy. All the information provided is based on an extensive literature search conducted on PubMed. We also examine the clinical characteristics and comorbidities that influence therapeutic choices. Furthermore, we present a practical decision-making platform, including a clinical table matching phenotypes with biologic agents, such as omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab. By integrating biomarker analysis with clinical assessment, based on current guidelines and our extensive real-life experience, we aim to offer a logical framework to help clinicians select the most suitable biologic treatment for patients with uncontrolled severe asthma. Future research should focus on identifying novel biomarkers, refining patient stratification, and evaluating long-term outcomes to further advance precision medicine in the management of severe asthma. Full article

Alzheimer’s disease (AD) and schizophrenia are traditionally considered distinct clinical entities, yet growing evidence highlights substantial overlap in their molecular and neuroinflammatory pathogenesis. This review explores current insights into the shared and divergent mechanisms underlying these disorders, with emphasis on neuroinflammation, autophagy dysfunction, blood–brain barrier (BBB) disruption, and cognitive impairment. We examine key signaling pathways, particularly spleen tyrosine kinase (SYK), the mechanistic (or mammalian) target of rapamycin (mTOR), and the S100 calcium-binding protein B (S100B)/receptor for advanced glycation end-products (RAGE) axis, that link glial activation, excitatory/inhibitory neurotransmitter imbalances, and impaired proteostasis across both disorders. Specific biomarkers such as S100B, matrix metalloproteinase 9 (MMP9), and soluble RAGE show promise for stratifying disease subtypes and predicting treatment response. Moreover, psychiatric symptoms frequently precede cognitive decline in both AD and schizophrenia, suggesting that mood and behavioral disturbances may serve as early diagnostic indicators. The roles of autophagic failure, cellular senescence, and impaired glymphatic clearance are also explored as contributors to chronic inflammation and neurodegeneration. Current treatments, including cholinesterase inhibitors and antipsychotics, primarily offer symptomatic relief, while emerging therapeutic approaches target upstream molecular drivers, such as mTOR inhibition and RAGE antagonism. Finally, we discuss the future potential of personalized medicine guided by genetic, neuroimaging, and biomarker profiles to optimize diagnosis and treatment strategies in both AD and schizophrenia. A greater understanding of the pathophysiological convergence between these disorders may pave the way for cross-diagnostic interventions and improved clinical outcomes. Full article

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are linked by shared genetic mutations and overlapping clinical features, forming a clinical spectrum. This systematic review and meta-analysis analysed 97 studies, including 3212 patients with key ALS/FTD gene mutations, to identify gene-specific behavioural profiles. Chromosome 9 open reading frame 72 (C9orf72) mutations were strongly associated with psychotic symptoms and aggression, while superoxide dismutase 1 (SOD1) mutations had minimal cognitive effects. Progranulin (PGRN) mutations correlated with apathy and hallucinations, microtubule-associated protein tau (MAPT) mutations with disinhibition, and charged multivesicular body protein 2B (CHMP2B) with social impairments. Fused in sarcoma (FUS) mutations caused early sleep disturbances, TANK-binding kinase 1 (TBK1) led to disinhibition, and presenilin 1 and 2 (PSEN1/2) was linked to severe aggression. Prodromal cognitive changes in PGRN, MAPT, and CHMP2B mutations suggested early disease onset. Despite overlapping symptoms and clinical heterogeneity, understanding gene-specific patterns could inform tailored care strategies to enhance the quality of life for ALS and FTD patients. This study calls for refined guidelines integrating genetic behavioural profiles to improve patient and family support. Full article

Background: Pediatric-onset multiple sclerosis (POMS) is a rare and heterogeneous condition, with clinical features, progression, and therapeutic response varying significantly according to age at onset. Early-onset MS (<10 years) presents particular diagnostic and management challenges due to atypical presentations and more active inflammatory profiles. Objectives: To identify age-related clinical, radiological, and therapeutic characteristics of pediatric MS, with a specific focus on early-onset cases, and to compare them with intermediate (10–12 years) and late-onset (>12 years) forms. Methods: We conducted a retrospective analysis of medical records from 120 pediatric patients diagnosed with MS at a tertiary neurology center between 2018 and 2024. Patients were grouped by age at onset and assessed for clinical presentation, number and timing of relapses, EDSS scores, imaging findings, and treatment patterns. Results: Early-onset MS was associated with atypical symptoms, delayed diagnosis, more frequent relapses, and multifocal brainstem and cerebellar involvement. The diagnosis was significantly delayed in younger children compared to adolescents. EDSS scores tended to remain stable in the first 2–3 years, but early-onset patients showed a notable decline after the fourth year. While most patients received disease-modifying therapies, high-efficacy agents were underused due to age-related restrictions. Intermediate-onset patients presented overlapping features of both early and late-onset MS and had the highest proportion of fully preserved motor function (EDSS 0) at the end of follow-up. MRI findings revealed more extensive and confluent lesions in younger patients, particularly in the first two years after onset. Conclusions: Age at disease onset is a key determinant of clinical course and treatment response in pediatric MS. Early recognition and timely initiation of appropriate therapy—especially high-efficacy agents—may improve outcomes and reduce long-term disability. Further multicenter studies with standardized imaging and cognitive assessment protocols are needed to optimize care for this vulnerable population. Full article