Personalized Management of Fatigue in Individuals With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Using a Smart Digital mHealth Solution: Protocol for a Participatory Design Approach.

BACKGROUND: Fatigue is the most common symptom in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, impacting patients' quality of life; however, there is currently a lack of evidence-based context-aware tools for fatigue self-management in these populations. OBJECTIVE: This study aimed to (1) address fatigue in ME/CFS and long COVID through the development of digital mobile health solutions for self-management, (2) predict perceived fatigue severity using real-time data, and (3) assess the feasibility and potential benefits of personalized digital mobile health solutions. METHODS: The MyFatigue project adopts a patient-centered approach within the participatory health informatics domain. Patient representatives will be actively involved in decision-making processes. This study combines inductive and deductive research approaches, using qualitative studies to generate new knowledge and quantitative methods to test hypotheses regarding the relationship between factors like physical activity, sleep behaviors, and perceived fatigue in ME/CFS and long COVID. Co-design methods will be used to develop a personalized digital solution for fatigue self-management based on the generated knowledge. Finally, a pilot study will evaluate the feasibility, acceptance, and potential benefits of the digital health solution. RESULTS: The MyFatigue project opened to enrollment in November 2023. Initial results are expected to be published by the end of 2024. CONCLUSIONS: This study protocol holds the potential to expand understanding, create personalized self-management approaches, engage stakeholders, and ultimately improve the well-being of individuals with ME/CFS and long COVID. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50157.

Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study.

BACKGROUND: Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers and illness severity in these conditions. METHODS: This single-site, prospective, cross-sectional, pilot cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers of endothelial function and systemic inflammation status. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched sedentary healthy controls were included. All study participants underwent non-invasive cardiovascular hemodynamic challenge testing (10 min NASA lean test) for assessment of orthostatic intolerance. Regression analysis was used to examine associations between outcome measures and circulating biomarkers in the study participants. Classification across groups was based on principal component and discriminant analyses. RESULTS: Four ME/CFS patients (13%), 1 with long COVID (4%), and 1 healthy control (3%) presented postural orthostatic tachycardia syndrome (POTS) using the 10-min NASA lean test. Compared with matched healthy controls, ME/CFS and long COVID subjects showed higher levels of ET-1 (p < 0.05) and VCAM-1 (p < 0.001), and lower levels of nitrites (NOx assessed as NO2- + NO3-) (p < 0.01). ME/CFS patients also showed higher levels of serpin E1 (PAI-1) and E-selectin than did both long COVID and matched control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and matched sedentary healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did matched healthy controls (p < 0.01 in both comparisons). Compared with controls, ME/CFS patients had higher levels of IL-1ß (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.01), IL-10 (p < 0.001), IP-10 (p < 0.05), and leptin (p < 0.001). Principal component analysis supported differentiation between groups based on self-reported outcome measures and biomarkers of endothelial function and inflammatory status in the study population. CONCLUSIONS: Our findings revealed that combining biomarkers of endothelial dysfunction and inflammation with outcome measures differentiate ME/CFS and Long COVID using robust discriminant analysis of principal components. Further research is needed to provide a more comprehensive characterization of these underlying pathomechanisms, which could be promising targets for therapeutic and preventive strategies in these conditions.

Yeast Beta-Glucan Supplementation with Multivitamins Attenuates Cognitive Impairments in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

This research aimed to examine the potential alleviative effects of beta-glucan administration on fatigue, unrefreshing sleep, anxiety/depression symptoms and health-related quality of life in ME/CFS. A 36-week unicenter, randomized, double-blind, placebo-controlled trial was conducted in 65 ME/CFS patients, who were randomly allocated to one of two arms to receive four capsules each one of 250 mg beta-glucan, 3.75 µg vitamin D3, 1.05 mg vitamin B6, and 7.5 mg zinc (n = 35), or matching placebo including only microcrystalline cellulose as an excipient (n = 30) once daily. The findings showed that the beta-glucan supplementation significantly improved cognitive fatigue (assessed with FIS-40 scores) after the 36-week treatment compared to the baseline (p = 0.0338). Taken together, this study presents the novel finding that yeast-derived beta-glucan may alleviate cognitive fatigue symptoms in ME/CFS. Thus, it offers valuable scientific insights into the potential use of yeast beta-glucan as a nutritional supplement and/or functional food to prevent or reduce cognitive dysfunction in patients with ME/CFS. Further interventions are warranted to validate these findings and also to delve deeper into the possible immunometabolic pathomechanisms of beta-glucans in ME/CFS.

Hierarchical Cluster Analysis Based on Clinical and Neuropsychological Symptoms Reveals Distinct Subgroups in Fibromyalgia: A Population-Based Cohort Study.

Fibromyalgia (FM) is a condition characterized by musculoskeletal pain and multiple comorbidities. Our study aimed to identify four clusters of FM patients according to their core clinical symptoms and neuropsychological comorbidities to identify possible therapeutic targets in the condition. We performed a population-based cohort study on 251 adult FM patients referred to primary care according to the 2010 ACR case criteria. Patients were aggregated in clusters by a K-medians hierarchical cluster analysis based on physical and emotional symptoms and neuropsychological variables. Four different clusters were identified in the FM population. Global cluster analysis reported a four-cluster profile (cluster 1: pain, fatigue, poorer sleep quality, stiffness, anxiety/depression and disability at work; cluster 2: injustice, catastrophizing, positive affect and negative affect; cluster 3: mindfulness and acceptance; and cluster 4: surrender). The second analysis on clinical symptoms revealed three distinct subgroups (cluster 1: fatigue, poorer sleep quality, stiffness and difficulties at work; cluster 2: pain; and cluster 3: anxiety and depression). The third analysis of neuropsychological variables provided two opposed subgroups (cluster 1: those with high scores in surrender, injustice, catastrophizing and negative affect, and cluster 2: those with high scores in acceptance, positive affect and mindfulness). These empirical results support models that assume an interaction between neurobiological, psychological and social factors beyond the classical biomedical model. A detailed assessment of such risk and protective factors is critical to differentiate FM subtypes, allowing for further identification of their specific needs and designing tailored personalized therapeutic interventions.

Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery.

Background: There is growing evidence of the significance of gastrointestinal complaints in the impairment of the intestinal mucosal barrier function and inflammation in fibromyalgia (FM) and in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, data on intestinal permeability and gut barrier dysfunction in FM and ME/CFS are still limited with conflicting results. This study aimed to assess circulating biomarkers potentially related to intestinal barrier dysfunction and bacterial translocation and their association with self-reported symptoms in these conditions. Methods: A pilot multicenter, cross-sectional cohort study with consecutive enrolment of 22 patients with FM, 30 with ME/CFS and 26 matched healthy controls. Plasma levels of anti-beta-lactoglobulin antibodies (IgG anti-ß-LGB), zonulin-1 (ZO-1), lipopolysaccharides (LPS), soluble CD14 (sCD14) and interleukin-1-beta (IL-1ß) were assayed using ELISA. Demographic and clinical characteristics of the participants were recorded using validated self-reported outcome measures. The diagnostic accuracy of each biomarker was assessed using the receiver operating characteristic (ROC) curve analysis. Results: FM patients had significantly higher levels of anti-ß-LGB, ZO-1, LPS, and sCD14 than healthy controls (all P < 0.0001). In ME/CFS patients, levels of anti-ß-LGB, ZO-1, LPS, and sCD14 were significantly higher than controls, but lower than in FM (all P < 0.01), while there was no significant difference in IL-1ß level. In the FM and ME/CFS cohorts, both anti-ß-LGB and ZO-1 correlated significantly with LPS and sCD14 (P < 0.001 for both). In the FM group, both anti-ß-LGB and ZO-1 were correlated significantly with physical and mental health components on the SF-36 scale (P < 0.05); whereas IL-1ß negatively correlated with the COMPASS-31 score (P < 0.05). In the ME/CFS cohort, ZO-1 was positively correlated with the COMPASS-31 score (P < 0.05). The ROC curve analysis indicated a strong ability of anti-ß-LGB, ZO-1, LPS and sCD14 to predictively distinguish between FM and ME/CFS from healthy controls (P < 0.0001). Conclusion: Biomarkers of intestinal barrier function and inflammation were associated with autonomic dysfunction assessed by COMPASS-31 scores in FM and ME/CFS respectively. Anti-ß-LGB antibodies, ZO-1, LPS, and sCD14 may be putative predictors of intestinal barrier dysfunction in these cohorts. Further studies are needed to assess whether these findings are causal and can therefore be applied in clinical practice.

The Conners Continuous Performance Test CPT3™: Is it a reliable marker to predict neurocognitive dysfunction in Myalgic encephalomyelitis/chronic fatigue syndrome?

Introduction: The main objective is to delimit the cognitive dysfunction associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in adult patients by applying the Continuous Performance Test (CPT3™). Additionally, provide empirical evidence on the usefulness of this computerized neuropsychological test to assess ME/CFS. Method: The final sample (n = 225; 158 Patients/67 Healthy controls) were recruited in a Central Sensitization Syndromes (CSS) specialized unit in a tertiary hospital. All participants were administered this neuropsychological test. Results: There were significant differences between ME/CFS and healthy controls in all the main measures of CPT3™. Mainly, patients had a worse indicator of inattentiveness, sustained attention, vigilance, impulsivity, slow reaction time, and more atypical T-scores, which is associated with a likelihood of having a disorder characterized by attention deficits, such as Attention Deficit Hyperactivity Disorder (ADHD). In addition, relevant correlations were obtained between the CPT3™ variables in the patient's group. The most discriminative indicators of ME/CFS patients were Variability and Hit Reaction Time, both measures of response speed. Conclusion: The CPT3™ is a helpful tool to discriminate neurocognitive impairments from attention and response speed in ME/CFS patients, and it could be used as a marker of ME/CFS severity for diagnosing or monitoring this disease.

Skin Temperature Circadian Rhythms and Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Role of Endothelin-1 in the Vascular Tone Dysregulation.

There is accumulating evidence of autonomic dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, little is known about its association with circadian rhythms and endothelial dysfunction. This study aimed to explore the autonomic responses through an orthostatic test and analysis of the peripheral skin temperature variations and vascular endothelium state in ME/CFS patients. Sixty-seven adult female ME/CFS patients and 48 healthy controls were enrolled. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Postural changes in blood pressure, heart rate, and wrist temperature were recorded during the orthostatic test. Actigraphy during one week was used to determine the 24-h profile of peripheral temperature and activity. Circulating endothelial biomarkers were measured as indicators of endothelial functioning. Results showed that ME/CFS patients presented higher blood pressure and heart rate values than healthy controls in the supine and standing position (p < 0.05 for both), and also a higher amplitude of the activity rhythm (p < 0.01). Circulating levels of endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in ME/CFS (p < 0.05). In ME/CFS, ET-1 levels were associated with the stability of the temperature rhythm (p < 0.01), and also with the self-reported questionnaires (p < 0.001). This suggests that ME/CFS patients exhibited modifications in circadian rhythm and hemodynamic measures, which are associated with endothelial biomarkers (ET-1 and VCAM-1). Future investigation in this area is needed to assess dysautonomia and vascular tone abnormalities, which may provide potential therapeutic targets for ME/CFS.

Does Coenzyme Q10 Plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neuroinflammatory, multifaceted chronic disorder of unknown cause. Accumulating data indicate a link between a redox imbalance, mitochondrial dysfunction, and inflammation status in ME/CFS. Coenzyme Q10 (CoQ10) and selenium as effective antioxidant and anti-inflammatory agents have shown potential clinical implications in chronic diseases; however, their therapeutic benefits in ME/CFS remain elusive. This open-label exploratory study aimed to evaluate the effectiveness of combined CoQ10 plus selenium supplementation on clinical features and circulating biomarkers in ME/CFS. Twenty-seven ME/CFS patients received an oral combination of 400 mg of CoQ10 and 200 µg of selenium daily for 8 weeks. The primary endpoint was patient-reported changes in outcome measures from baseline to 8 weeks' postintervention. Secondary endpoint included changes in circulating biomarkers from baseline to each participant. After an 8-week intervention, a significant improvement was found for overall fatigue severity (p = 0.021) and global quality of life (p = 0.002), while there was no significant effect on the sleep disturbances (p = 0.480) among participants. After 8 week's intervention, there was significantly increased total antioxidant capacity, and there were reduced lipoperoxide levels from the participants (p < 0.0001 for both). Circulating cytokine levels decreased significantly (p < 0.01 for all), but with no significant changes in the C-reactive protein, FGF21, and NT-proBNP biomarkers after supplementation. Based on these findings, we hypothesized that long-term supplementation of combined CoQ10 and selenium may indicate a potentially beneficial synergistic effect in ME/CFS. Antioxid. Redox Signal. 36, 729-739.

Identifying mindfulness and acceptance as mediators between negative affect, functional disability and emotional distress in patients with fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a prevalent disabling condition characterised by chronic widespread pain. It is considered a complex illness in which the prognosis is conditioned by affective and cognitive mediators still largely unknown in FM. To investigate the correlation between psychological variables (acceptance, negative affect, and mindfulness) and functional disability or physical impact, anxiety/depression symptoms and emotional distress, and also to evaluate the mediating role of acceptance and mindfulness between negative affect, physical impact, anxiety/depression and emotional distress in individuals with FM. METHODS: Two hundred and fifty-one patients with FM who met the 2010 ACR criteria were included and filled out validated self-reported screening measures. The study explored Pearson's correlation coefficients and multiple mediation using a Preacher and Hayes's computational software tool, including the indirect effect associated with the two mediators (mindfulness and acceptance). RESULTS: Functional disability or physical impact, anxiety/depression symptoms and emotional distress correlated positively with negative affect (r= 0.580) and negatively with acceptance and mindfulness (r= -0.579 and r= -0.471; all p-values <0.001), respectively. The mediation analyses showed that acceptance and mindfulness mediated the relationship between negative affect and dependent variables such as physical impact, anxiety/depression symptoms and distress. CONCLUSIONS: The findings highlight that mindfulness and acceptance have a significant indirect effect on physical impact, anxiety/depression and emotional distress when controlling for negative affect as an independent variable in the FM patients. Future investigation should replicate and extend these outcomes in other study populations to determine the mediating role of mindfulness and acceptance in FM.

Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping.

BACKGROUND: Routine blood analytics are systematically used in the clinic to diagnose disease or confirm individuals' healthy status. For myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disease relying exclusively on clinical symptoms for its diagnosis, blood analytics only serve to rule out underlying conditions leading to exerting fatigue. However, studies evaluating complete and large blood datasets by combinatorial approaches to evidence ME/CFS condition or detect/identify case subgroups are still scarce. METHODS: This study used unbiased hierarchical cluster analysis of a large cohort of 250 carefully phenotyped female ME/CFS cases toward exploring this possibility. RESULTS: The results show three symptom-based clusters, classified as severe, moderate, and mild, presenting significant differences (p < 0.05) in five blood parameters. Unexpectedly the study also revealed high levels of circulating complement factor C1q in 107/250 (43%) of the participants, placing C1q as a key molecule to identify an ME/CFS subtype/subgroup with more apparent pain symptoms. CONCLUSIONS: The results obtained have important implications for the research of ME/CFS etiology and, most likely, for the implementation of future diagnosis methods and treatments of ME/CFS in the clinic.

Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating neuroimmune disease, probably of post-viral multifactorial etiology. Unfortunately, no accurate diagnostic or laboratory tests have been established, nor are any universally effective approved drugs currently available for its treatment. This study aimed to examine whether oral coenzyme Q10 and NADH (reduced form of nicotinamide adenine dinucleotide) co-supplementation could improve perceived fatigue, unrefreshing sleep, and health-related quality of life in ME/CFS patients. A 12-week prospective, randomized, double-blind, placebo-controlled trial was conducted in 207 patients with ME/CFS, who were randomly allocated to one of two groups to receive either 200 mg of CoQ10 and 20 mg of NADH (n = 104) or matching placebo (n = 103) once daily. Endpoints were simultaneously evaluated at baseline, and then reassessed at 4- and 8-week treatment visits and four weeks after treatment cessation, using validated patient-reported outcome measures. A significant reduction in cognitive fatigue perception and overall FIS-40 score (p < 0.001 and p = 0.022, respectively) and an improvement in HRQoL (health-related quality of life (SF-36)) (p < 0.05) from baseline were observed within the experimental group over time. Statistically significant differences were also shown for sleep duration at 4 weeks and habitual sleep efficiency at 8 weeks in follow-up visits from baseline within the experimental group (p = 0.018 and p = 0.038, respectively). Overall, these findings support the use of CoQ10 plus NADH supplementation as a potentially safe therapeutic option for reducing perceived cognitive fatigue and improving the health-related quality of life in ME/CFS patients. Future interventions are needed to corroborate these clinical benefits and also explore the underlying pathomechanisms of CoQ10 and NADH administration in ME/CFS.

Effect of Melatonin Plus Zinc Supplementation on Fatigue Perception in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating condition, probably of multifactorial etiology. No effective approved drugs are currently available for its treatment. Several studies have proposed symptomatic treatment with melatonin and zinc supplementation in chronic illnesses; however, little is known about the synergistic effect of this treatment on fatigue-related symptoms in ME/CFS. The primary endpoint of the study was to assess the effect of oral melatonin plus zinc supplementation on fatigue in ME/CFS. Secondary measures included participants' sleep disturbances, anxiety/depression and health-related quality of life. A proof-of-concept, 16-week, randomized, placebo-controlled, double-blind trial was conducted in 50 ME/CFS patients assigned to receive either oral melatonin (1 mg) plus zinc (10 mg) supplementation (n = 24) or matching placebo (n = 26) once daily. Endpoint outcomes were evaluated at baseline, and then reassessed at 8 and 16 weeks of treatment and 4 weeks after treatment cessation, using self-reported outcome measures. The most relevant results were the significant reduction in the perception of physical fatigue in the Mel-Zinc group at the final treatment follow-up versus placebo (p < 0.05), and the significant improvement in the physical component summary at all follow-up visits in the experimental group. Urinary 6-sulfatoxymelatonin levels were significantly elevated though the treatment in experimental group vs. placebo (p < 0.0001); however, no significantly differences were observed for zinc concentration among participants. Our findings suggest that oral melatonin plus zinc supplementation for 16 weeks is safe and potentially effective in reducing fatigue and improving the quality of life in ME/CFS. This clinical study was registered on ClinicalTrials.gov (NCT03000777).

Are Circulating Fibroblast Growth Factor 21 and N-Terminal Prohormone of Brain Natriuretic Peptide Promising Novel Biomarkers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, disabling, and complex multisystem illness of unknown etiology. The protein fibroblast growth factor 21 (FGF21) regulates glucose homeostasis and lipid metabolism, and the protein N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is strongly associated with an elevated cardiovascular risk; however, little is known about their role in ME/CFS patients. To address this gap, we explored the association between FGF21 and NT-proBNP and oxidative stress and inflammatory markers in ME/CFS. Twenty-one ME/CFS patients and 20 matched healthy controls were included in the study. Participants filled out validated self-reported questionnaires on their current health status covering demographic and clinical characteristics. Plasma showed significantly decreased total antioxidant capacity and increased lipoperoxide levels (p = 0.009 and p = 0.021, respectively) in ME/CFS. These ME/CFS patients also had significantly increased levels of inflammatory cytokines (interleukin [IL]-1ß, IL-6, IL-10, TNF-α, and C-reactive protein) (p < 0.05 for all) but not for IL-8 (p = 0.833), indicating low-grade systemic inflammation status. Circulating FGF21 and NT-proBNP levels were significantly higher (p < 0.0001 and p = 0.005, respectively) in ME/CFS patients than in healthy controls. Significantly positive correlations were found between NT-proBNP levels and IL-1ß and IL-6 (p = 0.04 and p = 0.01) in ME/CFS patients but not between FGF21 and these cytokines. In contrast, no significant correlations were found for either FGF21 or NT-proBNP in controls. These findings lead to the hypothesis that elevated FGF21 and NT-proBNP levels and the association between NT-proBNP and inflammation may be promising novel diagnostic and therapeutic targets in ME/CFS. Antioxid. Redox Signal. 34, 1420-1427.

Myalgic encephalomyelitis/chronic fatigue Syndrome (ME/CFS): Investigating care practices pointed out to disparities in diagnosis and treatment across European Union.

ME/CFS is a chronic, complex, multisystem disease that often limits the health and functioning of the affected patients. Diagnosing patients with ME/CFS is a challenge, and many different case definitions exist and are used in clinical practice and research. Even after diagnosis, medical treatment is very challenging. Symptom relief and coping may affect how patients live with their disease and their quality of life. There is no consensus on which diagnostic criteria should be used and which treatment strategies can be recommended for patients. The purpose of the current project was to map the landscape of the Euromene countries in respect of national guidelines and recommendations for case definition, diagnosis and clinical approaches for ME/CFS patients. A 23 items questionnaire was sent out by email to the members of Euromene. The form contained questions on existing guidelines for case definitions, treatment/management of the disease, tests and questionnaires applied, and the prioritization of information for data sampling in research. We obtained information from 17 countries. Five countries reported having national guidelines for diagnosis, and five countries reported having guidelines for clinical approaches. For diagnostic purposes, the Fukuda criteria were most often recommended, and also the Canadian Consensus criteria, the International Consensus Criteria and the Oxford criteria were used. A mix of diagnostic criteria was applied within those countries having no guidelines. Many different questionnaires and tests were used for symptom registration and diagnostic investigation. For symptom relief, pain and anti-depressive medication were most often recommended. Cognitive Behavioral Therapy and Graded Exercise treatment were often recommended as disease management and rehabilitative/palliative strategies. The lack of consistency in recommendations across European countries urges the development of regulations, guidance and standards. The results of this study will contribute to the harmonization of diagnostic criteria and treatment for ME/CFS in Europe.

Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia?

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are complex and serious illnesses that affect approximately 2.5% and 5% of the general population worldwide, respectively. The etiology is unknown; however, recent studies suggest that mitochondrial dysfunction has been involved in the pathophysiology of both conditions. We have investigated the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS and FM. We studied 23 CFS patients, 20 FM patients, and 15 healthy controls. Peripheral blood mononuclear cell showed decreased levels of Coenzyme Q10 from CFS patients (p<0.001 compared with controls) and from FM subjects (p<0.001 compared with controls) and ATP levels for CFS patients (p<0.001 compared with controls) and for FM subjects (p<0.001 compared with controls). On the contrary, CFS/FM patients had significantly increased levels of lipid peroxidation, respectively (p<0.001 for both CFS and FM patients with regard to controls) that were indicative of oxidative stress-induced damage. Mitochondrial citrate synthase activity was significantly lower in FM patients (p<0.001) and, however, in CFS, it resulted in similar levels than controls. Mitochondrial DNA content (mtDNA/gDNA ratio) was normal in CFS and reduced in FM patients versus healthy controls, respectively (p<0.001). Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting were significantly lower in FM patients (p<0.001) and were normal in CFS subjects compared with healthy controls. These data lead to the hypothesis that mitochondrial dysfunction-dependent events could be a marker of differentiation between CFS and FM, indicating the mitochondria as a new potential therapeutic target for these conditions.

The association of apathy with central fatigue perception in patients with Parkinson's disease.

This study was designed to evaluate the association of different apathy conceptual domains with central fatigue perception in Parkinson's disease (PD), taking into consideration other nonmotor symptoms. To this end, 90 consecutive PD patients (66.7% men, mean age 61.44 ± 13.2 years) underwent a comprehensive neurological and psychiatric examination, including the Structured Clinical Interview for DSM-IV, Parkinson Fatigue Scale, Lille Apathy Rating Scale, Hamilton Depression Scale, and State-Trait Anxiety Inventory. A linear regression model was applied to analyze the relationship between apathy and its different conceptual domains with fatigue severity. Thirty-seven (41.1%) patients presented fatigue. Its presence was associated with higher apathy total scores and with 2 of the 4 apathy conceptual domains (less intellectual curiosity and action initiation) with no associations in the emotion and self-awareness apathy domains. Patients with fatigue scored higher in depression (p < .001), anxiety trait (p < .001), and anxiety state (p = .006). Regression analysis identified that Lille Apathy Rating Scale total score (p = .008), intellectual curiosity and action initiation apathy subscores (p = .001 and p = .003) were associated with fatigue severity in patients with right predominant motor symptoms. Sex, age, disease duration, clinical stage, motor complications, prior psychiatric disorders, and treatment were not significantly associated with presence of fatigue. The findings suggest that some apathy-related domains are more frequent in fatigued PD and may be related with fatigue severity.

Hemoperitoneo secundario a seudoaneurisma arterial intrahepático como complicación de una toracocentesis / Secondary hemoperitoneum to intrahepatic pseudoaneurysm as a complication of thoracocentesis

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