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Fitzgibbon-Collins LK, Pereira TJ, Edgell H. Women, orthostatic tolerance, and POTS: a narrative review. Auton Neurosci 2025; 259:103284. [PMID: 40311188 DOI: 10.1016/j.autneu.2025.103284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 02/28/2025] [Accepted: 04/23/2025] [Indexed: 05/03/2025]
Abstract
Young women experience orthostatic intolerance to a greater degree than men. Numerous physiological pathways could be responsible for this intolerance in both healthy and pathophysiological conditions. This review discusses sex differences in hemodynamics, ventilation, autonomic control, and cerebral blood flow. Further, we discuss these phenomena and their potential exacerbations in postural orthostatic tachycardiac syndrome (POTS). After normalization for body size women have lower stroke volume and blood volume, and while upright women have reduced ventilation, reduced venous return likely from attenuated respiratory pump and skeletal muscle pump activity, augmented parasympathetic withdrawal, attenuated neurovascular transduction of sympathetic outflow, and increased vasodilatory capacity compared to age-matched men. Women have greater middle cerebral artery blood velocity, potentially impaired cerebral dynamic autoregulation (depending on the timing), yet similar cerebrovascular reactivity to carbon dioxide exists between the sexes. Thus, we suggest that the greater incidence of orthostatic intolerance in women is primarily due to hemodynamic control and autonomic function; however, the enhanced parasympathetic withdrawal while upright could theoretically influence cerebral vasodilatory capacity and is proposed as a possibility in need of further investigation. POTS physiology is described briefly due to its increasing prevalence via post-COVID infections. We summarize some potential physiological changes in POTS including hemodynamic and ventilatory control, and we highlight that cerebral blood flow control is impaired and likely plays a role in the symptomology of POTS.
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Affiliation(s)
| | - T J Pereira
- School of Kinesiology and Health Science, York University, Toronto, ON M3J 1P3, Canada
| | - H Edgell
- School of Kinesiology and Health Science, York University, Toronto, ON M3J 1P3, Canada.
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Jensen MP, Robles S, Nash MG, May S, Ehde DM, Day MA, Gottlieb O, Sugarman LI, Alschuler KN. Hypnosis and mindfulness audio recordings for reducing fatigue in individuals with multiple sclerosis: A randomized controlled study. Mult Scler 2025:13524585251329820. [PMID: 40243256 DOI: 10.1177/13524585251329820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2025]
Abstract
BACKGROUND Fatigue is a common problem in individuals with multiple sclerosis (MS). OBJECTIVE The objective was to evaluate the effects on fatigue of having 4 weeks of access to audio recordings of therapeutic hypnosis (HYP) and mindfulness meditation (MM) practices. METHODS A total of 333 individuals with MS and fatigue were randomly assigned to one of the three treatment conditions for 28 weeks: (1) access to therapeutic HYP audio recordings, (2) access to MM audio recordings, or (3) no access to recordings (treatment as usual or TAU). Fatigue impact (primary outcome) and other outcomes were assessed at 4, 16, and 28 weeks after random assignment. RESULTS Participants assigned to the HYP and MM conditions reported significantly greater reductions in fatigue impact, sleep disturbance, and depressive symptom severity than participants assigned to the TAU condition after 4 weeks of access to audio recordings of these interventions. These improvements were maintained for 16 and 28 weeks following initial access and did not result in any serious adverse events. CONCLUSION Given the ease with which audio recordings of HYP and MM could be provided to individuals with MS, the findings support the feasibility of a simple approach to have a significant beneficial impact on people with MS-related fatigue.
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Affiliation(s)
- Mark P Jensen
- Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA
| | - Susan Robles
- Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA
| | - Michael G Nash
- Center for Biomedical Statistics, University of Washington, Seattle, WA, USA
| | - Susanne May
- Department of Biostatistics, University of Washington, Seattle, WA, USA
| | - Dawn M Ehde
- Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA
| | - Melissa A Day
- School of Psychology, Faculty of Health and Behavioral Sciences, The University of Queensland, Brisbane, QLD, Australia
| | - Owen Gottlieb
- School of Interactive Games and Media, Golisano College of Computing and Information Sciences, Rochester Institute of Technology, Rochester, NY, USA
| | - Laurence I Sugarman
- College of Health Sciences and Technology, Rochester Institute of Technology, Rochester, NY, USA
| | - Kevin N Alschuler
- Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA Department of Neurology, University of Washington, Seattle, WA, USA
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Sirotiak Z, Adamowicz JL, Thomas EBK. Depressive and anxiety symptoms in current, previous, and no history of ME/CFS: NHIS 2022 analysis. Qual Life Res 2025; 34:777-787. [PMID: 39579271 DOI: 10.1007/s11136-024-03854-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/17/2024] [Indexed: 11/25/2024]
Abstract
PURPOSE Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with anxiety and depressive symptoms. Psychological symptoms are predisposing factors for, as well as symptoms of, ME/CFS. Recovery from ME/CFS is poorly understood and heterogenous, and it is unclear how psychological symptoms may change with recovery. The aim of this study was to examine the associations of depressive and anxious symptoms among individuals with current, previous, and no history of ME/CFS. METHODS National Health Interview Survey 2022 data were analyzed to assess ME/CFS status, as well as anxiety and depression burden. Adults (unweighted N = 27,651) in the United States reported sociodemographic and health behavior characteristics, with 453 adults reporting current ME/CFS, while 119 reported previous ME/CFS. Sample weights and variance estimation variables were implemented. Multivariable linear regression models were used to analyze the associations between ME/CFS status and anxiety and depression severity after adjusting for sociodemographic and health behavior variables. RESULTS Participants were on average 48.1 years of age, and most identified as female (51.3%), white (76.6%), and not Hispanic or Latine (82.8%). Current and previous ME/CFS were associated with anxiety and depressive symptoms compared to individuals with no history of ME/CFS. Clinically significant levels of anxiety and depressive symptoms were substantial for individuals with current (37.6%; 49.0%) and previous (26.5%; 33.4%) ME/CFS compared to individuals with no history of ME/CFS (6.1%; 6.7%). CONCLUSION ME/CFS, regardless of current presence, was related to significantly greater anxiety and depressive symptom burden.
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Affiliation(s)
- Zoe Sirotiak
- Department of Kinesiology, Iowa State University, Ames, IA, USA.
- Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA.
| | - Jenna L Adamowicz
- Pain Research, Informatics, Multimorbidities, and Education (PRIME) Center, VA Connecticut Healthcare System: West Haven, West Haven, CT, USA
- Yale School of Medicine, Department of Psychiatry, New Haven, CT, USA
| | - Emily B K Thomas
- Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA
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van Campen C(LMC, Verheugt FWA, Rowe PC, Visser FC. The Cardiac Output-Cerebral Blood Flow Relationship Is Abnormal in Most Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with a Normal Heart Rate and Blood Pressure Response During a Tilt Test. Healthcare (Basel) 2024; 12:2566. [PMID: 39765993 PMCID: PMC11675211 DOI: 10.3390/healthcare12242566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION Orthostatic intolerance is highly prevalent in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is caused by an abnormal reduction in cerebral blood flow (CBF). In healthy controls (HCs), the regulation of CBF is complex and cardiac output (CO) is an important determinant of CBF: a review showed that a 30% reduction in CO results in a 10% reduction in CBF. In previous and separate ME/CFS studies, we showed that CO and CBF decreased to a similar extent during tilt testing. THE AIM OF THE STUDY to test the relationship between CBF and CO, which seems to be abnormal in ME/CFS patients and is different from that in HCs. METHODS In this retrospective study we analyzed this relationship in a large group of patients. To compare the patient data with those of HCs, we focused on patients with a normal heart rate (HR) and blood pressure (BP) response to upright tilt. Also, the influence of clinical data was analyzed. A total of 534 ME/CFS patients and 49 HCs underwent tilt testing with measurements of HR, BP, CBF, CO, and end-tidal PCO2. To measure CBF, extracranial Doppler flow velocity and vessel diameters were obtained using a GE echo system. The same device was used to measure suprasternal aortic flow velocities. End-tidal PCO2 was recorded using a Nonin Lifesense device. RESULTS In 46 (9%) patients, CO and CBF changes were in the normal range for HCs, and in 488 (91%) an abnormal CO and CBF reduction was found. In patients with abnormal CO and CBF reductions, the slope of the regression line of CO versus CBF reduction was almost 1. The multiple regression analysis of the latter group showed that the CO reduction for the most part predicted the CBF reduction, with a limited role for the PETCO2 reduction. CONCLUSIONS Two different patient groups with a normal HR and BP response during the tilt were identified: those with a CO and CBF in the normal range for HCs and those with an abnormal CO and CBF reduction during the tilt (91% of patients). In the latter group of patients, an almost 1:1 relationship between the CO and CBF reduction suggests the absence of compensatory vasodilation in the cerebral vasculature. This might indicate endothelial dysfunction in most ME/CFS patients and may have clinical and therapeutic implications.
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Affiliation(s)
| | - Freek W. A. Verheugt
- Department of Cardiology, Onze Lieve Vrouwe Gasthuis (OLVG), 1091 AC Amsterdam, The Netherlands
| | - Peter C. Rowe
- Department of Paediatrics, John Hopkins University School of Medicine, Baltimore, MD 21205, USA;
| | - Frans C. Visser
- Stichting Cardio Zorg, Kraayveld 5, 1171 JE Badhoevedorp, The Netherlands;
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Li Y, Xie T, Snieder H, Hartman CA. Associations between autistic and comorbid somatic problems of gastrointestinal disorders, food allergy, pain, and fatigue in adults. AUTISM : THE INTERNATIONAL JOURNAL OF RESEARCH AND PRACTICE 2024; 28:3105-3117. [PMID: 38813776 PMCID: PMC11575103 DOI: 10.1177/13623613241254619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Abstract
LAY ABSTRACT What is already known about the topic?Autistic children frequently often have accompanying physical health problems. However, this has been much less studied in autistic men and women during adulthood.What does this article add?This is one of the first studies to investigate the associations between autistic and somatic problems in adults from the general population. Using a continuous measure of autistic symptom scores and a categorical definition of autism (referred to below as probable autism) which considered symptom severity, childhood age of onset, and functional impairment, we found that autistic problems and irritable bowel syndrome, food allergy, pain, and fatigue were associated in adults. Sex differences were present for pain and fatigue, for which the associations with autistic symptom scores were somewhat stronger in females than males. Regarding age differences, the associations with fatigue and having food allergy were more pronounced in younger adults. Conversely, older individuals had a higher risk of developing irritable bowel syndrome or experiencing pain if they met the criteria for probable autism.Implications for practice, research, or policyThere is a need for providing routine programs of screening, assessment, and treatment of autism-related somatic problems and developing evidence-based interventions for autistic individuals. These could be tailored to the needs of specific autistic populations. For example, autistic females could be given extra attention about the potential presence of pain and fatigue, younger adults about the potential presence of food allergy and fatigue, and older adults concerning the potential presence of irritable bowel syndrome and pain.
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Affiliation(s)
- Yiran Li
- Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Tian Xie
- Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Harold Snieder
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Catharina A Hartman
- Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Silva J, Iwasaki A. Sex differences in postacute infection syndromes. Sci Transl Med 2024; 16:eado2102. [PMID: 39536120 DOI: 10.1126/scitranslmed.ado2102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 10/23/2024] [Indexed: 11/16/2024]
Abstract
Postacute infection syndromes like Long Covid disproportionately affect females, differing in prevalence, symptoms, and potential causes from males. This Viewpoint highlights these sex differences, gaps in current understanding, and the critical need for sex-based research.
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Affiliation(s)
- Julio Silva
- Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
| | - Akiko Iwasaki
- Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
- Center for Infection and Immunity, Yale School of Medicine, New Haven, CT 06520, USA
- Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
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Furlanis G, Buoite Stella A, Torresin G, Michelutti M, Ajčević M, Manganotti P. Neurological long-COVID: Associations among fatigue, dysautonomia, depression, and subjective memory complaints. Clin Neurol Neurosurg 2024; 246:108522. [PMID: 39276663 DOI: 10.1016/j.clineuro.2024.108522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 08/29/2024] [Accepted: 08/30/2024] [Indexed: 09/17/2024]
Abstract
INTRODUCTION Long-COVID is a multisystem disease characterized by a varied presentation of symptoms. According to most recent research, the most common symptom of long-COVID is fatigue, which up to this date lacks a universally accepted definition. This study aimed to investigate neurocognitive and physical manifestations of neurological long-COVID, particularly fatigue and its relation with autonomic disfunction, cognitive impairment (known as, brain fog), and depressive symptoms. Furthermore, the study provided insights into predictors of fatigue in long-COVID. METHODS The included patients (n=141) were referred to the neuro-long-COVID ambulatory service of Trieste from 30 September 2021-02 March 2022. Patients were given self-reporting questionnaires to screen for fatigue, autonomic dysfunction, cognitive impairment and depressive symptoms. The questionnaires adopted for these conditions to be assessed were Fatigue Severity Scale (FSS), COMPASS-31, Prospective-Retrospective Memory Questionnaire (PRMQ), and Beck Depression Inventory (BDI). Participants were divided into two groups, fatigued and non-fatigued patients, based on FSS scoring (scores > 4.67 indicate fatigued patients). The questionnaire scores of the two groups were then compared. RESULTS Fatigued patients had significantly higher scores in COMPASS (p<0.001, Cohen's d=1.077), BDI (p<0.001, Cohen's d=0.862), and PRMQ ( p<0.001, Cohen's d=1.159). Furthermore, the multivariate regression analysis showed that predictors of fatigue in long-COVID were symptomatological burden in acute infection (OR=1.38, 95 % CI 1.020-1.887, p=0.037) and in long-COVID (OR=1.78, 95 % CI 1.133-2.2824, p=0.013), COMPASS-31>16 (OR=3.44, 95 % CI 1240-9.560, p=0.018) and BDI>15 (OR=5.1, 95 % CI 1.715-15.164, p=0.003). CONCLUSION This study showed associations between fatigue, dysautonomia and depression, as well as with symptom burden in acute and long-COVID.
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Affiliation(s)
- Giovanni Furlanis
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, Trieste 447-34149, Italy
| | - Alex Buoite Stella
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, Trieste 447-34149, Italy
| | - Giovanna Torresin
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, Trieste 447-34149, Italy
| | - Marco Michelutti
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, Trieste 447-34149, Italy.
| | - Miloš Ajčević
- Department of Engineering and Architecture, University of Trieste, Via A. Valerio, Trieste 10 - 34127, Italy
| | - Paolo Manganotti
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, Trieste 447-34149, Italy
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Fall EA, Chen Y, Lin JMS, Issa A, Brimmer DJ, Bateman L, Lapp CW, Podell RN, Natelson BH, Kogelnik AM, Klimas NG, Peterson DL, Unger ER. Chronic Overlapping Pain Conditions in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a sample from the Multi-site Clinical Assessment of ME/CFS (MCAM) study. BMC Neurol 2024; 24:399. [PMID: 39425035 PMCID: PMC11488184 DOI: 10.1186/s12883-024-03872-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 09/19/2024] [Indexed: 10/21/2024] Open
Abstract
BACKGROUND Chronic overlapping pain conditions (COPCs), pain-related conditions that frequently occur together, may occur in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and could impact illness severity. This study aimed to identify comorbid COPCs in patients with ME/CFS and evaluate their impact on illness severity. METHODS We used data from 923 participants in the Multi-Site Clinical Assessment of ME/CFS study, conducted in seven U.S. specialty clinics between 2012 and 2020, who completed the baseline assessment (595 ME/CFS and 328 healthy controls (HC)). COPCs included chronic low back pain (cLBP), chronic migraine/headache (cMHA), fibromyalgia (FM), interstitial cystitis/irritable bladder (IC/IB), irritable bowel syndrome (IBS), temporomandibular disorder (TMD). Illness severity was assessed through questionnaires measuring symptoms and functioning. Multivariate analysis of variance and analysis of covariance models were used for analyses. Log-binomial regression analyses were used to compute prevalence of COPCs and prevalence ratios (PR) between groups with 95% confidence intervals. Both unadjusted and adjusted results with age and sex are presented. RESULTS 76% of participants with ME/CFS had at least one COPCs compared to 17.4% of HC. Among ME/CFS participants, cMHA was most prevalent (48.1%), followed by FM (45.0%), cLBP (33.1%), and IBS (31.6%). All individual COPCs, except TMD, were significantly more frequent in females than males. The unadjusted PR (ME/CFS compared to HC) was highest for FM [147.74 (95% confidence interval (CI) = 20.83-1047.75], followed by cLBP [39.45 (12.73-122.27)], and IC/IB [13.78 (1.88-101.24)]. The significance and order did not change after age and sex adjustment. The COPC comorbidities of cLBP and FM each had a significant impact on most health measures, particularly in pain attributes (Cohen's d effect size 0.8 or larger). While the impact of COPC comorbidities on non-pain attributes and quality of life measures was less pronounced than that on pain, statistically significant differences between ME/CFS participants with and without COPCs were still evident. CONCLUSIONS More than 75% of ME/CFS participants had one or more COPCs. Multiple COPCs further exacerbated illness severity, especially among females with ME/CFS. Assessment and management of COPCs may help improve the health and quality of life for patients with ME/CFS.
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Affiliation(s)
- Elizabeth A Fall
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
| | - Yang Chen
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
| | - Jin-Mann S Lin
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
| | - Anindita Issa
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Dana J Brimmer
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | | | | | | | - Benjamin H Natelson
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Nancy G Klimas
- Institute for Neuro Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
- Geriatric Research and Education Clinical Center, VA Medical Center, Miami, FL, USA
| | | | - Elizabeth R Unger
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
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Marcilla-Toribio I, Moratalla-Cebrián ML, Notario-Pacheco B, Escudero-Lopez MA, Morales-Cuenca N, Martinez-Andres M. Gender differences in symptomatology, socio-demographic information and quality of life in Spanish population with long COVID condition: a cross-sectional study. Front Public Health 2024; 12:1355973. [PMID: 38577278 PMCID: PMC10991816 DOI: 10.3389/fpubh.2024.1355973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 02/26/2024] [Indexed: 04/06/2024] Open
Abstract
Introduction Long COVID patients experience a decrease in their quality of life due to the symptomatology produced by the disease. It is also important to understand how long COVID affects both men and women. The objective of this study is to examine the impact of long COVID symptomatology on the quality of life of Spanish adults from a gender perspective. Methods An observational and cross-sectional study was carried out. Participants were able to complete an online questionnaire using an online platform. A sample of 206 people participated in the study. Results The 80.6% of the sample were women with a mean age of 46.51 (±8.28) and the 19.4% were men with a mean age of 48.03 (±9.50). The medium score in the PAC19-QoL test was 141.47 (±24.96) and segmented by gender, 141.65 (±23.95) for women and 140.82 (±28.66) for men. The most common symptoms in women were muscle and joint pain (94.6%), fatigue (94.0%), discomfort (92.2%), difficulty concentrating (91.0%), and memory loss (88.6%). For men the symptoms included muscle and joint pain (97.5%) and fatigue (97.5%) both occupying first position, discomfort (92.0%), difficulty concentrating (90.0%), mood disturbances (90.0%), and memory loss (87.5%). The chi-square test showed statistical significance (p < 0.005) for socio-demographic information, quality of life scores, and long COVID symptoms by intensities. Conclusion This study shows that there are gender differences in the way that long COVID is experienced.
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Affiliation(s)
- Irene Marcilla-Toribio
- Universidad de Castilla-La Mancha, Centro de Estudios Sociosanitarios, Cuenca, Spain
- Universidad de Castilla-La Mancha, Grupo de Investigación Health, Gender, Social Determinants, Cuenca, Spain
- Universidad de Castilla- La Mancha, Facultad de Enfermería de Albacete, Albacete, Spain
| | - Maria Leopolda Moratalla-Cebrián
- Universidad de Castilla-La Mancha, Grupo de Investigación Health, Gender, Social Determinants, Cuenca, Spain
- Universidad de Castilla- La Mancha, Facultad de Enfermería de Albacete, Albacete, Spain
| | - Blanca Notario-Pacheco
- Universidad de Castilla-La Mancha, Centro de Estudios Sociosanitarios, Cuenca, Spain
- Universidad de Castilla-La Mancha, Grupo de Investigación Health, Gender, Social Determinants, Cuenca, Spain
- Universidad de Castilla-La Mancha, Facultad de Enfermería de Cuenca, Cuenca, Spain
| | - Miguel Angel Escudero-Lopez
- Universidad de Castilla-La Mancha, Grupo de Investigación Health, Gender, Social Determinants, Cuenca, Spain
| | - Nagore Morales-Cuenca
- Universidad de Castilla-La Mancha, Grupo de Investigación Health, Gender, Social Determinants, Cuenca, Spain
- Universidad de Castilla-La Mancha, Facultad de Enfermería de Cuenca, Cuenca, Spain
| | - Maria Martinez-Andres
- Universidad de Castilla-La Mancha, Centro de Estudios Sociosanitarios, Cuenca, Spain
- Universidad de Castilla-La Mancha, Grupo de Investigación Health, Gender, Social Determinants, Cuenca, Spain
- Universidad de Castilla- La Mancha, Facultad de Enfermería de Albacete, Albacete, Spain
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Kitselman A K, Bédard-Matteau J, Rousseau S, Tabrizchi R, Daneshtalab N. Sex differences in vascular endothelial function related to acute and long COVID-19. Vascul Pharmacol 2024; 154:107250. [PMID: 38043758 DOI: 10.1016/j.vph.2023.107250] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 11/23/2023] [Accepted: 11/27/2023] [Indexed: 12/05/2023]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been at the forefront of health sciences research since its emergence in China in 2019 that quickly led to a global pandemic. As a result of this research, and the large numbers of infected patients globally, there were rapid enhancements made in our understanding of Coronavirus disease 2019 (COVID-19) pathology, including its role in the development of uncontrolled immune responses and its link to the development of endotheliitis and endothelial dysfunction. There were also some noted differences in the rate and severity of infection between males and females with acute COVID. Some individuals infected with SARS-CoV-2 also experience long-COVID, an important hallmark symptom of this being Myalgic Encephalomyelitis-Chronic Fatigue Syndrome (ME-CFS), also experienced differently between males and females. The purpose of this review is to discuss the impact of sex on the vasculature during acute and long COVID-19, present any link between ME-CFS and endothelial dysfunction, and provide evidence for the relationship between ME-CFS and the immune system. We also will delineate biological sex differences observed in other post viral infections and, assess if sex differences exist in how the immune system responds to viral infection causing ME-CFS.
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Affiliation(s)
- Kayla Kitselman A
- Faculty of Medicine, Division of Biomedical Sciences at Memorial University of Newfoundland and Labrador, Canada
| | - Jérôme Bédard-Matteau
- Faculty of Medicine, Department of Pharmacology and Therapeutics, McGill University, Québec, Canada; Meakins-Christie Laboratories, RI-MUHC, Block EOffice EM3.2244Lab E03.21371001 Decarie Blvd., Montreal, QC H4A 3J1, Canada
| | - Simon Rousseau
- Faculty of Medicine, Department of Pharmacology and Therapeutics, McGill University, Québec, Canada; Faculty of Medicine, Department of Experimental Medicine, McGill University, Québec, Canada; Meakins-Christie Laboratories, RI-MUHC, Block EOffice EM3.2244Lab E03.21371001 Decarie Blvd., Montreal, QC H4A 3J1, Canada
| | - Reza Tabrizchi
- Faculty of Medicine, Division of Biomedical Sciences at Memorial University of Newfoundland and Labrador, Canada
| | - Noriko Daneshtalab
- School of Pharmacy at Memorial University of Newfoundland and Labrador, Canada.
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Xie F, You Y, Gu Y, Xu J, Yao F. Effects of the Prolong Life With Nine Turn-Method Qigong on Fatigue, Insomnia, Anxiety, and Gastrointestinal Disorders in Patients With Chronic Fatigue Syndrome: Protocol for a Randomized Controlled Trial. JMIR Res Protoc 2024; 13:e53347. [PMID: 38407950 DOI: 10.2196/53347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/18/2023] [Accepted: 12/28/2023] [Indexed: 02/27/2024] Open
Abstract
BACKGROUND Chronic fatigue syndrome (CFS) is a debilitating multisystem disorder that can lead to various pathophysiological abnormalities and symptoms, including insomnia, gastrointestinal disorders, and anxiety. Due to the side effects of currently available drugs, there is a growing need for safe and effective nondrug therapies. The Prolong Life With Nine Turn (PLWNT) Qigong method is a system of mind-body exercise with restorative benefits that can alleviate the clinical symptoms of CFS and impart a significant inhibitory effect. Various studies have proven the treatment efficacy of PLWNT; however, the impact on insomnia, gastrointestinal disorders, and anxiety in patients with CFS has not yet been investigated. OBJECTIVE This study aims to evaluate the efficacy and safety of the PLWNT method in terms of its effects on fatigue, insomnia, anxiety, and gastrointestinal symptoms in patients with CFS. METHODS We will conduct a randomized, analyst-blinded, parallel-controlled trial with a 12-week intervention and 8-week follow-up. A total of 208 patients of age 20-60 years will be recruited. The patients will be randomly divided into a PLWNT Qigong exercise group (PLWNT Group) and a control group treated with cognitive behavioral therapy at a ratio of 1:1. Participants from the treatment groups will be taught by a highly qualified professor at the Shanghai University of Traditional Chinese Medicine once a week and will be supervised via web during the remaining 6 days at home, over 12 consecutive weeks. The primary outcome will be the Multidimensional Fatigue Inventory 20, while the secondary outcomes include the Pittsburgh Sleep Quality Index, Gastrointestinal Symptom Rating Scale, Hospital Anxiety and Depression Scale, functional magnetic resonance imaging, gut microbiota, and peripheral blood. RESULTS The study was approved by the ethics committee of Shanghai Municipal Hospital of Traditional Chinese Medicine in March 2022 (Ethics Approval Number 2022SHL-KY-05). Recruitment started in July 2022. The intervention is scheduled to be completed in December 2024, and data collection will be completed by the end of January 2025. Over the 3-year recruitment period, 208 participants will be recruited. Data management is still in progress; therefore, data analysis has yet to be performed. CONCLUSIONS This randomized trial will evaluate the effectiveness of the PLWNT method in relieving fatigue, insomnia, anxiety, and gastrointestinal symptoms in patients with CFS. If proven effective, it will provide a promising alternative intervention for patients with CFS. TRIAL REGISTRATION China Clinical Trials Registry ChiCTR2200061229; https://www.chictr.org.cn/showproj.html?proj=162803. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/53347.
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Affiliation(s)
- Fangfang Xie
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 200071, Shanghai, China
- Shanghai University of Traditional Chinese Medicine, 201203, 1200 Cailun Road, Pudong New District, Shanghai 201203, China, Shanghai, China
| | - Yanli You
- ChangHai Hospital, Naval Medical University, 200071, Shanghai, China
| | - Yuanjia Gu
- Shanghai University of Traditional Chinese Medicine, 201203, 1200 Cailun Road, Pudong New District, Shanghai 201203, China, Shanghai, China
| | - Jiatuo Xu
- Shanghai University of Traditional Chinese Medicine, 201203, 1200 Cailun Road, Pudong New District, Shanghai 201203, China, Shanghai, China
| | - Fei Yao
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 200071, Shanghai, China
- Shanghai University of Traditional Chinese Medicine, 201203, 1200 Cailun Road, Pudong New District, Shanghai 201203, China, Shanghai, China
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12
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Kridli N, Sturza J, Michniacki TF. Patient-Reported Outcomes and Medical Provider Satisfaction Among Adult and Pediatric Ataxia-Telangiectasia Patients. J Clin Immunol 2024; 44:51. [PMID: 38231422 DOI: 10.1007/s10875-024-01652-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 01/06/2024] [Indexed: 01/18/2024]
Abstract
PURPOSE Ataxia-telangiectasia (A-T) is a rare genetic condition with malfunctioning DNA repair processes resulting in significant clinical findings, including progressive neurologic decline, elevated malignancy risk, immunodeficiency, oculocutaneous telangiectasias, and severe pulmonary disease. Research has been limited into the quality of life of such patients and yet to be completed are studies quantitatively analyzing psychosocial, physical, and cognitive patient-reported outcomes (PROs) within the A-T population. METHODS PRO evaluations of 90 international adult and pediatric A-T patients and their caregivers were completed via secure online administration of Patient-Reported Outcomes Measurement Information System (PROMIS) short forms evaluating anger, cognition, mood, social health, fatigue, pain, anxiety, and upper extremity function. The impact of age, gender, race/ethnicity, prior malignancy diagnosis, and current supportive treatment interventions on such PROs was additionally assessed. Finally, given the importance of medical providers in the care of A-T patients and the impact of patient satisfaction on healthcare outcomes, we further analyzed, via a novel survey, how patients and caregivers perceived their primary A-T healthcare provider's A-T expertise, trustworthiness, accessibility, and level of compassion. RESULTS/CONCLUSION It was found that a diagnosis of A-T complexly impacts patient PROs, but such data offers the potential for preventative and therapeutic interventions to improve the care of such patients. While most A-T patients and their caregivers feel their primary A-T medical provider has expertise and compassion in addition to being accessible and trustworthy, a significant percentage of study subjects did not agree that their provider was an expert in A-T or overall trustworthy.
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Affiliation(s)
- Nadine Kridli
- University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Julie Sturza
- Department of Statistics, University of Michigan, Ann Arbor, MI, USA
| | - Thomas F Michniacki
- Department of Pediatrics, Pediatric Hematology/Oncology, University of Michigan, D4202 Medical Professional Building, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109-5718, USA.
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13
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Liu X, Liu S, Ren R, Wang X, Han C, Liu Z. A cross-sectional study exploring the relationship between symptoms of anxiety/depression and P50 sensory gating in adult patients diagnosed with chronic fatigue syndrome/myalgic encephalomyelitis. Front Neurosci 2024; 17:1286340. [PMID: 38249591 PMCID: PMC10796775 DOI: 10.3389/fnins.2023.1286340] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 12/07/2023] [Indexed: 01/23/2024] Open
Abstract
Introduction Chronic fatigue syndrome (CFS) is a clinical disease that affects multiple body systems. It is characterized by persistent or recurring fatigue, which may be linked to immune, neuroendocrine, and energy metabolism dysfunctions. Individuals with CFS may experience pain, sleep disorders, anxiety, and depression. This research analyzed the fundamental characteristics of anxiety/depression symptoms in patients with CFS and investigated the association between these symptoms and the P50 SG (sensory gate) ratio. Methods Two hundred and forty-nine subjects fulfilled the CDC-1994 criteria for CFS and were included in the study. The subjects successively completed the Symptom CheckList-90-Revised (SCL-90-R), Hamilton Anxiety Rating Scale-14 (HAMA-14), and Hamilton Depression Rating Scale-24 (HAMD-24). Auditory-evoked potential P50 were measured using the 128-lead-electroencephalograph. Result According to HAMA and HAMD, 17.3% (n = 43) of the patients did not exhibit anxiety/depression, with a threshold score of 7 and 7 for HAMA and HAMD. When the threshold score was 14 and 20 respectively, 43.3% (n = 108) of the patients did not exhibit anxiety/depression. The SCL-90-R results indicated that 69.5% (n = 173) of these individuals with the score arranging from 0 to 160 did not present mental problems. There was a correlation between somatization scores and P50 SG ratio in the overall sample and no anxiety or depression (NAOD) group delimited by 14 and 20, respectively, (p < 0.05). Regression analysis showed that anxiety and depression were risk factors associated with an abnormal P50 SG ratio. Discussion A significant correlation exists between the P50 SG ratio and clinical symptoms such as fatigue, anxiety, and depression. Abnormalities in brain function among patients with CFS may play a crucial role in the pathogenesis of the condition, leading to their classification as being prone to functional neurological disorders. The P50 SG ratio cannot be used as a diagnostic marker for CFS but show some significance on the mechanism, classification, treatment, and prognosis of CFS.
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Affiliation(s)
- Xinyi Liu
- Department of Neurology, Health Care Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Sitong Liu
- Department of Neurology, Health Care Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Runtao Ren
- Department of Neurology, Health Care Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xue Wang
- Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Chunyu Han
- Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhandong Liu
- Department of Neurology, Health Care Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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14
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Mantle D, Hargreaves IP, Domingo JC, Castro-Marrero J. Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview. Int J Mol Sci 2024; 25:574. [PMID: 38203745 PMCID: PMC10779395 DOI: 10.3390/ijms25010574] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/19/2023] [Accepted: 12/30/2023] [Indexed: 01/12/2024] Open
Abstract
Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.
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Affiliation(s)
- David Mantle
- Pharma Nord (UK) Ltd., Morpeth, Northumberland NE61 2DB, UK
| | - Iain Parry Hargreaves
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK;
| | - Joan Carles Domingo
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain;
| | - Jesus Castro-Marrero
- Research Unit in ME/CFS and Long COVID, Rheumatology Division, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
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15
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Khairallah GM, Makarem NN, Rahme DV, El Jaouni MA, Brome D. The effect of workplace bullying on fatigue in school teachers: the moderating roles of gender and spirituality. Libyan J Med 2023; 18:2266239. [PMID: 37851853 PMCID: PMC10586066 DOI: 10.1080/19932820.2023.2266239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 09/29/2023] [Indexed: 10/20/2023] Open
Abstract
Workplace bullying is quite prevalent and has been linked to many health complaints. The relationship between workplace bullying and fatigue was documented in previous studies. However, knowledge on how this relationship develops with the interplaying factors of spirituality and gender was not investigated before especially among schoolteachers. The aim of this study is to explore the relationship between workplace bullying and fatigue as moderated by spirituality and gender among schoolteachers in Lebanon. This is a cross-sectional study, where 215 schoolteachers aged 18 till 64 and employed for a minimum of 6 months were recruited through systematic sampling. Six private and six public schools in Beirut participated in the study. Online questionnaires using validated scales were used. Both simple and multiple ordinal logistic regression were performed for the statistical analysis. Results showed that workplace bullying is a predictor of fatigue with an odds ratio of 2.74 and p-value 0.008. Gender was found to be an effect modifier for this relationship, mainly among females (OR 2.66, p-value 0.047) but not among males. Anxiety and depression also predicted higher levels of fatigue (OR 5.75, p-value 0.017). Spirituality did not moderate this relationship.
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Affiliation(s)
- Ghassan M Khairallah
- Department of Family Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Nisrine N Makarem
- Department of Family Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Diana V Rahme
- Department of Family Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | | | - Dayana Brome
- Department of Psychology, American University of Beirut Medical Center, Beirut, Lebanon
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16
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Yagin FH, Alkhateeb A, Raza A, Samee NA, Mahmoud NF, Colak C, Yagin B. An Explainable Artificial Intelligence Model Proposed for the Prediction of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and the Identification of Distinctive Metabolites. Diagnostics (Basel) 2023; 13:3495. [PMID: 38066735 PMCID: PMC10706650 DOI: 10.3390/diagnostics13233495] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 11/03/2023] [Accepted: 11/17/2023] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and debilitating illness with a significant global prevalence, affecting over 65 million individuals. It affects various systems, including the immune, neurological, gastrointestinal, and circulatory systems. Studies have shown abnormalities in immune cell types, increased inflammatory cytokines, and brain abnormalities. Further research is needed to identify consistent biomarkers and develop targeted therapies. This study uses explainable artificial intelligence and machine learning techniques to identify discriminative metabolites for ME/CFS. MATERIAL AND METHODS The model investigates a metabolomics dataset of CFS patients and healthy controls, including 26 healthy controls and 26 ME/CFS patients aged 22-72. The dataset encapsulated 768 metabolites into nine metabolic super-pathways: amino acids, carbohydrates, cofactors, vitamins, energy, lipids, nucleotides, peptides, and xenobiotics. Random forest methods together with other classifiers were applied to the data to classify individuals as ME/CFS patients and healthy individuals. The classification learning algorithms' performance in the validation step was evaluated using a variety of methods, including the traditional hold-out validation method, as well as the more modern cross-validation and bootstrap methods. Explainable artificial intelligence approaches were applied to clinically explain the optimum model's prediction decisions. RESULTS The metabolomics of C-glycosyltryptophan, oleoylcholine, cortisone, and 3-hydroxydecanoate were determined to be crucial for ME/CFS diagnosis. The random forest model outperformed the other classifiers in ME/CFS prediction using the 1000-iteration bootstrapping method, achieving 98% accuracy, precision, recall, F1 score, 0.01 Brier score, and 99% AUC. According to the obtained results, the bootstrap validation approach demonstrated the highest classification outcomes. CONCLUSION The proposed model accurately classifies ME/CFS patients based on the selected biomarker candidate metabolites. It offers a clear interpretation of risk estimation for ME/CFS, aiding physicians in comprehending the significance of key metabolomic features within the model.
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Affiliation(s)
- Fatma Hilal Yagin
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Inonu University, Malatya 44280, Türkiye;
| | | | - Ali Raza
- Institute of Computer Science, Khwaja Fareed University of Engineering and Information Technology, Rahim Yar Khan 64200, Pakistan;
| | - Nagwan Abdel Samee
- Department of Information Technology, College of Computer and Information Sciences, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia;
| | - Noha F. Mahmoud
- Rehabilitation Sciences Department, Health and Rehabilitation Sciences College, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia;
| | - Cemil Colak
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Inonu University, Malatya 44280, Türkiye;
| | - Burak Yagin
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Inonu University, Malatya 44280, Türkiye;
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Lacasa M, Alegre-Martin J, Sentañes RS, Varela-Sende L, Jurek J, Castro-Marrero J. Yeast Beta-Glucan Supplementation with Multivitamins Attenuates Cognitive Impairments in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients 2023; 15:4504. [PMID: 37960157 PMCID: PMC10647745 DOI: 10.3390/nu15214504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 10/18/2023] [Accepted: 10/23/2023] [Indexed: 11/15/2023] Open
Abstract
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.
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Affiliation(s)
- Marcos Lacasa
- E-Health Center, Universitat Oberta de Catalunya, 08018 Barcelona, Spain;
| | - Jose Alegre-Martin
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Research Unit, Division of Rheumatology, Vall d´Hebron University Hospital Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; (J.A.-M.); (R.S.S.); (J.J.)
| | - Ramon Sanmartin Sentañes
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Research Unit, Division of Rheumatology, Vall d´Hebron University Hospital Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; (J.A.-M.); (R.S.S.); (J.J.)
| | - Luisa Varela-Sende
- Clinical Research Department, VITAE Health Innovation, Montmeló, 08160 Barcelona, Spain;
| | - Joanna Jurek
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Research Unit, Division of Rheumatology, Vall d´Hebron University Hospital Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; (J.A.-M.); (R.S.S.); (J.J.)
| | - Jesus Castro-Marrero
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Research Unit, Division of Rheumatology, Vall d´Hebron University Hospital Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; (J.A.-M.); (R.S.S.); (J.J.)
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18
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Li Y, Yang J, Chau CI, Shi J, Chen X, Hu H, Ung COL. Is there a role for traditional and complementary medicines in managing chronic fatigue? a systematic review of randomized controlled trials. Front Pharmacol 2023; 14:1266803. [PMID: 37942489 PMCID: PMC10628447 DOI: 10.3389/fphar.2023.1266803] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 09/27/2023] [Indexed: 11/10/2023] Open
Abstract
Introduction: Chronic fatigue syndrome (CFS) is an increasingly common condition that is challenging to treat due to unclear etiology and a lack of consensus on clinical diagnosis and treatment guidance. Many affected people resorted to using traditional and complementary medicines (T&CMs). However, the evidence for T&CMs for CFS has been inconclusive and continues to evolve. The study aims to identify, summarize and assess the most recent evidence on the efficacy and safety of T&CMs for CFS. Methods: Randomized controlled trials (RCTs) investigating T&CMs for CFS published in English of Chinese between 1 January 2013 and 31 December 2022 were searched from 7 databases. RCTs comparing T&CMs with no treatment, placebo, or pharmacological medicine were included, irrespective of language or blinding. The Consolidated Standards of Reporting Trials Statement extensions for Chinese herbal medicine Formulas (CONSORT-CHM) and the Cochrane Collaboration's Risk of Bias tool were used to evaluate the quality and risk of bias of included studies. Results: A total of 62 RCTs investigating 43 types of T&CMs and involving 5,231 participants with CFS were included in this review. The primary outcome measures mainly included the scoring of fatigue symptoms using the validated tool Fatigue Scale-14 (FS-14) or the TCM syndrome score. The main interventions showing overall efficacy were Chaihu Guizhi Decoction and Buzhong Yiqi combined with Xiao Chaihu Decoction, and 148 ingredients were identified, including Astragali Radix, Glycyrrhizae Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Bupleuri Radix. The most significant effect was the improvement of fatigue, followed by TCM-diagnosed symptoms and other psychological conditions. No serious adverse effect had been reported. However, the quality of the RCTs included RCTs were found to be suboptimal, and the risk of bias remained uncertain. Conclusion: Some evidence from RCTs supported the efficacy and safety of T&CM in CFS. However, given the methodological and quality heterogenicity of the included studies, the recommendations of T&CMs in treating CFS remain inconclusive. To develop better quality evidence about T&CMs for CFS, future studies should employ more objective diagnosis standards and outcome measurements, larger sample size, and better bias control, and ensure the compliance with the corresponding reporting guidelines. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022362268, identifier CRD42022362268.
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Affiliation(s)
- Yuxiao Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
| | - Jingya Yang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
| | - Chi Ian Chau
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
| | - Junnan Shi
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
| | - Xianwen Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
| | - Hao Hu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
- Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao SAR, China
| | - Carolina Oi Lam Ung
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
- Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao SAR, China
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Guo C, Yi B, Wu J, Lu J. The microbiome in post-acute infection syndrome (PAIS). Comput Struct Biotechnol J 2023; 21:3904-3911. [PMID: 37602232 PMCID: PMC10432703 DOI: 10.1016/j.csbj.2023.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 08/03/2023] [Accepted: 08/03/2023] [Indexed: 08/22/2023] Open
Abstract
Post-Acute Infection Syndrome (PAIS) is a relatively new medical terminology that represents prolonged sequelae symptoms after acute infection by numerous pathogenic agents. Imposing a substantial public health burden worldwide, PASC (post-acute sequelae of COVID-19 infection) and ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) are two of the most recognized and prevalent PAIS conditions. The presences of prior infections and similar symptom profiles in PAIS reflect a plausible common etiopathogenesis. The human microbiome is known to play an essential role in health and disease. In this review, we reviewed and summarized available research on oral and gut microbiota alterations in patients with different infections or PAIS conditions. We discussed key theories about the associations between microbiome dysbiosis and PAIS disease development, aiming to explore the mechanistic roles and potential functions the microbiome may have in the process. Additionally, we discuss the areas of knowledge gaps and propose the potential clinical applications of the microbiome for prevention and treatment of PAIS conditions.
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Affiliation(s)
- Cheng Guo
- Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, USA
| | - Boyang Yi
- School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Jianyong Wu
- School of Public Health, Xinjiang Medical University, Urumqi, China
| | - Jiahai Lu
- School of Public Health, Sun Yat-Sen University, Guangzhou, China
- Hainan Key Novel Thinktank “Hainan Medical University ‘One Health’ Research Center”, Haikou, China
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Gamer J, Van Booven DJ, Zarnowski O, Arango S, Elias M, Kurian A, Joseph A, Perez M, Collado F, Klimas N, Oltra E, Nathanson L. Sex-Dependent Transcriptional Changes in Response to Stress in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Project. Int J Mol Sci 2023; 24:10255. [PMID: 37373402 PMCID: PMC10299261 DOI: 10.3390/ijms241210255] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/23/2023] [Accepted: 06/04/2023] [Indexed: 06/29/2023] Open
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multi-symptom illness characterized by debilitating fatigue and post-exertional malaise (PEM). Numerous studies have reported sex differences at the epidemiological, cellular, and molecular levels between male and female ME/CFS patients. To gain further insight into these sex-dependent changes, we evaluated differential gene expression by RNA-sequencing (RNA-Seq) in 33 ME/CFS patients (20 female, 13 male) and 34 matched healthy controls (20 female and 14 male) before, during, and after an exercise challenge intended to provoke PEM. Our findings revealed that pathways related to immune-cell signaling (including IL-12) and natural killer cell cytotoxicity were activated as a result of exertion in the male ME/CFS cohort, while female ME/CFS patients did not show significant enough changes in gene expression to meet the criteria for the differential expression. Functional analysis during recovery from an exercise challenge showed that male ME/CFS patients had distinct changes in the regulation of specific cytokine signals (including IL-1β). Meanwhile, female ME/CFS patients had significant alterations in gene networks related to cell stress, response to herpes viruses, and NF-κβ signaling. The functional pathways and differentially expressed genes highlighted in this pilot project provide insight into the sex-specific pathophysiology of ME/CFS.
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Affiliation(s)
- Jackson Gamer
- Institute for Neuro-Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (J.G.); (N.K.)
- Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (O.Z.); (S.A.); (M.E.); (A.K.); (A.J.); (M.P.)
| | - Derek J. Van Booven
- Dr. J.P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA;
| | - Oskar Zarnowski
- Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (O.Z.); (S.A.); (M.E.); (A.K.); (A.J.); (M.P.)
| | - Sebastian Arango
- Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (O.Z.); (S.A.); (M.E.); (A.K.); (A.J.); (M.P.)
| | - Mark Elias
- Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (O.Z.); (S.A.); (M.E.); (A.K.); (A.J.); (M.P.)
| | - Asha Kurian
- Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (O.Z.); (S.A.); (M.E.); (A.K.); (A.J.); (M.P.)
| | - Andrew Joseph
- Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (O.Z.); (S.A.); (M.E.); (A.K.); (A.J.); (M.P.)
| | - Melanie Perez
- Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (O.Z.); (S.A.); (M.E.); (A.K.); (A.J.); (M.P.)
| | - Fanny Collado
- Department of Veterans Affairs, Miami VA Healthcare System, Geriatric Research Education and Clinical Center (GRECC), Miami, FL 33125, USA;
- South Florida Veterans Affairs Foundation for Research and Education Inc., Fort Lauderdale, FL 33125, USA
| | - Nancy Klimas
- Institute for Neuro-Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (J.G.); (N.K.)
- Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (O.Z.); (S.A.); (M.E.); (A.K.); (A.J.); (M.P.)
- Department of Veterans Affairs, Miami VA Healthcare System, Geriatric Research Education and Clinical Center (GRECC), Miami, FL 33125, USA;
- South Florida Veterans Affairs Foundation for Research and Education Inc., Fort Lauderdale, FL 33125, USA
| | - Elisa Oltra
- School Medicine, Universidad Católica de Valencia San Vicente Mártir, 46001 Valencia, Spain;
| | - Lubov Nathanson
- Institute for Neuro-Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (J.G.); (N.K.)
- Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (O.Z.); (S.A.); (M.E.); (A.K.); (A.J.); (M.P.)
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Patel P, Ali H, Inayat F, Pamarthy R, Giammarino A, Ilyas F, Smith-Martinez LA, Satapathy SK. Racial and gender-based disparities and trends in common psychiatric conditions in liver cirrhosis hospitalizations: A ten-year United States study. World J Hepatol 2023; 15:289-302. [PMID: 36926245 PMCID: PMC10011900 DOI: 10.4254/wjh.v15.i2.289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/01/2023] [Accepted: 01/31/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Chronic liver disease is associated with various neuropsychiatric conditions. There are currently no large studies assessing and comparing the prevalence of psychiatric illnesses based on patient profiles and the etiology of cirrhosis. AIM To examine the trends of hospitalizations among psychiatric conditions in cirrhosis. METHODS We used the National Inpatient Sample database 2016-2019 for the primary diagnosis of liver cirrhosis. The outcomes included the prevalence, trends, and associations of psychiatric diagnoses in these hospitalizations. Chi-square for categorical variables and the Wilcoxon rank test for continuous variables were utilized. RESULTS The prevalence of generalized anxiety disorder (GAD) in liver cirrhosis hospitalizations increased from 0.17% in 2009 to 0.92% in 2019 (P < 0.001). The prevalence of depression increased from 7% in 2009 to 12% in 2019 (P < 0.001). Attention deficit hyperactivity disorder (ADHD) prevalence increased from 0.06% to 0.24%. The prevalence of schizophrenia increased from 0.59% to 0.87% (P < 0.001). Schizoaffective disorder prevalence increased from 0.10% to 0.35% (P < 0.001). Post-traumatic stress disorder (PTSD) prevalence displayed increasing trends from 0.36% in 2009 to 0.93% in 2019 (P < 0.001). The prevalence of suicidal ideation increased from 0.23% to 0.56% in 2019. Cirrhosis related to alcoholic liver disease [adjusted odds ratios (aOR) 1.18, 95%CI 1.08-1.29, P < 0.001] and non-alcoholic fatty liver disease (NAFLD) (aOR 1.14, 95%CI 1.01-1.28, P = 0.025) was associated with depression more than other causes. Alcohol- and NAFLD-associated cirrhosis had a stronger link to psychiatric disorders. Females had a higher association with GAD (aOR 2.56, 95%CI 2.14-3.06, P < 0.001), depression (aOR 1.78, 95%CI 1.71-1.84, P < 0.001), bipolar disorder (aOR 1.64, 95%CI 1.52-1.77, P < 0.001] and chronic fatigue (aOR 2.31, 95%CI 1.31-4.07, P < 0.001) when compared to males. Blacks, Hispanics, and Asian/Native Americans had a significantly lower association with GAD, depression, bipolar disorder, PTSD, and ADHD when compared to the white race. CONCLUSION The prevalence of psychiatric comorbidities in liver cirrhosis hospitalizations has increased over the last decade. Females had a higher association with psychiatric disorders compared to males. Blacks, Hispanics, and Asian/Native Americans had lower associations with psychiatric comorbidities compared to the white race.
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Affiliation(s)
- Pratik Patel
- Department of Gastroenterology, Mather Hospital and Hofstra University Zucker School of Medicine, Port Jefferson, NY 11777, United States
| | - Hassam Ali
- Department of Internal Medicine, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States.
| | - Faisal Inayat
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore 54550, Punjab, Pakistan
| | - Rahul Pamarthy
- Department of Internal Medicine, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Alexa Giammarino
- Department of Internal Medicine, North Shore University Hospital and Hofstra University Zucker School of Medicine, Port Jefferson, NY 11777, United States
| | - Fariha Ilyas
- Department of Internal Medicine, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Lucia Angela Smith-Martinez
- Department of Psychiatry, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Sanjaya K Satapathy
- Department of Hepatology, North Shore University Hospital and Hofstra University Zucker School of Medicine, Manhasset, NY 11030, United States
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22
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Hulens M, Dankaerts W, Rasschaert R, Bruyninckx F, De Mulder P, Bervoets C. The Link Between Empty Sella Syndrome, Fibromyalgia, and Chronic Fatigue Syndrome: The Role of Increased Cerebrospinal Fluid Pressure. J Pain Res 2023; 16:205-219. [PMID: 36721849 PMCID: PMC9884441 DOI: 10.2147/jpr.s394321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 01/17/2023] [Indexed: 01/26/2023] Open
Abstract
The etiopathogenesis of fibromyalgia (FM) and chronic fatigue syndrome (CFS) is not yet elucidated. Hypothalamo-pituitary-adrenal (HPA) axis dysfunction is reflected in the hormonal disturbances found in FM and CFS. Some study groups have introduced a novel hypothesis that moderate or intermittent intracranial hypertension may be involved in the etiopathogenesis of FM and CFS. In these conditions, hormonal disturbances may be caused by the mechanical effect of increased cerebrospinal fluid pressure, which hampers blood flow in the pituitary gland. Severe intracranial pressure may compress the pituitary gland, resulting in primary empty sella (ES), potentially leading to pituitary hormone deficiencies. The aim of this narrative review was to explore whether similar hormonal changes and symptoms exist between primary ES and FM or CFS and to link them to cerebrospinal fluid pressure dysregulation. A thorough search of the PubMed and Web of Science databases and the reference lists of the included studies revealed that several clinical characteristics were more prevalent in primary ES, FM or CFS patients than in controls, including increased cerebrospinal fluid pressure, obesity, female sex, headaches and migraine, fatigue, visual disturbances (visual acuity and eye motility abnormalities), vestibulocochlear disturbances (vertigo and neurosensorial hearing loss), and bodily pain (radicular pain and small-fiber neuropathy). Furthermore, challenge tests of the pituitary gland showed similar abnormalities in all three conditions: blunted adrenocorticotropic hormone, cortisol, growth hormone, luteinizing hormone, and thyroid stimulating hormone responses and an increased prolactin response. The findings of this narrative review provide further support for the hypothesis that moderately or intermittently increased cerebrospinal fluid pressure is involved in the pathogenesis of FM and CFS and should stimulate further research into the etiopathogenesis of these conditions.
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Affiliation(s)
- Mieke Hulens
- Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium,Correspondence: Mieke Hulens, Department of Rehabilitation Sciences, KU Leuven, Overwegstraat 14, 3051 Sint-Joris-Weert, Leuven, Belgium, Tel +32 477 338003, Fax +32 16 329197, Email
| | - Wim Dankaerts
- Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium
| | | | - Frans Bruyninckx
- Department of Physical Medicine & Rehabilitation, University Hospitals of Leuven, Leuven, Belgium
| | - Peter De Mulder
- Department of Anesthesiology and Pain Therapy, Imelda Hospital, Bonheiden, Belgium
| | - Chris Bervoets
- Department of Neurosciences, KU Leuven, Leuven, Belgium,Department of Ophthalmology, University Hospitals of Leuven, Leuven, Belgium,Department Adult Psychiatry, University Psychiatric Center of KU Leuven, Leuven, Belgium
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23
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Maya J, Leddy SM, Gottschalk CG, Peterson DL, Hanson MR. Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int J Mol Sci 2023; 24:2010. [PMID: 36768336 PMCID: PMC9916395 DOI: 10.3390/ijms24032010] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/14/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling multisystem illness in which individuals are plagued with fatigue, inflammatory symptoms, cognitive dysfunction, and the hallmark symptom, post-exertional malaise. While the cause of this disease remains unknown, there is evidence of a potential infectious component that, along with patient symptoms and common onsets of the disease, implicates immune system dysfunction. To further our understanding of the state of ME/CFS lymphocytes, we characterized the role of fatty acids in isolated Natural Killer cells, CD4+ T cells, and CD8+ T cells in circulation and after overnight stimulation, through implicit perturbations to fatty acid oxidation. We examined samples obtained from at least 8 and as many as 20 subjects for immune cell fatty acid characterization in a variety of experiments and found that all three isolated cell types increased their utilization of lipids and levels of pertinent proteins involved in this metabolic pathway in ME/CFS samples, particularly during higher energy demands and activation. In T cells, we characterized the cell populations contributing to these metabolic shifts, which included CD4+ memory cells, CD4+ effector cells, CD8+ naïve cells, and CD8+ memory cells. We also discovered that patients with ME/CFS and healthy control samples had significant correlations between measurements of CD4+ T cell fatty acid metabolism and demographic data. These findings provide support for metabolic dysfunction in ME/CFS immune cells. We further hypothesize about the consequences that these altered fuel dependencies may have on T and NK cell effector function, which may shed light on the illness's mechanism of action.
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Affiliation(s)
- Jessica Maya
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA
| | - Sabrina M. Leddy
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA
| | | | - Daniel L. Peterson
- Simmaron Research, Incline Village, NV 89451, USA
- Sierra Internal Medicine, Incline Village, NV 89451, USA
| | - Maureen R. Hanson
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA
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24
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Oter-Quintana C, Esteban-Hernández J, Cuéllar-Pompa L, Gil-Carballo MC, Brito-Brito PR, Martín-García A, Alcolea-Cosín MT, Martínez-Marcos M, Alameda-Cuesta A. Nursing Diagnoses of Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Research Protocol for a Qualitative Synthesis. Healthcare (Basel) 2022; 10:healthcare10122506. [PMID: 36554030 PMCID: PMC9777975 DOI: 10.3390/healthcare10122506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 12/05/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
Although previously developed qualitative studies have explored the experience of illness of individuals with myalgic encephalomyelitis/chronic fatigue syndrome, these findings have not been undertaken for the purpose of enabling the identification of nursing care needs in such patients. This study aims to identify NANDA-I nursing diagnoses of adults with myalgic encephalomyelitis/chronic fatigue syndrome based on a qualitative literature review of their experience of illness. The protocol includes: searches in the electronic databases Medline, Embase, CINAHL, PsycINFO, SCI-EXPANDED, SSCI, SciELO, LILACS, and Cuiden; and manual searches in specialised journals and the references of the included studies. The authors will systematically search qualitative research studies published in databases from 1994 to 2021. Searches are limited to studies in Spanish and English. All stages of the review process will be carried out independently by two reviewers. Any disagreements shall be resolved through joint discussions, involving a third reviewer if necessary. The findings will be synthesised into a thematic analysis informed by the Domains and Classes of the NANDA-I Classification of Nursing Diagnoses, which will then serve to identify nursing diagnoses. This review will enable nursing professionals to identify the care needs of individuals with myalgic encephalomyelitis/chronic fatigue syndrome by taking into consideration their experience of illness in its entirety.
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Affiliation(s)
- Cristina Oter-Quintana
- Member of the Nursing and Health Care Research Group IDIPHISA, 28222 Majadahonda, Spain
- Nursing Department, Faculty of Medicine, Autonomous University of Madrid, 28029 Madrid, Spain
- Faculty of Health Sciences, Rey Juan Carlos University, 28922 Alcorcón, Spain
- Correspondence: ; Tel.: +34-914-975-855
| | - Jesús Esteban-Hernández
- Medical Specialties and Public Health Department, Faculty of Health Sciences, Rey Juan Carlos University, 28922 Alcorcón, Spain
| | - Leticia Cuéllar-Pompa
- Care Research Institute, Illustrious Professional Association of Nurses of Santa Cruz de Tenerife, 30001 Santa Cruz de Tenerife, Spain
| | | | - Pedro Ruymán Brito-Brito
- Primary Care Management of Tenerife, The Canary Islands Health Service, 38204 La Laguna, Spain
- Nursing Department, La Laguna University, 38200 La Laguna, Spain
| | - Angel Martín-García
- Health Care Directorate (Southern District), Primary Care, Madrid Health Service, 28981 Parla, Spain
| | | | - Mercedes Martínez-Marcos
- Member of the Nursing and Health Care Research Group IDIPHISA, 28222 Majadahonda, Spain
- Nursing Department, Faculty of Medicine, Autonomous University of Madrid, 28029 Madrid, Spain
| | - Almudena Alameda-Cuesta
- Nursing and Oral Medicine Department, Faculty of Health Sciences, Rey Juan Carlos University, 28922 Alcorcón, Spain
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25
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Michelutti M, Furlanis G, Buoite Stella A, Bellavita G, Frezza N, Torresin G, Ajčević M, Manganotti P. Sex-dependent characteristics of Neuro-Long-COVID: Data from a dedicated neurology ambulatory service. J Neurol Sci 2022; 441:120355. [PMID: 35994869 PMCID: PMC9328838 DOI: 10.1016/j.jns.2022.120355] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 07/19/2022] [Accepted: 07/24/2022] [Indexed: 01/19/2023]
Abstract
"Long-COVID" is a clinical entity that consists of persisting post-infectious symptoms that last for more than three months after the onset of the first acute COVID-19 symptoms. Among these, a cluster of neurological persisting symptoms defines Neuro-Long-COVID. While the debate about the pathogenesis of Long-COVID is still ongoing, sex differences have been individuated for both the acute and the chronic stage of the infection. We conducted a retrospective study describing sex differences in a large sample of patients with Neuro-Long-COVID. Demographic and clinical data were collected in a specifically designed Neuro-Long-Covid outpatient service. Our sample included 213 patients: 151 were females and 62 were males; the mean age was similar between females (53 y, standard deviation 14) and males (55 y, standard deviation 15); no significant differences was present between the demographic features across the two groups. Despite the prevalence of the specific chronic symptoms between male and females showed no significant differences, the total number of females accessing our service was higher than that of males, confirming the higher prevalence of Neuro-Long-COVID in female individuals. Conversely, a worse acute phase response in males rather than females was confirmed by a significant difference in the rates of acute respiratory symptoms (p = 0.008), dyspnea (p = 0.018), respiratory failure (p = 0.010) and the consequent need for ventilation (p = 0.015), together with other acute symptoms such as palpitations (p = 0.049), headache (p = 0.001) and joint pain (p = 0.049). Taken together, these findings offer a subgroup analysis based on sex-dependent characteristics, which can support a tailored-medicine approach.
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Affiliation(s)
- Marco Michelutti
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy
| | - Giovanni Furlanis
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy
| | - Alex Buoite Stella
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy
| | - Giulia Bellavita
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy
| | - Niccolò Frezza
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy
| | - Giovanna Torresin
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy
| | - Milos Ajčević
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy; Department of Engineering and Architecture, University of Trieste, Via A. Valerio, 10, 34127 Trieste, Italy
| | - Paolo Manganotti
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
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26
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Putra HA, Park K, Yamashita F. Sex Differences in the Correlation between Fatigue Perception and Regional Gray Matter Volume in Healthy Adults: A Large-Scale Study. J Clin Med 2022; 11:jcm11206037. [PMID: 36294358 PMCID: PMC9604802 DOI: 10.3390/jcm11206037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 10/10/2022] [Accepted: 10/10/2022] [Indexed: 11/16/2022] Open
Abstract
The relationship between fatigue perception and regional gray matter volume (rGMV) has seldom been studied in healthy adults. Therefore, this study aimed to analyze sex differences in the correlation between rGMV and fatigue perception using Chalder’s fatigue questionnaire (CFQ). The CFQ was used to analyze the sexual features of rGMV related to the degree of perceived fatigue in 2955 healthy adults (male = 1560, female = 1395) of various ages (20–89 years, median 56). A higher CFQ score denotes a higher perceived fatigue level by the participant. According to the CFQ scores in males, the volumes of the right orbital part of the inferior frontal gyrus and left precuneus were negatively correlated (i.e., smaller rGMV had a higher CFQ score), whereas the left angular gyrus was positively correlated. In females, the right inferior temporal gyrus was negative, whereas the left middle temporal gyrus and right putamen were positive (i.e., larger rGMV had a higher CFQ score). The lack of identified regions in this large-scale study between males and females might be related to sex differences in clinical or pathological fatigue morbidities. Additionally, the sex differences in the negative or positive correlations between rGMV and fatigue perception may contribute to a better understanding of the neuronal mechanism in the early stages of fatigue development.
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Affiliation(s)
- Handityo Aulia Putra
- Research Organization for Regional Alliances, Kochi University of Technology, Kochi 782-8502, Japan
- Correspondence: ; Tel.: +81-887-57-2025
| | - Kaechang Park
- Research Organization for Regional Alliances, Kochi University of Technology, Kochi 782-8502, Japan
| | - Fumio Yamashita
- Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Iwate 028-3694, Japan
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27
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Merone L, Tsey K, Russell D, Daltry A, Nagle C. Self-Reported Time to Diagnosis and Proportions of Rediagnosis in Female Patients with Chronic Conditions in Australia: A Cross-sectional Survey. WOMEN'S HEALTH REPORTS (NEW ROCHELLE, N.Y.) 2022; 3:749-758. [PMID: 36185069 PMCID: PMC9518795 DOI: 10.1089/whr.2022.0040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 07/19/2022] [Indexed: 06/16/2023]
Abstract
Background The diagnosis of chronic conditions in women is complicated by the historical androcentricity in medical research. Sex and gender gaps in health research may translate to unequal healthcare for women. This cross-sectional survey study aimed to ascertain the median time to diagnosis, proportions of rediagnosis and time to rediagnosis for Australian women with chronic conditions. Methods An online survey collected anonymous data from voluntary participants. Data were analyzed using Stata14. Cox Proportional Hazards model was used to analyze time to diagnosis and rediagnosis. Logistic regression analysis was used to assess the significance of rediagnosis rates by diagnosis, age at diagnosis, income, employment, state of residence, disability status, and Indigenous status. Results The median time from first appointment to initial diagnosis was 6 months (range 1 day-50 years) (interquartile range [IQR] 3.74 years). The median time to rediagnosis was 4 years (IQR 9) with a range of 1 day-43 years. Almost half of the women (n = 161/343, 47%) reported their primary condition being rediagnosed. From the complete responses, 40% were rediagnosed from one organic condition to another organic condition, however, 32% of women originally diagnosed with psychological, medically unexplained syndromes, or chronic pain were later rediagnosed with organic conditions. Conclusion Median wait times for a diagnosis for women in Australia, when factoring in high rates of rediagnosis and time to rediagnosis, was 4 years. It is important that clinicians are aware of the high rediagnosis rates in female patients with chronic conditions and understand the potential impact of systemic biases on the diagnostic process for women under their care.
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Affiliation(s)
- Lea Merone
- College of Healthcare Sciences, James Cook University, Townsville, Australia
| | - Komla Tsey
- College of Arts, Society and Education, James Cook University, Smithfield, Australia
| | | | - Andrew Daltry
- Cairns and Hinterland Hospital and Health Service, Cairns, Australia
| | - Cate Nagle
- College of Healthcare Sciences, James Cook University, Townsville, Australia
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28
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Maes M, Al-Rubaye HT, Almulla AF, Al-Hadrawi DS, Stoyanova K, Kubera M, Al-Hakeim HK. Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:10362. [PMID: 36011997 PMCID: PMC9408685 DOI: 10.3390/ijerph191610362] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/15/2022] [Accepted: 08/17/2022] [Indexed: 06/15/2023]
Abstract
The physio-affective phenome of Long COVID-19 is predicted by (a) immune-inflammatory biomarkers of the acute infectious phase, including peak body temperature (PBT) and oxygen saturation (SpO2), and (b) the subsequent activation of immune and oxidative stress pathways during Long COVID. The purpose of this study was to delineate the effects of PBT and SpO2 during acute infection, as well as the increased neurotoxicity on the physical, psychological, social and environmental domains of health-related quality of life (HR-QoL) in people with Long COVID. We recruited 86 participants with Long COVID and 39 normal controls, assessed the WHO-QoL-BREF (World Health Organization Quality of Life Instrument-Abridged Version, Geneva, Switzerland) and the physio-affective phenome of Long COVID (comprising depression, anxiety and fibromyalgia-fatigue rating scales) and measured PBT and SpO2 during acute infection, and neurotoxicity (NT, comprising serum interleukin (IL)-1β, IL-18 and caspase-1, advanced oxidation protein products and myeloperoxidase, calcium and insulin resistance) in Long COVID. We found that 70.3% of the variance in HR-QoL was explained by the regression on the physio-affective phenome, lowered calcium and increased NT, whilst 61.5% of the variance in the physio-affective phenome was explained by calcium, NT, increased PBT, lowered SpO2, female sex and vaccination with AstraZeneca and Pfizer. The effects of PBT and SpO2 on lowered HR-QoL were mediated by increased NT and lowered calcium yielding increased severity of the physio-affective phenome which largely affects HR-QoL. In conclusion, lowered HR-Qol in Long COVID is largely predicted by the severity of neuro-immune and neuro-oxidative pathways during acute and Long COVID.
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Affiliation(s)
- Michael Maes
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Department of Psychiatry, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria
- Research Institute, Medical University Plovdiv, 4002 Plovdiv, Bulgaria
- School of Medicine, Barwon Health, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong 3217, Australia
| | | | - Abbas F. Almulla
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf 54001, Iraq
| | | | - Kristina Stoyanova
- Department of Psychiatry, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria
- Research Institute, Medical University Plovdiv, 4002 Plovdiv, Bulgaria
| | - Marta Kubera
- Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St., 31-343 Krakow, Poland
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Faraji J, Bettenson D, Babatunde S, Gangur-Powell T, Yong VW, Metz GA. Thermoregulatory dynamics reveal sex-specific inflammatory responses to experimental autoimmune encephalomyelitis in mice: Implications for multiple sclerosis-induced fatigue in females. Brain Behav Immun Health 2022; 23:100477. [PMID: 35677535 PMCID: PMC9167694 DOI: 10.1016/j.bbih.2022.100477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/21/2022] [Accepted: 05/30/2022] [Indexed: 11/21/2022] Open
Abstract
The course of multiple sclerosis (MS) is characterized by striking sex differences in symptoms such as fatigue and impaired thermal regulation, which are associated with aggravated systemic pro-inflammatory processes. The purpose of this study was to replicate these symptoms in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice in the quest to advance the preclinical study of non-motor symptoms of MS. Male and female C57BL/6 mice exposed to a mild form of EAE were evaluated for the progression of clinical, behavioural, thermal, and inflammatory processes. We show higher susceptibility in females to EAE than males based on greater clinical score and cumulative disease index (CDI), fatigue-like and anxiety-like behaviours. Accordingly, infrared (IR) thermography indicated higher cutaneous temperatures in females from post-induction days 12-23. Females also responded to EAE with greater splenic and adrenal gland weights than males as well as sex-specific changes in pro- and anti-inflammatory cytokines. These findings provide the first evidence of a sex-specific thermal response to immune-mediated demyelination, thus proposing a non-invasive assessment approach of the psychophysiological dynamics in EAE mice. The results are discussed in relation to the thermoregulatory correlates of fatigue and how endogenously elevated body temperature without direct heat exposure may be linked to psychomotor inhibition in patients with MS.
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Affiliation(s)
- Jamshid Faraji
- Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
| | - Dennis Bettenson
- Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
| | - Stella Babatunde
- Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
| | - Tabitha Gangur-Powell
- Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
| | - Voon Wee Yong
- Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta T2N 4N1, Canada
| | - Gerlinde A.S. Metz
- Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
- Southern Alberta Genome Sciences Centre, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
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CD4+ Cytotoxic T Cells Involved in the Development of EBV-Associated Diseases. Pathogens 2022; 11:pathogens11080831. [PMID: 35894054 PMCID: PMC9330826 DOI: 10.3390/pathogens11080831] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/17/2022] [Accepted: 07/22/2022] [Indexed: 11/17/2022] Open
Abstract
Activated cytotoxic CD4 T cells (HLA-DR+) play an important role in the control of EBV infection, especially in cells with latency I (EBNA-1). One of the evasion mechanisms of these latency cells is generated by gp42, which, via peripherally binding to the β1 domain of the β chain of MHC class II (HLA-DQ, -DR, and -DP) of the infected B lymphocyte, can block/alter the HLA class II/T-cell receptor (TCR) interaction, and confer an increased level of susceptibility towards the development of EBV-associated autoimmune diseases or cancer in genetically predisposed individuals (HLA-DRB1* and DQB1* alleles). The main developments predisposing the factors of these diseases are: EBV infection; HLA class II risk alleles; sex; and tissue that is infiltrated with EBV-latent cells, forming ectopic lymphoid structures. Therefore, there is a need to identify treatments for eliminating cells with EBV latency, because the current treatments (e.g., antivirals and rituximab) are ineffective.
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Joseph P, Pari R, Miller S, Warren A, Stovall MC, Squires J, Chang CJ, Xiao W, Waxman AB, Systrom DM. Neurovascular Dysregulation and Acute Exercise Intolerance in ME/CFS: A Randomized, Placebo-Controlled Trial of Pyridostigmine. Chest 2022; 162:1116-1126. [PMID: 35526605 DOI: 10.1016/j.chest.2022.04.146] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 04/22/2022] [Accepted: 04/22/2022] [Indexed: 10/18/2022] Open
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by intractable fatigue, postexertional malaise, and orthostatic intolerance, but its pathophysiology is poorly understood. Pharmacologic cholinergic stimulation was used to test the hypothesis that neurovascular dysregulation underlies exercise intolerance in ME/CFS. RESEARCH QUESTION Does neurovascular dysregulation contribute to exercise intolerance in ME/CFS, and can its treatment improve exercise capacity? STUDY DESIGN AND METHODS Forty-five subjects with ME/CFS were enrolled in a single-center, randomized, double-blind, placebo-controlled trial. Subjects were assigned in a 1:1 ratio to receive a 60-mg dose of oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test (iCPET). A second iCPET was performed 50 min later. The primary end point was the difference in peak exercise oxygen uptake (Vo2). Secondary end points included exercise pulmonary and systemic hemodynamics and gas exchange. RESULTS Twenty-three subjects were assigned to receive pyridostigmine and 22 to receive placebo. The peak Vo2 increased after pyridostigmine but decreased after placebo (13.3 ± 13.4 mL/min vs -40.2 ± 21.3 mL/min; P < .05). The treatment effect of pyridostigmine was 53.6 mL/min (95% CI, -105.2 to -2.0). Peak vs rest Vo2 (25.9 ± 15.3 mL/min vs -60.8 ± 25.6 mL/min; P < .01), cardiac output (-0.2 ± 0.6 L/min vs -1.9 ± 0.6 L/min; P < .05), and right atrial pressure (1.0 ± 0.5 mm Hg vs -0.6 ± 0.5 mm Hg; P < .05) were greater in the pyridostigmine group compared with placebo. INTERPRETATION Pyridostigmine improves peak Vo2 in ME/CFS by increasing cardiac output and right ventricular filling pressures. Worsening peak exercise Vo2, cardiac output, and right atrial pressure following placebo may signal the onset of postexertional malaise. We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov; No.: NCT03674541; URL: www. CLINICALTRIALS gov.
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Affiliation(s)
- Phillip Joseph
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale-New Haven Hospital, Yale University, New Haven, CT
| | - Rosa Pari
- Department of Medicine, University of Rochester Medical Center, Rochester, NY
| | - Sarah Miller
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Arabella Warren
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Mary Catherine Stovall
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Johanna Squires
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Chia-Jung Chang
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Wenzhong Xiao
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Aaron B Waxman
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - David M Systrom
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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König RS, Albrich WC, Kahlert CR, Bahr LS, Löber U, Vernazza P, Scheibenbogen C, Forslund SK. The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Front Immunol 2022; 12:628741. [PMID: 35046929 PMCID: PMC8761622 DOI: 10.3389/fimmu.2021.628741] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 12/09/2021] [Indexed: 12/16/2022] Open
Abstract
Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.
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Affiliation(s)
- Rahel S König
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Werner C Albrich
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Christian R Kahlert
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.,Division of Infectious Diseases and Hospital Epidemiology, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland
| | - Lina Samira Bahr
- Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,Experimental and Clinical Research Center, A Joint Cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Ulrike Löber
- Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,Experimental and Clinical Research Center, A Joint Cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.,Host-Microbiome Factors in Cardiovascular Disease, Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Pietro Vernazza
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Carmen Scheibenbogen
- Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Sofia K Forslund
- Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.,Experimental and Clinical Research Center, A Joint Cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.,Host-Microbiome Factors in Cardiovascular Disease, Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.,European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany
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Shi Y, Hu X, Cui J, Li J, Bi Z, Li J, Fu H, Wang Y, Cui L, Xu J. Correlation Analysis of Data of Tongue and Pulse in Patients With Disease Fatigue and Sub-health Fatigue. INQUIRY: THE JOURNAL OF HEALTH CARE ORGANIZATION, PROVISION, AND FINANCING 2022; 59:469580211060781. [PMID: 35112891 PMCID: PMC8819780 DOI: 10.1177/00469580211060781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
Fatigue is one of the most common subjective symptoms of abnormal health state,
there is still no reliable and stable evaluation method to distinguish disease
fatigue and non-disease fatigue. Studies have shown that tongue diagnosis and
pulse diagnosis are the reflection of overall state of the body. This study aims
to explore the distribution rules and correlation of data of tongue and pulse in
population with disease fatigue and sub-health fatigue and provide a new method
of clinical diagnosis of fatigue from the perspective of tongue diagnosis and
pulse diagnosis. In this study, a total of 736 people were selected and divided
into healthy controls (n = 250), sub-health fatigue group (n = 242), and disease
fatigue group (n = 244). TFDA-1 tongue diagnosis instrument and PDA-1 pulse
diagnosis instrument were used to collect tongue image and sphygmogram, simple
correlation analysis and canonical correlation analysis were used to analyze the
correlation of tongue and pulse data about the two groups of fatigue people. The
study had shown that tongue and pulse data could provide a certain reference for
the diagnosis of different types of fatigue, tongue and pulse data in disease
fatigue and sub-health fatigue population had different distribution rules, and
there was a simple correlation and canonical correlation in the disease fatigue
population, the coefficient of canonical correlation was .649 (P <.05).
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Affiliation(s)
- Yulin Shi
- Department of Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaojuan Hu
- Shanghai Collaborative Innovation Center of Health Service in Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ji Cui
- Department of Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jun Li
- Department of Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zijuan Bi
- Department of Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiacai Li
- Department of Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hongyuan Fu
- Department of Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yu Wang
- Department of Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Longtao Cui
- Department of Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiatuo Xu
- Department of Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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James LM, Georgopoulos AP. At the Root of 3 “Long” Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome. Neurosci Insights 2022; 17:26331055221114817. [PMID: 35910083 PMCID: PMC9335483 DOI: 10.1177/26331055221114817] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 06/28/2022] [Indexed: 12/16/2022] Open
Abstract
Several foreign antigens such as those derived from viruses and bacteria have been linked to long-term deleterious effects on the brain and other organs; yet, health outcomes subsequent to foreign antigen exposure vary depending in large part on the host’s immune system, in general, and on human leukocyte antigen (HLA) composition, in particular. Here we first provide a brief description of 3 conditions characterized by persistent long-term symptoms, namely long-COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and Gulf War Illness (GWI), followed by a brief overview of the role of HLA in the immune response to foreign antigens. We then discuss our Persistent Antigen (PA) hypothesis and highlight associations between antigen persistence due to HLA-antigen incongruence and chronic health conditions in general and the 3 “long” diseases above in particular. This review is not intended to cover the breadth and depth of symptomatology of those diseases but is specifically focused on the hypothesis that the presence of persistent antigens underlies their pathogenesis.
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Affiliation(s)
- Lisa M James
- Department of Veterans Affairs Health Care System, Brain Sciences Center, Minneapolis, MN, USA
- Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA
- Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA
- Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA
| | - Apostolos P Georgopoulos
- Department of Veterans Affairs Health Care System, Brain Sciences Center, Minneapolis, MN, USA
- Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA
- Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA
- Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA
- Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA
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The relevant factors of work-related fatigue for occupational vibration-exposed employees. Ann Occup Environ Med 2022; 34:e6. [PMID: 35425618 PMCID: PMC9005887 DOI: 10.35371/aoem.2022.34.e6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 02/28/2022] [Indexed: 11/20/2022] Open
Abstract
Background To date, little is known about the effects of factors linked to work-related fatigue on vibration-exposed workers. Thus, the purpose of this study was (1) to assess the effects of vibration exposure time per week and work-related fatigue on workers and (2) to identify factors associated with work-related fatigue caused by long-term exposure to occupational vibration. Methods This study used data collected from the 5th Korean Working Conditions Survey. A total of 34,820 non-vibration-exposed and 10,776 vibration-exposed employees were selected from the data. The χ2 and multiple logistic regression were used to determine the effect of vibration exposure time per week and the effects of factors of work-related fatigue on workers. Results The prevalence of work-related fatigue in vibration-exposed workers (30.5%) was higher than that of non-exposed workers (15.9%). The prevalence of work-related fatigue was higher for female and workers with depression, anxiety, and shift work, and those with authority to control their work pace had statistically significantly higher odds than those who did not. The employees who had the authority to control their order of work (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.81–0.95) and method of work (OR: 0.90; 95% CI: 0.82–0.98) had statistically significantly lower odds than those who did not. The OR of work-related fatigue symptoms was highest among employees whose vibration exposure time per week were 30.0%–40.0% (OR: 2.36; 95% CI: 1.96–2.83). Lower OR was observed as vibration exposure time per week decreased. Conclusions The results of the present study suggest an association between occupational vibration and work-related fatigue and longer vibration exposure time per week, causing an increased prevalence of work-related fatigue symptoms. Measures to protect workers exposed to occupational vibration from work-related fatigue must be taken.
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36
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Campbell KA, Ford-Gilboe M, Kennedy K, Jackson K, Mantler T, Oudshoorn A. Women’s experiences of navigating chronic pain within the context of living with an episodic disability. WOMEN'S HEALTH 2022; 18:17455057221103994. [PMID: 35726445 PMCID: PMC9218444 DOI: 10.1177/17455057221103994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Objectives: Of the 6.2 million Canadians aged 15 years or older who live with disability, 61% have disabilities that are not static or continuous. These dynamic conditions are known as episodic disabilities and many disproportionately experienced by women. Chronic pain is also a common feature associated with many episodic disabilities. The purpose of this article is to explore the experience of chronic pain for women living with episodic disabilities. Methods: This qualitative study draws on the tenets of interpretive description. Thirty women, with one or more episodic disabilities and chronic pain, participated in a semi-structured interview and answered questions about their chronic pain levels, using Von Korff et al.’s graded chronic pain scale. Results: Women experienced gendered treatment within the healthcare system and reported that they were frequently dismissed by their healthcare providers, most often physicians. Healthcare professionals’ practices around pain assessment were another common challenge for women. Women who were able to access financial support from government disability programs were more likely to access allied health professionals. Many of the holistic strategies that women researched and used to treat chronic pain were self-enacted. While diet, exercise, and other self-care activities are general health promotion strategies for all, they were seen as essential aspects of living that helped women have control over chronic pain and modifying the course of their episodic disability. Conclusion: Living with chronic pain and an episodic disability is complex. The findings of this study present the impact that gendered treatment in the healthcare system has on women who live with an episodic disability and experience chronic pain. It is evident that the current system did not meet the needs of the women in our study and system changes could result in better experiences, more disclosure of alternative therapies, and increase women’s agency in their care.
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Deumer US, Varesi A, Floris V, Savioli G, Mantovani E, López-Carrasco P, Rosati GM, Prasad S, Ricevuti G. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Overview. J Clin Med 2021; 10:4786. [PMID: 34682909 PMCID: PMC8538807 DOI: 10.3390/jcm10204786] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/12/2021] [Accepted: 10/15/2021] [Indexed: 12/20/2022] Open
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic systemic disease that manifests via various symptoms such as chronic fatigue, post-exertional malaise, and cognitive impairment described as "brain fog". These symptoms often prevent patients from keeping up their pre-disease onset lifestyle, as extended periods of physical or mental activity become almost impossible. However, the disease presents heterogeneously with varying severity across patients. Therefore, consensus criteria have been designed to provide a diagnosis based on symptoms. To date, no biomarker-based tests or diagnoses are available, since the molecular changes observed also largely differ from patient to patient. In this review, we discuss the infectious, genetic, and hormonal components that may be involved in CFS pathogenesis, we scrutinize the role of gut microbiota in disease progression, we highlight the potential of non-coding RNA (ncRNA) for the development of diagnostic tools and briefly mention the possibility of SARS-CoV-2 infection causing CFS.
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Affiliation(s)
- Undine-Sophie Deumer
- Department of Biological Sciences, Faculty of Natural Sciences and Mathematics, University of Cologne, 50674 Cologne, Germany;
| | - Angelica Varesi
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy
- Almo Collegio Borromeo, 27100 Pavia, Italy
| | - Valentina Floris
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy;
| | - Gabriele Savioli
- Emergency Department, IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Elisa Mantovani
- Department of Neurosciences, Biomedicine and Movement Sciences, Neurology Section, University of Verona, 37129 Verona, Italy;
| | - Paulina López-Carrasco
- División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico;
| | | | - Sakshi Prasad
- National Pirogov Memorial Medical University, 21018 Vinnytsya, Ukraine;
| | - Giovanni Ricevuti
- School of Pharmacy, Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
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Molnar T, Varnai R, Schranz D, Zavori L, Peterfi Z, Sipos D, Tőkés-Füzesi M, Illes Z, Buki A, Csecsei P. Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in Patients with Post-COVID Symptoms. J Clin Med 2021; 10:jcm10194337. [PMID: 34640355 PMCID: PMC8509483 DOI: 10.3390/jcm10194337] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/17/2021] [Accepted: 09/21/2021] [Indexed: 12/27/2022] Open
Abstract
Background: Post-COVID manifestation is defined as persistent symptoms or long-term complications beyond 4 weeks from disease onset. Fatigue and memory impairment are common post-COVID symptoms. We aimed to explore associations between the timeline and severity of post-COVID fatigue and anti-SARS-CoV-2 antibodies. Methods: Fatigue and memory impairment were assessed in a total of 101 post-COVID subjects using the Chalder fatigue scale (CFQ-11) and a visual analogue scale. Using the bimodal scoring system generated from CFQ-11, a score ≥4 was defined as severe fatigue. Serum anti-SARS-CoV-2 spike (anti-S-Ig) and nucleocapsid (anti-NC-Ig) antibodies were examined at two time points: 4–12 weeks after onset of symptoms, and beyond 12 weeks. Results: The serum level of anti-S-Ig was significantly higher in patients with non-severe fatigue compared to those with severe fatigue at 4–12 weeks (p = 0.006) and beyond 12 weeks (p = 0.016). The serum level of anti-NC-Ig remained high in patients with non-severe fatigue at both time points. In contrast, anti-NC-Ig decreased significantly in severe fatigue cases regardless of the elapsed time (4–12 weeks: p = 0.024; beyond 12 weeks: p = 0.005). The incidence of memory impairment was significantly correlated with lower anti-S-Ig levels (−0.359, p < 0.001). Conclusion: The systemic immune response reflected by antibodies to SARS-CoV-2 is strongly correlated with the severity of post-COVID fatigue.
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Affiliation(s)
- Tihamer Molnar
- Department of Anaesthesiology and Intensive Care, University of Pecs, Medical School, H7632 Pecs, Hungary;
| | - Reka Varnai
- Department of Primary Health Care, University of Pecs, Medical School, H7632 Pecs, Hungary
- Correspondence: ; Tel.: +36-72535900
| | - Daniel Schranz
- Department of Neurology, University of Pecs, Medical School, H7632 Pecs, Hungary;
| | - Laszlo Zavori
- Salisbury NHS Foundation Trust, Salisbury SP2 8BJ, UK;
| | - Zoltan Peterfi
- 1st Department of Internal Medicine, Division of Infectology, University of Pecs, Medical School, H7632 Pecs, Hungary; (Z.P.); (D.S.)
| | - David Sipos
- 1st Department of Internal Medicine, Division of Infectology, University of Pecs, Medical School, H7632 Pecs, Hungary; (Z.P.); (D.S.)
| | - Margit Tőkés-Füzesi
- Department of Laboratory Medicine, University of Pecs, Medical School, H7632 Pecs, Hungary;
| | - Zsolt Illes
- Department of Neurology, Odense University Hospital, University of Southern Denmark, 5230 Odense, Denmark;
| | - Andras Buki
- Department of Neurosurgery, University of Pecs, Medical School, H7632 Pecs, Hungary; (A.B.); (P.C.)
| | - Peter Csecsei
- Department of Neurosurgery, University of Pecs, Medical School, H7632 Pecs, Hungary; (A.B.); (P.C.)
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Bi Y, Zhang L, Li X, Kan Y, Li S, Zou Y, Liu L, Yuan Y, Gong W, Zhang Y. Contributing factors of fatigue in patients with type 2 diabetes: A systematic review. Psychoneuroendocrinology 2021; 130:105280. [PMID: 34049018 DOI: 10.1016/j.psyneuen.2021.105280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 05/16/2021] [Accepted: 05/17/2021] [Indexed: 11/29/2022]
Abstract
Remarkable evidence supports the link between type 2 diabetes (T2DM) and fatigue. However, a unifying recommendation to identify and prevent fatigue or to prevent its clinical consequences in T2DM is not available at present. Therefore, this study aimed to conduct a systematic review to summarize the definition, measurement tools, and contributing factors of fatigue in T2DM. Nine articles were included for analysis, and results showed that T2DM fatigue was associated with five major factors, including sociodemographic factors, clinical disease factors, inflammatory factors, psychological factors, and behavior and lifestyle. The contributing factors of T2DM fatigue are reviewed, and clinical benefits provide a theoretical basis for further clinical intervention to prevent the occurrence of fatigue and improve the patient's treatment compliance and self-management ability and may be beneficial to their quality of life.
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Affiliation(s)
- Yaxin Bi
- School of Nursing, Yangzhou University, Yangzhou, China
| | - Lu Zhang
- School of Nursing, Yangzhou University, Yangzhou, China
| | - Xiangning Li
- School of Nursing, Yangzhou University, Yangzhou, China
| | - Yinshi Kan
- School of Nursing, Yangzhou University, Yangzhou, China
| | - Shuang Li
- School of Nursing, Yangzhou University, Yangzhou, China
| | - Yan Zou
- School of Nursing, Yangzhou University, Yangzhou, China
| | - Lin Liu
- School of Nursing, Yangzhou University, Yangzhou, China
| | - Yuan Yuan
- Affiliated Hospital of Yangzhou University, Yangzhou, China
| | - Weijuan Gong
- School of Nursing, Yangzhou University, Yangzhou, China; Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China
| | - Yu Zhang
- School of Nursing, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, China.
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Wunsch E, Stadnik A, Kruk B, Szczepankiewicz B, Kotarska K, Krawczyk M, Górnicka B, Wójcicki M, Milkiewicz P. Chronic Fatigue Persists in a Significant Proportion of Female Patients After Transplantation for Primary Sclerosing Cholangitis. Liver Transpl 2021; 27:1032-1040. [PMID: 33641247 DOI: 10.1002/lt.26033] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 01/27/2021] [Accepted: 02/08/2021] [Indexed: 12/15/2022]
Abstract
Chronic fatigue and an impairment of general health-related quality of life (HRQoL) are frequently reported by patients with primary sclerosing cholangitis (PSC). Studies on patients with primary biliary cholangitis (PBC) suggest that, unlike pruritus, fatigue may not be ameliorated by liver transplantation (LT). However, there are few data regarding the assessment of fatigue before and after transplantation in PSC. To investigate the effect of LT on fatigue and HRQoL in patients with PSC, 81 patients with PSC (median age 33 years; 69% men) were prospectively enrolled in this study. The PBC-40 and Short Form 36 (SF-36) questionnaires were used for assessment before and twice after LT. A total of 26 patients who received a transplant for PBC were included as controls. The potential impact of the clinical and laboratory parameters was evaluated by univariate and multivariate analyses. Although in addition to other well-being indexes the median fatigue score improved after LT (P < 0.001), a detailed analysis demonstrated that fatigue persists in one-third of patients. A significant fatigue reduction was seen in men (P < 0.001) but not women (P = 0.25). Posttransplant fatigue did not depend on concomitant inflammatory bowel disease, laboratory indexes of cholestasis, or disease recurrence. In the multivariate regression model, female sex was the only independent covariate associated with persistent fatigue. In terms of other measures of HRQoL, LT caused a substantial improvement in the majority of SF-36 and PBC-40 domains. Recurrent PSC and unemployment negatively affected the well-being of patients. Patients who received a transplant for PSC had significantly better HRQoL than those patients with PBC. LT improves various measures of HRQoL, but it does not ameliorate fatigue in female patients with PSC.
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Affiliation(s)
- Ewa Wunsch
- Translational Medicine Group, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Anna Stadnik
- Department of Radiology, Medical University of Warsaw, Warsaw, Poland
| | - Beata Kruk
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | | | - Katarzyna Kotarska
- Faculty of Physical Culture and Health, University of Szczecin, Szczecin, Poland
| | - Marcin Krawczyk
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.,Department of Medicine II, Saarland University Medical, Homburg, Germany.,European Reference Network, Saarland University Medical Center, Homburg, Germany
| | - Barbara Górnicka
- Department of Pathology, Medical University of Warsaw, Warsaw, Poland
| | - Maciej Wójcicki
- European Reference Network, Saarland University Medical Center, Homburg, Germany.,Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Milkiewicz
- Translational Medicine Group, Pomeranian Medical University in Szczecin, Szczecin, Poland.,Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.,European Reference Network, Medical University of Warsaw Hospital, Warsaw, Poland
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Weigel B, Eaton-Fitch N, Passmore R, Cabanas H, Staines D, Marshall-Gradisnik S. A preliminary investigation of nutritional intake and supplement use in Australians with myalgic encephalomyelitis/chronic fatigue syndrome and the implications on health-related quality of life. Food Nutr Res 2021; 65:5730. [PMID: 34262415 PMCID: PMC8254462 DOI: 10.29219/fnr.v65.5730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 04/01/2021] [Accepted: 04/02/2021] [Indexed: 01/08/2023] Open
Abstract
Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem illness without a currently recognized pharmacological treatment. Dietary supplementation and modification have been posited as potential management strategies; however, their efficacy is controversial. Objective This study aimed to assess the nutritional intake and supplement use of Australian ME/CFS patients and the perceived effect on health-related quality of life (HRQoL) for the first time in an Australian patient population. Design Between February 2019 and January 2020, ME/CFS patients across Australia volunteered in this cross-sectional study in response to online advertisements. Eligible respondents were invited to complete three online self-administered questionnaires investigating their supplement use, nutritional intake, and HRQoL. The study participants’ supplement use and nutritional intake were summarized and compared with the population data returned from the Australian Health Survey (2011–2012). Multiple linear regression analysis was also performed to determine the effect of participants’ supplement use and nutrient intake on HRQoL. Results Twenty-four eligible ME/CFS patients (54.2% meeting the International Consensus Criteria, 79.2% female, mean age = 43.4 ± 10.5 years) completed the online questionnaires. Supplement use was highly prevalent among the study sample (87.5%) and considerably more common when compared with population data (31.9%). Daily total fats and caffeine intakes were significantly higher among ME/CFS patients when compared with the Australian population (P = 0.009 and P = 0.033, respectively), whereas daily intakes of total carbohydrates and alcohol were significantly lower (both P < 0.001). No consistent trends between nutrition and supplement use with patients’ HRQoL could be identified. Conclusions The daily diet and supplement use of ME/CFS patients appear to vary considerably from those of the general Australian population. Although the role of nutritional intake and supplement use on ME/CFS patients’ HRQoL remains unclear, dietary changes and the use of supplements appear to be of value to ME/CFS patients.
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Affiliation(s)
- Breanna Weigel
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,School of Medical Science, Griffith University, Gold Coast, Australia
| | - Natalie Eaton-Fitch
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,School of Medical Science, Griffith University, Gold Coast, Australia
| | - Rachel Passmore
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,School of Medical Science, Griffith University, Gold Coast, Australia
| | - Hélène Cabanas
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,School of Medical Science, Griffith University, Gold Coast, Australia
| | - Donald Staines
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia
| | - Sonya Marshall-Gradisnik
- The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.,Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia
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Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol. Healthcare (Basel) 2021; 9:healthcare9060683. [PMID: 34198946 PMCID: PMC8230194 DOI: 10.3390/healthcare9060683] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/03/2021] [Accepted: 06/03/2021] [Indexed: 11/17/2022] Open
Abstract
(1) Introduction: Multiple studies have shown that peak oxygen consumption is reduced in the majority of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS )patients, using the gold standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 2-day CPET protocol has shown different results on day 2 in ME/CFS patients compared to sedentary controls. No comparison is known between ME/CFS and idiopathic chronic fatigue (ICF) for 2-day CPET protocols. We compared ME/CFS patients with patients with chronic fatigue who did not fulfill the ME/CFS criteria in a male population and hypothesized a different pattern of response would be present during the 2nd day CPET. (2) Methods: We compared 25 male patients with ICF who had completed a 2-day CPET protocol to an age-/gender-matched group of 26 male ME/CFS patients. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were collected at maximal (peak) and ventilatory threshold (VT) intensities. (3) Results: Baseline characteristics for both groups were similar for age, body mass index (BMI), body surface area, (BSA), and disease duration. A significant difference was present in the number of patients with fibromyalgia (seven ME/CFS patients vs. zero ICF patients). Heart rate at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between 0.002 and <0.0001). ME/CFS patients showed a deterioration of performance on CPET2 as reflected by VO2 and workload at peak exercise and ventilatory threshold, whereas ICF patients showed improved performance on CPET2 with no significant change in peak workload. (4) Conclusion: This study confirms that male ME/CFS patients have a reduction in exercise capacity in response to a second-day CPET. These results are similar to published results in male ME/CFS populations. Patients diagnosed with ICF show a different response on day 2, more similar to sedentary and healthy controls.
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Female Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Idiopathic Chronic Fatigue: Comparison of Responses to a Two-Day Cardiopulmonary Exercise Testing Protocol. Healthcare (Basel) 2021; 9:healthcare9060682. [PMID: 34198913 PMCID: PMC8229058 DOI: 10.3390/healthcare9060682] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 05/01/2021] [Accepted: 06/03/2021] [Indexed: 11/18/2022] Open
Abstract
Introduction: Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients, using the golden standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 2-day CPET protocol has shown different results on day 2 in ME/CFS patients compared to sedentary controls. No comparison is known between ME/CFS and idiopathic chronic fatigue (ICF) for 2-day CPET protocols. We compared ME/CFS patients with patients with chronic fatigue who did not fulfil the ME/CFS criteria in a male population and hypothesized a different pattern of response would be present during the 2nd day CPET. Methods: Fifty-one female patients with ICF completed a 2-day CPET protocol and were compared to an age/sex-matched group of 50 female ME/CFS patients. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were collected at maximal (peak) and ventilatory threshold (VT) intensities. Results: Baseline characteristics for both groups were similar for age, BMI, BSA, and disease duration. A significance difference was present in the number of patients with fibromyalgia (seven ME/CFS patients vs zero ICF patients). Heart rate at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between 0.002 and <0.0001). ME/CFS patients showed a deterioration of performance on CPET2 as reflected by VO2 and workload at peak exercise and ventilatory threshold, whereas ICF patients showed improved performance on CPET2 with no significant change in peak workload. Conclusion: This study confirms that female ME/CFS patients have a reduction in exercise capacity in response to a second day CPET. These results are similar to published results in female ME/CFS populations. Patients diagnosed with ICF show a different response on day 2, more similar to sedentary and healthy controls.
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Noor N, Urits I, Degueure A, Rando L, Kata V, Cornett EM, Kaye AD, Imani F, Narimani-Zamanabadi M, Varrassi G, Viswanath O. A Comprehensive Update of the Current Understanding of Chronic Fatigue Syndrome. Anesth Pain Med 2021; 11:e113629. [PMID: 34540633 PMCID: PMC8438707 DOI: 10.5812/aapm.113629] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 05/31/2021] [Accepted: 06/03/2021] [Indexed: 02/07/2023] Open
Abstract
This is a comprehensive literature review of chronic fatigue syndrome (CFS). We provide a description of the background, etiology, pathogenesis, diagnosis, and management regarding CFS. CFS is a multifaceted illness that has many symptoms and a wide array of clinical presentations. As of recent, CFS has been merged with myalgic encephalomyelitis (ME). Much of the difficulty in its management has stemmed from a lack of a concrete understanding of its etiology and pathogenesis. There is a potential association between dysfunction of the autoimmune, neuroendocrine, or autonomic nervous systems and the development of CFS. Possible triggering events, such as infections followed by an immune dysregulation resulting have also been proposed. In fact, ME/CFS was first described following Epstein Barr virus (EBV) infections, but it was later determined that it was not always preceded by EBV infection. Patient diagnosed with CFS have shown a noticeably earlier activation of anaerobic metabolism as a source of energy, which is suggestive of impaired oxygen consumption. The differential diagnoses range from tick-borne illnesses to psychiatric disorders to thyroid gland dysfunction. Given the many overlapping symptoms of CFS with other illnesses makes diagnosing it far from an easy task. The Centers for Disease Control and Prevention (CDC) considers it a diagnosing of exclusion, stating that self-reported fatigue for at minimum of six months and four of the following symptoms are necessary for a proper diagnosis: memory problems, sore throat, post-exertion malaise, tender cervical or axillary lymph nodes, myalgia, multi-joint pain, headaches, and troubled sleep. In turn, management of CFS is just as difficult. Treatment ranges from conservative, such as cognitive behavioral therapy (CBT) and antidepressants, to minimally invasive management. Minimally invasive management involving ranscutaneous electrical acupoint stimulation of target points has demonstrated significant improvement in fatigue and associated symptoms in a 2017 randomized controlled study. The understanding of CFS is evolving before us as we continue to learn more about it. As further reliable studies are conducted, providing a better grasp of what the syndrome encompasses, we will be able to improve our diagnosis and management of it.
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Affiliation(s)
- Nazir Noor
- Mount Sinai Medical Center, Department of Anesthesiology, Miami Beach, FL, USA
| | - Ivan Urits
- Louisiana State University Health Shreveport, Department of Anesthesiology, Shreveport, LA, USA
- Southcoast Health, Southcoast Physician Group Pain Medicine, MA, USA
| | - Arielle Degueure
- Louisiana State University Health Shreveport School of Medicine, Shreveport, LA, USA
| | - Lauren Rando
- Louisiana State University Health Shreveport School of Medicine, Shreveport, LA, USA
| | - Vijay Kata
- Louisiana State University Health Shreveport School of Medicine, Shreveport, LA, USA
| | - Elyse M. Cornett
- Louisiana State University Health Shreveport, Department of Anesthesiology, Shreveport, LA, USA
| | - Alan D. Kaye
- Louisiana State University Health Shreveport, Department of Anesthesiology, Shreveport, LA, USA
| | - Farnad Imani
- Pain Research Center, Department of Anesthesiology and Pain Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | | | - Omar Viswanath
- Louisiana State University Health Shreveport, Department of Anesthesiology, Shreveport, LA, USA
- Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ, USA
- Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, USA
- University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA
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Kuo CF, Shi L, Lin CL, Yao WC, Chen HT, Lio CF, Wang YTT, Su CH, Hsu NW, Tsai SY. How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight. Sci Rep 2021; 11:7520. [PMID: 33824394 PMCID: PMC8024330 DOI: 10.1038/s41598-021-87018-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 03/22/2021] [Indexed: 02/08/2023] Open
Abstract
Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS. Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed. We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan. The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75-2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.
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Affiliation(s)
- Chien-Feng Kuo
- Department of Medicine, Graduate Institute of Long-Term Care, Graduate Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan
- Department of Cosmetic Applications and Management, MacKay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan
- Division of Infectious Diseases, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Leiyu Shi
- Department of Health Policy and Management, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Cheng-Li Lin
- College of Medicine, China Medical University, Taichung City, Taiwan
- Management Office for Health Data, China Medical University Hospital, Taichung City, Taiwan
| | - Wei-Cheng Yao
- Department of Anesthesiology and Pain Medicine, Min-Sheng General Hospital, Tao-Yuan, 330, Taiwan
| | - Hsiang-Ting Chen
- Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chon-Fu Lio
- Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Yu-Ting Tina Wang
- Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Ching-Huang Su
- Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Nai-Wei Hsu
- Department of Medicine, Graduate Institute of Long-Term Care, Graduate Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan
- Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Shin-Yi Tsai
- Department of Medicine, Graduate Institute of Long-Term Care, Graduate Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan.
- Department of Cosmetic Applications and Management, MacKay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan.
- Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
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Wright A, Fisher PL, Baker N, O'Rourke L, Cherry MG. Perfectionism, depression and anxiety in chronic fatigue syndrome: A systematic review. J Psychosom Res 2021; 140:110322. [PMID: 33278659 DOI: 10.1016/j.jpsychores.2020.110322] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 11/19/2020] [Accepted: 11/27/2020] [Indexed: 11/17/2022]
Abstract
OBJECTIVE High levels of depression and anxiety are experienced alongside Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Psychological causal and maintenance factors are not well-understood. Perfectionism is a multifactorial, transdiagnostic risk factor for various physical and mental health conditions. This systematic review assesses the association between perfectionism and depression and/or anxiety in people with CFS/ME. METHOD Systematic literature searches used a combination of terms for 'perfectionism', 'depression', 'anxiety' and 'CFS/ME'. Peer-reviewed English-language papers reporting quantitative data regarding the relationship between perfectionism and depression and/or anxiety in adults (aged 18-65 years) with a clinical diagnosis of CFS/ME were included. Screening, selection and assessment of risk of bias was completed independently by two authors. Bivariate and multivariate associations between perfectionism and anxiety and depression were extracted. Data were synthesised narratively. RESULTS Seven studies, reported in eight papers, were included. Seven examined the relationship between perfectionism and depression. Moderate-strong significant positive associations were found between depression and maladaptive perfectionism (r = 0.42 to .48, p < .01), and its component factors of concern over mistakes (r = 0.40 to .60, p < .01) and doubts about actions (r = 0.51 to .60, p < .01). Methodological limitations included sample size justification and selection, psychometric measures, and control of potential confounders. CONCLUSION Maladaptive perfectionism is consistently associated with depression in patients with CFS/ME. The relationship between perfectionism and anxiety is under-researched. Corroboration is required from longitudinal, cross-cultural studies. Clinical understanding may be increased through examining the interplay between maladaptive perfectionism, depression and anxiety and the physical and cognitive symptoms of CFS/ME.
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Affiliation(s)
- Amelia Wright
- Department of Primary Care and Mental Health, University of Liverpool, Whelan Building, Quadrangle, Brownlow Hill, Liverpool L69 3GB, UK
| | - Peter L Fisher
- Department of Primary Care and Mental Health, University of Liverpool, Whelan Building, Quadrangle, Brownlow Hill, Liverpool L69 3GB, UK; Clinical Health Psychology Service, Linda McCartney Centre, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK
| | - Nita Baker
- Midlands Partnership NHS Foundation Trust, Physical Health Psychology Department, Tamworth, UK
| | - Louise O'Rourke
- Department of Primary Care and Mental Health, University of Liverpool, Whelan Building, Quadrangle, Brownlow Hill, Liverpool L69 3GB, UK
| | - Mary Gemma Cherry
- Department of Primary Care and Mental Health, University of Liverpool, Whelan Building, Quadrangle, Brownlow Hill, Liverpool L69 3GB, UK; Clinical Health Psychology Service, Linda McCartney Centre, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK.
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Zou S, Liu ZH, Yan X, Wang H, Li Y, Xu X, Du X, Zhang L, Zhang Q, Jackson T, Ungvari GS, Xiang YT. Prevalence and correlates of fatigue and its association with quality of life among clinically stable older psychiatric patients during the COVID-19 outbreak: a cross-sectional study. Global Health 2020; 16:119. [PMID: 33339523 PMCID: PMC7748982 DOI: 10.1186/s12992-020-00644-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 11/13/2020] [Indexed: 12/15/2022] Open
Abstract
Background The pattern of fatigue in older psychiatric patients during the COVID-19 outbreak was unknown. This study examined the prevalence of fatigue and its association with overall quality of life (overall QOL) in clinically stable older patients with psychiatric disorders during the COVID-19 outbreak. Methods This was a multicenter, cross-sectional study. Fatigue, depressive symptoms, pain, insomnia symptoms, and overall QOL were assessed with standardized instruments. Results A total of 1063 patients were recruited. The prevalence of fatigue was 47.1% (95%CI: 44.1–50.1%). An analysis of covariance revealed that overall QOL was significantly lower in patients with fatigue compared to those without (P = 0.011). A multiple logistic regression analysis revealed that more severe depressive symptoms (OR = 1.15, P < 0.001), insomnia symptoms (OR = 1.08, P < 0.001) and pain (OR = 1.43, P < 0.001) were significantly associated with fatigue. Conclusions Fatigue is common among clinically stable older patients with psychiatric disorders during the COVID-19 outbreak. Considering its negative impact on overall QOL, regular assessment of fatigue and appropriate treatment warrant attention in this subpopulation.
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Affiliation(s)
- Siyun Zou
- Medical College of Soochow University, Suzhou, Jiangsu Province, China.,Guangji Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, China
| | - Zi-Han Liu
- Unit of Psychiatry, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Building E12, Avenida da Universidade, Taipa, Macau SAR, China.,Center for Cognition and Brain Sciences, University of Macau, Macao SAR, China.,Institute of Advanced Studies in Humanities and Social Sciences, University of Macau, Macao SAR, China
| | - Xiaona Yan
- Department of Psychiatry, Xiamen Xianyue Hospital, Xiamen, China
| | - Huan Wang
- Department of Psychiatry, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China
| | - Yulong Li
- Department of Psychiatry, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China
| | - Xiuying Xu
- Department of Psychiatry, Xiamen Xianyue Hospital, Xiamen, China
| | - Xiangdong Du
- Medical College of Soochow University, Suzhou, Jiangsu Province, China.,Guangji Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, China
| | - Lan Zhang
- Department of Psychiatry, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China
| | - Qinge Zhang
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, School of Mental Health, Beijing, China.
| | - Todd Jackson
- Department of Psychology, University of Macau, Macau SAR, China
| | - Gabor S Ungvari
- Division of Psychiatry, School of Medicine, University of Western Australia, Perth, Australia.,University of Notre Dame Australia, Fremantle, Australia
| | - Yu-Tao Xiang
- Unit of Psychiatry, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Building E12, Avenida da Universidade, Taipa, Macau SAR, China. .,Center for Cognition and Brain Sciences, University of Macau, Macao SAR, China. .,Institute of Advanced Studies in Humanities and Social Sciences, University of Macau, Macao SAR, China.
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Townsend L, Dyer AH, Jones K, Dunne J, Mooney A, Gaffney F, O'Connor L, Leavy D, O'Brien K, Dowds J, Sugrue JA, Hopkins D, Martin-Loeches I, Ni Cheallaigh C, Nadarajan P, McLaughlin AM, Bourke NM, Bergin C, O'Farrelly C, Bannan C, Conlon N. Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLoS One 2020; 15:e0240784. [PMID: 33166287 PMCID: PMC7652254 DOI: 10.1371/journal.pone.0240784] [Citation(s) in RCA: 573] [Impact Index Per Article: 114.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 10/02/2020] [Indexed: 12/12/2022] Open
Abstract
Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. However, it is unknown if COVID-19 results in persistent fatigue in those recovered from acute infection. We examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). We further examined potential predictors of fatigue following COVID-19 infection, evaluating indicators of COVID-19 severity, markers of peripheral immune activation and circulating pro-inflammatory cytokines. Of 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (67/128; 52.3%) at median of 10 weeks after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention.
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Affiliation(s)
- Liam Townsend
- Department of Infectious Diseases, St James’s Hospital, Dublin, Ireland
- Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
| | - Adam H. Dyer
- Department of Immunology, St James’s Hospital, Dublin, Ireland
- Department of Medical Gerontology, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
| | - Karen Jones
- Department of Immunology, St James’s Hospital, Dublin, Ireland
| | - Jean Dunne
- Department of Immunology, St James’s Hospital, Dublin, Ireland
| | - Aoife Mooney
- Department of Immunology, St James’s Hospital, Dublin, Ireland
| | - Fiona Gaffney
- Department of Immunology, St James’s Hospital, Dublin, Ireland
| | - Laura O'Connor
- Department of Immunology, St James’s Hospital, Dublin, Ireland
| | - Deirdre Leavy
- Department of Immunology, St James’s Hospital, Dublin, Ireland
| | - Kate O'Brien
- Department of Physiotherapy, St James’s Hospital, Dublin, Ireland
| | - Joanne Dowds
- Department of Physiotherapy, St James’s Hospital, Dublin, Ireland
| | - Jamie A. Sugrue
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
| | - David Hopkins
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | | | - Cliona Ni Cheallaigh
- Department of Infectious Diseases, St James’s Hospital, Dublin, Ireland
- Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
| | | | | | - Nollaig M. Bourke
- Department of Medical Gerontology, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
| | - Colm Bergin
- Department of Infectious Diseases, St James’s Hospital, Dublin, Ireland
- Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
| | - Cliona O'Farrelly
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
- Department of Comparative Immunology, School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Ciaran Bannan
- Department of Infectious Diseases, St James’s Hospital, Dublin, Ireland
- Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
| | - Niall Conlon
- Department of Immunology, St James’s Hospital, Dublin, Ireland
- Department of Immunology, School of Medicine, Trinity College Dublin, Dublin, Ireland
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van Campen C(LMC, Rowe PC, Visser FC. Validation of the Severity of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome by Other Measures than History: Activity Bracelet, Cardiopulmonary Exercise Testing and a Validated Activity Questionnaire: SF-36. Healthcare (Basel) 2020; 8:healthcare8030273. [PMID: 32823979 PMCID: PMC7551321 DOI: 10.3390/healthcare8030273] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 08/12/2020] [Accepted: 08/13/2020] [Indexed: 11/29/2022] Open
Abstract
Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe and disabling chronic disease. Grading patient’s symptom and disease severity for comparison and therapeutic decision-making is necessary. Clinical grading that depends on patient self-report is subject to inter-individual variability. Having more objective measures to grade and confirm clinical grading would be desirable. Therefore, the aim of this study was to validate the clinical severity grading that has been proposed by the authors of the ME International Consensus Criteria (ICC) using more standardized measures like questionnaires, and objective measures such as physical activity tracking and cardiopulmonary exercise testing. Methods and results: The clinical database of a subspecialty ME/CFS clinic was searched for patients who had completed the SF 36 questionnaire, worn a SensewearTM armband for five days, and undergone a cardiopulmonary exercise test. Only patients who completed all three investigations within 3 months from each other—to improve the likelihood of stable disease—were included in the analysis. Two-hundred-eighty-nine patients were analyzed: 121 were graded as mild, 98 as moderate and 70 as having severe disease. The mean (SD) physical activity subscale of the SF-36 was 70 (11) for mild, 43 (8) for moderate and 15 (10) for severe ME/CFS patients. The mean (SD) number of steps per day was 8235 (1004) for mild, 5195 (1231) for moderate and 2031 (824) for severe disease. The mean (SD) percent predicted oxygen consumption at the ventilatory threshold was 47 (11)% for mild, 38 (7)% for moderate and 30 (7)% for severe disease. The percent peak oxygen consumption was 90 (14)% for mild, 64 (8)% for moderate and 48 (9)% for severe disease. All comparisons were p < 0.0001. Conclusion: This study confirms the validity of the ICC severity grading. Grading assigned by clinicians on the basis of patient self-report created groups that differed significantly on measures of activity using the SF-36 physical function subscale and objective measures of steps per day and exercise capacity. There was variability in function within severity grading groups, so grading based on self-report can be strengthened by the use of these supplementary measures.
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Affiliation(s)
| | - Peter C. Rowe
- Department of Paediatrics, John Hopkins University School of Medicine, Baltimore, MD 21205, USA;
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Thapaliya K, Marshall-Gradisnik S, Staines D, Barnden L. Mapping of pathological change in chronic fatigue syndrome using the ratio of T1- and T2-weighted MRI scans. Neuroimage Clin 2020; 28:102366. [PMID: 32777701 PMCID: PMC7417892 DOI: 10.1016/j.nicl.2020.102366] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Revised: 07/28/2020] [Accepted: 07/29/2020] [Indexed: 02/06/2023]
Abstract
Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) subjects suffer from a variety of cognitive complaints indicating that the central nervous system plays a role in its pathophysiology. Recently, the ratio T1w/T2w has been used to study changes in tissue myelin and/or iron levels in neurodegenerative diseases such as multiple sclerosis and schizophrenia. In this study, we applied the T1w/T2w method to detect changes in tissue microstructure in ME/CFS patients relative to healthy controls. We mapped the T1w/T2w signal intensity values in the whole brain for forty-five ME/CFS patients who met Fukuda criteria and twenty-seven healthy controls and applied both region- and voxel-based quantification. We also performed interaction-with-group regressions with clinical measures to test for T1w/T2w relationships that are abnormal in ME/CFS at the population level. Region-based analysis showed significantly elevated T1w/T2w values (increased myelin and/or iron) in ME/CFS in both white matter (WM) and subcortical grey matter. The voxel-based group comparison with sub-millimetre resolution voxels detected very significant clusters with increased T1w/T2w in ME/CFS, mostly in subcortical grey matter, but also in brainstem and projection WM tracts. No areas with decreased T1w/T2w were found in either analysis. ME/CFS T1w/T2w regressions with heart-rate variability, cognitive performance, respiration rate and physical well-being were abnormal in both gray and white matter foci. Our study demonstrates that the T1w/T2w approach is very sensitive and shows increases in myelin and/or iron in WM and basal ganglia in ME/CFS.
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Affiliation(s)
- Kiran Thapaliya
- National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Australia; Centre for Advanced Imaging, The University of Queensland, Australia.
| | - Sonya Marshall-Gradisnik
- National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Australia
| | - Don Staines
- National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Australia
| | - Leighton Barnden
- National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Australia
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