Case Report Life-Threatening Malnutrition in Very Severe ME/CFS

Abstract:

Very severe Myalgic Encephalomyelitis (ME), (also known as Chronic Fatigue Syndrome) can lead to problems with nutrition and hydration. The reasons can be an inability to swallow, severe gastrointestinal problems tolerating food or the patient being too debilitated to eat and drink. Some patients with very severe ME will require tube feeding, either enterally or parenterally. There can often be a significant delay in implementing this, due to professional opinion, allowing the patient to become severely malnourished. Healthcare professionals may fail to recognize that the problems are a direct consequence of very severe ME, preferring to postulate psychological theories rather than addressing the primary clinical need. We present five case reports in which delay in instigating tube feeding led to severe malnutrition of a life-threatening degree. This case study aims to alert healthcare professionals to these realities.

Source: Helen Baxter, Nigel Speight, andWilliam Weir. Case Report Life-Threatening Malnutrition in Very Severe ME/CFS. Healthcare 2021, 9(4), 459; https://doi.org/10.3390/healthcare9040459  https://www.mdpi.com/2227-9032/9/4/459 (Full text)

Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue

Abstract:

COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.

Source: Theoharides TC, Cholevas C, Polyzoidis K, Politis A. Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue. Biofactors. 2021 Apr 12. doi: 10.1002/biof.1726. Epub ahead of print. PMID: 33847020. https://pubmed.ncbi.nlm.nih.gov/33847020/

Recovery from chronic fatigue syndrome: a systematic review-heterogeneity of definition limits study comparison

Abstract:

Background: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a common illness with a major impact on quality of life. Recovery is poorly understood. Our aim was to describe definitions of recovery in paediatric CFS/ME, the rate of recovery and the time to recovery.

Methods: This systematic review included a detailed search of MEDLINE, EMBASE, PsycInfo and Cochrane Library between 1994 and July 2018. Inclusion criteria were (1) clinical trials and observational studies, (2) participants aged <19 years with CFS/ME, (3) conducted in Western Healthcare systems and (4) studies including a measure of recovery and time taken to recover.

Results: Twelve papers (10 studies) were identified, involving 826 patients (range 23-135). Recovery rates were highly varied, ranging between 4.5% and 83%.Eleven distinct definitions of recovery were used; six were composite outcomes while five used unidimensional outcomes. Outcome measures used to define recovery were highly heterogeneous. School attendance (n=8), fatigue (n=6) and physical functioning (n=4) were the most common outcomes included in definition of recovery. Only five definitions included a personal measure of recovery.

Implications: Definitions of recovery are highly variable, likely secondary to differences in study design, outcomes used, follow-up and study populations. Heterogeneous definitions of recovery limit meaningful comparison between studies, highlighting the need for a consensus definition going forward. Recovery is probably best defined from the child’s own perspective with a single self-reported measure. If composite measures are used for research, there should be agreement on the core outcome set used.

Source: Moore Y, Serafimova T, Anderson N, King H, Richards A, Brigden A, Sinai P, Higgins J, Ascough C, Clery P, Crawley EM. Recovery from chronic fatigue syndrome: a systematic review-heterogeneity of definition limits study comparison. Arch Dis Child. 2021 Apr 12:archdischild-2020-320196. doi: 10.1136/archdischild-2020-320196. Epub ahead of print. PMID: 33846138. https://pubmed.ncbi.nlm.nih.gov/33846138/

Response to Adamson et al. (2020): ‘Cognitive behavioural therapy for chronic fatigue and chronic fatigue syndrome: Outcomes from a specialist clinic in the UK’

Abstract:

In a paper published in the Journal of the Royal Society of Medicine, Adamson et al. (2020) interpret data as showing that cognitive behavioural therapy leads to improvement in patients with chronic fatigue syndrome and chronic fatigue. Their research is undermined by several methodological limitations, including: (a) sampling ambiguity; (b) weak measurement; (c) survivor bias; (d) missing data and (e) lack of a control group. Unacknowledged sample attrition renders statements in the published Abstract misleading with regard to points of fact. That the paper was approved by peer reviewers and editors illustrates how non-rigorous editorial processes contribute to systematic publication bias.

Source: Hughes BM, Tuller D. Response to Adamson et al. (2020): ‘Cognitive behavioural therapy for chronic fatigue and chronic fatigue syndrome: Outcomes from a specialist clinic in the UK’. J Health Psychol. 2021 Apr 10:13591053211008203. doi: 10.1177/13591053211008203. Epub ahead of print. PMID: 33840241. https://pubmed.ncbi.nlm.nih.gov/33840241/

Acupuncture therapy on chronic fatigue syndrome based on radar plot: A protocol for an overview of systematic reviews

Abstract:

Background: Chronic fatigue syndrome (CFS) is a debilitating chronic disease of unknown etiology that is recognized by the World Health Organization (WHO) and the United States Center for Disease Control and Prevention (US CDC) as a disorder of the brain. CFS affects 1% (17-24 million people) of the world’s population and is a major and costly public health problem. In traditional Chinese medicine (TCM), acupuncture can achieve a certain effect in the treatment of chronic fatigue syndrome, but evidence-based medicine is controversial. This protocol aims to multi-evaluate the literature quality and evidence quality of the current systematic reviews (SRs)/meta-analyses (MAs) of acupuncture treatment for chronic fatigue syndrome, and provide intuitive and reliable evidence synthesis and decision-making basis for clinical treatment.

Methods: Eight databases will be searched from their inception to 1 June, 2020: the Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), Web of Science, Embase, PubMed, and Cochrane Library. Published systematic reviews that were reported in Chinese or English, and the included studies were randomized controlled clinical trials (RCTs) for acupuncture in people with CFS will be included. Reviews selection, data extraction and management, and assessment of the study quality will be completed independently by 2 or more reviewers. The quality of evidence, methodological quality, and reporting quality will be evaluated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), A Measurement Tool to Assessment of Multiple Systematic Reviews-2 (AMSTAR-2), Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and Adobe Illustrator Creative Cloud (Adobe Illustrator CC) will be used to draw and optimize the radar plot.

Results: The article in this overview will be submitted for publication in a peer-reviewed journal.

Conclusion: We hope to collect evidence from accessible and useful systematic reviews of acupuncture treatment for chronic fatigue syndrome, to provide visual and scientific decision-making methods for more clinical practice and medical research.

Source: Tang L, Jiang T, ZHu FY, Liu Z, Wu X. Acupuncture therapy on chronic fatigue syndrome based on radar plot: A protocol for an overview of systematic reviews. Medicine (Baltimore). 2021 Apr 9;100(14):e24572. doi: 10.1097/MD.0000000000024572. PMID: 33832063. https://pubmed.ncbi.nlm.nih.gov/33832063/

Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study

Abstract:

Introduction: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Dysfunction of the blood vessel endothelium could be an underlying biological mechanism, resulting in inability to fine-tune regulation of blood flow according to the metabolic demands of tissues. The objectives of the present study were to investigate endothelial function in ME/CFS patients compared to healthy individuals, and assess possible changes in endothelial function after intervention with IV cyclophosphamide.

Methods: This substudy to the open-label phase II trial “Cyclophosphamide in ME/CFS” included 40 patients with mild-moderate to severe ME/CFS according to Canadian consensus criteria, aged 18-65 years. Endothelial function was measured by Flow-mediated dilation (FMD) and Post-occlusive reactive hyperemia (PORH) at baseline and repeated after 12 months. Endothelial function at baseline was compared with two cohorts of healthy controls (N = 66 and N = 30) from previous studies. Changes in endothelial function after 12 months were assessed and correlated with clinical response to cyclophosphamide. Biological markers for endothelial function were measured in serum at baseline and compared with healthy controls (N = 30).

Results: Baseline FMD was significantly reduced in patients (median FMD 5.9%, range 0.5-13.1, n = 35) compared to healthy individuals (median FMD 7.7%, range 0.7-21, n = 66) (p = 0.005), as was PORH with patient score median 1,331 p.u. (range 343-4,334) vs. healthy individuals 1,886 p.u. (range 808-8,158) (p = 0.003). No significant associations were found between clinical response to cyclophosphamide intervention (reported in 55% of patients) and changes in FMD/PORH from baseline to 12 months. Serum levels of metabolites associated with endothelial dysfunction showed no significant differences between ME/CFS patients and healthy controls.

Conclusions: Patients with ME/CFS had reduced endothelial function affecting both large and small vessels compared to healthy controls. Changes in endothelial function did not follow clinical responses during follow-up after cyclophosphamide IV intervention.

Source: Sørland K, Sandvik MK, Rekeland IG, Ribu L, Småstuen MC, Mella O, Fluge Ø. Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study. Front Med (Lausanne). 2021 Mar 22;8:642710. doi: 10.3389/fmed.2021.642710. PMID: 33829023; PMCID: PMC8019750. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019750/ (Full text)

Specifics of chronic fatigue syndrome coping strategies identified in a French flash survey during the COVID-19 containment

Abstract:

The COVID-19 pandemic has focused health systems on supporting patients affected by this virus. Meanwhile in the community, many other contained patients could only use self-care strategies, especially in countries that have set up a long and strict containment such as France. The study aimed to compare coping strategies deployed by patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS; a poorly recognised syndrome) to those with better known and referenced chronic conditions. An online flash survey was conducted during the containment period in partnership with French Patients Organizations including ME/CFS national association. Therefore, ‘Brief COPE’ version of Lazarus and Folkman’s Ways of Coping Check List has been adapted to the specificity of the containment.

The survey was e-distributed in France from 15 April to 11 May 2020. Differences of coping strategies were analyzed using Wilcoxon-Mann-Withney test. Amongst 637 responses, 192 were complete, presenting a wide variety of diseases, including 93 ME/CFS. The latter have significantly different coping strategies than recognised diagnosed diseases patients: similar uses of emotion focused coping but less uses of seek social support and problem-focused copings.

In conclusion, coping strategies are different for those who deal with the daily experience of ME/CFS, highly disabling chronic condition with diagnostic ambiguity, low degree of medical and social recognition and without treatment. Better understanding of those strategies is needed to provide the means for health promotion researchers, managers and clinicians, to accompany those patients.

Source: Moncorps F, Jouet E, Bayen S, Fornasieri I, Renet S, Las-Vergnas O, Messaadi N. Specifics of chronic fatigue syndrome coping strategies identified in a French flash survey during the COVID-19 containment. Health Soc Care Community. 2021 Apr 6. doi: 10.1111/hsc.13376. Epub ahead of print. PMID: 33825299. https://pubmed.ncbi.nlm.nih.gov/33825299/

How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight

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.

Source: Kuo CF, Shi L, Lin CL, Yao WC, Chen HT, Lio CF, Wang YT, 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 Apr 6;11(1):7520. doi: 10.1038/s41598-021-87018-z. PMID: 33824394. https://pubmed.ncbi.nlm.nih.gov/33824394/

Evaluation of natural killer cell assay performance on shipped blood specimens

Abstract:

Documenting the importance of NK cell function as a biomarker for diseases and physiologic conditions including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), will require assays amenable to clinical implementation and standardization. Research studies typically perform NK functional assays on the day of sample collection. This pilot study was conducted to compare assay formats and specimen processing to identify those that are most tolerant of conditions required for shipping and amenable to standardization as shown by inter-assay and inter-laboratory correlation of results.

We compared performance within and between assays that measure NK cell function using direct cytotoxicity [chromium-51 release (CRCA) or fluorescence (Flow Cytometry Cytotoxicity Assay, FCCA)] or an indirect surrogate marker (CD107a surface expression)]. Additional variables for within/between assay comparisons included time of testing (same day as specimen collection or next day within 24 h), specimen types [whole blood or isolated peripheral blood mononuclear cells (PBMCs)], and processing method (fresh or cryopreserved). Statistical measures included number of samples tested in assay conditions (n), medians (x͂), interquartile range (IQR), Pearson correlation coefficient (R2), and correlation p-value (p).

Samples came from 3 clinics and included 31 participants. Same day testing was only available for the subset of participants enrolled from the site of the laboratory performing CRCA. Results from same day CRCA testing of whole blood were considered the gold standard [n = 10, x͂=10.0%, IQR = 7.2%], and correlated well with PBMCs isolated next day [n = 26, x͂= 15.6%, IQR = 13.1%] [R2 = 0.59, p = 0.03]. Next day CRCA results were compromised using whole blood or frozen PBMCs. Next day FCCA cytotoxicity in PBMC [n = 30, x͂=34.1%, IQR = 15.5%] correlated with same day CRCA PMBC [R2 = 0.8, p = 0.001] and next day CRCA PMBC [R2 = 0.5, p < 0.0001]. CD107a expression after induction by PMA and ionomycin did not correlate with other cytotoxicity measures. NK function can be measured in PBMCs isolated after overnight shipping/storage at ambient temperature and CRCA and FCCA results on this sample type are well correlated.

Source: Querec TD, Abrams J, Stewart JJ, Barnes Z, Balbin E, Klimas N, Fletcher MA, Brown L, Bertolli J, Unger ER. Evaluation of natural killer cell assay performance on shipped blood specimens. J Immunol Methods. 2021 Apr 2:113049. doi: 10.1016/j.jim.2021.113049. Epub ahead of print. PMID: 33819446. https://pubmed.ncbi.nlm.nih.gov/33819446/

Re-analysis of genetic risks for Chronic Fatigue Syndrome from 23andMe data finds few remain

Abstract:

It is tempting to mine the abundance of DNA data that is now available from direct-to-consumer genetic tests but this approach also has its pitfalls A recent study put forth a list of 50 single nucleotide polymorphisms (SNPs) that predispose to Chronic Fatigue Syndrome (CFS), a potentially major advance in understanding this still mysterious condition. However, only the patient cohort data came from a commercial company (23andMe) while the control was from a genetic database. The extent to which 23andMe data agree with genetic reference databases is unknown.

We reanalyzed the 50 purported CFS SNPs by comparing to control data specifically from 23andMe which are available through public platform OpenSNP. In addition, large high-quality database ALFA was used as an additional control. The analysis lead to dramatic change with the top of the leaderboard for CFS risk reduced and reversed from an astronomical 129,000 times to 0.8. Errors were found both within 23andMe data and the original study-reported Kaviar database control. Only 3 of 50 SNPs survived initial study criterion of at least twice as prevalent in patients, EFCAB4B, involved in calcium ion channel activation, LINC01171, and MORN2 genes.

We conclude that the reported top-50 deleterious polymorphisms for Chronic Fatigue Syndrome were more likely the top-50 errors in the 23andMe and Kaviar databases. In general, however, correlation of 23andMe control with ALFA was a respectable 0.93, suggesting an overall usefulness of 23andMe results for research purposes but only if caution is taken with chips and SNPs.

Source: Felice L. Bedford, Bastian Greshake Tzovaras. Re-analysis of genetic risks for Chronic Fatigue Syndrome from 23andMe data finds few remain. medRxiv 2020.10.27.20220939; doi: https://doi.org/10.1101/2020.10.27.20220939
Now published in Frontiers in Pediatrics doi: 10.3389/fped.2021.590040 https://www.medrxiv.org/content/10.1101/2020.10.27.20220939v2.full-text (Full text)