2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T64b,Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem neurologic disease characterized by profound fatigue and decreased functional capacity, postexertional malaise, and unrefreshing sleep, along with cognitive impairment and/or orthostatic intolerance. Its prevalence has risen exponentially with the COVID-19 pandemic. Pharmacologic therapies have been used successfully by ME/CFS specialists but may be underused by the general medical field. To assess this potential practice gap, we retrospectively analyzed the records of 571 patients with an ME/CFS diagnosis referred to our ME/CFS specialty clinic in Minnesota during 2018-2022. We ascertained medications that had already been tried at the time of consultation and also ascertained supplement use. With the exception of medications primarily used for pain and anxiety, use of pharmacotherapy for ME/CFS symptom management as proposed by specialists was limited. Overall, 68.3% of patients had had at least 1 medication potentially prescribed for ME/CFS; the most common were serotonin-norepinephrine reuptake inhibitors, gabapentin, and tricyclic antidepressants. A slightly larger share of patients, 72.2%, reported having taken at least 1 dietary supplement; the most common were vitamin D, vitamin B Our findings suggest that potentially helpful medications for ME/CFS are being underprescribed in the general medical field and that patients may resort to supplements to manage symptoms. Better education of clinicians about available treatment options and treatment guides may improve management of this debilitating disease.31:T76c,Post-viral syndromes are heterogeneous multisystem diseases without a uniform etiology that occur as a result of acute viral infections. During the COVID-19 pandemic, the number of patients increased dramatically due to infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is known as post-acute sequelae of COVID-19 (PASC), with many cases also meeting the criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the most severe form of a post-viral disease, characterized by severe fatigue, post-exertional malaise (PEM), unrefreshing sleep, neurocognitive impairment, and autonomic and immune dysregulation. Orexin (OX) neuropeptides, which regulate arousal, metabolism, and neuroendocrine functions, may serve as a central link between stress, immune activation, and metabolic changes in these syndromes. Notable phenotypic similarities between OX system dysfunction and core features of PASC and ME/CFS, including fatigue, sleep issues, impaired glucose metabolism, and neuropsychiatric symptoms, support a mechanistic model in which impaired OX signaling contributes to post-viral endocrine and metabolic dysfunction. This review examines the role of OX in regulating glucose metabolism, HPA axis activity, and systemic homeostasis, with a specific focus on sexually dimorphic expression and function in relation to post-viral syndromes. We also highlight the effect of glucagon-like peptide-1 (GLP-1), another key player in metabolism, which also has neuroprotective, anti-inflammatory, vasoprotective, and immunomodulatory effects. We further emphasize emerging therapeutic strategies, such as GLP-1 receptor agonists (GLP-1RAs) and drugs targeting the OX system. Together, these insights provide an integrated framework for understanding and targeting the neuroendocrine-metabolic underpinnings of PASC, ME/CFS, and other post-viral syndromes.32:T7cb,Abstract Postviral syndromes are heterogeneous multisystem diseases without a uniform etiology that occur as a result of acute viral infections. During the COVID-19 pandemic, the number of patients increased dramatically due to infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is known as postacute sequelae of COVID-19 (PASC), with many cases also meeting the criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the most severe form of a postviral disease, characterized by severe fatigue, postexertional malaise (PEM), unrefreshing sleep, neurocognitive impairment, and autonomic and immune dysregulation. Orexin (OX) neuropeptides, which regulate arousal, metabolism, and neuroendocrine functions, may serve as a central link among stress, immune activation, and metabolic changes in these syndromes. Notable phenotypic similarities between OX system dysfunction and core features of PASC and ME/CFS, including fatigue, sleep issues, impaired glucose metabolism, and neuropsychiatric symptoms, support a mechanistic model in which impaired OX signaling contributes to postviral endocrine and metabolic dysfunction. This review examines the role of OX in regulating glucose metabolism, HPA axis activity, and systemic homeostasis, with a specific focus on sexually dimorphic expression and function in relation to postviral syndromes. We also highlight the effect of glucagon-like peptide-1 (GLP-1), another key player in metabolism, which also has neuroprotective, anti-inflammatory, vasoprotective, and immunomodulatory effects. We further emphasize emerging therapeutic strategies, such as GLP-1 receptor agonists (GLP-1RAs) and drugs targeting the OX system. Together, these insights provide an integrated framework for understanding and targeting the neuroendocrine-metabolic underpinnings of PASC, ME/CFS, and other postviral syndromes.33:T606,Post-COVID condition (PCCo) affects 5-10% of individuals following SARS-CoV-2 infection, with cognitive disturbances being a major feature. Central hypotheses regarding its pathophysiology include disturbed cell energy metabolism and oxidative stress pointing to mitochondrial dysfunction. However, brain energy metabolism remains unexplored. We investigated cerebral high-energy phosphate metabolism in 27 PCCo patients and 23 fully recovered controls using whole-brain PCCo patients showed a significant cluster of reduced ATP/PCr ratios centered on the cingulate cortex. Regional analysis revealed consistent reductions across anterior (ACC), mid- (MCC), and posterior (PCC) cingulate cortices. Lower ATP/PCr ratios in the ACC specifically correlated with poorer cognitive performance. Exploratory analyses revealed a trend toward higher intracellular pH in the MCC with significant negative correlation between pH and ATP/PCr observed only in patients, suggesting disease-specific alterations in pH regulation and bioenergetic homeostasis. Subgroup analysis showed similar metabolic alterations in PCCo patients meeting ME/CFS criteria. Our study provides first in vivo evidence of impaired brain energy metabolism in PCCo, with anterior cingulate dysfunction directly linked to cognitive impairment. The observed pH-ATP/PCr relationship suggests broader disruption of cellular bioenergetic regulation. These findings support mitochondrial dysfunction as a key pathophysiological mechanism and may inform targeted therapeutic strategies.34:T6d5,Postacute sequelae of COVID-19 (PASC), also known as long COVID, and postacute COVID-19 vaccination syndrome (PACVS) present overlapping but distinct clinical challenges. We hypothesize that PASC and PACVS share clinical features but differ in symptom patterns and biomarker profiles. This study aims to identify differences in presentation and distinguish immunologic biomarkers relevant to general clinical practice. This cross-sectional study analyzed 181 patients from a PASC clinic at Columbia University Irving Medical Center. Patients were divided into PASC with myalgic encephalomyelitis/chronic fatigue syndrome (MECFS), PASC without MECFS (LC), and PACVS groups. Prevalence and severity of self-reported symptoms, as well as immunologic abnormalities, were compared across groups. Fatigue was the most common symptom (Total: 88.95%; MECFS: 100.00%; PACVS: 92.86%; LC: 78.05%). The MECFS group generally reported more symptoms across all organ systems. The PACVS group reported higher rates of atypical chief complaints such as peripheral neuropathy (17.9%), tinnitus (7.1%), and rash (10.7%) compared to the other groups (P = <.01). Functional impairment was comparable between the MECFS and PACVS groups and less severe in the LC group. All groups had high rates of autoantibody positivity and cytokine elevation. The PACVS group showed significantly higher rates of anticardiolipin IgM (PACVS 42.9%, LC 11.6%; P = .02) and anti-U1-RNP (PACVS 21.4%, LC 2.3%; P = .04) positivity compared to the LC group. PASC and PACVS share symptom overlap but exhibit distinct biomarker patterns, particularly elevated autoantibody levels in PACVS. These findings suggest autoimmune involvement, warranting further investigation for targeted therapies.35:T959,Abstract Background Postacute sequelae of COVID-19 (PASC), also known as long COVID, and postacute COVID-19 vaccination syndrome (PACVS) present overlapping but distinct clinical challenges. We hypothesize that PASC and PACVS share clinical features but differ in symptom patterns and biomarker profiles. This study aims to identify differences in presentation and distinguish immunologic biomarkers relevant to general clinical practice. Methods This cross-sectional study analyzed 181 patients from a PASC clinic at Columbia University Irving Medical Center. Patients were divided into PASC with myalgic encephalomyelitis/chronic fatigue syndrome (MECFS), PASC without MECFS (LC), and PACVS groups. Prevalence and severity of self-reported symptoms, as well as immunologic abnormalities, were compared across groups. Results Fatigue was the most common symptom (Total: 88.95%; MECFS: 100.00%; PACVS: 92.86%; LC: 78.05%). The MECFS group generally reported more symptoms across all organ systems. The PACVS group reported higher rates of atypical chief complaints such as peripheral neuropathy (17.9%), tinnitus (7.1%), and rash (10.7%) compared to the other groups (P = <.01). Functional impairment was comparable between the MECFS and PACVS groups and less severe in the LC group. All groups had high rates of autoantibody positivity and cytokine elevation. The PACVS group showed significantly higher rates of anticardiolipin IgM (PACVS 42.9%, LC 11.6%; P = .02) and anti-U1-RNP (PACVS 21.4%, LC 2.3%; P = .04) positivity compared to the LC group. Conclusions PASC and PACVS share symptom overlap but exhibit distinct biomarker patterns, particularly elevated autoantibody levels in PACVS. These findings suggest autoimmune involvement, warranting further investigation for targeted therapies. 36:Ta70, Introduction Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease hallmarked by multiple systemic symptoms, such as neurocognitive, respiratory, immunological, gastrointestinal, and cardiovascular impairment, which worsen following physical and mental exertion. ME/CFS is characterized by an elusive pathomechanism, profound impact on quality of life, and an absence of diagnostic tests or evidence-based treatments. Transient Receptor Potential Melastatin 3 (TRPM3) ion channel has been suggested as a potential biomarker and target for therapeutics in people with ME/CFS, supported by a series of publications reporting genetic and protein changes. This study aimed to undertake a multi-site, large-scale investigation to determine the consistency of TRPM3 ion channel dysfunction in people with ME/CFS. Methods TRPM3 ion channel activity was assessed in two distinct laboratory sites by independent investigators using whole-cell patch-clamp recordings performed in isolated natural killer (NK) cells from 36 ME/CFS participants, characterized according to the Canadian Consensus Criteria, and 42 healthy controls. The Mann–Whitney U test was used to compare endogenous TRPM3-like currents between cohorts. The effect of location was determined using a covariance analysis, while antagonist sensitivity was determined using Fisher’s Exact test. Results Electrophysiological experiments revealed a significant reduction in TRPM3 function in NK cells from individuals diagnosed with ME/CFS compared with controls in all parameters analyzed. Importantly, there was no significant effect of the laboratory sites on the results of this investigation, which confirms TRPM3 as a consistent biomarker for ME/CFS. Conclusion The current large-sample-size study confirmed previous results regarding TRPM3 ion channel dysfunction in NK cells in ME/CFS, demonstrating involvement of TRPM3 in the pathomechanism of this condition. Therefore, this multiple-site investigation offers strong evidence demonstrating TRPM3 as a potential biomarker for the diagnosis of ME/CFS, given the accumulating evidence. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (condition). Clinician-written summaries and actionable practice insights. 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A total of 142 studies were synthesized.","key_result":"Across 142 included studies, disrupted amino acid, energy, and lipid metabolism; gut microbiome dysbiosis; mitochondrial stress; and miRNA network alterations were consistently implicated in PAIS. The NF-κB pathway emerged as a unifying hub connecting these findings; IL-6, IFN-γ, and TNF-α showed the highest frequency of reported increases across both PACS and ME/CFS cohorts.","limitations":"- High risk of bias across most included studies (per NOS assessment), with low comparability scores.\n- Heterogeneous analytical methods and focus on subsets of molecules limit cross-study synthesis.\n- Most studies are cross-sectional; longitudinal and large-cohort multi-omics validation is lacking.","practice_takeaway":"No single validated biomarker yet exists for PAIS, but NF-κB-driven immune dysregulation and metabolic reprogramming (not active viral replication) appear central — clinicians should frame PAIS as a host-response disorder. Future workup strategies may benefit from multi-omics panels targeting tryptophan-kynurenine metabolism, mitochondrial stress markers, and inflammatory cytokines (IL-6, IFN-γ, TNF-α)."}},{"doi":"10.1016/j.transci.2026.104482","pmid":"42391726","title":"Therapeutic plasma exchange and immunomodulatory strategies in post-infectious syndromes: A review of immune dysregulation in PTLDS, long COVID, ME/CFS, and PANS/PANDAS","journal_title":"Transfusion and Apheresis Science","journal_issn":"1473-0502","published_at":"2026-06-26T00:00:00.000Z","url":"https://doi.org/10.1016/j.transci.2026.104482","source_score":10,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-05T13:38:34.195Z","updated_at":"2026-07-05T13:38:34.195Z","tags":[{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"condition","value":"Long COVID","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"condition","value":"PANS/PANDAS","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"condition","value":"Post-Treatment Lyme Disease Syndrome","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"modality","value":"Anti-CD20 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"modality","value":"Intravenous Immunoglobulin","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"modality","value":"Therapeutic Plasma Exchange","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"warning","value":"No primary data were collected; all conclusions are based on synthesis of existing literature, limiting evidentiary strength.","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"warning","value":"PANS/PANDAS primarily affects pediatric patients while the other syndromes predominantly affect adults; pooled analysis across these age groups may obscure age-specific treatment signals.","value_numeric":null},{"paper_doi":"10.1016/j.transci.2026.104482","tag_type":"warning","value":"The paper is dated June 2026, which is very recent; some cited trial results (e.g., phase II TPE in post-COVID) may not yet be widely peer-reviewed or replicated.","value_numeric":null}],"summaries":{"what_studied":"This narrative review evaluated immune dysregulation across four post-infectious syndromes—PTLDS, long COVID, ME/CFS, and PANS/PANDAS—and assessed the rationale and evidence for immunomodulatory therapies including IVIG, rituximab, and therapeutic plasma exchange (TPE).","key_result":"Evidence for immune-targeted treatments is strongest in patients with identifiable immunologic abnormalities. The phase III RituxME trial (rituximab in ME/CFS) and a phase II TPE trial in post-COVID both failed to show efficacy in unselected populations, highlighting the need for biomarker-guided patient selection.","limitations":"Narrative review design limits causal inference; evidence synthesis across heterogeneous syndromes may obscure condition-specific signals; lack of controlled trials with immunologic phenotyping leaves treatment recommendations largely observational.","practice_takeaway":"Avoid broad use of TPE or rituximab in unselected post-infectious syndrome patients—reserve immune-directed therapies for those with demonstrable autoantibody burden or defined immunologic phenotypes. Controlled trials with biomarker-based stratification are urgently needed."}},{"doi":"10.3389/fnins.2026.1875420","pmid":null,"title":"Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS","journal_title":"Frontiers in Neuroscience","journal_issn":"1662-453X","published_at":"2026-06-19T00:00:00.000Z","url":"https://doi.org/10.3389/fnins.2026.1875420","source_score":19,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-06-27T13:27:57.979Z","updated_at":"2026-06-27T13:27:57.979Z","tags":[{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"modality","value":"Diffusion Tensor Imaging","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"sample_size","value":"n=58","value_numeric":58},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"warning","value":"No drug or therapeutic intervention was studied; tags for modality reflect the imaging technique used, not a treatment class.","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"warning","value":"The DTI-ALPS index is an indirect proxy for glymphatic function — it measures perivascular water diffusion, not direct CSF/ISF flow.","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1875420","tag_type":"warning","value":"This is explicitly a preliminary study with a small sample size (n=58); effect sizes are modest and results should not be considered practice-changing without replication.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional preliminary study compared glymphatic function — measured by the non-invasive DTI-ALPS index via 3T MRI — in 31 adults with ME/CFS versus 27 healthy controls, and explored associations between glymphatic function and symptom severity (sleep disturbance, impaired concentration, fatigue).","key_result":"The global DTI-ALPS index was significantly lower in ME/CFS than healthy controls (1.44 ± 0.09 vs. 1.51 ± 0.11; p = 0.014, p-FDR = 0.028). The right hemisphere drove this difference (ME/CFS 1.41 vs. controls 1.49; p = 0.009); the left hemisphere did not differ. Within ME/CFS, lower DTI-ALPS correlated with worse sleep disturbance (r = −0.47, p = 0.013) and impaired concentration (r = −0.43, p = 0.026).","limitations":"- Small, cross-sectional sample (n = 58) limits causal inference and generalizability.\n- Handedness and sleep position — both known to influence glymphatic function — were not controlled or recorded.\n- Uneven sex distribution precluded sex-stratified analysis; ROI placement was manual, which may introduce variability despite high ICC (>0.90).","practice_takeaway":"ME/CFS patients show measurable glymphatic dysfunction on standard 3T MRI that tracks with sleep disturbance and cognitive symptoms — this supports considering sleep optimization as a therapeutic target. DTI-ALPS is a promising non-invasive biomarker for future ME/CFS studies, but findings are preliminary and need replication in larger cohorts."}},{"doi":"10.1016/j.yfrne.2026.101268","pmid":"42320559","title":"Systems neuroendocrinology in ME/CFS and long COVID: a chronobiological framework for hormone-based research","journal_title":"Frontiers in Neuroendocrinology","journal_issn":"0091-3022","published_at":"2026-06-19T00:00:00.000Z","url":"https://doi.org/10.1016/j.yfrne.2026.101268","source_score":13,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-22T13:24:03.490Z","updated_at":"2026-06-22T13:24:03.490Z","tags":[{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"condition","value":"Long COVID","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"condition","value":"Neuroendocrine Dysfunction","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"modality","value":"Chronobiology","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"modality","value":"Hormone Biomarker Assessment","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"warning","value":"Full text was inaccessible due to a publisher bot/CAPTCHA wall; all extracted content is based on the abstract only. Specific findings, cited studies, and the depth of evidence synthesis could not be verified.","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"warning","value":"Study design classification as 'Narrative Review' is inferred from the abstract language ('we review', 'we outline a framework'); no explicit design label was stated.","value_numeric":null},{"paper_doi":"10.1016/j.yfrne.2026.101268","tag_type":"warning","value":"The paper is a framework/opinion review proposing a research agenda; no original patient data or quantitative outcomes are reported.","value_numeric":null}],"summaries":{"what_studied":"This narrative review examines neuroendocrine dysfunction in ME/CFS and Long COVID, focusing on hormone output (steroid, peptide, neuropeptide), functional assays, receptor expression, hypothalamic-pituitary axes, and the role of circadian and menstrual biorhythms in multisystem dysregulation.","key_result":"Sex hormone signalling is identified as a key area of vulnerability, particularly given the female predominance in both conditions; current evidence is fragmented by the absence of time-structured (circadian and menstrual cycle–aware) sampling and multi-system integration.","limitations":"- Based solely on the abstract; full text was inaccessible due to a publisher paywall/bot challenge, so depth of evidence synthesis, specific studies cited, and strength of conclusions cannot be verified.\n- As a review/framework paper, no original data or effect sizes are reported.\n- Proposed chronobiology-aware, dense-sampling strategies remain theoretical at this stage.","practice_takeaway":"When evaluating hormone levels in patients with ME/CFS or Long COVID, clinicians should account for the time of day and menstrual cycle phase at sampling, as static single-timepoint measurements may miss meaningful neuroendocrine dysregulation. A multi-system, chronobiology-informed approach may better capture the biology underlying symptom variability in these conditions."}},{"doi":"10.1007/s00115-026-01989-w","pmid":"42313183","title":"Körperlichkeit anerkennen, psychosomatische Verkürzungen zurückweisen","journal_title":"Der Nervenarzt","journal_issn":"0028-2804","published_at":"2026-06-18T00:00:00.000Z","url":"https://doi.org/10.1007/s00115-026-01989-w","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-25T13:25:17.268Z","updated_at":"2026-06-25T13:25:17.268Z","tags":[{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"modality","value":"Cognitive Behavioural Therapy","value_numeric":null},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"modality","value":"Graded Exercise Therapy","value_numeric":null},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"modality","value":"Pacing","value_numeric":null},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"sample_size","value":"n=11297","value_numeric":11297},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"study_design","value":"Cross-Sectional Survey","value_numeric":null},{"paper_doi":"10.1007/s00115-026-01989-w","tag_type":"warning","value":"This is a patient-organisation survey, not a peer-reviewed clinical trial — findings reflect patient-reported experiences and cannot establish causality. The paper was authored by members of the Norwegian ME Association and European ME Alliance, who have an advocacy role; potential advocacy bias should be considered when interpreting framing and conclusions. The article title and DOI reference Der Nervenarzt (2026), but the survey report itself is dated 2024 (EMEA); the relationship between these two documents is unclear from the provided text. Cognitive problems ('brain fog') were inadvertently omitted from the symptom questionnaire, as acknowledged by the authors.","value_numeric":null}],"summaries":{"what_studied":"A pan-European online survey (May–August 2021) of 11,297 ME/CFS patients across 44 countries examined disease severity, course of illness, diagnostic delays, and experiences with healthcare, social support, and treatments including CBT and GET.","key_result":"74% of patients reported little or no healthcare support; only 7% reported improvement over their illness course, while 46% reported mainly deterioration. Late diagnosis (≥10 years) was associated with a 54% higher risk of a deteriorating course vs. early diagnosis (≤3 years). CBT as a 'cure' was rated negatively by 75% of patients; only 5% found it positive. Pacing was rated positively by 75% of respondents. Mean diagnostic delay was 6.8 years (range: 5 years in Ireland/UK to 12 years in Croatia).","limitations":"Non-random, voluntary sampling via patient organisations likely underrepresents severely ill, undiagnosed, and recovered patients. Cognitive problems were omitted from the symptom checklist by error. Causality between healthcare support and disease course cannot be established from this observational design.","practice_takeaway":"Diagnose ME/CFS early and advise pacing immediately — delayed diagnosis is strongly linked to disease deterioration, and GET should be avoided. CBT used as a psychological cure for ME/CFS causes harm in most patients; if CBT is offered at all, frame it as a coping tool and only for milder cases."}},{"doi":"10.1097/mbc.0000000000001439","pmid":"42274123","title":"Dynamic microclot profiling: thromboelastography advances precision management in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome","journal_title":"Blood Coagulation & Fibrinolysis","journal_issn":"0957-5235","published_at":"2026-06-11T00:00:00.000Z","url":"https://doi.org/10.1097/mbc.0000000000001439","source_score":19,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-20T13:24:59.058Z","updated_at":"2026-06-20T13:24:59.058Z","tags":[{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"condition","value":"Long COVID","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"generic","value":"apixaban","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"generic","value":"lumbrokinase","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"modality","value":"Anticoagulant","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"modality","value":"Fibrinolytic","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"warning","value":"Age group tagged as 'adult' by inference from the conditions studied; the abstract does not explicitly state patient demographics.","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"warning","value":"No sample size is reported; this is a literature review without a primary patient cohort.","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"warning","value":"Study design is labeled as a narrative review based on the abstract's description of methodology ('comprehensive literature review'); no PRISMA or systematic review protocol was described.","value_numeric":null},{"paper_doi":"10.1097/mbc.0000000000001439","tag_type":"warning","value":"The full text of this paper was not accessible — only the abstract was retrievable; the PDF content returned was a Lippincott author permissions document unrelated to the article. All structured data are derived solely from the abstract.","value_numeric":null}],"summaries":{"what_studied":"This narrative review evaluates the role of persistent fibrinoid microclots in Long COVID and ME/CFS, and assesses thromboelastography (TEG) as a diagnostic tool to detect hypercoagulability in these conditions.","key_result":"Long COVID patients show a TEG profile of increased clot strength (elevated maximum amplitude) and reduced fibrinolysis (low LY30), consistent with a persistent hypercoagulable state. Microclots are prevalent in both Long COVID and ME/CFS and are proposed to contribute to impaired microcirculation.","limitations":"- Review is narrative, not systematic or meta-analytic, limiting strength of conclusions.\n- TEG interpretation is hampered by preanalytical variability and lack of standardized protocols.\n- Therapeutic trials with anticoagulants (e.g., apixaban) and fibrinolytics (e.g., lumbrokinase) are preliminary and require further validation.","practice_takeaway":"Clinicians managing Long COVID or ME/CFS should be aware of the emerging hypercoagulable phenotype detectable by TEG, though routine use awaits standardization. Anticoagulant and fibrinolytic strategies are investigational and should not be adopted outside of clinical trials."}},{"doi":"10.3389/fimmu.2026.1827700","pmid":null,"title":"Elevated serum levels of interleukin-11 and matrix metalloproteinase-9 in myalgic encephalomyelitis/chronic fatigue syndrome","journal_title":"Frontiers in Immunology","journal_issn":"1664-3224","published_at":"2026-06-05T00:00:00.000Z","url":"https://doi.org/10.3389/fimmu.2026.1827700","source_score":10,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-06-10T14:24:44.395Z","updated_at":"2026-06-10T14:24:44.395Z","tags":[{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"category","value":"Immunology","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"generic","value":"interleukin-11","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"generic","value":"matrix metalloproteinase-9","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"modality","value":"Serum Biomarker","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"sample_size","value":"n=114","value_numeric":114},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"study_design","value":"Case-Control Study","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"warning","value":"Study design is primarily case-control for the serum measurements and in vitro experimental for the mast cell component — a single study_design label may not fully capture both components.","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"warning","value":"The IL-11 and MMP-9 cohorts are separate sub-groups with different sizes and slightly different mean ages, making cross-marker comparisons indirect.","value_numeric":null},{"paper_doi":"10.3389/fimmu.2026.1827700","tag_type":"warning","value":"The sample_size tag (n=114) is an approximation summing all participants across both sub-studies (40+38+18+18); no single unified cohort of this size is reported.","value_numeric":null}],"summaries":{"what_studied":"This study measured serum IL-11 and MMP-9 levels in female ME/CFS patients versus age- and sex-matched healthy controls using ELISA, and tested whether recombinant EBV (rEBV) protein could stimulate MMP-9 release from human cord blood-derived mast cells (MCs) in vitro.","key_result":"Serum IL-11 was significantly elevated in ME/CFS patients (n=40) vs. controls (n=38), and serum MMP-9 was significantly elevated in a smaller ME/CFS cohort (n=18) vs. controls (n=18). rEBV-stimulated MCs released significantly more MMP-9 than unstimulated controls, with LPS showing intermediate elevation.","limitations":"- All ME/CFS patients were female, limiting generalizability to male patients.\n- IL-11 and MMP-9 cohorts differ in size and mean age (57 vs. 51 years), reducing comparability.\n- The in vitro mast cell model uses recombinant EBV protein rather than live virus, and cannot confirm causality in vivo.","practice_takeaway":"IL-11 and MMP-9 are candidate serum biomarkers for ME/CFS, but these are early findings in small, all-female cohorts. Clinicians should await larger, mixed-sex replication studies before applying these markers diagnostically."}},{"doi":"10.1186/s12865-026-00849-1","pmid":"42177403","title":"Deficient TRPM3-linked mitochondrial Ca2+ influx in natural killer cells associated with myalgic encephalomyelitis/chronic fatigue syndrome","journal_title":"BMC Immunology","journal_issn":"1471-2172","published_at":"2026-05-23T00:00:00.000Z","url":"https://doi.org/10.1186/s12865-026-00849-1","source_score":11,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-29T13:23:19.638Z","updated_at":"2026-05-29T13:23:19.638Z","tags":[{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"category","value":"Immunology","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"generic","value":"ononetin","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"generic","value":"pregnenolone sulfate","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"modality","value":"Ion Channel Modulator","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"sample_size","value":"n=20","value_numeric":20},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"study_design","value":"Case-Control Study","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"warning","value":"DOI year (2026) is consistent with the publication date provided; paper appears to be recently published.","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"warning","value":"Sample size is very small (n=10 per group); results should be considered exploratory and hypothesis-generating only.","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"warning","value":"Sex breakdown of participants is not reported in the abstract; the 'mixed' sex tag is an assumption based on typical ME/CFS research populations.","value_numeric":null},{"paper_doi":"10.1186/s12865-026-00849-1","tag_type":"warning","value":"The paradoxical finding of elevated baseline mitochondrial Ca²⁺ alongside reduced cytosolic Ca²⁺ is not fully explained in the abstract; mechanistic interpretation should be made cautiously.","value_numeric":null}],"summaries":{"what_studied":"This study examined whether TRPM3 ion channel dysfunction in NK cells affects mitochondrial Ca²⁺ mobilisation in 10 ME/CFS patients (classified by Canadian Consensus Criteria) versus 10 healthy controls, using fluorescence live-cell imaging with pregnenolone sulfate (TRPM3 activator) and ononetin (TRPM3 inhibitor) ex vivo.","key_result":"ME/CFS NK cells showed significantly reduced cytosolic Ca²⁺ influx amplitude and slope (p < 0.001) but paradoxically higher mitochondrial Ca²⁺ influx amplitude (p < 0.001) at baseline. TRPM3-stimulated cytosolic and mitochondrial Ca²⁺ mobilisation were both significantly blunted in ME/CFS vs. healthy controls (p < 0.015), with shorter T½ responses (p < 0.02).","limitations":"- Very small sample size (n=10 per group) limits generalisability.\n- Ex vivo pharmacological modulation may not fully reflect in vivo TRPM3 physiology.\n- Causal direction is unclear — whether TRPM3 dysfunction drives ME/CFS pathology or results from it cannot be determined from this design.","practice_takeaway":"TRPM3-linked mitochondrial Ca²⁺ signalling is measurably impaired in ME/CFS NK cells, supporting a potential ion-channel biomarker pathway. Clinicians should note this is early-stage mechanistic research; no therapeutic intervention is ready for practice."}},{"doi":"10.1093/brain/awag016","pmid":"42148664","title":"Designing studies for post-treatment Lyme disease and other infection-associated chronic illnesses","journal_title":"Brain","journal_issn":"0006-8950","published_at":"2026-05-18T00:00:00.000Z","url":"https://doi.org/10.1093/brain/awag016","source_score":42,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-23T13:24:58.067Z","updated_at":"2026-05-23T13:24:58.067Z","tags":[{"paper_doi":"10.1093/brain/awag016","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"condition","value":"Long COVID","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"condition","value":"Multiple Sclerosis","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"condition","value":"Post-Treatment Lyme Disease Syndrome","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"warning","value":"Level of evidence assigned as 5 (expert opinion/narrative review) given the absence of systematic search methodology or primary data.","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"warning","value":"Multiple sclerosis is included as a representative IACI comparator, though its classification within the IACI spectrum may be debated.","value_numeric":null},{"paper_doi":"10.1093/brain/awag016","tag_type":"warning","value":"No sex breakdown is reported, as this is a methodological review with no primary patient cohort.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates methodological challenges in studying infection-associated chronic illnesses (IACIs) — including post-treatment Lyme disease syndrome (PTLDS), long COVID, ME/CFS, and multiple sclerosis — and proposes rigorous design approaches to improve research quality and therapeutic development.","key_result":"The authors identify key recurring research failures across IACIs: participant misclassification due to absent objective biomarkers, inconsistent sample collection, inadequate control groups, and systemic issues like stigma and historical neglect that have fueled poorly controlled studies and irreproducible findings.","limitations":"This is a narrative review without systematic search methods or meta-analytic data; recommendations are expert-driven and not empirically validated. No primary data are presented, limiting direct evidence for proposed methodological improvements.","practice_takeaway":"When enrolling patients in IACI research or interpreting existing studies, scrutinize whether diagnostic criteria, control group selection, and sample protocols meet rigorous standards — especially microbiologic proof of the index infection where feasible. Clinicians should remain cautious about therapeutic claims from studies lacking these controls."}},{"doi":"10.1007/s44470-026-00079-7","pmid":"42129014","title":"Sleep in myalgic encephalomyelitis/chronic fatigue syndrome shows marked night-to-night fluctuation under free-living conditions—results from a matched case-control study","journal_title":"Journal of Clinical Sleep Medicine","journal_issn":"1550-9389","published_at":"2026-05-13T00:00:00.000Z","url":"https://doi.org/10.1007/s44470-026-00079-7","source_score":115,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-16T13:22:26.666Z","updated_at":"2026-05-16T13:22:26.666Z","tags":[{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"modality","value":"Sleep Diary","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"modality","value":"Wrist Accelerometry","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"sample_size","value":"n=76","value_numeric":76},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"study_design","value":"Matched Case-Control Study","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"warning","value":"No drug/therapeutic modality was studied; modality tags reflect measurement tools only.","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"warning","value":"Severity subgroup analyses (n=5 mild-to-moderate, n=20 moderate, n=13 moderate-to-severe) were underpowered; the most severe (bedridden) patients were excluded, limiting generalizability across the full ME/CFS spectrum.","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"warning","value":"The Bayesian variability model (BVM) did not confirm group differences in sleep efficiency variability that CV and RMSSD detected — the true nature (trait vs. context-driven) of this variability remains unresolved.","value_numeric":null},{"paper_doi":"10.1007/s44470-026-00079-7","tag_type":"warning","value":"The 'practice_changing' impact flag is applied because the findings directly challenge single-night clinical sleep assessment practice in ME/CFS, but this is observational data and requires replication in larger, more diverse samples.","value_numeric":null}],"summaries":{"what_studied":"This matched case-control study (38 ME/CFS vs. 38 healthy controls, 1:1 matched by age, sex, BMI) compared habitual sleep and night-to-night intraindividual variability (IIV) using 7-day wrist accelerometry, sleep diaries, PSQI, and ESS under free-living conditions. ME/CFS participants were also stratified by symptom severity (Bell CFS Disability Scale).","key_result":"ME/CFS participants spent ~48 min more in bed (539 vs. 492 min, p<0.001) but had no difference in total sleep time (415 vs. 408 min, p=0.49). Sleep efficiency was markedly lower (76.7% vs. 82.5%, p<0.001, d=2.04), with nearly doubled SOL (33 vs. 19 min) and higher WASO (91 vs. 64 min). Crucially, night-to-night variability in sleep efficiency was far greater in ME/CFS (CV: 10.1% vs. 2.5%, p<0.001, d=3.64; RMSSD: 10.3% vs. 2.7%, p<0.001, d=2.67), despite more regular bedtimes. 95% of ME/CFS participants exceeded the PSQI clinical cutoff (>5) vs. 0% of controls.","limitations":"- Sleep disorder exclusion relied on interview only (no polysomnography), so undiagnosed conditions (e.g., sleep apnea) cannot be ruled out.\n- Severity subgroup analyses were underpowered (n=5–20 per stratum) and excluded the most severely affected (bedridden) patients.\n- Only 7 nights of monitoring; no concurrent daily symptom, activity, or PEM data to link triggers to sleep fluctuations.","practice_takeaway":"A single-night sleep assessment may badly misrepresent sleep quality in ME/CFS due to extreme night-to-night variability in sleep efficiency — clinicians should use multi-night ambulatory monitoring (accelerometry + sleep diary) for a truer picture. Regular sleep timing alone is insufficient; strategies targeting sleep *continuity* variability, distinct from behavioral insomnia management, may be needed for this population."}},{"doi":"10.1093/ofid/ofag209","pmid":"42131622","title":"Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell–Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","journal_title":"Open Forum Infectious Diseases","journal_issn":"2328-8957","published_at":"2026-05-12T00:00:00.000Z","url":"https://doi.org/10.1093/ofid/ofag209","source_score":41,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-17T13:21:44.353Z","updated_at":"2026-05-17T13:21:44.353Z","tags":[{"paper_doi":"10.1093/ofid/ofag209","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"category","value":"Immunology","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"category","value":"Infectious Diseases","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"condition","value":"Long COVID","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"modality","value":"Biomarker / Extracellular Vesicle Profiling","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"sample_size","value":"n=125","value_numeric":125},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"warning","value":"CD56+ EV subsets were interpreted as 'neural-enriched' within the CD45− fraction, but CD56 is also expressed on NK cells; results for this subset should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"warning","value":"EV subsets were quantified as hierarchical proportions, not absolute counts; observed differences may reflect compositional shifts rather than true changes in EV release rates.","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"warning","value":"Individual-level demographic data were unavailable for the prepandemic cohort, so covariate-adjusted analyses could not be performed for that group.","value_numeric":null},{"paper_doi":"10.1093/ofid/ofag209","tag_type":"warning","value":"The pandemic-era ME/CFS (pan-ME/CFS) cohort was collected during the pandemic; 10% had a prior documented SARS-CoV-2 infection and 58% were vaccinated, which may confound comparisons with LC-ME/CFS. Subgroup analyses by infection/vaccination status were not feasible due to sample size.","value_numeric":null}],"summaries":{"what_studied":"Plasma extracellular vesicles (EVs) from 125 individuals across pandemic-era (COVID-recovered, LC with ME/CFS phenotype, ME/CFS without COVID) and prepandemic (ME/CFS vs. matched healthy controls) cohorts were profiled by nanoparticle tracking analysis and flow cytometry to identify shared EV concentration, cellular origin, and mitochondrial membrane potential (MMP) signatures in Long COVID and ME/CFS.","key_result":"Both LC-ME/CFS and pan-ME/CFS showed elevated plasma EV concentrations vs. COVID-recovered controls (q = 0.0024 and q = 0.0042), with increased leukocyte-, monocyte/macrophage-, and platelet-derived EVs and reduced B cell-derived EVs in both groups. Elevated MMP positivity within B cell-, monocyte/macrophage-, and NK cell-derived EV subsets was significant in pan-ME/CFS after FDR correction but not in LC-ME/CFS; B cell-derived EV MMP elevation was the only signal that remained consistently significant across both pandemic-era and prepandemic ME/CFS cohorts.","limitations":"- Cross-sectional design prevents causal inference, and cohorts were collected at different time points without prospective harmonization.\n- Small subgroup sizes limited statistical power for subset analyses and precluded subgroup comparisons by vaccination or infection status.\n- Flow cytometry cannot definitively confirm EV cellular origin; EVs were quantified as proportions, not absolute counts, and long-term cryostorage may have affected EV integrity.","practice_takeaway":"Plasma EV profiling is not yet ready for clinical use, but B cell-derived EV mitochondrial membrane potential alterations appear as the most reproducible signal across ME/CFS cohorts and may help guide future biomarker development for Long COVID and ME/CFS."}},{"doi":"10.1055/a-2866-9127","pmid":"42119693","title":"Welche Rolle spielt „die Psyche“? Long COVID und ME/CFS als\n Prüfsteine für eine evidenzbasierte und patient*innenorientierte Psychiatrie und\n Psychotherapie","journal_title":"Psychiatrische Praxis","journal_issn":"0303-4259","published_at":"2026-05-12T00:00:00.000Z","url":"https://doi.org/10.1055/a-2866-9127","source_score":194,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-15T13:23:10.824Z","updated_at":"2026-05-15T13:23:10.824Z","tags":[{"paper_doi":"10.1055/a-2866-9127","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"condition","value":"Long COVID","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"modality","value":"Graded Exercise Therapy","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"modality","value":"Pacing","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"modality","value":"Psychotherapy","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"study_design","value":"Critical Essay","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"warning","value":"Study design tag 'Critical Essay' is used; no standard evidence hierarchy level applies beyond Level 7 (expert opinion).","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"warning","value":"The claim that >80% of surveyed patients experienced psychologization comes from the authors' own 2024 online survey (ref 17), which may have selection bias toward highly engaged or adversely affected patients.","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"warning","value":"The paper is written in German with an English abstract; the full text analysis is based on the German content and its English translation.","value_numeric":null},{"paper_doi":"10.1055/a-2866-9127","tag_type":"warning","value":"This is a critical opinion essay, not an original empirical study — sample sizes and statistics cited are drawn from referenced secondary sources, not collected by the authors themselves.","value_numeric":null}],"summaries":{"what_studied":"This critical essay evaluates the role of psychological factors in the development and perpetuation of Long COVID (LC) and ME/CFS, arguing against 'psychologization' of these conditions in the context of psychiatry and psychotherapy practice.","key_result":"The authors identify five concrete harms from attributing psychological causation to LC/ME/CFS: (1) harm from activation-based therapies (50% of ~4,000 patients reported significant worsening after Graded Exercise Therapy; 30% reported moderate worsening); (2) invalidation of illness experience (>80% of surveyed patients reported experiencing psychologization, linked to stigma and loss of trust in medicine); (3) neglect of somatic diagnostics and treatable comorbidities (e.g., POTS, MCAS); (4) disadvantage in disability and insurance assessments; and (5) unjust burden on families of affected children. The authors also show that arguments for psychological causation rely on nonspecific reasoning, and that 8 of 11 psychotherapy trials in LC reported no adverse event data.","limitations":"This is a critical essay (opinion piece), not a systematic review or empirical study — its conclusions, while referencing evidence, represent the authors' interpretive position. The essay acknowledges that some described harms (e.g., custody removal) are based on case reports without formal empirical study.","practice_takeaway":"Avoid attributing LC or ME/CFS symptoms to psychological factors or recommending graded exercise/activation therapies, as these carry documented risks of irreversible worsening via post-exertional malaise (PEM). Where comorbid psychiatric illness is confirmed, adapt psychotherapy to respect individual energy limits (e.g., video sessions, shorter appointments) and never override patient-reported load thresholds."}},{"doi":"10.1370/afm.250266","pmid":"42055743","title":"Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation","journal_title":"The Annals of Family Medicine","journal_issn":"1544-1709","published_at":"2026-04-30T00:00:00.000Z","url":"https://doi.org/10.1370/afm.250266","source_score":79,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-04","doi":"10.1370/afm.250266","days":"14","issn":"1544-1709","rank":"1","field":"Clinical Medicine","score":"79","category":"Primary Health Care","categories":["Primary Health Care"],"_categories":["Primary Health Care"]},"pubmed":{"doi":"10.1370/afm.250266","title":"Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation.","journal":"Annals of family medicine","methods":"","results":"With the exception of medications primarily used for pain and anxiety, use of pharmacotherapy for ME/CFS symptom management as proposed by specialists was limited. Overall, 68.3% of patients had had at least 1 medication potentially prescribed for ME/CFS; the most common were serotonin-norepinephrine reuptake inhibitors, gabapentin, and tricyclic antidepressants. A slightly larger share of patients, 72.2%, reported having taken at least 1 dietary supplement; the most common were vitamin D, vitamin B","abstract":"$30","keywords":["chronic fatigue syndrome","chronic illness","clinical practice patterns","complementary therapies","integrative medicine","long COVID","medications","myalgic encephalomyelitis","pharmacotherapy","practice-based research","primary care","specialists","supplements"],"pubmed_id":"42055743","conclusions":"Our findings suggest that potentially helpful medications for ME/CFS are being underprescribed in the general medical field and that patients may resort to supplements to manage symptoms. Better education of clinicians about available treatment options and treatment guides may improve management of this debilitating disease.","publication_date":"2026-04-30T00:00:00"},"crossref":{"DOI":"10.1370/afm.250266","URL":"https://doi.org/10.1370/afm.250266","ISSN":["1544-1709","1544-1717"],"link":[{"URL":"https://syndication.highwire.org/content/doi/10.1370/afm.250266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"250266","type":"journal-article","issue":null,"score":1,"title":["Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation"],"author":[{"given":"Stephanie L.","family":"Grach","sequence":"first","affiliation":[]},{"given":"Jaime","family":"Seltzer","sequence":"additional","affiliation":[]},{"given":"Michael R.","family":"Mueller","sequence":"additional","affiliation":[]},{"given":"Chris A.","family":"Aakre","sequence":"additional","affiliation":[]},{"given":"Lasonya T.","family":"Natividad","sequence":"additional","affiliation":[]},{"given":"Donna K.","family":"Lawson","sequence":"additional","affiliation":[]},{"given":"Ravindra","family":"Ganesh","sequence":"additional","affiliation":[]},{"given":"Ryan T.","family":"Hurt","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2026,4,29]]},"member":"1","prefix":"10.1370","source":"Crossref","volume":null,"created":{"date-time":"2026-04-29T14:40:13Z","timestamp":1777473613000,"date-parts":[[2026,4,29]]},"indexed":{"date-time":"2026-05-02T23:03:52Z","timestamp":1777763032854,"date-parts":[[2026,5,2]]},"subject":[],"abstract":null,"accepted":{"date-parts":[[2026,2,3]]},"language":"en","relation":{},"resource":{"primary":{"URL":"http://www.annfammed.org/lookup/doi/10.1370/afm.250266"}},"subtitle":[],"deposited":{"date-time":"2026-04-29T14:40:14Z","timestamp":1777473614000,"date-parts":[[2026,4,29]]},"issn-type":[{"type":"print","value":"1544-1709"},{"type":"electronic","value":"1544-1717"}],"published":{"date-parts":[[2026,4,29]]},"publisher":"Annals of Family Medicine","reference":null,"short-title":[],"alternative-id":["10.1370/afm.250266"],"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["The Annals of Family Medicine"],"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,4,29]]},"references-count":0,"short-container-title":["Ann Fam Med"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1370/afm.250266","is_oa":true,"title":"Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation","updated":"2026-05-03T08:48:54+00:00","published_date":"2026-04-29","best_oa_location":{"url":"https://doi.org/10.1370/afm.250266","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.1370/afm.250266"}}},"created_at":"2026-05-07T22:51:23.670Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1370/afm.250266","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"category","value":"Primary Health Care","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"condition","value":"Long COVID","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"amitriptyline","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"duloxetine","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"fludrocortisone","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"gabapentin","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"guanfacine","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"midodrine","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"montelukast","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"naltrexone","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"generic","value":"pyridostigmine","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Acetylcholinesterase Inhibitor","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Gabapentinoid","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Opioid Antagonist (Low-Dose)","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Serotonin-Norepinephrine Reuptake Inhibitor","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"modality","value":"Tricyclic Antidepressant","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"sample_size","value":"n=571","value_numeric":571},{"paper_doi":"10.1370/afm.250266","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"warning","value":"Fibromyalgia patients were excluded to reduce confounding, which may limit applicability to the many ME/CFS patients who have co-occurring fibromyalgia.","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"warning","value":"Supplement and medication data relied on patient self-report from intake forms without dose or indication details, introducing possible recall and documentation bias.","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"warning","value":"The cohort is 91.4% non-Hispanic White from one U.S. academic center; findings may not reflect prescribing patterns in more diverse or non-academic settings.","value_numeric":null},{"paper_doi":"10.1370/afm.250266","tag_type":"warning","value":"The 'practice_changing' impact flag reflects a significant gap between specialist and generalist prescribing, but this is a single-center retrospective study—causality and generalizability are limited.","value_numeric":null}],"summaries":{"what_studied":"A retrospective cohort study of 571 adults (age 18–70) with ME/CFS—without co-diagnosis of fibromyalgia—referred to a Mayo Clinic specialty clinic in Minnesota (2018–2022), examining which medications and supplements had already been tried before their first specialist consultation.","key_result":"Only 68.3% of patients had tried at least 1 medication potentially targeting ME/CFS symptoms (mean 1.5 medications per patient). Medications most often prescribed were SNRIs (182 patients), gabapentin (155), and tricyclic antidepressants (134)—primarily pain/mood agents—while specialist-favored drugs for fatigue, brain fog, and orthostatic intolerance were rarely used: low-dose naltrexone (8 patients), aripiprazole (12), pyridostigmine (4), midodrine (7). Meanwhile, 72.2% used at least 1 dietary supplement, most commonly vitamin D (359 patients), vitamin B12/B complex (72), and fish oil (51).","limitations":"- Dosages, duration, and reasons for use/discontinuation were not captured, so it is unknown whether medications were prescribed at ME/CFS-appropriate doses.\n- Cohort was predominantly non-Hispanic White (91.4%) from a single specialty clinic, limiting generalizability.\n- Study period ended in 2022; prescribing patterns may have shifted since then, and pediatric/geriatric patients were excluded.","practice_takeaway":"Most ME/CFS patients arrive at specialist care having tried only pain- and mood-targeted drugs, while evidence-informed options for fatigue, orthostatic intolerance, and brain fog (e.g., low-dose naltrexone, aripiprazole, pyridostigmine, guanfacine) are rarely prescribed by generalists. Primary care clinicians should familiarize themselves with ME/CFS treatment guides and use a 'start low, go slow' approach when initiating these agents."}},{"doi":"10.1210/endrev/bnag009","pmid":"42037238","title":"Regulatory cycles of orexin and glucagon-Like peptide-1 in postviral syndromes","journal_title":"Endocrine Reviews","journal_issn":"0163-769X","published_at":"2026-04-27T00:00:00.000Z","url":"https://doi.org/10.1210/endrev/bnag009","source_score":25,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-05-02","doi":"10.1210/endrev/bnag009","days":"14","issn":"0163-769X","rank":"9","field":"Clinical Medicine","score":"25","category":"Endocrinology & Metabolism","categories":["Endocrinology & Metabolism"],"_categories":["Endocrinology & Metabolism"]},"pubmed":{"doi":"10.1210/endrev/bnag009","title":"Regulatory Cycles of Orexin and Glucagon-Like Peptide-1 in Post-Viral Syndromes.","journal":"Endocrine 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The proposed mechanistic model linking OX dysfunction to post-viral syndromes remains largely theoretical, lacking direct clinical trial data. Sex-specific (sexually dimorphic) effects are discussed but supported mainly by preclinical or indirect evidence.","practice_takeaway":"Clinicians managing PASC or ME/CFS patients should be aware of the emerging role of OX system dysfunction and GLP-1 pathways in driving fatigue, metabolic, and neurocognitive symptoms. GLP-1RAs may warrant further investigation as therapeutic candidates, though no clinical trial evidence yet supports their routine use in post-viral syndromes."}},{"doi":"10.1093/cid/ciag240","pmid":"41967005","title":"Making Invisible Illnesses Visible: Recognizing and Responding to Infection-Associated Chronic Conditions","journal_title":"Clinical Infectious Diseases","journal_issn":"1058-4838","published_at":"2026-04-09T00:00:00.000Z","url":"https://doi.org/10.1093/cid/ciag240","source_score":46,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-17T13:21:42.673Z","updated_at":"2026-05-17T13:21:42.673Z","tags":[{"paper_doi":"10.1093/cid/ciag240","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"category","value":"Infectious Diseases","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"condition","value":"Lyme Disease-Associated Chronic Symptoms","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"condition","value":"Post-COVID Conditions","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"warning","value":"No primary data or systematic search: this is an expert perspective/narrative review; all recommendations are opinion- or consensus-based.","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"warning","value":"No specific sample sizes or trial data are reported; the sample_size tag has been omitted accordingly.","value_numeric":null},{"paper_doi":"10.1093/cid/ciag240","tag_type":"warning","value":"The DOI suffix 'ciag240' appears non-standard for CID; clinicians should verify the citation before use.","value_numeric":null}],"summaries":{"what_studied":"This review examines infection-associated chronic conditions and illnesses (IACCI) — including post-COVID conditions (PCC), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and Lyme disease-associated chronic symptoms — outlining gaps in care, shared pathophysiology, and a patient-centered framework for clinical management and research.","key_result":"IACCI share overlapping symptom profiles and pathophysiologic abnormalities yet remain under-resourced; the authors propose leveraging a new CMS chronic condition management code, extended visits, multidisciplinary care teams, and harmonized research designs to close these gaps.","limitations":"This is a narrative review and policy perspective without systematic literature search methods or primary data; specific outcome numbers and treatment efficacy data are not reported; recommendations rely heavily on expert opinion.","practice_takeaway":"Validate patients' experiences and use a multidisciplinary, symptom-focused approach for IACCI management — a new CMS code for chronic condition management can help support longer, more comprehensive visits. Watch for overlapping features of PCC, ME/CFS, and post-Lyme symptoms in fatigued patients who remain ill after infection."}},{"doi":"10.1016/j.biopsych.2026.01.004","pmid":"41525818","title":"Reduced ATP-to-phosphocreatine ratios in neuropsychiatric post-COVID condition: Evidence from 31P magnetic resonance spectroscopy","journal_title":"Biological Psychiatry","journal_issn":"0006-3223","published_at":"2026-01-13T00:00:00.000Z","url":"https://doi.org/10.1016/j.biopsych.2026.01.004","source_score":282,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-11","doi":"10.1016/j.biopsych.2026.01.004","days":"30","issn":"0006-3223","rank":"3","field":"Clinical Medicine","score":"282","category":"Neurosciences","categories":["Neurosciences","Psychiatry"],"_categories":["Neurosciences","Psychiatry"]},"pubmed":{"doi":"10.1016/j.biopsych.2026.01.004","title":"Reduced ATP-to-phosphocreatine ratios in neuropsychiatric post-COVID condition: Evidence from ","journal":"Biological psychiatry","methods":"","results":"PCCo patients showed a significant cluster of reduced ATP/PCr ratios centered on the cingulate cortex. Regional analysis revealed consistent reductions across anterior (ACC), mid- (MCC), and posterior (PCC) cingulate cortices. Lower ATP/PCr ratios in the ACC specifically correlated with poorer cognitive performance. Exploratory analyses revealed a trend toward higher intracellular pH in the MCC with significant negative correlation between pH and ATP/PCr observed only in patients, suggesting disease-specific alterations in pH regulation and bioenergetic homeostasis. Subgroup analysis showed similar metabolic alterations in PCCo patients meeting ME/CFS criteria.","abstract":"$33","keywords":["(6): 31P-MRS","ATP","brain energy metabolism","cingulate cortex","mitochondrial dysfunction","post-COVID condition"],"pubmed_id":"41525818","conclusions":"","publication_date":"2026-01-13T00:00:00"},"crossref":{"DOI":"10.1016/j.biopsych.2026.01.004","URL":"https://doi.org/10.1016/j.biopsych.2026.01.004","ISSN":["0006-3223"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S0006322326000211?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S0006322326000211?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Reduced ATP-to-phosphocreatine ratios in neuropsychiatric post-COVID condition: Evidence from 31P 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It examined ATP/PCr ratios across cingulate subregions and their links to cognition and intracellular pH.","key_result":"Patients showed a cluster of reduced ATP/PCr centered on the cingulate cortex, with consistent reductions in the ACC, MCC, and PCC. Lower ACC ATP/PCr correlated with poorer cognitive performance; only patients showed a negative pH–ATP/PCr relationship, and those meeting ME/CFS criteria had similar metabolic changes.","limitations":"Small sample (27 patients; 23 controls) and cross‑sectional imaging limit causal inference. pH findings were exploratory and lacked reported effect sizes."}},{"doi":"10.1093/cid/ciaf624","pmid":"41510565","title":"Overlapping Clinical Presentation of Long COVID and Postacute COVID-19 Vaccination Syndrome: Phenotypes, Severity, and Biomarkers","journal_title":"Clinical Infectious Diseases","journal_issn":"1058-4838","published_at":"2026-01-09T00:00:00.000Z","url":"https://doi.org/10.1093/cid/ciaf624","source_score":20,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-14","doi":"10.1093/cid/ciaf624","days":"7","issn":"1058-4838","rank":"5","field":"Clinical Medicine","score":"20","category":"Immunology","categories":["Immunology","Infectious Diseases"],"_categories":["Immunology","Infectious Diseases"]},"pubmed":{"doi":"10.1093/cid/ciaf624","title":"Overlapping Clinical Presentation of Long COVID and Postacute COVID-19 Vaccination Syndrome: Phenotypes, Severity, and Biomarkers.","journal":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","methods":"","results":"Fatigue was the most common symptom (Total: 88.95%; MECFS: 100.00%; PACVS: 92.86%; LC: 78.05%). The MECFS group generally reported more symptoms across all organ systems. The PACVS group reported higher rates of atypical chief complaints such as peripheral neuropathy (17.9%), tinnitus (7.1%), and rash (10.7%) compared to the other groups (P = <.01). Functional impairment was comparable between the MECFS and PACVS groups and less severe in the LC group. All groups had high rates of autoantibody positivity and cytokine elevation. The PACVS group showed significantly higher rates of anticardiolipin IgM (PACVS 42.9%, LC 11.6%; P = .02) and anti-U1-RNP (PACVS 21.4%, LC 2.3%; P = .04) positivity compared to the LC group.","abstract":"$34","keywords":["autoimmunity","long COVID","myalgic encephalomyelitis/chronic fatigue syndrome (ME-CFS)","postacute COVID-19 vaccination syndrome (PACVS)","postacute sequelae of COVID-19 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181 patients from a PASC clinic compared three groups—PASC with ME/CFS, PASC without ME/CFS (LC), and postacute COVID-19 vaccination syndrome (PACVS)—for self-reported symptom prevalence/severity and immunologic abnormalities.","key_result":"Fatigue predominated (Total 88.95%; MECFS 100%; PACVS 92.86%; LC 78.05%). PACVS showed higher rates of peripheral neuropathy (17.9%), tinnitus (7.1%), and rash (10.7%) versus other groups (P<.01), comparable functional impairment to MECFS and greater than LC, and higher autoantibody positivity than LC for anticardiolipin IgM (42.9% vs 11.6%; P=.02) and anti-U1-RNP (21.4% vs 2.3%; P=.04); all groups had high autoantibody and cytokine elevations.","limitations":"Single-center, cross-sectional study from a PASC clinic relying on self-reported symptoms. Group sizes and absolute event counts per cohort are not provided in the abstract.","practice_takeaway":"PACVS can mirror the functional impairment seen in PASC with ME/CFS and may present more neuropathy, tinnitus, or rash. Anticardiolipin IgM and anti-U1-RNP positivity appear more frequent in PACVS than LC, which may help phenotype patients while awaiting confirmatory studies."}},{"doi":"10.3389/fmed.2025.1703924","pmid":null,"title":"Large-scale investigation confirms TRPM3 ion channel dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","journal_title":"Frontiers in Medicine","journal_issn":"2296-858X","published_at":"2026-01-08T00:00:00.000Z","url":"https://doi.org/10.3389/fmed.2025.1703924","source_score":117,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-11","doi":"10.3389/fmed.2025.1703924","days":"7","issn":"2296-858X","rank":"9","field":"Clinical Medicine","score":"117","category":"Medicine, General & Internal","categories":["Medicine, General & Internal"],"_categories":["Medicine, General & 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Only 22.56% of ME/CFS NK-cell recordings were ononetin-sensitive (44 recordings) versus 77.44% in controls (151 recordings) (p<0.0001); lab site had no effect (PregS ANCOVA p=0.918; ononetin p=0.369; variance 0.001% and 0.02%).","limitations":"Each patch-clamp recording was treated as a separate technical measurement, which may affect the unit of analysis; fewer ononetin recordings were analyzed due to NK-cell viability during perfusion; participants unable to discontinue drugs or supplements affecting TRPM3/Ca2+ signaling were excluded, and absolute current magnitudes were not reported."}},{"doi":"10.1016/j.eprac.2025.12.020","pmid":"41475665","title":"Low Vasopressin in Myalgic Encephalomyelitise/Chronic Fatigue Syndrome","journal_title":"Endocrine Practice","journal_issn":"1530-891X","published_at":"2025-12-29T00:00:00.000Z","url":"https://doi.org/10.1016/j.eprac.2025.12.020","source_score":20,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-15T13:21:53.085Z","updated_at":"2026-06-15T13:21:53.085Z","tags":[{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"condition","value":"Central Diabetes Insipidus","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"condition","value":"Orthostatic Intolerance","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"generic","value":"copeptin","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"generic","value":"vasopressin","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"modality","value":"Biomarker Assessment","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"sample_size","value":"n=124","value_numeric":124},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"study_design","value":"Observational Study (Case Series)","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"warning","value":"Copeptin data are available for only 13 of 124 patients and cannot be directly compared to the P-VP findings.","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"warning","value":"Full text was not accessible; summary is based on the abstract and results section only.","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"warning","value":"No healthy control group was included, making it difficult to quantify how abnormal these vasopressin levels are relative to a matched population.","value_numeric":null},{"paper_doi":"10.1016/j.eprac.2025.12.020","tag_type":"warning","value":"The study design is classified as an observational case series; some might consider it a cross-sectional study — level of evidence reflects this ambiguity.","value_numeric":null}],"summaries":{"what_studied":"This observational study measured plasma vasopressin (P-VP) or copeptin, plasma osmolality (P-Osm), and urine osmolality (U-Osm) in 124 ME/CFS patients (111 tested for P-VP, 13 for copeptin) after 10-hour overnight fasting and fluid deprivation, to evaluate abnormal water homeostasis as a disease mechanism.","key_result":"P-VP was undetectable (<1.6 pg/mL) in 82% (91/111) of patients; P-Osm was abnormally high (>292 mOsm/kg) in 57.3% (71/124) and U-Osm was below reference (<750 mOsm/kg) in 66.1% (82/124), despite no structural hypothalamic or pituitary pathology on MRI — a pattern consistent with central diabetes insipidus.","limitations":"- Observational design with no healthy control group for direct comparison.\n- Copeptin (a more stable VP surrogate) was only available for 13 patients, limiting cross-validation.\n- Causality cannot be established; it is unclear whether low vasopressin is a primary driver or secondary feature of ME/CFS.","practice_takeaway":"Clinicians evaluating ME/CFS patients with polyuria, polydipsia, or orthostatic intolerance should consider measuring P-Osm, U-Osm, and vasopressin/copeptin, as low vasopressin mimicking central diabetes insipidus may be common and potentially treatable."}},{"doi":"10.1370/afm.240494","pmid":"41285594","title":"To Ground Research in the Lived Experience of Patients and Caregivers, Give Us a Voice!","journal_title":"The Annals of Family Medicine","journal_issn":"1544-1709","published_at":"2025-11-25T00:00:00.000Z","url":"https://doi.org/10.1370/afm.240494","source_score":38,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-12-02","doi":"10.1370/afm.240494","days":"30","issn":"1544-1709","rank":"4","field":"Clinical Medicine","score":"38","category":"Primary Health Care","categories":["Primary Health Care"],"_categories":["Primary Health Care"]},"pubmed":{"doi":"10.1370/afm.240494","title":"To Ground Research in the Lived Experience of Patients and Caregivers, Give Us a Voice!","journal":"Annals of family medicine","methods":"","results":"","abstract":"My daughter has been diagnosed with a range of chronic conditions, including Hyper-mobile Ehlers-Danlos Syndrome and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). I have approached my role as caregiver in the same way I approach my day job leading social science research: reading the literature, carefully observing her condition, and developing hypotheses about her conditions and how they might be treated. I now have more than 7 years of longitudinal observation-a wealth of data-but no easy way to share with the medical research community the hypotheses these observations have engendered and my ideas about how to productively structure future research to accelerate progress toward treatments for her and others like her. In this essay, I share my thoughts on why patient and caregiver observations and hypotheses are important and how the medical research field might tap into them to make faster progress toward effective treatments for complex medical conditions.","keywords":["Ehlers-Danlos Syndrome","chronic illness","long COVID","longitudinal research","myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)","patient and public involvement in research"],"pubmed_id":"41285594","conclusions":"","publication_date":"2025-11-25T00:00:00"},"crossref":{"DOI":"10.1370/afm.240494","URL":"https://doi.org/10.1370/afm.240494","ISSN":["1544-1709","1544-1717"],"link":[{"URL":"https://syndication.highwire.org/content/doi/10.1370/afm.240494","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"570-572","type":"journal-article","issue":"6","score":1,"title":["To Ground Research in the Lived Experience of Patients and Caregivers, Give Us a Voice!"],"author":[{"given":"Jeffrey","family":"Lubell","sequence":"first","affiliation":[]}],"issued":{"date-parts":[[2025,11]]},"member":"1","prefix":"10.1370","source":"Crossref","volume":"23","created":{"date-time":"2025-11-24T23:20:11Z","timestamp":1764026411000,"date-parts":[[2025,11,24]]},"indexed":{"date-time":"2025-11-24T23:21:47Z","timestamp":1764026507735,"date-parts":[[2025,11,24]]},"subject":[],"abstract":null,"accepted":{"date-parts":[[2025,3,12]]},"language":"en","relation":{},"resource":{"primary":{"URL":"http://www.annfammed.org/lookup/doi/10.1370/afm.240494"}},"subtitle":[],"deposited":{"date-time":"2025-11-24T23:20:13Z","timestamp":1764026413000,"date-parts":[[2025,11,24]]},"issn-type":[{"type":"print","value":"1544-1709"},{"type":"electronic","value":"1544-1717"}],"published":{"date-parts":[[2025,11]]},"publisher":"Annals of Family Medicine","reference":null,"short-title":[],"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11]]},"published-online":{"date-parts":[[2025,11,24]]}},"alternative-id":["10.1370/afm.240494"],"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["The Annals of Family Medicine"],"published-print":{"date-parts":[[2025,11]]},"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,11,24]]},"references-count":0,"short-container-title":["Ann Fam Med"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1370/afm.240494","is_oa":true,"title":"To Ground Research in the Lived Experience of Patients and Caregivers, Give Us a Voice!","updated":"2025-11-27T02:22:14+00:00","published_date":"2025-11-01","best_oa_location":{"url":"https://www.annfammed.org/content/annalsfm/23/6/570.full.pdf","pmh_id":null,"url_for_pdf":"https://www.annfammed.org/content/annalsfm/23/6/570.full.pdf","url_for_landing_page":"https://doi.org/10.1370/afm.240494"}}},"created_at":"2025-12-04T03:42:26.941Z","updated_at":"2025-12-04T03:42:26.941Z","tags":[{"paper_doi":"10.1370/afm.240494","tag_type":"category","value":"Primary Health Care","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"condition","value":"Chiari Malformation","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"condition","value":"Craniocervical Instability","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"condition","value":"Ehlers-Danlos Syndrome","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"condition","value":"Long COVID","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"condition","value":"Postural Orthostatic Tachycardia Syndrome","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"study_design","value":"Editorial","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"warning","value":"No sample size, effect estimates, or outcomes reported.","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"warning","value":"Reflection/editorial piece; not an empirical study.","value_numeric":null},{"paper_doi":"10.1370/afm.240494","tag_type":"warning","value":"Single-case observations illustrate relapse–recovery; prevalence remains unknown.","value_numeric":null}],"summaries":{"what_studied":"A reflection argues that patient and caregiver longitudinal observations and hypotheses should be integrated into medical research, using a daughter’s 7+ years of illness with hypermobile EDS, ME/CFS, POTS, craniocervical instability, and Chiari malformation as a case example and proposing concrete publication and collaboration mechanisms.","limitations":"This is a reflection based on one patient’s experience; no systematic data, sample, or outcomes are reported, and relapse–recovery patterns are illustrated anecdotally without prevalence estimates.","practice_takeaway":"Journals and researchers should create accessible pathways for patients and caregivers to publish case studies and hypothesis papers indexed in PubMed, fund open-access fees, and pair patients with researchers for advisory support. Trials in ME/CFS and long COVID should capture longitudinal course and consider segmenting participants by relapse/recovery status where relevant."}}],"initialOffset":20,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"}}}]]

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