Clinical effects of Kneipp hydrotherapy: a systematic review of randomised controlled trials.

OBJECTIVE: Hydrotherapy is a traditional prevention and treatment strategy. This study's aim is to systematically review all available randomised controlled trials (RCTs) investigating clinical effects of hydrotherapy according to Kneipp which is characterised by cold water applications. METHODS: RCTs on disease therapy and prevention with Kneipp hydrotherapy were included. Study participants were patients and healthy volunteers of all age groups. MEDLINE (via PubMed), Scopus, Central, CAMbase, and opengrey.eu were systematically searched through April 2021 without language restrictions and updated by searching PubMed until April 6th 2023. Risk of bias was assessed using the Cochrane tool version 1.ResultsTwenty RCTs (N=4247) were included. Due to high heterogeneity of the RCTs, no meta-analysis was performed. Risk of bias was rated as unclear in most of the domains. Of 132 comparisons, 46 showed significant positive effects in favour of hydrotherapy on chronic venous insufficiency, menopausal symptoms, fever, cognition, emotional function and sickness absenteeism. However, 81 comparisons showed no differences between groups and 5 were in favour of the respective control group. Only half of the studies reported safety issues. CONCLUSION: Although RCTs on Kneipp hydrotherapy seem to show positive effects in some conditions and outcomes, it remains difficult to ascertain treatment effects due to the high risk of bias and heterogeneity of most of the considered studies. Further high-quality RCTs on Kneipp hydrotherapy are urgently warranted. PROSPERO REGISTRATION NUMBER: CRD42021237611.

Expression of the fructose transporter GLUT5 in patients with fructose malabsorption.

BACKGROUND: Patients with abdominal symptoms are frequently diagnosed with fructose malabsorption (FM). Fructose is absorbed by monosaccharide transporters located in the brush border of the human small intestine. The aim of this study was to investigate the histoanatomical distribution of the main fructose transporter GLUT5. MATERIALS AND METHODS: We studied 223 patients diagnosed with FM by a hydrogen breath test and grouped according to their response to a fructose-free diet. The control group were 42 healthy individuals and 29 patients with celiac disease (CD). The fructose breath test was done with 50 g fructose. The expression of Glut5 in duodenal biopsy specimens was studied by immunohistochemistry. The Kruskal-Wallis-test and Mann-Whitney U-test were used to carry out the statistical analysis. RESULTS: The histoanatomical expression pattern of GLUT5 did not differ significantly between those patients with FM who responded completely to a fructose-free diet (n = 183) and healthy individuals (n = 42); nor did it correlate to H2 production measured in fructose breath testing. In patients with FM, the GLUT5 expression pattern did not differ between those individuals responding to a fructose-free diet and those who did not. However, GLUT5 expression pattern was significantly different in patients with CD (n = 29) compared to patients with FM and to healthy individuals (p = 0.009). CONCLUSION: GLUT5 expression patterns are not be related to adult patients with FM. However, in secondary malabsorption, a decreased GLUT5 expression was found. Further investigation is needed to understand the essential factors in FM and the influence on functional gastrointestinal disorders.

Diagnostic Performance of Simultaneous [18F]-FDG PET/MR for Assessing Endoscopically Active Inflammation in Patients with Ulcerative Colitis: A Prospective Study.

Background: To investigate the diagnostic performance of simultaneous 18F-fluoro-deoxyglucose ([18F]-FDG) PET/MR enterography in assessing and grading endoscopically active inflammation in patients with ulcerative colitis. Methods: 50 patients underwent PET/MR 24 h before ileocolonoscopy. Inflammatory activities of bowel segments were evaluated with both Mayo endoscopic subscore and Nancy histologic index. MR, DWI (Diffusion-weighted imaging) and PET were utilized as qualitative parameters for detecting endoscopically active inflammation. SUVmaxQuot in each segment (maximum of standard uptake value relative to liver) was calculated to quantify inflammation. Results: In the study arm without bowel purgation, combined reading of PET and MR resulted in significantly increased specificity against each submodality alone (0.944 vs. 0.82 for MR and 0.843 for PET, p < 0.05) and highest overall accuracy. In the study arm with bowel purgation, the significantly lower specificity of PET (0.595) could be markedly improved by a combined reading of PET and MR. Metabolic conditions in bowel segments with both endoscopic and histological remission were significantly lower than in segments with endoscopic remission but persistent microscopic inflammation (SUVmaxQuot 0.719 vs. 0.947, p < 0.001). SUVmaxQuot correlated highly with Mayo endoscopic subscore (ρ = 0.718 and 0.606) and enabled grading of inflammatory activity. Conclusions: Simultaneous [18F]-FDG PET/MR may be considered as an alternative to endoscopy in clinical trials.

Comparative efficacy of different exercise interventions in chronic non-specific low back pain: protocol of a systematic review and network meta-analysis.

INTRODUCTION: Chronic non-specific low back pain is a major public health problem. Evidence supports the effectiveness of exercise as an intervention. Due to a paucity of direct comparisons of different exercise categories, medical guidelines were unable to make specific recommendations regarding the type of exercise working best in improving chronic low back pain. This network meta-analysis (NMA) of randomised controlled trials aims to investigate the comparative efficacy of different exercise interventions in patients with chronic non-specific low back pain. METHODS AND ANALYSIS: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database, SPORTDiscus, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform search portal were searched on November 2019 and without language restrictions. The search will be updated after data analysis. Studies on adults with non-specific low back pain of at least 12 weeks duration comparing exercise to either no specific intervention (ie, no treatment, wait-list or usual care at the treating physician's discretion) and/or functionally inert interventions (ie, sham or attention control interventions) will be eligible. Pain intensity and back-specific disability are defined as primary outcomes. Secondary outcomes will include health-related physical and mental quality of life, work disability, frequency of analgesic use and adverse events. All outcomes will be analysed short-term, intermediate-term and long-term. Data will be extracted independently by two review authors. Risk of bias will be assessed using the recommendations by the Cochrane Back and Neck Group and be based on an adaptation of the Cochrane Risk of Bias tool. ETHICS AND DISSEMINATION: This NMA will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses_NMA checklist. The results will be presented in peer-reviewed journals, implemented in existing national and international guidelines and will be presented to health care providers and decision makers. The planned completion date of the study is 1 July 2021. PROSPERO REGISTRATION NUMBER: CRD42020151472.

Comparison of 18F-FDG PET-MR and fecal biomarkers in the assessment of disease activity in patients with ulcerative colitis.

OBJECTIVE: To compare the diagnostic performance of fecal biomarkers and 18F-fludeoxyglucose (18F-FDG) positron emmision tomography-MR (PET-MR) in the assessment of disease activity in patients with ulcerative colitis. METHODS: This study was conducted under the framework of a single-center clinical trial (clinicaltrials.gov [NCT03781284]). N = 50 participants were enrolled. Fecal samples were collected before bowel preparation. All patients underwent whole-body 18F-FDG PET-MR followed by ileocolonoscopy within 24 h. Diagnostic performance of five fecal biomarkers (calprotectin, lactoferrin, polymorphonuclear leukocyte elastase, S100A12 and eosinophil-derived neurotoxin), MR morphological parameters (MRmorph), diffusion-weighted imaging and PET in detecting active disease determined by Rachmilewitz endoscopic activity index (EAI) were evaluated and compared with each other. Correlations between fecal biomarkers, PET and endoscopy were calculated. RESULTS: According to EAI, n = 38 patients presented with endoscopically active disease (16 mild, 19 moderate and 3 severe). All five biomarkers, PET and MRmorph could differentiate endoscopically active disease from endoscopic remission without significant difference regarding their operating characteristics (accuracies between 0.673 for calprotectin and 0.898 for lactoferrin). In predicting endoscopically moderate to severe disease, PET showed the highest diagnostic performance (accuracy = 0.857) compared to calprotectin and lactoferrin (accuracy = 0.633 and 0.735). PET had also the strongest correlation with endoscopy (ρ = 0.685, p < 0.001), while within fecal biomarkers the levels of lactoferrin and eosinophil-derived neurotoxin correlated significantly with EAI (ρ = 0.423 and 0.528, both p < 0.05). CONCLUSION: Both fecal biomarkers and PET-MR were excellent non-invasive diagnostic tools in the assessment of disease activity in ulcerative colitis. ADVANCES IN KNOWLEDGE: Both fecal biomarkers and PET-MR parameters are able to predict endoscopically active disease with comparable diagnostic performance. PET had the highest correlation with endoscopy and outperformed fecal biomarkers in differentiating moderate to severe from mild disease.

18F-FDG PET-MR enterography in predicting histological active disease using the Nancy index in ulcerative colitis: a randomized controlled trial.

PURPOSE: To evaluate the diagnostic performance of PET-MR enterography in detecting histological active inflammation in patients with ulcerative colitis and the impact of bowel purgation on diagnostic accuracies of PET-MR parameters. METHODS: Fifty patients were enrolled in this randomized controlled trial (clinicaltrials.gov [NCT03781284]). Forty patients were randomized in two study arms, in which bowel purgation was performed either before or after PET-MR enterography. All patients underwent ileocolonoscopy with mucosal biopsies after PET-MR within 24 h. Diagnostic performance of MR morphological parameters (MRmorph), diffusion-weighted imaging (DWI), and PET in detecting histological inflammation determined by the Nancy index was compared with each other and between study arms. Correlation between PET and histological inflammatory severity was calculated. RESULTS: In study arm without previous bowel purgation, SUVmax ratio of bowel segment (relative to SUVmax of the liver) facilitated the highest specificity and diagnostic accuracy compared with MRmorph and DWI. Bowel cleansing led to markedly increased metabolic activity of bowel segments, resulting in significantly reduced specificity of PET compared with study arm without purgation (0.808 vs. 0.966, p = 0.007, respectively). Inter-observer concordance for assessing MRmorph was clearly increased after bowel cleansing (Cohen's κ, 0.847 vs. 0.665; p = 0.013, respectively), though diagnostic performance of MRmorph was not significantly improved. Our findings suggested that the change of metabolic status was mainly associated with the grade of neutrophil infiltrate and less dependent on chronic infiltrate. CONCLUSION: PET-MR enterography was an excellent non-invasive diagnostic method in the assessment of histological active inflammation in ulcerative colitis without the need of previous bowel purgation. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03781284.

Assessment of Ileocolonic Inflammation in Crohn's Disease: Which Surrogate Marker Is Better-MaRIA, Clermont, or PET/MR Index? Initial Results of a Feasibility Trial.

Our objective was to define an 18F-FDG PET/MR enterography index as a hybrid surrogate marker for active ileocolonic inflammation in Crohn's disease (CD) and assess its diagnostic performance in comparison to validated MR indices (MR index of activity [MaRIA], Clermont score). Methods: Fifty-two CD patients with recurrent symptoms underwent ileocolonoscopy and 18F-FDG PET/MR enterography. Three hundred three ileocolonic segments were assessed for inflammation using MaRIA and the Clermont score as well as the newly defined PET/MR index. On the basis of tobit regression, the PET/MR index was defined as (0.87 × wall thickness) + (1.97 × edema) + (0.83 × ulceration) + (0.55 × SUVmax ratio) + 1.14. The endoscopic activity of inflammation was determined by the simplified endoscopic activity score for CD (SES-CD). Receiver-operating-characteristic curves for each surrogate marker were created and tested against each other using the DeLong test, and diagnostic accuracies were compared using the McNemar test. Correlations between surrogate markers and SES-CD were tested with the Spearman rank correlation test. Results: The PET/MR index showed a comparable sensitivity but a significantly higher specificity and accuracy than MaRIA and the Clermont score in predicting both active and severe inflammation (active inflammation: specificities of 0.933, 0.711, and 0.707 and accuracies of 0.921, 0.739, and 0.736, P < 0.001; severe inflammation: specificities of 0.91, 0.81, and 0.785 and accuracies of 0.914, 0.818, and 0.795, P < 0.01, respectively). All surrogate markers correlated moderately with SES-CD on a segmental basis and a global level (0.5 < ρ < 0.7, all P < 0.001). Conclusion: As a hybrid surrogate marker comprising MR parameters and the PET component, the PET/MR index yielded significantly improved specificity and diagnostic accuracy compared with conventional MR indices (MaRIA and the Clermont score), demonstrating its high potential for noninvasive assessment of CD.

Herbal Medicines for Gastrointestinal Disorders in Children and Adolescents: A Systematic Review.

CONTEXT: Gastrointestinal disorders are common childhood complaints. Particular types of complementary and alternative medicine, such as herbal medicine, are commonly used among children. Research information on efficacy, safety, or dosage forms is still lacking. OBJECTIVES: To systematically summarize effectiveness and safety of different herbal treatment options for gastrointestinal disorders in children. DATA SOURCES: Medline/PubMed, Scopus, and the Cochrane Library were searched through July 15, 2016. STUDY SELECTION: Randomized controlled trials comparing herbal therapy with no treatment, placebo, or any pharmaceutical medication in children and adolescents (aged 0-18 years) with gastrointestinal disorders were eligible. DATA EXTRACTION: Two authors extracted data on study design, patients, interventions, control interventions, results, adverse events, and risk of bias. RESULTS: Fourteen trials with 1927 participants suffering from different acute and functional gastrointestinal disorders were included in this review. Promising evidence for effectiveness was found for Potentilla erecta, carob bean juice, and an herbal compound preparation including Matricaria chamomilla in treating diarrhea. Moreover, evidence was found for peppermint oil in decreasing duration, frequency, and severity of pain in children suffering from undifferentiated functional abdominal pain. Furthermore, evidence for effectiveness was found for different fennel preparations (eg, oil, tea, herbal compound) in treating children with infantile colic. No serious adverse events were reported. LIMITATIONS: Few studies on specific indications, single herbs, or herbal preparations could be identified. CONCLUSIONS: Because of the limited number of studies, results have to be interpreted carefully. To underpin evidence outlined in this review, more rigorous clinical trials are needed.