Altered Cerebellar Activity in Visceral Pain-Related Fear Conditioning in Irritable Bowel Syndrome.

There is evidence to support a role of the cerebellum in emotional learning processes, which are demonstrably altered in patients with chronic pain. We tested if cerebellar activation is altered during visceral pain-related fear conditioning and extinction in irritable bowel syndrome (IBS). Cerebellar blood oxygenation level-dependent (BOLD) data from N = 17 IBS patients and N = 21 healthy controls, collected as part of a previous fMRI study, was reanalyzed utilizing an advanced normalizing method of the cerebellum. The differential fear conditioning paradigm consisted of acquisition, extinction, and reinstatement phases. During acquisition, two visual conditioned stimuli (CS) were presented either paired (CS+) or unpaired (CS-) with painful rectal distension as unconditioned stimulus (US). In the extinction phase, the CS+ and CS- were presented without US. For reinstatement, unpaired US presentations were followed by unpaired CS+ and CS- presentations. Group differences in cerebellar activation were analyzed for the contrasts CS+ > CS- and CS- > CS+. During acquisition, IBS patients revealed significantly enhanced cerebellar BOLD responses to pain-predictive (CS+) and safety (CS-) cues compared to controls (p < 0.05, family-wise error corrected). Increased activation was found in three main clusters, including the vermis (maximum in vermal lobule VI), intermediate cerebellum (maximum in lobule VIII), and the posterolateral cerebellar hemisphere (maximum in lobule VI). Areas overlapped for the contrasts CS+ > CS- and CS- > CS+. Group differences were most prominent in the contrast CS- > CS+. During extinction and reinstatement, no significant group differences were found. During visceral pain-related fear conditioning, IBS patients showed increased activations in circumscribed areas of the medial, intermediate, and lateral cerebellum. These areas are involved in autonomic, somatosensory, and cognitive functions and likely contribute to the different aspects of pain-related fear. The cerebellum contributes to altered pain-related fear learning in IBS.

[Complementary and alternative procedures for fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Komplementäre und alternative Verfahren beim Fibromyalgiesyndrom : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A search of the literature for systematic reviews of randomized controlled trials of complementary and alternative therapies from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was formed by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: Meditative movement therapies (e.g. qi gong, tai chi and yoga) are strongly recommended. Acupuncture and weight reduction in cases of obesity can be considered.

A systematic review and meta-analysis of exercise interventions for colorectal cancer patients.

The aim of this systematic review and meta-analysis was to investigate the effectiveness of exercise for colorectal cancer patients. PubMed/Medline, Scopus and the Cochrane Library were searched through December 2012 without language restrictions. Randomised controlled trials (RCTs) comparing exercise interventions to control conditions were analysed when they assessed health-related quality of life, fatigue, physical fitness, survival and/or tumour-associated biomarkers in colorectal cancer patients. Risk of bias was assessed using the risk of bias tool recommended by the Cochrane Back Review Group. Literature search identified 342 non-duplicate records of which five RCTs with a total of 238 patients were included; three RCTs had low risk of bias. No evidence was found for short-term effects on quality of life [standardised mean difference (SMD) = 0.18; 95% confidence interval (CI) -0.39, 0.76; P = 0.53] or fatigue (SMD = 0.18; 95% CI -0.22, 0.59; P = 0.38). There was strong evidence for short-term improvements of physical fitness after aerobic exercise compared with controls (SMD = 0.59; 95% CI 0.25, 0.93; P < 0.01). One RCT each assessed immune parameters and oxidative DNA damage. No study reported survival rates or safety data. Given this insufficient evidence and the lack of safety data, no recommendation can be made regarding exercise interventions as a routine intervention for colorectal cancer patients.

[Mental disorders in patients with fibromyalgia syndrome: screening in centres of different medical specialties]. / Psychische Störungen beim Fibromyalgiesyndrom: Screening in Einrichtungen verschiedener Fachrichtungen.

BACKGROUND: Systematic reviews have reported a wide range of prevalence rates for depressive, anxiety and posttraumatic stress disorders (PTSD) in patients with fibromyalgia syndrome (FMS) which have been partially explained by setting differences. No data are currently available on the prevalence of potential mental disorders depending on the medical specialty in Germany. MATERIAL AND METHODS: All consecutive FMS patients of 8 study centres (3 rheumatology/orthopaedic surgery, 3 psychosomatic/pain medicine, 2 physical/integrative medicine) were assessed from February 1 to July 31, 2012 with standardised questionnaires. Patients with FMS diagnosed by a study physician were included. Non-German speaking and mentally retarded patients were excluded. The German version of the Patient Health Questionnaire 4 was used to screen for potential depressive and anxiety disorders. Severe life events were assessed by the trauma list of the Munich Composite International Diagnostic Interview and symptom criteria of PTSD of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) using the Posttraumatic Diagnostic Scale. RESULTS: Of 538 patients, 396 patients (93.9 % women, mean age 52.3 years, mean duration since chronic widespread pain 12.8 years, mean duration since FMS diagnosis 4.5 years) were analysed. In all, 65.7 % of patients met the criteria of a potential depressive disorder, 67.9 % of a potential anxiety disorder and 45.5 % of a potential PTSD. Potential depressive disorders were more frequent in the psychosomatic/pain medicine setting than in the rheumatology setting. CONCLUSION: Potential mental disorders were frequent in FMS patients regardless of the medical specialty. All FMS patients of all types of clinical settings should be screened for mental disorders.

[Urticaria. Sometimes IgE-mediated?]. / Urtikaria. Manchmal doch IgE-vermittelt?

There are specific diagnostic recommendations for approaching chronic spontaneous urticaria, physical urticaria and special forms of urticaria. They include the detection of subclinical viral and bacterial infections, particularly with Helicobacter pylori. Frequently an autoimmune urticaria is diagnosed by using the autologous serum test. Less specific findings, such as leukocytosis and elevated CRP can sometimes be helpful in suggesting subclinical infections as the cause of acute urticaria; usually no further procedures are recommended. However, in cases with a long history of intermittent attacks, particularly with severe and generalized symptoms, it is recommended to look for IgE-mediated reactions (e.g. alpha-Gal, Omega-5-Gliadin). In our hands at the Department of Dermatology and Allergy at the Hannover Medical School a standardized set of diagnostic procedures was successfully established, and is now individually completed with selected single allergens and allergen components.

[Are members of fibromyalgia syndrome self-help groups "different"? Demographic and clinical characteristics of members and non-members of fibromyalgia syndrome self-help groups]. / Sind Mitglieder von Fibromyalgiesyndrom-Selbsthilfegruppen "anders"? Demografische und klinische Charakteristika von Mitgliedern und Nicht-Mitgliedern von Fibromyalgiesyndrom-Selbsthilfegruppen.

BACKGROUND: No data were available on demographic and clinical characteristics of members of fibromyalgia syndrome (FMS) self-help groups in Germany. MATERIAL AND METHODS: The study was carried out from November 2010 to April 2011. A set of questionnaires was distributed by the German League Against Rheumatism and the German Fibromyalgia Association to members and to all consecutive FMS patients at nine clinical centres of different levels of care. The set included a self-developed questionnaire on demographic and medical data and on previously and currently used therapies, the patient health questionnaire (PHQ 4) and the fibromyalgia survey questionnaire. RESULTS: Members of FMS self-help groups (N = 1,014) were older and reported a longer duration of chronic widespread pain, less anxiety and depression and a more frequent current use of aerobic exercise, relaxation training and complementary alternative medication than participants not affiliated with FMS self-help groups (N = 630). CONCLUSIONS: Membership in FMS self-help groups was associated with less psychological distress and a more frequent use of active self-management strategies.

[Complementary and alternative therapies for fibromyalgia syndrome. Systematic review, meta-analysis and guideline]. / Komplementäre und alternative Verfahren beim Fibromyalgiesyndrom. Systematische Übersicht, Metaanalyse und Leitlinie.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The recommendations were based on level of evidence, efficacy (meta-analysis of the outcomes pain, sleep, fatigue and health-related quality of life), acceptability (total dropout rate), risks (adverse events) and applicability of treatment modalities in the German health care system. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies. RESULTS AND CONCLUSION: Meditative movement therapies (qi gong, tai chi, yoga) are strongly recommended. Acupuncture can be considered. Mindfulness-based stress reduction as monotherapy and dance therapy as monotherapy are not recommended. Homeopathy is not recommended. In a minority vote, homeopathy was rated as "can be considered". Nutritional supplements and reiki are not recommended. The English full-text version of this article is available at SpringerLink (under "Supplemental").

[German fibromyalgia consumer reports. Benefits and harms of fibromyalgia syndrome therapies]. / Der deutsche Fibromyalgieverbraucherbericht. Nutzen und Schaden von Behandlungen des Fibromyalgiesyndroms.

BACKGROUND: Consumer reports provide information on benefits and harms in routine clinical care. We report the first fibromyalgia syndrome (FMS) consumer reports in Europe. MATERIAL AND METHODS: The study was carried out from November 2010 to April 2011. The benefits and harms of pharmacological and non-pharmacological therapies experienced by the patient were assessed in an 11-point Likert scale (0=no, 10=very high benefit or harm) by a questionnaire. The questionnaire was distributed by the German League against Rheumatism and the German Fibromyalgia Association to their members and to all consecutive FMS patients of nine clinical centers of different levels of care. RESULTS: A total of 1,661 questionnaires (95% women, mean age 54 years) were analyzed. Self-management strategies (distraction, resting, aerobic exercise), physical therapies (warm and pool therapies), psychological therapies (education, psychotherapy), and inpatient multicomponent therapies were judged to be more efficacious and less harmful than all types of pharmacological therapies. CONCLUSION: The German fibromyalgia consumer reports highlight the importance of non-pharmcological therapies in the long-term management of FMS.

[Validation of the German version of the Regional Pain Scale for the diagnosis of fibromyalgia syndrome]. / Validierung der deutschen Version der regionalen Schmerzskala zur Diagnose des Fibromyalgiesyndroms.

OBJECTIVE: Use of the American College of Rheumatology classification criteria for the clinical diagnosis of fibromyalgia syndrome (FMS) is under debate. The Regional Pain Scale (RPS) had been developed for the diagnosis of FMS in clinical practice and in survey settings (survey criteria of FMS). So far a German version has not been validated. METHODS: A total of 216 patients with FMS, 53 with active rheumatoid arthritis (RA) and 60 with depressive disorder, recruited from clinical institutions completed the RPS. Forty-three patients with FMS filled in the RPS within 8 weeks a second time. RESULTS: The intraclass coefficient of FMS diagnosis after 8 weeks was 0.78 (test-retest reliability). The 7-day interval of pain was criticized by physicians. The absence of some articular pain regions was criticized by patients (face validity). The concordance of FMS diagnoses to survey and ACR criteria was 84.7% (+/-1.1); 45.3% of the patients with RA and 38.3% of the patients with depressive disorder met the survey criteria of FMS (discriminant validity). CONCLUSION: The RPS has good reliability and convergent validity, but limited discriminant validity. The RPS is suited as a screening instrument for the diagnosis of FMS in clinical practice.

[Impressive picture of a melanosis coli after chronic anthraquinone laxative use--is there an increased risk for colorectal cancer?].

We report the case of a 74-year-old female with an extreme picture of melanosis coli of the whole colon after chronic use of anthraquinone laxatives for the treatment of constipation over many decades. Endoscopic work-up revealed an impressive deep black pigmentation of the whole colon mucosa which could be verified by histopathology as a widespread lipofuscin granulation. In addition, various adenomas but no colorectal carcinoma could be detected. The term melanosis coli describes a brown or black pigmentation of the colonic mucosa. Induction of melanosis coli by anthraquinone laxatives and their derivatives can be regarded as verified. The question if melanosis coli predisposes for colorectal neoplasia is discussed controversially. Based on the current literature, an association of melanosis coli between colorectal adenomas, but not colorectal carcinomas, is under discussion but the mechanisms to effect the development of colorectal neoplasia are not completely understood. Considering our case and the current scientific backround, we conclude that due to pharmaceutical side effects of anthraquinone derivatives such as electrolytic shift and water loss in addition to the risk of developing melanosis coli, anthraquinone laxatives should not be used for long-term therapy of constipation.

Faecal S100A12 as a non-invasive marker distinguishing inflammatory bowel disease from irritable bowel syndrome.

OBJECTIVE: S100A12 is a pro-inflammatory protein that is secreted by granulocytes. S100A12 serum levels increase during inflammatory bowel disease (IBD). We performed the first study analysing faecal S100A12 in adults with signs of intestinal inflammation. METHODS: Faecal S100A12 was determined by ELISA in faecal specimens of 171 consecutive patients and 24 healthy controls. Patients either suffered from infectious gastroenteritis confirmed by stool analysis (65 bacterial, 23 viral) or underwent endoscopic and histological investigation (32 with Crohn's disease, 27 with ulcerative colitis, and 24 with irritable bowel syndrome; IBS). Intestinal S100A12 expression was analysed in biopsies obtained from all patients. Faecal calprotectin was used as an additional non-invasive surrogate marker. RESULTS: Faecal S100A12 was significantly higher in patients with active IBD (2.45 +/- 1.15 mg/kg) compared with healthy controls (0.006 +/- 0.03 mg/kg; p<0.001) or patients with IBS (0.05 +/- 0.11 mg/kg; p<0.001). Faecal S100A12 distinguished active IBD from healthy controls with a sensitivity of 86% and a specificity of 100%. We also found excellent sensitivity of 86% and specificity of 96% for distinguishing IBD from IBS. Faecal S100A12 was also elevated in bacterial enteritis but not in viral gastroenteritis. Faecal S100A12 correlated better with intestinal inflammation than faecal calprotectin or other biomarkers. CONCLUSIONS: Faecal S100A12 is a novel non-invasive marker distinguishing IBD from IBS or healthy individuals with a high sensitivity and specificity. Furthermore, S100A12 reflects inflammatory activity of chronic IBD. As a marker for neutrophil activation, faecal S100A12 may significantly improve our arsenal of non-invasive biomarkers of intestinal inflammation.

Randomised clinical trial: yoga vs a low-FODMAP diet in patients with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome is the most frequent gastrointestinal disorder. It is assumed that lifestyle interventions might be a rational treatment approach. AIM: To examine the effect of a yoga-based intervention vs a low-FODMAP diet on patients with irritable bowel syndrome. METHODS: Fifty-nine patients with irritable bowel syndrome undertook a single-blind, randomised controlled trial involving yoga or a low-FODMAP diet for 12 weeks. Patients in the yoga group received two sessions weekly, while patients in the low-FODMAP group received a total of three sessions of nutritional counselling. The primary outcome was a change in gastrointestinal symptoms (IBS-SSS). Secondary outcomes explored changes in quality of life (IBS-QOL), health (SF-36), perceived stress (CPSS, PSQ), body awareness (BAQ), body responsiveness (BRS) and safety of the interventions. Outcomes were examined in weeks 12 and 24 by assessors "blinded" to patients' group allocation. RESULTS: No statistically significant difference was found between the intervention groups, with regard to IBS-SSS score, at either 12 (Δ = 31.80; 95%CI = -11.90, 75.50; P = .151) or 24 weeks (Δ = 33.41; 95%CI = -4.21, 71.04; P = .081). Within-group comparisons showed statistically significant effects for yoga and low-FODMAP diet at both 12 and 24 weeks (all P < .001). Comparable within-group effects occurred for the other outcomes. One patient in each intervention group experienced serious adverse events (P = 1.00) and another, also in each group, experienced nonserious adverse events (P = 1.00). CONCLUSIONS: Patients with irritable bowel syndrome might benefit from yoga and a low-FODMAP diet, as both groups showed a reduction in gastrointestinal symptoms. More research on the underlying mechanisms of both interventions is warranted, as well as exploration of potential benefits from their combined use.

Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission.

OBJECTIVE: Psychological stress has been implicated in the pathophysiology of both inflammatory and functional gastrointestinal (GI) diseases. The goal of this study was to address neuroendocrine modulation of cytokine production by peripheral blood cells in GI diseases. METHODS: We analyzed the in vitro effects of the beta-adrenergic agonist terbutaline and the glucocorticoid agonist dexamethasone on TNF-alpha and IL-10 production by LPS-stimulated monocytes in whole cell blood cultures in patients with inflammatory bowel diseases in remission (N=10), diarrhoea-predominant irritable bowel syndrome (IBS, N=12), patients with a recent gastroenteritis (post-infectious group, N=10), and healthy controls (N=15). RESULTS: In response to terbutaline, there was a significant increase in IL-10 production (concentration effect: p<0.05), which was diminished in IBD (group effect: p<0.01), comparable in IBS and controls, but enhanced in the post-infectious group (group x concentration effect: p<0.05). In contrast, terbutaline resulted in a concentration-dependent suppression of TNF-alpha production, which was comparable in all groups. Dexamethasone suppressed TNF-alpha production in a dose-dependent manner in all groups, but this effect was significantly more pronounced in post-infectious subjects (group effect: p<0.05). CONCLUSIONS: In IBD, disturbed adrenergic regulation of IL-10 could be part of the mechanism(s) underlying the modulation of disease activity by psychological stress. Diarrhoea-predominant IBS was not associated with altered adrenergic or glucocorticoid regulation of cytokine production by peripheral blood cells, whereas a recent history of gastroenteritis was associated with disturbed neuroendocrine modulation of cytokine production, which may play role in the pathophysiology of post-infectious IBS.