Altered serum bile acid profile in fibromyalgia is associated with specific gut microbiome changes and symptom severity.

ABSTRACT: Alterations in the composition and function of the gut microbiome in women with fibromyalgia have recently been demonstrated, including changes in the relative abundance of certain bile acid-metabolizing bacteria. Bile acids can affect multiple physiological processes, including visceral pain, but have yet to be explored for association to the fibromyalgia gut microbiome. In this study, 16S rRNA sequencing and targeted metabolomic approaches were used to characterize the gut microbiome and circulating bile acids in a cohort of 42 women with fibromyalgia and 42 healthy controls. Alterations in the relative abundance of several bacterial species known to metabolize bile acids were observed in women with fibromyalgia, accompanied by significant alterations in the serum concentration of secondary bile acids, including a marked depletion of α-muricholic acid. Statistical learning algorithms could accurately detect individuals with fibromyalgia using the concentration of these serum bile acids. Serum α-muricholic acid was highly correlated with symptom severity, including pain intensity and fatigue. Taken together, these findings suggest serum bile acid alterations are implicated in nociplastic pain. The changes observed in the composition of the gut microbiota and the concentration of circulating secondary bile acids seem congruent with the phenotype of increased nociception and are quantitatively correlated with symptom severity. This is a first demonstration of circulating bile acid alteration in individuals with fibromyalgia, potentially secondary to upstream gut microbiome alterations. If corroborated in independent studies, these observations may allow for the development of molecular diagnostic aids for fibromyalgia as well as mechanistic insights into the syndrome.

Dietary Intake Is Unlikely to Explain Symptom Severity and Syndrome-Specific Microbiome Alterations in a Cohort of Women with Fibromyalgia.

BACKGROUND: Significant alterations were recently identified in the composition and putative function of the gut microbiome in women with fibromyalgia. As diet can influence the composition of the gut microbiome, differences in nutritional intake could, in theory, account for some of these specific fibromyalgia microbiome alterations. The current study aims to compare the diet of women with fibromyalgia to that of controls in order to explore possible associations between the intake of certain nutrients, symptom severity and gut microbiome composition. METHODS: The study population was comprised of 56 women with fibromyalgia and 68 controls. Dietary intake was assessed using the NIH Automated Self-Administered 24 h recall, following dietitian's instructions and the completion of a three-day dietary recall. The gut microbiome was assessed by 16S ribosomal RNA gene sequencing of stool samples. RESULTS: Most demographic and anthropometric characteristics were comparable between groups. The average energy and macronutrient intake (total and relative) and overall diet quality score were not different between patients and controls, nor were the main vitamins, minerals, fatty acids, alcohol, caffeine, sugar or fiber intakes. The daily intake of micronutrients and normalized macronutrients in women with fibromyalgia was largely not correlated with disease-specific measures, including pain intensity, fatigue, cognitive symptoms and quality of sleep, or with the relative quantity of almost any of the gut microbiome bacterial taxa differentially abundant in fibromyalgia. CONCLUSION: These data demonstrate that dietary intakes, as evaluated by self-reported questionnaires, probably cannot explain the syndrome-specific differences in gut microbiome or the clinical phenotype of fibromyalgia.

Fibromyalgia in Older Individuals.

Fibromyalgia (FM) is a condition of chronic widespread pain (CWP) that can occur throughout the life cycle and is likely underrecognized in older patients. FM is associated with considerable suffering and reduction in quality of life and may occur as a unique condition, but in older patients is most likely to be associated with another medical illness. Understood mechanistically to be a sensitization of the nervous system, recently identified as nociplastic pain, FM is accepted as a valid medical illness that requires a positive diagnosis and directed treatments. The cornerstone of treatments for FM are nonpharmacologic interventions, with the understanding that medications provide only modest benefit for most patients, and with particular concern about adverse effects in older patients. If FM is not recognized, treatments may be misdirected to the other medical condition, with failure to address FM symptoms, leading to overall poor outcome. In contrast, new complaints in older patients should not immediately be attributed to FM, and physicians should be vigilant to ensure that onset of a new illness is not ignored. As FM is most often a lifelong condition, patients should be encouraged to identify their own personal strategies that can attenuate symptoms, especially when symptoms flare. Continued life participation should be the outcome goal.

Effects of a patient-tailored integrative oncology intervention in the relief of pain in palliative and supportive cancer care.

CONTEXT AND OBJECTIVES: The present study examined the impact of an integrative oncology treatment program in the relief of pain in patients undergoing chemotherapy and/or palliative care. METHODS: In this pragmatic prospective controlled study, patients undergoing chemotherapy and/or palliative care were referred by their oncology healthcare providers to an integrative physician (IP) consultation, followed by weekly integrative treatments. Patients attending ≥ 4 sessions during the first 6 weeks of the study were considered to be highly adherent to integrative care (AIC). Pain was assessed at baseline and at 6 and 12 weeks using the ESAS (Edmonton Symptom Assessment Scale) and EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) tools. RESULTS: Of 815 eligible patients, 484 (59.4%) were high-AIC and 331 low-AIC. Mean pain scores decreased significantly from baseline to 6 and 12 weeks in both groups. However, ESAS and EORTC pain scores improved significantly more in the high-AIC group at 6 weeks (p= 0.008), though not at 12 weeks. Between-group analysis of participants undergoing adjuvant/neo-adjuvant chemotherapy showed higher pain reduction in the high-AIC group at 6 weeks (ESAS, p = 0.006; EORTC, p = 0.046), as was the case with patients receiving palliative care (ESAS p = 0.04; EORTC p = 0.056). CONCLUSIONS: High adherence to integrative care was found to be associated with a greater effect on pain relief at 6 weeks but not at 12 weeks in patients undergoing chemotherapy and/or palliative care.

Interventional Pain Management for Cancer Pain: An Analysis of Outcomes and Predictors of Clinical Response.

BACKGROUND: Interventional procedures are offered routinely to patients seen in McGill University's interdisciplinary cancer pain management program. However, publications on these procedures are scarce, making it difficult to predict which patients may benefit from them. OBJECTIVES: We hypothesized that interventional pain procedures offered to cancer patients could provide relief of pain as well as other symptoms. Furthermore, some variables may predict the efficacy of such procedures. STUDY DESIGN: We conducted a retrospective chart review of interventional pain management procedures. SETTING: The procedures reviewed were conducted at the Cancer Pain Program and performed at the interventional suites of the McGill University Health Centre. METHODS: The retrospective chart review included interventional pain management procedures performed between June 2015 and March 2017. Demographic data, details about the underlying cancer and about the procedure and peripTrocedural patients' reported outcomes were recorded for analysis. RESULTS: Eighty-two of 126 procedures were included for analysis. Most patients presented with metastatic disease (75%). Eighty percent of the patients reported pain relief, with the average pain severity decreasing by more than 2 points on a 0-to-10 Numeric Rating Scale for pain (from 6.5 of 10 to 4.2 of 10). Forty-three percent of patients were considered responders (>= 50% pain relief). Responders also reported a significant decrease in fatigue, depression, anxiety, drowsiness, and improved well-being. Among responders, average daily opioid use decreased significantly, by 60% on average. None of the analyzed variables correlated with the response; however, psychosocial variables like anxiety and depression showed a nonsignificant trend towards predicting procedure failure. LIMITATIONS: The core limitations of this study are its size and retrospective nature. CONCLUSIONS: In this cohort of cancer pain patients, interventional cancer pain procedures provided effective pain relief and other benefits, including pain relief, reduced burden of symptoms, and reduction of opioid intake, while demonstrating a favorable safety profile. Patients with poorer ratings of depression and fatigue derived less benefit from procedures, suggesting that offering such procedures as part of patients' treatment plan would be sensible, rather than leaving interventions for later stages.

The Case for Comorbid Myofascial Pain-A Qualitative Review.

Myofascial pain syndrome is widely considered to be among the most prevalent pain conditions, both in the community and in specialized pain clinics. While myofascial pain often arises in otherwise healthy individuals, evidence is mounting that its prevalence may be even higher in individuals with various comorbidities. Comorbid myofascial pain has been observed in a wide variety of medical conditions, including malignant tumors, osteoarthritis, neurological conditions, and mental health conditions. Here, we review the evidence of comorbid myofascial pain and discuss the diagnostic and therapeutic implications of its recognition.

Gut microbiome: pertinence in fibromyalgia.

The human gut microbiome constitutes a diverse and dynamic community of microorganisms that inhabit the digestive tract. In recent years, there is growing appreciation for the role of the gut microbiome in host health and disease. Gut bacteria are involved in the pathogenesis of numerous medical conditions in a variety of medical fields including gastroenterology, metabolic, rheumatologic, neurologic and psychiatric disorders. Recently, evidence is mounting that gut bacteria could also play a role in chronic pain and specifically fibromyalgia (FM). The composition of the gut bacterial community is altered in individuals with FM, with an altered abundance of a small subset of bacterial species. Some of these species, either with increased or decreased abundance in patients, have established metabolic activity which could have pertinence in the expression of FM symptoms. The putative mechanisms which could allow these bacterial species to affect pain, fatigue, mood and other symptoms include the entry of short-chain-fatty-acids, bile acids, neurotransmitters and bacterial antigens into the host circulation. While these are merely the first steps in understanding the role of the gut microbiome in chronic pain and specifically FM, one might envision exciting future perspectives for better mechanistic understanding of FM, for the development of objective diagnostic aids and potentially for new therapeutic modalities.

Altered microbiome composition in individuals with fibromyalgia.

Fibromyalgia (FM) is a prevalent syndrome, characterised by chronic widespread pain, fatigue, and impaired sleep, that is challenging to diagnose and difficult to treat. The microbiomes of 77 women with FM and that of 79 control participants were compared using 16S rRNA gene amplification and whole-genome sequencing. When comparing FM patients with unrelated controls using differential abundance analysis, significant differences were revealed in several bacterial taxa. Variance in the composition of the microbiomes was explained by FM-related variables more than by any other innate or environmental variable and correlated with clinical indices of FM. In line with observed alteration in butyrate-metabolising species, targeted serum metabolite analysis verified differences in the serum levels of butyrate and propionate in FM patients. Using machine-learning algorithms, the microbiome composition alone allowed for the classification of patients and controls (receiver operating characteristic area under the curve 87.8%). To the best of our knowledge, this is the first demonstration of gut microbiome alteration in nonvisceral pain. This observation paves the way for further studies, elucidating the pathophysiology of FM, developing diagnostic aids and possibly allowing for new treatment modalities to be explored.

Medical Cannabis for Older Patients.

Interest in the medicinal use of cannabis and cannabinoids is mounting worldwide. Fueled by enthusiastic media coverage, patients perceive cannabinoids as a natural remedy for many symptoms. Cannabinoid use is of particular interest for older individuals who may experience symptoms such as chronic pain, sleep disturbance, cancer-related symptoms and mood disorders, all of which are often poorly controlled by current drug treatments that may also incur medication-induced side effects. This review provides a summary of the evidence for use of cannabinoids, and medical cannabis in particular, for this age group, with attention to efficacy and harms. Evidence of efficacy for relief of an array of symptoms is overall scanty, and almost all study participants are aged < 60 years. The risk of known and potential adverse effects is considerable, with concerns for cognitive, cardiovascular and gait and stability effects in older adults. Finally, in light of the paucity of clinical evidence and increasing patient requests for information or use, we propose a pragmatic clinical approach to a rational dialogue with older patients, highlighting the importance of individual benefit-risk assessment and shared patient-clinician decision making.

[The approach to the treatment of lower-limb varicose veins].

Varicose veins have been described as early as the classical period of ancient Greece, and continue to affect the quality of life of up to one third of the population in the industrialized world. In recent years considerable progress has been achieved in understanding the pathological basis of this condition and in the development of new treatment modalities. The treatment of varicose veins of the lower limbs is primarily aimed at alleviating the symptoms, which include pain, pruritus, heaviness, ulceration, hemorrhage, and at improving unaesthetic appearance, but has also been shown to significantly improve measurable parameters of patients' quality of life and functional scales. This work reviews the current evidence on the four major treatment methods at hand: 1. Compression; 2. Stripping surgery; 3. Ultrasound guided foam sclerotherapy; 4. Thermal ablation by laser, radiofrequency or steam. Compression is a simple, low-cost treatment, but has low rates of patient compliance. The remaining invasive interventions are equally efficacious but differ considerably in their demand of skilled personnel and equipment, their adverse effects, the length of expected recovery and their economic costs. The new endovenous interventions can be performed in an ambulatory clinic under local anesthesia. They are at least as efficacious as surgery in short- and medium-term follow-up, but evidence on their long-term efficacy is still Lacking.