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This pilot study harnessed the power of network medicine to unravel the complex pathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). By utilizing a network analysis on whole genome sequencing (WGS) data from the Severely Ill Patient Study (SIPS), we identified ME/CFS-associated proteins and delineated the corresponding network-level module, termed the SIPS disease module, together with its relevant pathways. This module demonstrated significant overlap with genes implicated in fatigue, cognitive disorders, and neurodegenerative diseases. Our pathway analysis revealed potential associations between ME/CFS and conditions such as COVID-19, Epstein–Barr virus (EBV) infection, neurodegenerative diseases, and pathways involved in cortisol synthesis and secretion, supporting the hypothesis that ME/CFS is a neuroimmune disorder. Additionally, our findings underscore a potential link between ME/CFS and estrogen signaling pathways, which may elucidate the higher prevalence of ME/CFS in females. These findings provide insights into the pathogenesis of ME/CFS from a network medicine perspective and highlight potential therapeutic targets. Further research is needed to validate these findings and explore their implications for improving diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Xiaoyao San (XYS) has been increasingly used in China for treating chronic fatigue syndrome (CFS), but its efficacy and safety remain unclear. Objective: To systematically evaluate the efficacy and safety of XYS compared to standard biomedical treatments (SBT) in CFS patients. Methods: A comprehensive search of English and Chinese databases was conducted up to December 2024. Eligible studies included randomized controlled trials comparing XYS or XYS + SBT to SBT alone. Primary outcomes were effective rate (ER) and fatigue scale-14 (FS-14). Secondary outcomes included self-rating anxiety scale (SAS), self-rating depression scale (SDS), and adverse events (AEs). Data were analyzed using Review Manager 5.4, and evidence quality was assessed using the GRADE approach. Results: Six studies involving 623 patients were included. The meta-analysis showed that XYS-based interventions significantly improved ER (RR = 1.27, 95% CI: 1.18–1.37, I2 = 0%) and FS-14 (MD = 1.77, 95% CI: 1.49–2.06, I2 = 54%). Subgroup analyses confirmed consistent efficacy for both XYS vs. SBT and XYS + SBT vs. SBT. Anxiety and depression improved significantly in the XYS + SBT group, with SAS (MD = 5.16, 95% CI: 3.84–6.48, I2 = 24%) and SDS (MD = 4.62, 95% CI: 3.15–6.09, I2 = 0%). Additionally, the risk of AEs was significantly reduced in the XYS + SBT group compared to SBT alone (RR = 0.48, 95% CI: 0.32–0.72, I2 = 0%). However, the quality of evidence was rated "low" due to risk of bias and potential publication bias among the studies. Conclusion: XYS, whether alone or with SBT, is effective and safe for improving ER, fatigue, anxiety, and depression in CFS patients. However, due to the low quality of the evidence, results should be interpreted cautiously. High-quality RCTs with larger sample sizes and longer follow-up are needed to provide stronger evidence for the clinical use of XYS in managing CFS. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display%5frecord.php?RecordID=493084, identifier CRD42023493084. [ABSTRACT FROM AUTHOR]

Background: Mandibular reconstruction poses challenges in achieving functional and aesthetic outcomes. Effective oral rehabilitation is crucial for restoring function and improving quality of life; however, the altered neomandibular anatomy complicates oral hygiene, increasing the risk of peri-implant complications and making successful rehabilitation more difficult. This study introduces a novel approach combining vestibuloplasty with patient-specific implant-retained splints to enhance oral health and improve rehabilitation outcomes. Methods: Three patients underwent mandibular reconstruction with a free vascularized fibula flap (FFF). After 6 months of osseointegration, vestibuloplasty and soft tissue refinement were performed, with a split-thickness skin graft placed on the FFF periosteum. An implant-retained splint was secured to the abutments for two weeks to support soft tissue healing. Implant survival, bone loss, and peri-implant health were evaluated over a 2-year follow-up. Results: A total of 12 implants were placed, primarily in the neomandible (83.3%), with a 100% survival rate. Implant survival was assessed. Implant survival was assessed based on established criteria for clinical success, including stability, presence of pain, bleeding on probing (BOP), pocketdepth, bone loss and lack of peri-implant radiolucency. Functional outcomes included normal mouth opening, laterotrusion, and protrusion. Pocket depths ranged from 3 to 4 mm, except for one implant in cases 1 and 2. The mean BOP was 51.7%. Conclusions: This case series introduces a surgical technique that combines CAD/CAM and vestibuloplasty to optimize dental rehabilitation in mandibular FFF reconstructions, demonstrating safe thinning of soft tissues for improved oral hygiene and survival. [ABSTRACT FROM AUTHOR]

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease of unknown aetiology characterised by symptoms of post-exertional malaise (PEM) and fatigue leading to substantial impairment in functioning. Other key symptoms include cognitive impairment and unrefreshing sleep, with many experiencing pain. To date there is no complete understanding of the triggering pathomechanisms of disease, and no quantitative biomarker available with sufficient sensitivity, specificity, and adoptability to provide conclusive diagnosis. Clinicians thus eliminate differential diagnoses, and rely on subjective, unspecific, and disputed clinical diagnostic criteria—a process that often takes years with patients being misdiagnosed and receiving inappropriate and sometimes detrimental care. Without a quantitative biomarker, trivialisation, scepticism, marginalisation, and misunderstanding of ME/CFS continues despite the significant disability for many. One in four individuals are bed-bound for long periods of time, others have difficulties maintaining a job/attending school, incurring individual income losses of thousands, while few participate in social activities. Main body: Recent studies have reported promising quantifiable differences in the biochemical and electrophysiological properties of blood cells, which separate ME/CFS and non-ME/CFS participants with high sensitivities and specificities—demonstrating potential development of an accessible and relatively non-invasive diagnostic biomarker. This includes profiling immune cells using Raman spectroscopy, measuring the electrical impedance of blood samples during hyperosmotic challenge using a nano-electronic assay, use of metabolomic assays, and certain techniques which assess mitochondrial dysfunction. However, for clinical application, the specificity of these biomarkers to ME/CFS needs to be explored in more disease controls, and their practicality/logistics considered. Differences in cytokine profiles in ME/CFS are also well documented, but finding a consistent, stable, and replicable cytokine profile may not be possible. Increasing evidence demonstrates acetylcholine receptor and transient receptor potential ion channel dysfunction in ME/CFS, though how these findings could translate to a diagnostic biomarker are yet to be explored. Conclusion: Different biochemical and electrophysiological properties which differentiate ME/CFS have been identified across studies, holding promise as potential blood-based quantitative diagnostic biomarkers for ME/CFS. However, further research is required to determine their specificity to ME/CFS and adoptability for clinical use. [ABSTRACT FROM AUTHOR]

Background Earlier studies revealed that 10%–50% of patients reported remaining complaints after treatment for Lyme neuroborreliosis (LNB). The aim of our study was to assess symptoms and quality of life in patients with diagnosed and treated LNB and to compare them with findings in the general population. Methods Adults with LNB receiving adequate antibiotics were included between 2015 and 2021 in 2 tertiary hospitals. Two controls without Lyme borreliosis history were included for each case patient, matched by age and geographic area. All participants were interviewed to answer a standardized questionnaire. Fatigue was assessed by the Fatigue Severity Scale (FSS) and quality of life by the 12-Item Short Form Survey, including physical component summary (PCS) and mental component summary (MCS) scores. Results Fifty-three patients and 104 controls were included. The mean age (SD) was 62 (13) years in both groups; 66% were male in the LNB group and 44% in the control group (P =.01). Fatigue (68% vs 48%, respectively; P =.02), memory disorders (60% vs 38%; P <.01), and attention disorders (32% vs 17%; P =.05) were significantly more frequent in the LNB group than in controls. In multivariable analysis, no association was found between LNB and FSS scores (odds ratio, 1.6 [95% confidence interval,.9–3.0]; P =.15) or between LNB and MCS scores (0.8 [.4–1.5]; P =.45); however, patients with LNB had lower PCS scores (0.5 [.3–.9]; P =.03). Conclusions Several symptoms were similar in patients with LNB and controls. Quality of life was slightly impaired in patients with LNB and PCS scores were lower, but there were no differences in MCS or FSS scores. Reassurance and specific rehabilitation measures could be provided to these patients. [ABSTRACT FROM AUTHOR]

Fibromyalgia is a multifaceted syndrome primarily characterized by chronic widespread pain and fatigue. Despite its significant prevalence and incidence, the mechanisms mediating the disease pathogenesis have remained poorly understood; however, increasing evidence suggests a potentially central role of intestinal dysbiosis. Researchers have been examining possible diagnostic biomarkers, such as Helicobacter pylori infection, urine metabolite profiles, and cytokine levels, which reflect these microbiome changes. Additionally, evaluation of therapeutic interventions targeting the gut microbiome, including probiotics, fecal microbiota transplantation, and antibiotics for specific infections, has highlighted their potential in alleviating fibromyalgia symptoms. This article delves into the emerging role of the gut microbiome in fibromyalgia pathogenesis, illustrating how alterations in gut bacterial composition and diversity are implicated in the pathophysiology of the disease through the gut-brain axis, and sets a direction for future research to enhance diagnostic accuracy and therapeutic efficacy of this complex condition. [ABSTRACT FROM AUTHOR]

Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmunological disorder with limited treatment options. Despite the widespread use of Dietary Supplements (DSs) among ME/CFS patients to alleviate fatigue and associated symptoms, evidence remains inconclusive. This systematic review aims to provide an updated synthesis of the efficacy of DS interventions and explore possible mechanisms underlying their therapeutic effects. Methods: This systematic review was conducted according to PRISMA guidelines. Several databases (Ebsco Host, PubMed, Scopus, Google Scholar) were used for the systematic search, which was based on the broad search terms ME/CFS and DS with a focus on publications between 1994 and 2024. The primary outcome was fatigue, with additional considerations including psychological well-being, physical activity, and biochemical markers. Two independent researchers screened the studies for eligibility in a multi-stage process and assessed quality and bias using Cochrane's risk of bias tools (RoB-2, ROBINS-I). Results: Fourteen studies (N = 809) of heterogeneous designs were included, showing a high risk of bias, mostly due to missing data and selection bias. While some interventions (L-carnitine and guanidinoacetic acid, oxaloacetate, CoQ10–selenium combination, NADH and NADH-CoQ10 combination) showed significant reductions in fatigue, methodological limitations, like small sample sizes and missing data, prevent firm conclusions. Mixed results were reported for secondary outcomes like cognitive function and inflammatory markers. Six studies noted adverse effects, including nausea and insomnia. Conclusions: Though some DSs showed potential in reducing fatigue in ME/CFS, methodological limitations and inconsistent results hinder definitive conclusions. Future research should improve diagnostic criteria and include more diverse populations. [ABSTRACT FROM AUTHOR]

Post-COVID syndrome has been defined as signs and symptoms that develop after an infection consistent with COVID-19 and continue for more than 12 weeks, including neurocognitive signs and symptoms that have an impact on the functioning and quality of life of middle-aged adult and older survivors. This systematic review describes the current knowledge of long-term cognitive impairments in COVID-19 survivors, approaches strategies, and their impact on public and private health services worldwide. The systematic review was conducted under the criteria and flowchart established in the PRISMA statement, considering studies from the PubMed, Scopus, and Web of Science databases between 2020 and 2023. The included studies considered participants over 40 years of age, COVID-19 survivors. A total of 68 articles were included, most of which had high to excellent quality. The analysis showed the presence of heterogeneous cognitive symptoms in COVID survivors, persistent for at least 12 weeks from the onset of infection, mostly unsystematized and nonspecific approaches strategies, and a lack of methods for monitoring their effectiveness, with a significant economic and logistical impact on health systems. Specific protocols are required for the rehabilitation of persistent cognitive dysfunction in COVID-19 survivors, as well as longitudinal studies to evaluate the effectiveness of these interventions. [ABSTRACT FROM AUTHOR]

The immune system is a complex and fundamental network for organism protection. A minimal unbalance in the host defense system homeostasis can originate severe repercussions in human health. Fundamentally, immune-related diseases can arise from its compromise (immunodeficiency diseases), overactivation against itself (autoimmune diseases) or harmless substances (allergies), and failure of eliminating the harmful agent (chronic inflammation). The notable advances and achievements in the immune system diseases pathophysiology have been allowing for a dramatic improvement of the available treatments. Nevertheless, they present some drawbacks, including the inappropriate benefit/risk ratio. Therefore, there is a strong and urgent need to develop effective therapeutic strategies. Nature is a valuable source of bioactive compounds that can be explored for the development of new drugs. Particularly, plants produce a broad spectrum of secondary metabolites that can be potential prototypes for innovative therapeutic agents. This review describes the immune system and the inflammatory response and examines the current knowledge of eight plants traditionally used as immunomodulatory medicines (Boswellia serrata, Echinacea purpurea, Laurus nobilis, Lavandula angustifolia, Olea europaea, Salvia officinalis, Salvia rosmarinus, and Taraxacum officinale). Moreover, the issues responsible for possible biologic readout inconsistencies (plant species, age, selected organ, developmental stage, growth conditions, geographical location, drying methods, storage conditions, solvent of extraction, and extraction method) will also be discussed. Furthermore, a detailed list of the chemical composition and the immunomodulatory mechanism of action of the bioactive compounds of the selected plant extracts are presented. This review also includes future perspectives and proposes potential new avenues for further investigation. [ABSTRACT FROM AUTHOR]

Objectives: Functional Disorders (FD) are highly prevalent conditions that are diagnosed based on the presence of specific patterns of somatic symptoms. Examples of FDs include Fibromyalgia and Irritable Bowel Syndrome. Many patients who meet the criteria do not receive a formal diagnostic label. This systematic review aims to assess factors associated with receiving an FD diagnostic label. Methods: A systematic search of PubMed, PsycINFO, and Embase was performed following the PRISMA guidelines. All research methodologies and languages were included with a focus on experiences and impacts of receiving/having an FD diagnostic label. Excluded studies were those not mentioning diagnostic labels, only involving single pain symptoms, and studies solely focusing on functional neurological symptoms. Screening, data extraction and quality ratings (using the QuADS instrument) were performed by two independent reviewers. Results: 15 Studies were identified (10 quantitative and 5 qualitative). Our results show that female patients were more likely to receive an FD diagnostic label for their symptoms; other associations were less consistent and only found for specific labels or research designs. In general, quality of life and healthcare use did not seem to differ between patients with and without an FD diagnostic label. From the healthcare professional's perspective there was doubt about giving an FD diagnostic label, mainly due to concerns of harm for patients. Quality of included studies was rated low to moderate. Conclusion: Better understanding of factors associated with receiving or having an FD diagnostic label, independently from symptom development can help healthcare professionals make evidence-based decisions in labelling or not; however, high quality studies on this topic are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia (FM) is a disease characterized by chronic widespread pain concomitant with various symptoms such as fatigue and anxiety. Although chronic inflammation has been implicated in the immunological abnormalities of FM, there are few human studies on complement and immunoglobulins. In this study, we investigated the immunological characteristics of FM patients and the association between their clinical symptoms and immunological indices, including complement and immunoglobulins. Methods: 1) The serum 50% hemolytic complement activity (CH50), C3, C4, IgG, IgM, and hsCRP of 36 FM patients and 30 healthy sex- and age-matched controls (HC) were measured and compared. 2) Data from the Brief Pain Inventory (pain intention and pain interference subscales), the visual analog scale (VAS) (low back pain, knee pain, and fatigue), the State-Trait Anxiety Inventory and the Center for Epidemiologic Studies Depression Scale (anxiety and depression), and CH50, IgG, and hsCRP as immunological indices were acquired for 41 FM patients. Correlation analysis was done of the clinical symptom and immunological indices. Results: 1) The FM group had significantly higher CH50 and lower IgG and IgM than the HC group after adjusting for body mass index (BMI). 2) Correlation analysis of immunological indices and clinical symptoms showed a positive, partial correlation between CH50 and fatigue and trait anxiety after adjusting for sex, age, and BMI. Conclusions: FM patients had higher CH50 and lower immunoglobulin levels than HCs. CH50 was also associated with the fatigue and trait anxiety of FM patients. Further studies are needed to determine whether changes in these immunological indices can be used as biomarkers and/or therapeutic targets for FM. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease and irritable bowel syndrome may both cause abdominal pain and diarrhea. Irritable bowel syndrome not only is an important differential diagnosis for Crohn's disease but also occurs in one out of three patients with Crohn's disease in remission in parallel. If not adequately diagnosed and treated, additional functional symptoms such as fatigue and/or muscle pain may develop, indicating a more severe course. Case presentation: A 64-year-old Caucasian male with long-standing, widely inactive Crohn's disease presented with persistent diarrhea, bloating, abdominal pain, general fatigue, unexplained hip pain, and frequent shivering with cold extremities, which had worsened following a gastrointestinal infection and psychological stress. A plausible explanation of his symptoms, based on an understanding of mind–body interactions, the autonomic nervous system, and temperature regulation, combined with symptom relief, was associated with rapid and sustainable improvement. After 2.5 years of follow-up, the patient is almost symptom-free. Conclusions: This case report exemplifies the interrelation between organic (Crohn's disease) and functional diseases (irritable bowel syndrome, chronic fatigue syndrome, and somatoform pain). It further demonstrates that these connections may be overlooked in daily practice and that providing a plausible explanation in combination with symptom relief may be important for patients with functional syndromes. [ABSTRACT FROM AUTHOR]