Autoantibody Correlation Signatures in Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Association with Symptom Severity.

Recent studies provide some evidence for the contribution of antibody-mediated autoimmune mechanisms to the nature of fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Much attention was paid to the autoantibodies (AAb) targeting G protein-coupled receptors as natural components of the immune system. However, the natural AAb network is much more extensive, and has not been previously investigated in these disorders. The enzyme immunoassays ELI-Viscero-Test and ELI-Neuro-Test were used to determine changes in serum content of 33 natural AAb to neural, organ-specific and non-tissue-specific autoantigens (a) in 11 ME/CFS patients with comorbid FM; (b) in 11 ME/CFS patients without FM; (c) in 11 healthy controls. Individual AAb profiles and their correlation with some clinical symptoms were analyzed. Both patients with ME/CFS(-)FM and ME/CFS(+)FM were characterized by more frequent and pronounced deviations in the immunoreactivity to GABA-receptors than healthy controls. Although the level of other natural AAb did not differ between study groups, AAb correlation signatures were altered in patients compared to healthy controls. Both in patients and healthy controls the level of natural AAb to various neural and tissue-specific antigens correlated with the severity of fatigue, bodily pain, depression, anxiety, physical and mental health-related quality of life. Notably, widely different correlation patterns were observed between study groups. Findings from this pilot study provide some evidence that the homeostasis of autoimmune relationships, which are possibly a physiological part of our immune system, may be altered in FM and ME/CFS. The correlation of disease-induced perturbations in individual AAb profiles with some clinical symptoms may arise from the immune system's ability to reflect qualitative and quantitative changes in antigenic composition of the body.

New Clinical Phenotype of the Post-Covid Syndrome: Fibromyalgia and Joint Hypermobility Condition.

Fibromyalgia can be defined as a chronic pain condition, affecting the musculoskeletal system, etiology and pathophysiology of which is sufficiently understudied. Despite the fact that many authors consider this entity to be a manifestation of central sensitization, and not an autoimmune disease, the high prevalence of fibromyalgia in patients with post-COVID-19 conditions requires taking a fresh look at the causes of the disease development. During the patient examination, the authors identified a combination of symptoms that occurs so often, that they can be carefully described as a clinical pattern. These manifestations include young age, female gender, joint hypermobility, the onset of pain after COVID-19, physical traumatization of one particular tendon and the development of the fibromyalgia pain syndrome during the next several weeks. As well as an increase in the titer of antinuclear antibodies and some other systemic inflammation factors. It can be assumed with great caution that local damage to the connective tissue in patients with joint hypermobility, having COVID-19 as a trigger factor can lead to the development of fibromyalgia syndrome. This article presents three clinical cases that illustrated this hypothesis.

Small Fiber Neuropathy in Sarcoidosis.

Sarcoidosis (SC) is a granulomatous disease of an unknown origin. The most common SC-related neurological complication is a small fiber neuropathy (SFN) that is often considered to be the result of chronic inflammation and remains significantly understudied. This study aimed to identify the clinical and histological correlates of small fiber neuropathy in sarcoidosis patients. The study was performed in 2018-2019 yy and included 50 patients with pulmonary sarcoidosis (n = 25) and healthy subjects (n = 25). For the clinical verification of the SFN, the "Small Fiber Neuropathy Screening List" (SFN-SL) was used. A punch biopsy of the skin was performed followed by enzyme immunoassay analysis with PGP 9.5 antibodies. Up to 60% of the sarcoidosis patients reported the presence of at least one complaint, and it was possible that these complaints were associated with SFN. The most frequent complaints included dysfunctions of the cardiovascular and musculoskeletal systems and the gastrointestinal tract. A negative, statistically significant correlation between the intraepidermal nerve fiber density (IEND) and SFN-SL score was revealed. In patients with pulmonary sarcoidosis, small fiber neuropathy might develop as a result of systemic immune-mediated inflammation. The most common symptoms of this complication were dysautonomia and mild sensory dysfunction.

Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?

Chronic pain may affect 30-50% of the world's population and an important cause is small fiber neuropathy (SFN). Recent research suggests that autoimmune diseases may be one of the most common causes of small nerve fiber damage. There is low awareness of SFN among patients and clinicians and it is difficult to diagnose as routine electrophysiological methods only detect large fiber abnormalities, and specialized small fiber tests, like skin biopsy and quantitative sensory testing, are not routinely available. Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible method for quantifying small nerve fiber degeneration and regeneration, and could be an important tool for diagnosing SFN. This review considers the advantages and disadvantages of CCM and highlights the evolution of this technique from a research tool to a diagnostic test for small fiber damage, which can be a valuable contribution to the study and management of autoimmune disease.

Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.

Observational data have shown that some cancer survivors develop chronic conditions like frailty, sarcopenia, cardiac dysfunction, and mild cognitive impairment earlier and/or at a greater burden than similarly aged individuals never diagnosed with cancer or exposed to systemic or targeted cancer therapies. In aggregate, cancer- and treatment-related physical, cognitive, and psychosocial late- and long-term morbidities experienced by cancer survivors are hypothesized to represent accelerated or accentuated aging trajectories. However, conceptual, measurement, and methodological challenges have constrained efforts to identify, predict, and mitigate aging-related consequences of cancer and cancer treatment. In July 2018, the National Cancer Institute convened basic, clinical, and translational science experts for a think tank titled "Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors." Through the resulting deliberations, several research and resource needs were identified, including longitudinal studies to examine aging trajectories that include detailed data from before, during, and after cancer treatment; mechanistic studies to elucidate the pathways that lead to the emergence of aging phenotypes in cancer survivors; long-term clinical surveillance to monitor survivors for late-emerging effects; and tools to integrate multiple data sources to inform understanding of how cancer and its therapies contribute to the aging process. Addressing these needs will help expand the evidence base and inform strategies to optimize healthy aging of cancer survivors.

Prevalence and correlates of vaginal estrogenization in postmenopausal women in the United States.

OBJECTIVE: This work aims to establish current population-based vaginal estrogenization norms for postmenopausal US women. METHODS: Using a US national probability sample of 868 postmenopausal women ages 57 to 85 years (mean age 67.6 ±â€Š0.3 y, 21.6 ±â€Š0.5 y since menopause), we calculated the epithelial maturation value (MV) generated from self-collected vaginal specimens and compared findings with historical clinical data. Linear and logistic regressions were used to describe the relationship between vaginal estrogenization and sociodemographic, physical, gynecologic, and sexual characteristics. RESULTS: Among postmenopausal women, mean MV was 46.6 ±â€Š0.8 (SD 17.4, range 2.5-100) and stable across age groups. In every age group, vaginal estrogenization was higher among postmenopausal nonusers of hormone therapy (HT) in the 2005-2006 US cohort than reported for the 1960s Canadian clinical cohort. MV was also higher among women who used postmenopausal HT in the prior 12 months compared with those who did not (55.1 ±â€Š1.2 vs 44.4 ±â€Š0.9, P < 0.001). In multivariate analyses, HT use, obesity and African American race were each independently associated with higher MV. Overall, MV was not associated with sexual activity, but low MV was associated with vaginal dryness during intercourse among sexually active women. CONCLUSIONS: Compared to 1960s clinical data, current population estimates revealed higher vaginal estrogenization across all age groups and no decline with age. The strongest independent correlates of vaginal estrogenization in postmenopausal US women were current HT use, obesity, and African American race. Postmenopause, half of all women exhibit low vaginal estrogenization.

Salivary sex hormone measurement in a national, population-based study of older adults.

OBJECTIVES: To describe the methods used for, correlates of cooperation with, and validity of in-home salivary specimens collected from older adults. METHODS: Salivary specimens were collected between 2005 and 2006 during in-home interviews with a probability sample of 3,005 U.S. men and women, ages 57-85 years. Sex hormone levels were assessed by enzyme-linked immunoassay conducted at Salimetrics, LLC (State College, PA). Mean salivary sex hormone concentrations were compared by gender and in relation to medication use and health conditions. RESULTS: Self-collected saliva specimens were provided by 2,722 (90.6%) individuals; 95.8% of these were adequate for analysis. Black participants were significantly less likely than individuals of other racial/ethnic groups to provide a salivary specimen; age, gender, education, and self-rated health were not associated with participation. Mean testosterone levels were higher in men compared with women, and estradiol levels were higher in women using estrogens. Salivary hormone measurements obtained in the National Social Life, Health, and Aging Project (NSHAP) and other studies are of similar magnitude. CONCLUSION: NSHAP is the first large, population-based study of older adults to measure salivary estradiol, progesterone, dehydroepiandrosterone (DHEA), and, in women, testosterone. These data demonstrate a high cooperation rate with in-home salivary specimen collection from older adults and good validity of sex hormone measurements.

Sexual morbidity in very long term survivors of vaginal and cervical cancer: a comparison to national norms.

OBJECTIVES: To compare sexuality among very long term survivors of vaginal and cervical cancer to national norms and assess quality of care for sexual problems. METHODS: A survey of survivors in a cancer registry (n=221) provided data comparable to the 1992 National Health and Social Life Survey (NHSLS). The NHSLS sample was individually matched on age and race to survivors at a 2:1 ratio. Responses were compared using conditional logistic regression and two-sample t-tests. Correlates of sexual problems among survivors were analyzed using multivariate logistic regression. RESULTS: Survivors' mean age was 49 years (SD=6.0); median survivorship was 26.8 years (range 5.5-39.7). Survivors and controls reported similar levels of sexual partnership and activity, but sexual problems were significantly more prevalent among survivors (mean number of problems 2.6 versus 1.1, P<0.001). Satisfaction with care for sexual problems was lower than with cancer care overall (5.5 versus 8.0/10, P<0.001). While 74% believed that physicians should discuss sex, 62% reported never discussing the effect of genital tract cancer on sexuality. In adjusted analysis, survivors reporting no such discussion were significantly more likely to exhibit current complex sexual morbidity (> or =3 concurrent sexual problems) (OR 2.74, 95% CI 1.14-6.58). CONCLUSIONS: Despite profoundly more sexual problems, survivors' rate of sexual partnership and activity was similar to population controls. Satisfaction with care relating to sexuality was significantly lower than with cancer care overall. Conversation with a physician about the sexual effects of cancer is associated with significantly lower likelihood of complex sexual morbidity among very long term survivors.

Pathology effects at radiation doses below those causing increased mortality.

Mortality data from experiments conducted at the Argonne National Laboratory (ANL) on the long-term effects of external whole-body irradiation on B6CF(1) mice were used to investigate radiation-induced effects at intermediate doses of (60)Co gamma rays or fission-spectrum neutrons either delivered as a single exposure or protracted over 60 once-weekly exposures. Kaplan-Meier analyses were used to identify the lowest dose in the ANL data (within radiation quality, pattern of exposure, and sex) at which radiation-induced mortality caused by primary tumors could be detected (approximately 1-2 Gy for gamma rays and 10-15 cGy for neutrons). Doses at and below these levels were then examined for radiation-induced shifts in the spectrum of pathology detected at death. To do this, specific pathology events were pooled into larger assemblages based on whether they were cancer, cardiovascular disease or non-neoplastic diseases detected within the lungs and pleura, liver and biliary tract, reproductive organs, or urinary tract. Cancer and cardiovascular disease were further subdivided into categories based on whether they caused death, contributed to death, or were simply observed at death. Counts of how often events falling within each of these combined pathology categories occurred within a mouse were then used as predictor variables in logistic regression to determine whether irradiated mice could be distinguished from control mice. Increased pathology burdens were detected in irradiated mice at doses lower than those causing detectable shifts in mortality-22 cGy for gamma rays and 2 cGy for neutrons. These findings suggest that (1) models based on mortality data alone may underestimate radiation effects, (2) radiation may have adverse health consequences (i.e. elevated health risks) even when mortality risks are not detected, and (3) radiation-induced pathologies other than cancer do occur, and they involve multiple organ systems.