Treatment of dyspeptic symptoms with YamatoGast. A non-interventional study of a registered traditional herbal Rikkunshito extract product from Japanese Kampo Medicine in routine practice in Germany.

INTRODUCTION: Dyspeptic symptoms belong to the most frequent reasons to seek medical advice and are a burden both for the individual affected and the healthcare system. In Japan, the traditional herbal Kampo prescription rikkunshito has proven benefit for this indication. METHODS: In a prospective, multicentre, non-interventional study (NIS), the effectiveness, safety, and tolerability of a two-week treatment with the registered rikkunshito extract product YamatoGast was assessed in German patients with an acute episode of dyspeptic symptoms of functional origin under real-world conditions. The primary endpoint was the responsiveness to treatment assessed by the overall treatment effect (OTE) score. Secondary endpoints were the change in severity of dyspeptic symptoms and the change in quality of life (QoL). Safety evaluation was based on reported adverse drug reactions, drug compliance, and ratings of tolerability by physicians and patients. RESULTS: Sixty-six patients were enrolled (mean age 48.9 years, 74% females). The treatment was well tolerated and highly beneficial, as expressed by pronounced responder rates of 78.9% for the primary endpoint OTE. All secondary endpoints were also met. The severity of dyspeptic symptoms significantly improved by 62-77% compared to baseline, confirmed by a remarkable improvement of QoL. Significant symptom relief started from the third day of treatment onwards. CONCLUSION: In this non-interventional study, two-week treatment with YamatoGast resulted in a significant improvement of dyspeptic symptoms and was associated with high patient response and satisfaction. YamatoGast was confirmed as a safe and clinically relevant therapeutic option for patients suffering upper gastrointestinal complaints in routine practice.

The serotonin receptor 3E variant is a risk factor for female IBS-D.

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.

Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS). AIM: To assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODS: In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTS: Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSION: We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function.

BACKGROUND: This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. METHODS: Twenty-nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face-to-face and three remote meetings to derive consensus between 2014 and 2018. KEY RECOMMENDATIONS: The IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia. CONCLUSIONS AND INFERENCES: This framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much-needed standardization to these techniques.

Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications.

OBJECTIVES: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size. DESIGNS: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre. RESULTS: A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis. CONCLUSIONS: This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients. TRIAL REGISTRATION NUMBER: DRKS00007768; Pre-results.

[Interpretation und performance of high-resolution esophageal manometry: Recommendations of the German Association of Neurogastroenterology and Motility (DGNM) and the German Association of Gastroenterology, Digestive and Metabolic Diseases (DGVS)]. / Interpretation und Durchführung der hochauflösenden Ösophagusmanometrie: Empfehlungen der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) sowie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselerkrankungen (DGVS).

Esophageal manometry provides a detailed evaluation of esophageal contractility and, therefore, represents the reference method for diagnosis of esophageal motility disorders. Significance and clinical relevance have been further increased by implementation of high-resolution esophageal manometry (HRM), which reveals the functional anatomy of the esophagus in a visually-intuitive manner. The current 3 rd version of the international Chicago Classification (CC v3.0) gives standardized recommendations on performance and interpretation of HRM and serves as the basis for much of this expert consensus document. However, CC v3.0 gives only limited information with regards to the function of the lower and upper esophageal sphincters, the use of adjunctive tests including solid test meals and long-term ambulatory HRM measurements. In this expert consensus, we describe how to perform and interpret HRM on the basis of the CC v3.0 with additional recommendations based on the results of recent, high-quality clinical studies concerning the use of this technology to assess the causes of esophageal symptoms in a variety of clinical scenarios.

Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients.

BACKGROUND & AIMS: The causes of gastrointestinal complaints in irritable bowel syndrome (IBS) remain poorly understood. Altered nerve function has emerged as an important pathogenic factor as IBS mucosal biopsy supernatants consistently activate enteric and sensory neurons. We investigated the neurally active molecular components of such supernatants from patients with IBS and quiescent ulcerative colitis (UC). METHOD: Effects of supernatants from 7 healthy controls (HC), 20 IBS and 12 UC patients on human and guinea pig submucous neurons were studied with neuroimaging techniques. We identify differentially expressed proteins with proteome analysis. RESULTS: Nerve activation by IBS supernatants was prevented by the protease activated receptor 1 (PAR1) antagonist SCHE79797. UC supernatants also activated enteric neurons through protease dependent mechanisms but without PAR1 involvement. Proteome analysis of the supernatants identified 204 proteins, among them 17 proteases as differentially expressed between IBS, UC and HC. Of those the four proteases elastase 3a, chymotrypsin C, proteasome subunit type beta-2 and an unspecified isoform of complement C3 were significantly more abundant in IBS compared to HC and UC supernatants. Of eight proteases, which were upregulated in IBS, the combination of elastase 3a, cathepsin L and proteasome alpha subunit-4 showed the highest prediction accuracy of 98% to discriminate between IBS and HC groups. Elastase synergistically potentiated the effects of histamine and serotonin-the two other main neuroactive substances in the IBS supernatants. A serine protease inhibitor isolated from the probiotic Bifidobacterium longum NCC2705 (SERPINBL), known to inhibit elastase-like proteases, prevented nerve activation by IBS supernatants. CONCLUSION: Proteases in IBS and UC supernatants were responsible for nerve activation. Our data demonstrate that proteases, particularly those signalling through neuronal PAR1, are biomarker candidates for IBS, and protease profiling may be used to characterise IBS.

Reduced Responses of Submucous Neurons from Irritable Bowel Syndrome Patients to a Cocktail Containing Histamine, Serotonin, TNFα, and Tryptase (IBS-Cocktail).

BACKGROUND AND AIMS: Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS). Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC). METHODS: Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase, and TNF-α (IBS-cocktail) was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. RESULTS: Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P = 0.097 or P = 0.448). However, the neuronal response after application of the IBS-cocktail was significantly decreased (P = 0.039) independent of whether diarrhea (n = 12), constipation (n = 5) or bloating (n = 5) was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P = 0.019) when compared to incubation with HC supernatant. CONCLUSION: We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients.

Irritable bowel syndrome--the main recommendations.

BACKGROUND: Irritable bowel syndrome is characterized by chronic abdominal symptoms and irregular bowel movements without any cause than can be revealed by routine diagnostic assessment. In recent years, its pathophysiology has come to be much better understood, and new therapeutic approaches have been developed. These advances were taken into consideration and assessed for their relevance to clinical practice in the framework of a new interdisciplinary S3 guideline. METHODS: A systematic search of the literature retrieved a total 5573 articles, from which 243 were selected on the basis of criteria relating to their form and content, individually assessed, and summarized in evidence tables. The recommendations formulated in this way were discussed in a Delphi procedure and a consensus conference, then accordingly modified and finalized. RESULTS: Variable symptom constellations are caused by disturbances of gastrointestinal regulation at multiple levels. The diagnosis of irritable bowel syndrome requires both chronic bowel symptoms that interfere with everyday life and the exclusion of relevant differential diagnoses. Its treatment is based on general therapeutic principles, dietary recommendations, psychological components, and symptomatic medication. Bulking agents, laxatives, spasmolytics, loperamide, and probiotic agents are recommended (with variable recommendation strengths), as are--for selected patients--antidepressants, 5-HT4 agonists, 5-HT3 antagonists, and topical antibiotics. CONCLUSION: The first German S3 guideline on irritable bowel syndrome translates up-to-date scientific knowledge as represented in current publications into concrete recommendations for diagnosis and treatment in clinical practice. In the future, it is likely that further causative pathophysiological mechanisms will be discovered; this should lead, in turn, to the development of new, causally directed treatments, which will supplement or replace the traditional, purely symptomatic treatments that are still in use today.

Fecal calprotectin is a useful screening parameter for hepatic encephalopathy and spontaneous bacterial peritonitis in cirrhosis.

OBJECTIVE: Bacterial translocation, causing intestinal inflammation, is one of the key mechanisms in the pathogenesis of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP) The presence of fecal calprotectin quantitatively relates to intestinal neutrophil migration and is therefore considered as a marker of intestinal inflammation. We aimed to assess the role of fecal calprotectin concentrations (FCCs) in diagnosing the onset and severity of HE and SBP. METHODS: Sixty-one cirrhotics were prospectively included. Forty-two subjects served as controls. Several complications of cirrhosis were diagnosed by reference methods. Stool samples were collected for measuring FCCs. Patients revealing other causes of abnormal calprotectin results, e.g. gastrointestinal bleeding or inflammatory bowel disease were excluded. Multivariate analysis of cirrhosis-associated complications and their relation to FCCs was performed. RESULTS: Fecal calprotectin concentrations were higher in cirrhotics compared with controls (P<0.001). Among cirrhotics, FCCs were elevated dependent on the severity of liver disease as assessed by Child- and model for end-stage liver disease-scores. The corresponding correlation co-efficients by Spearman's were 0.577 (P<0.001) and 0.303 (P=0.018) respectively. A correlation emerged between elevated FCCs and HE grading as measured by West-Haven criteria and critical flicker frequency (both P<0.001; sensitivity=0.94 and 0.93, specificity=0.95 and 0.89 respectively) and SBP (P<0.02; sensitivity=0.71, specificity=0.79). FCCs were higher in cirrhotic subjects with additional extra-intestinal inflammation (P<0.01; sensitivity=0.65, specificity=0.8). The Pearsons correlation coefficients were 0.190 and 0.164 revealing no influence (P=0.142 and P=0.207) of laboratory parameters of systemic inflammation on FCCs in cirrhotic subgroup. CONCLUSIONS: Fecal calprotectin concentrations serve as a screening tool for HE and SBP. Assessment of FCCs may faciliate grading of HE-severity.

Nonhepatic cancer in liver cirrhosis: a retrospective study of prevalence, complication rate after specific oncological treatment, follow-up and prognostic predictors of outcome in 354 patients with cirrhosis.

BACKGROUND: Nonhepatic cancer risk of cirrhotic patients seems to be increased. Major surgery and chemotherapy in cirrhosis are associated with increased mortality and morbidity, which limits treatment. AIM: The aims of this study were analysis of (a) prevalence, (b) outcome after treatment, (c) of survival rate and (d) predictors of survival in a cirrhotic population. PATIENTS AND METHODS: The study population was assembled retrospectively from a database of hospitalized patients (n=354). The Kaplan-Meier method was used to calculate the survival rate, and Cox regression analysis was performed to identify prognostic parameters. RESULTS: Altogether, 84 neoplasms in 70 patients were observed. A total of 54 were nonhepatic (15.3%) mainly colorectal carcinoma, prostate cancer and tobacco-related neoplasms. TNM stage was the best prognostic parameter (p<0.0001). Low bilirubin (p=0.01), normal albumin (p=0.005) and absence of ascites (p<0.0001) were also related significantly to longer survival. The rate of postinterventional death after specific treatment was high. A proportion of patients received no specific therapy due to reduced physical performance, even in cases of limited disease. CONCLUSION: Our data confirm the increased risk of cirrhotic patients for developing nonhepatic cancer. Advanced TNM stage was associated with reduced long-term survival. Scoring systems, such as Child's classification and Model of Elevated Liver Disease (MELD) score, were suitable parameters to predict mortality. Oncological management in patients with cirrhosis must be on an individual basis, independent from TNM classification.

Longitudinal study of intestinal symptoms and fecal continence in patients with conformal radiotherapy for prostate cancer.

PURPOSE: To prospectively assess the intestinal symptoms and fecal continence in patients who had undergone conformal radiotherapy (CRT) for prostate cancer. METHODS AND MATERIALS: A total of 78 men who had undergone definitive CRT for prostate cancer were evaluated. The patients were assessed before, during (treatment Weeks 4 and 6), and 2, 12, and 24 months after CRT completion. The intestinal symptoms and fecal continence were evaluated with comprehensive standardized questionnaires. RESULTS: The intestinal symptoms were mostly intermittent, with only a small minority of patients affected daily. Defecation pain, fecal urge, and rectal mucous discharge increased significantly during therapy. Defecation pain and rectal mucous discharge had returned to baseline levels within 8 weeks and 1 year after CRT, respectively. However, fecal urge remained significantly elevated for ≤1 year and then returned toward the pretreatment values. The prevalence of rectal bleeding was significantly elevated 2 years after CRT. Fecal continence deteriorated during CRT and remained impaired at 1 year after treatment. Incontinence was mostly minor, occurring less than once per week and predominantly affecting incontinence for gas. CONCLUSION: Intestinal symptoms and fecal incontinence increased during prostate CRT. Except for rectal bleeding, the intestinal symptoms, including fecal incontinence, returned to baseline levels within 1-2 years after CRT. Thus, the rate of long-term late radiation-related intestinal toxicity was low.

Multiple intraluminal impedance measurement and manometry in the jejunum of healthy subjects: a new tool for diagnosis of small bowel motility.

BACKGROUND: The relationships between contractile activity and transport of intraluminal contents in the human small intestine are not well understood. AIM: To study both phenomena by combined measurements of intraluminal impedance and pressurein the jejunum of healthy subjects. METHODS: 12 healthy volunteers (m 4, f 8), mean age 32.3 years (24-49 years), underwent jejunal combined impedance/manometry recordings (six channels at 2-cm intervals). Fasting (one MMC cycle) and postprandial motility were recorded. RESULTS: Intestinal transport differed with the phases of motility. No transport was seen in phase I, regular bolus transport occurred during phase III. The longest duration of transport was observed in late phase II preceding phase III. Irregular and intermittent bolus transport occurred during early phase II and in the postprandial period. Three types of relationship between contractions and bolus transport were identified: transport with single contractions or migrating clustered contractions and transport without contractile activity. The frequency of these events differed with the direction of bolus transport, and a relationship between propagation velocity and bolus presence time was established. CONCLUSION: Combined simultaneous measurement of intraluminal impedance and manometry is a promising new method to elucidate the relationships between bolus transport and contractile activity in the human small bowel.

How close do gastroenterologists follow specific guidelines for nutrition recommendations in liver cirrhosis? A survey of current practice.

AIM: Malnutrition is a common feature of terminal chronic liver disease. In Great Britain earlier studies revealed a widespread use of inappropriate dietary management for example, protein restriction in patients with liver cirrhosis (LC). Therefore, it was the aim of this study to evaluate the current dietary recommendations for patients with LC, recommended by gastroenterologists in Germany. METHODS: Anonymous questionnaires were sent to 576 members of the Bavarian Society of Gastroenterology. Information was requested on the dietary management and on the diagnostic assessment of nutritional status of all patients with LC seen in the past 12 months. Further questions were included concerning knowledge of recent guidelines on enteral nutrition (EN) in LC, use of an adequate EN and estimated prevalence of malnutrition. RESULTS: Forty-four percent of all questionnaires were returned within 4 weeks; of those 94% were fully completed and appropriate for further analysis. Fifty-six percent respondents stated that they were familiar with guidelines concerning EN in patients with LC and 92% believed that evidence-based recommendations are both important and relevant for everyday practice. Only 23% of the respondents gave a correct estimate of the prevalence of protein-calorie malnutrition in patients with chronic liver disease. The majority underestimated the correct amount of energy and protein intake that is recommended by the European Society for Parenteral and Enteral Nutrition guidelines on EN for patients with LC. Only 42% respondents recommended a protein-rich diet whereas most of the respondents under or overestimated the required daily energy (55%) and protein intake (58%). As simple bedside methods such as the subjective global assessment or anthropometry are considered adequate to identify malnutrition in LC, these methods were familiar only to 24 and 55% of the respondents, respectively. Forty-one percent, however, believed that an evaluation of the body mass index represents the best diagnostic tool to detect malnourished patients although body mass index may be misleading in cirrhotics with tense ascites. CONCLUSION: The dietary management of German cirrhotic patients should be improved, especially concerning the required daily energy and protein intake. Simple bedside methods for the diagnosis of malnutrition are widely unknown. In general, malnutrition in LC clearly represents a widely underestimated problem even in a highly specialized sample of medical practitioners in digestive and hepatological diseases. At the same time the number of nutrition support teams in German speaking countries are very low. A higher number of multidisciplinary teams including dietitians, psychologists and physical activity supervisors caring for undernourished patients might be an important step for an improvement towards correct management of malnutrition in LC.

[Nutrition in liver cirrhosis]. / Ernährung bei Leberzirrhose.

BACKGROUND: Malnutrition is highly prevalent among patients with liver cirrhosis. This includes the supply with macronutrients and micronutrients. The pathogenesis is variable and often depends on metabolic characteristics and complications of the chronic liver disease. A reduced nutritional status, i.e., protein and energy malnutrition, has prognostic significance resulting in an increased morbidity and mortality rate. The assessment of malnutrition is frequently a major problem in daily practice. CONCLUSION: A sufficient daily energy supply should be guaranteed in patients with liver cirrhosis, which is higher compared to the normal population. Furthermore, the increased turnover of amino acids requires a sufficient protein supplementation. Ascites may benefit from a restriction of daily low-salt fluid intake. Additional substitution of vitamins and trace elements is indicated when symptoms of deficiency are apparent. Associated hepatic osteopathy is a frequent complication of liver cirrhosis. Nutritional advice in patients with cirrhosis requires an individual management regarding the dominating complications of the disease.

pH probe positioning for 24-hour pH-metry by manometry or pH step-up.

OBJECTIVES: Before pH measurement, manometry is recommended for precise pH probe positioning. We investigated whether the pH probe could be positioned accurately by the pH difference between the oesophagus and the stomach (pH step-up). METHODS: Dual-channel 24-h pH-metry with probes positioned 5 cm above either the manometrically determined upper lower oesophageal sphincter margin or the pH step-up was performed in healthy volunteers and reflux patients. To determine the pH step-up, the pH probe was pulled back from the stomach until a sudden rise to pH greater than four occurred. Probe position, reflux episodes and the fraction of the time pH was less than four were compared using the Wilcoxon test for difference and the Hodges-Lehman estimate inclusive confidence interval for equivalence. The pH step-up method was evaluated further during proton pump inhibitor therapy and after drug discontinuation. RESULTS: The pH probe was positioned 2 cm and 1 cm closer to the stomach by the pH step-up method in the volunteers and reflux patients, respectively. A small increase in upright reflux episodes but not in supine reflux episodes was registered by the probe positioned by pH step-up. No significant differences in the fraction of the time pH was less than four were obtained between the two probes. The Hodges-Lehman calculation proved equivalence for both methods of probe positioning for 24-h pH-metry. During proton pump inhibitor therapy, no pH step-up was detectable in three volunteers and in one patient. On the first day after discontinuing therapy, the pH step-up method yielded clear-cut results again. CONCLUSION: The pH probe for diagnostic 24-h pH-metry and, with some limitations, also for 24-h pH-metry for therapy control, can be positioned accurately by the pH step-up method.