Search Results (989)

Background: Sjögren’s disease (SjD) is a chronic systemic autoimmune disorder primarily characterized by lymphocytic infiltration of exocrine glands, leading to xerostomia and xerophthalmia. Beyond glandular involvement, the disease frequently presents with a broad spectrum of systemic and neuropsychiatric manifestations that significantly affect patients’ quality of life. Methods: A review of the literature was conducted to identify studies addressing neuropsychological symptoms in patients with SjD. Relevant publications describing cognitive dysfunction, mood disorders, sleep disturbances, fatigue, and sexual dysfunction, as well as potential underlying mechanisms and therapeutic approaches, were included and analyzed. Results: Available evidence indicates that neuropsychological symptoms are common among patients with SjD. Cognitive impairment, often described as “brain fog”, may involve deficits in memory, attention, and executive functioning. Depression and anxiety appear to occur more frequently than in the general population and may interact with chronic fatigue and sleep disturbances, contributing to functional impairment. While somatic causes of sexual dysfunctions such as vaginal dryness are well recognized, psychological and psychosexual aspects, including reduced sexual desire, have received comparatively little attention. The pathogenesis of these manifestations is likely multifactorial and may involve immune-mediated processes, cytokine dysregulation, neuroendocrine alterations, microvascular changes, and psychosocial factors. Conclusions: Neuropsychological manifestations represent a significant component of the overall disease burden in SjD. Increased awareness and multidisciplinary management strategies may help improve symptom recognition, patient care, and quality of life. Full article

Heart failure (HF) is a heterogeneous clinical syndrome with increasing prevalence among adults worldwide. It is characterized by complex central and peripheral alterations that contribute to exercise intolerance, fatigue, dyspnea, and reduced quality of life. Inspiratory muscle weakness (IMW) plays a key role in this vicious cycle by exacerbating symptoms and further limiting functional capacity. Inspiratory muscle training (IMT) has emerged as a potential adjuvant in comprehensive HF management and is a physiologically grounded and promising tool in the contemporary HF therapeutic toolkit. Its integration into multimodal rehabilitation programs may mitigate the cycle of dyspnea and deconditioning in patients with HF. On this basis, we provide an overview of the pathophysiological mechanisms underlying IMW and present the practical characteristics of IMT programs, synthesizing current evidence regarding its clinical efficacy and implementation challenges. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long Coronavirus Disease 2019 (long COVID) are complex chronic conditions that often follow infectious triggers with overlapping clinical features but poorly defined pathophysiological relationships. This study aimed to identify disease-specific immune signatures through multiparameter immunophenotyping of monocytes, dendritic cells, and T cell subsets. A total of 207 participants were included (ME/CFS: n = 103; long COVID: n = 63; healthy controls: n = 41). Peripheral blood mononuclear cells were analyzed using multiparameter flow cytometry. Statistical analyses included non-parametric testing, age-adjusted Analysis of covariance (ANCOVA), correlation network analysis, and principal component analysis (PCA). Long COVID was characterized by increased M2-like monocyte polarization, elevated CD80 expression across monocyte subsets, expansion of dendritic cells, and reduced expression of activation markers, indicating persistent immune activation with features of immune exhaustion. In contrast, ME/CFS exhibited reduced costimulatory molecule expression, impaired C-C chemokine receptor type 7 (CCR7)-mediated immune cell trafficking, and less coordinated activation patterns, consistent with a state of immune suppression. Correlation network analysis revealed more extensive and integrated immune interactions in long COVID, while PCA identified distinct immunophenotypic components and enabled moderate discrimination between the two conditions. These findings demonstrate that ME/CFS and long COVID are characterized by distinct immune profiles, supporting the concept of divergent immunopathological mechanisms. The identified signatures may contribute to biomarker development and guide targeted therapeutic approaches. Full article

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system disease characterized by a multitude of symptoms across various organ systems. Diagnosis has relied heavily on heterogeneous clinical symptom presentation and evolving case definitions, with treatment focused on addressing presenting symptoms due to the paucity of validated biomarkers. Meanwhile, advances have been made in understanding the underlying pathophysiology through strong epidemiologic, clinical, and basic science studies. This narrative review synthesizes recent advances that are likely to drive a shift in understanding from symptom-based classification toward a molecularly defined understanding of the disease. This shift in understanding will likely provide the foundation for future research efforts focused on targeting diagnosis and treatment more effectively. Specifically, we reference the identification of rare genetic risk variants through the HEAL2 deep learning framework, the large-scale DecodeME genome-wide association study, and dynamic epigenetic markers of disease state. In addition, the findings revealed the downstream consequences of this genetic and epigenetic priming: chronic innate immune activation, CD8+ T cell exhaustion characterized by upregulation of the exhaustion-driving transcription factors Thymocyte Selection-Associated HMG Box (TOX) and Eomesodermin (EOMES), and a cellular energy crisis centered on mitochondrial dysfunction. Furthermore, results of recent studies have revealed sex-specific transcriptomic and proteomic signatures of maladaptive recovery. We also highlight the role of machine learning and artificial intelligence integrations in translating high-dimensional multi-omics data into actionable biological insights, including the identification of monocyte subsets via Positive Unlabeled Learning, circulating cell-free RNA diagnostic signatures, and integrated multi-modal disease models such as BioMapAI. The combination of these findings, which highlight multiple identifiable mechanisms of molecular activity, support the feasibility of molecular subtyping, precision diagnostics, and targeted therapeutic strategies for ME/CFS. Full article

Human endogenous retroviruses (HERVs) are potential driving forces of the pathophysiology of Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), linking post-infectious immune dysfunction to chronic inflammation and immune and neurocognitive dysfunction that are hallmark features of ME/CFS. Accumulating evidence from related autoimmune diseases and cancers has shown that reactivated HERVs can contribute to disease pathogenesis by amplifying immune activation through viral protein-mediated innate sensing, long terminal repeat (LTR)-driven transcription, and disrupting epigenetic silencing. HERV signatures are therefore promising biomarkers for diagnosis, patient stratification for drug-repurposing trials, and therapy monitoring. Accumulating evidence suggests a possible correlation between HERV expression and ME/CFS symptom severity, alterations in immune phenotypes, function and inflammatory gene networks. Importantly, locus-specific HERV profiling is a promising approach for distinguishing ME/CFS from overlapping or co-morbid conditions and healthy controls. Furthermore, HERV-targeted antibodies, immune modulators, epigenetic and antiviral interventions offer promise as concomitant therapeutic strategies for ME/CFS. Additional research incorporating viromics and other-omics validation, functional assays, and HERV-stratified clinical trials is now needed to realise this potential and to transform ME/CFS from a symptom-based syndrome into a mechanism-driven, treatable condition. Full article

Restless legs syndrome (RLS) is a common yet underrecognized neurological disorder characterized by uncomfortable sensations and an irresistible urge to move he legs, typically following a circadian pattern. RLS frequently co-occurs with various other neurological diseases, raising questions about shared mechanisms and clinical consequences. This review synthesizes evidence on the prevalence, outcomes, and pathophysiology of RLS in various neurological disorders, including Parkinson’s disease, multiple sclerosis, migraine, dementia, stroke, epilepsy, and peripheral neuropathy. In Parkinson’s disease, RLS is linked to disease progression and dopaminergic therapy. In stroke and multiple sclerosis, RLS is associated with structural lesions at specific locations, such as the pons or spinal cord. In epilepsy, RLS is associated with refractory or nocturnal seizures. In neuropathies, disruption of small sensory fibers may contribute to RLS symptoms. In dementia, RLS adds diagnostic complexity. Overlapping mechanisms between RLS and its neurological comorbidities include altered sensorimotor processing, brainstem and spinal circuitry, and sleep/arousal regulation. RLS in neurological conditions often worsens sleep quality, mood, and fatigue, and contributes to reduced quality of life and worse outcomes. Future research should prioritize longitudinal designs, standardized diagnostic approaches, and mechanistically driven studies to clarify relationships between RLS and these neurological comorbidities. Full article

Background: With the global rise in the ageing population and type 2 diabetes mellitus (T2DM), elderly individuals are increasingly prone to complications like sarcopenia and frailty, which are conditions linked to muscle loss and functional decline. These syndromes contribute significantly to morbidity and healthcare burden but remain underestimated in older adults with diabetes. Indian data regarding their prevalence and correlation with glycemic control is limited. Materials and Methods: This hospital-based observational study was conducted over 22 months at Kasturba Medical College, Manipal, involving 160 diabetic patients aged ≥60 years. Clinical features, comorbidities, and diabetes-related complications were recorded. Frailty was assessed using the Edmonton Frailty Scale (EFS), and sarcopenia risk was evaluated using the SARC-F questionnaire. Descriptive statistics and Spearman’s correlation were used for analysis. Results: The mean age of participants was 69.98 ± 5.86 years, with 63.1% being male. Fatigue was the most common clinical presentation at 10.6%, while cardiovascular disease was the leading complication at 28.1%. Frailty or pre-frailty was identified in 35% of the population, and 36.9% were at risk for sarcopenia. A strong correlation was found between frailty and sarcopenia risk (p < 0.001). Conclusions: Frailty and sarcopenia are common and closely linked in elderly diabetes, though not significantly associated with glycemic control as both hypoglycemia and hyperglycemia could contribute to frailty. Full article

Background and clinical significance: Autoimmune hepatitis (AIH) and ankylosing spondylitis (AS) are distinct immune-mediated disorders that only rarely coexist. Diagnostic interpretation becomes especially challenging when the liver biochemistry is not classically hepatocellular and the histology is unavailable. Case presentation: We report a 51-year-old man with inflammatory back pain, polyarthralgia, weight loss, fatigue, night sweats and fever. Laboratory tests showed marked systemic inflammation, anemia and a cholestatic-predominant liver profile with associated aminotransferase elevation. Imaging demonstrated bilateral sacroiliitis and syndesmophytosis. Liver workup excluded viral, obstructive, metabolic, hereditary and inflammatory bowel disease-associated cholangiopathic causes. Antinuclear antiboidies (ANA) and anti liver cyotsole 1 antiboidies (anti-LC-1) were positive, IgG was mildly elevated, magnetic resonance cholangio-pancreatography (MRCP) was negative for primary sclerosing cholangitis and the simplified AIH score was six. A liver biopsy was proposed but refused. The patient received a short course of prednisone for rheumatologic flare control, followed by nonsteroidal anti-inflammatory treatment and sulfasalazine, with normalization of liver tests during follow-up. Conclusions: This case is suggestive, but not diagnostic, of autoimmune hepatitis in a patient with ankylosing spondylitis. In the absence of histology and in the setting of a cholestatic-predominant biochemical profile, the findings may be more appropriately interpreted as an autoimmune hepatitis-like syndrome. The main teaching point is that abnormal liver tests in AS warrant structured evaluation beyond drug toxicity and viral hepatitis, particularly when autoimmune serology is positive, even in a cholestatic-predominant presentation. Full article

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID-19 syndrome share a symptom profile, including severe fatigue, cognitive dysfunction, exertional intolerance, sleep disturbances, hypervigilance, and the paradoxical state of being “wired but tired.” A well-established finding is sympathetic hyperactivity with reduced vagal tone, typically interpreted as autonomic nervous system dysfunction. Emerging evidence, however, suggests a broader disturbance across multiple neurotransmitter systems. This paper reviews current knowledge on neurotransmitter systems implicated in ME/CFS and Long COVID, focusing on potential mechanisms of dysregulation and their roles in disease pathology and symptom generation, as well as implications for treatment. In addition to abnormalities of the noradrenergic system, disturbances in serotonergic, GABAergic, and glutamatergic signaling have been reported. Contributing factors may include autoimmunity, neuroinflammation, gut dysbiosis, epigenetic influences, and stressors such as orthostatic intolerance, metabolic strain, and pain. A shift favoring excitatory over inhibitory neurotransmission can lead to excessive neural activation, autonomic dysfunction, sensory hypersensitivities, sleep disturbances, and cognitive impairment. Reduced GABAergic tone combined with increased glutamatergic and noradrenergic activity may elevate skeletal muscle tone, contributing to calcium overload, mitochondrial dysfunction, exertional intolerance, and post-exertional malaise. Various pharmacological treatments may partially rebalance these neurotransmitter systems, but limited efficacy highlights the need for systematic investigation and individualized strategies. Full article

Background/Objectives: Quality of life (QoL) and functional recovery are essential outcomes in patients undergoing rectal cancer surgery. In addition to oncological results, bowel dysfunction and stoma-related issues may significantly affect postoperative well-being. We aimed to evaluate QoL changes at 1 and 6 months postoperatively and functional outcomes in rectal cancer patients who underwent curative surgical treatment, sphincter-preserving surgeries (SPS) or abdominoperineal resection (APR). Owing to its impact on QoL, several functions were assessed using the Low Anterior Resection Syndrome (LARS) score. Methods: This retrospective observational study consisted of 99 patients who underwent curative rectal cancer surgery, of which 38 patients had colostomy, and 61 no colostomy. To assess patient-reported outcomes related to QoL, the EORTC QLQ-C30 questionnaire, QLQ-CR29 questionnaire, and LARS instrument were sent to the patients at 1 and 6 months postoperatively. Changes over time were analyzed using paired statistical tests, and subgroup analyses were performed according to colostomy status and surgical approach. Results: Significant improvements were observed in the global health status and all major functional domains between 1 and 6 months postoperatively. The global health status increased from 74.9% to 86.5% (p < 0.001). Symptom burden decreased significantly, particularly for fatigue (−18.31), pain (−14.48), diarrhea (−12.46), and insomnia (−11.45), representing clinically meaningful improvements. Patients who underwent abdominoperineal resection or resection with colostomy had lower QoL scores at 1 month but showed substantial improvement at 6 months, becoming comparable to those who underwent SPS. LARS outcomes demonstrated progressive functional recovery, with the proportion of patients without LARS increasing from 39 to 46, while major LARS decreased from 7 to 3 patients. However, approximately 40% of patients in the SPS group continued to report moderate-to-severe LARS symptoms. Conclusions: In this study, QoL and bowel function improved significantly during the first 6 months after colorectal cancer surgery. Although most patients demonstrated recovery, persistent bowel dysfunction and stoma-related challenges remain important issues. These findings highlight the need for comprehensive postoperative care and routine assessment of both QoL and functional outcomes. Full article

Explosive ordnance (EO), including AXO (abandoned explosive ordnance), IEDs (improvised explosives devices), and UXO (unexploded ordnance), are widely recognised for their blast and fragmentation hazards, but they also represent a persistent and under-addressed source of occupational chemical exposure for explosive ordnance disposal (EOD) personnel. EOD core activities liberate mixed metals and energetic chemicals, resulting in exposures that are multi-route (inhalation of dusts and fumes, dermal loading amplified by sweat and glove occlusion, and ingestion via hand-to-mouth transfer during eating, drinking, or smoking) and multi-temporal (repeated low-dose background plus task-driven spikes), as well as chemically complex. Clinically, this can present as syndromic overlap across acute and chronic domains, with symptoms that are easily misattributed to heat stress, dehydration, infection, or fatigue. Acute effects of concern include neurotoxic presentations (headache, dizziness, confusion, tremor, and seizure), respiratory and mucosal irritation following dust or fume events, gastrointestinal symptoms, and patterns suggestive of acute hepatic or renal stress, particularly when high-intensity tasks occur in hot environments that compound physiologic strain. Chronic outcomes relevant to repeatedly exposed EOD personnel include renal function decline, neurocognitive effects that can degrade operational decision making and safety, persistent haematologic abnormalities, and endocrine disruption signals, with long-latency risks requiring cautious interpretation given sparse longitudinal data and confounding co-exposures. This review synthesises the current evidence base through an EOD lens and translates it into pragmatic clinical and programmatic actions: task-based exposure characterisation; tiered biomonitoring and medical surveillance aligned to operational tempo; incident-triggered assessment pathways after high-residue events; and prevention strategies that work under field constraints, including contamination control zones, hygiene enforcement, glove and respiratory protection optimisation, tool and vehicle decontamination, and measures to prevent secondary transfer and take-home exposure. The central takeaway is practical: EOD programs can reduce morbidity and improve readiness by treating explosive ordnance as a chemical mixture exposure problem, adopting mixture-aware clinical triage, and embedding surveillance and controls that match how EOD work is actually performed. Full article

Background/Objectives: Work stress (WS), occupational fatigue (OF), and Burnout syndrome (BS) among administrative workers are associated with negative psychosocial and metabolic effects. Although antioxidant-rich nutritional strategies have been proposed to help manage stress, evidence from real-world occupational settings is still limited. This study evaluated the total antioxidant capacity (TAC) of a multi-antioxidant dietary supplement 2.0 (DS2.0; apple polyphenols, [APP], astaxanthin [AXT], and fucoxanthin [FXT]; 387:12:1 ratio) and explored its association with metabolic parameters, OF, psychosocial outcomes, and hair cortisol concentration (HCC) in administrative workers with and without obesity. Methods: A quasi-experimental pilot study was conducted among 22 workers, who received DS2.0 (52.13 mg/day, n = 17) or a placebo (n = 5) for 30 days. TAC was analytically assessed using standardized assays. Metabolic outcomes (lipid profile, fasting plasma glucose), psychosocial variables (SOFI-SM, CESQT/SBI, and IMSS tests), and HCC (competitive immunoassay) were evaluated before and after supplementation. Statistical analyses included within-group pre–post comparisons, independent-sample tests, and effect size estimation. Results: DS2.0 demonstrated high TAC. Supplementation was associated with reductions in total lipids, total cholesterol, and non-HDL cholesterol, as well as decreases in OF, BS, and WS scores. HCC decreased in the overall sample (217.19 vs. 31.64 pg/mg; p = 0.000) and among workers with obesity (276.80 vs. 34.13 pg/mg; p = 0.002). Stress-related symptoms, including sleep deprivation, exhaustion, appetite changes, difficulty waking, and palpitations, also improved (p ≤ 0.05). Conclusions: An antioxidant-rich DS2.0 supplement may be associated with psychosocial and stress-related biomarkers; however, these exploratory findings require confirmation in larger randomized controlled trials. Trial registration: ISRCTN 12762846. Full article

Background: The aim of this study is to determine the prevalence of malnutrition, frailty, and cachexia in patients with different cancer subtypes undergoing oncological treatment using various screening scales and to evaluate the distribution of these conditions by geriatric age groups. Methods: This cross-sectional study included 4595 patients with different cancer subtypes undergoing oncological treatment. Nutritional status was assessed using the Mini Nutritional Assessment—Short (MNA-S) form; frailty was evaluated with the Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight (FRAIL) scale; and cachexia was determined based on >5% weight loss in the last 6 months or a body mass index (BMI) < 20 kg/m², together with an additional >2% weight loss. Patients were divided into two groups by geriatric age. Results: A total of 36% of the patients included in the study were geriatric (≥65 years old). The prevalence of malnutrition, frailty, and cachexia in the general population was determined to be 40%, 45%, and 44%, respectively. All three conditions were found to be statistically significantly more prevalent in the geriatric age group (p < 0.001 for all comparisons). Conclusions: It was determined that the prevalence of malnutrition, frailty, and cachexia was high in cancer patients receiving systemic oncological treatments including chemotherapy, hormonal therapy, targeted therapy, and immunotherapy; these syndromes are significantly more common, particularly in the geriatric patient group. Full article

Background: The alternative Overlap Syndrome (aOVS), the coexistence of bronchial asthma and Obstructive Sleep Apnea (OSA), represents a distinct clinical phenotype associated with worse clinical outcomes, but little is yet known about its characteristics. We aimed to investigate differences in sleep stability and clinical burden between OSA and aOVS patients matched for age, gender, BMI and Apnea-Hypopnea Index (AHI). Methods: 45 aOVS and 45 OSA patients were compared using demographic, clinical and polysomnographic data. Results: Patients with aOVS exhibited significantly higher odds ratio product (ORP) values for total sleep time (ORPmed: 0.8 ± 0.2 vs. 0.5 ± 0.1, p < 0.001) and Non-Rapid Eye Movement (ORPnr: 0.7 ± 0.3 vs. 0.4 ± 0.1, p < 0.001) sleep compared with OSA patients. Furthermore, patients with aOVS showed a significantly higher risk of developing clinically significant anxiety and fatigue, showing a significantly higher General Anxiety Disorder-7 (GAD-7: 8.7 ± 5.6 vs. 5.7 ± 4.7, p = 0.02) and significantly higher prevalence of fatigue (71% vs. 41%, p = 0.01). These associations remained significant after multivariable adjustment and were independent of OSA severity (AHI). Conclusions: Our findings support the concept that aOVS is characterised by significantly more unstable sleep and a greater psychological burden, even after matching with OSA patients for age, gender, BMI and AHI. Our study also highlights the need to integrate traditional sleep measures with more recent ones, such as ORP, in order to better capture the multidimensional burden of aOVS. Full article

Background: Post-exertional malaise (PEM), which is the cardinal feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is also reported in a proportion of patients with post-COVID-19 syndrome (PCS). Our objective was to identify determinants that may be linked to the emergence of PEM in PCS patients. Methods: Patients fulfilling the World Health Organization definition for PCS who attended the post-COVID unit of the Internal Medicine Department of Angers University Hospital, France, between June 2020 and December 2023 were included retrospectively. Their medical records were reviewed to extract information on COVID-19 infection history, characteristics of post-exertional malaise (PEM), fatigue severity, and relevant epidemiological variables. Results: The study included 220 patients, grouped according to whether post-exertional malaise was present (PCS/PEM+) or absent (PCS/PEM–). PEM was observed in 26.4% of patients and was significantly linked to earlier COVID onset in 2020/2021 (OR 5.68 (95% CI: 1.66–19.45), p = 0.006), as well as higher fatigue levels (OR 2.07 (95% CI: 1.22–3.50), p = 0.007). Conclusions: Patients who contracted COVID-19 during the pre-Omicron period reported PEM more frequently than those infected in later waves. This observation could reflect differences in viral characteristics following the emergence of the Omicron variant; however, alternative explanations—such as increasing vaccination coverage, accumulating post-infectious immunity, or other unmeasured factors—cannot be ruled out. Based on the observed link between PEM and symptom severity, PCS patients should be systematically assessed for the presence of PEM. Full article