STW5 (Iberogast®) for constipation in Parkinson's disease.

BACKGROUND: Chronic constipation is one of the most frequent non-motor symptoms in Parkinson's disease (PD), and impairs patients' quality of life. OBJECTIVE: The aim of this pilot study was to assess the efficacy and the tolerability of STW5, a phytotherapeutic agent composed of nine plant extracts, for the treatment of constipation in patients with PD. METHODS: We carried out an open monocentric study of STW5 in the treatment of constipation in parkinsonian patients. Forty-four PD patients with a mean age of 66.4±7.3 years (range, 35-78), a mean disease duration of 12.6±5.4 years (range, 3-27) and with constipation defined by Rome III criteria for functional constipation were included. Following a two-week laxative-free baseline period, all the patients were treated with 20 drops STW5 t.i.d for 28 days, after a seven-day titration period. Treatment efficacy was defined as marked improvement of stool frequency with an increase of three exonerations during the last week of treatment when compared to the week before the initiation of treatment. Responder rate for stool frequency was estimated at 29/45 patients. RESULTS: An increase of stool frequency≥three eliminations/week was observed in only four out of 44 patients (9.0%) at the end of the study. The only significant difference observed before and after treatment was a decrease in stool consistency (P=0.0272). CONCLUSIONS: Our results suggest that STW5 has a safety profile but is not effective as a phytotherapeutic agent in constipation related to Parkinson's disease.

[Guidelines for the management of chronic cough in adults]. / Recommandations de prise en charge de la toux chronique de l'adulte.

Patients with chronic cough experience major alteration in their quality of life. Given its numerous etiologies and treatments, this disease is a complex entity. To help clinicians involved in patient management of patients, guidelines have been issued by a group of French experts. They address definitions of chronic cough and initial management of patients with this pathology. We present herein the second-line tests that might be considered in patients whose coughing has persisted, notwithstanding initial management. The experts have also put forward a definition of unexplained or refractory chronic cough (URCC), the objective being to more precisely identify those patients whose cough persists despite optimal management. Lastly, these guidelines indicate the pharmacological and non-pharmacological interventions of use in URCC. Amitriptyline, pregabalin, gabapentin or morphine combined with speech and/or physical therapy are mainstays in treatment strategies. Other treatment options, such as P2X3 antagonists, are being developed and have generated high hopes among physicians and patients alike.

Wireless pH capsule--yield in clinical practice.

Wireless pH monitoring is one of the recent technologies that focus on improving the diagnosis of gastroesophageal reflux disease (GERD). The capsule, which is fixed within the esophagus, transmits data via telemetry to an external receiver. The capsule is usually inserted 6 cm above the squamocolumnar junction during an upper endoscopy. The standard recording duration is 48 hours but this can be extended to 96 hours. The wireless capsule has been shown to be at least as accurate as the conventional catheter for the monitoring of esophageal pH. Normal pH values have been established in three different series. The use of a wireless capsule provides an increased diagnostic yield for GERD compared with the conventional catheter. The increased yield is the result of higher sensitivity to detect both abnormal acid esophageal exposure and positive symptom-reflux association. This may be related both to the prolonged recording duration and to fewer dietary modifications and restrictions on activities. Several studies have shown that the pH capsule was better tolerated by patients than the conventional pH catheter. Mild-to-moderate chest pain represents the main side effect of the pH capsule: severe chest pain requiring endoscopic removal of the capsule is rare. The main indication for wireless capsule application is monitoring of distal esophageal pH for diagnostic purpose, particularly in patients with a normal endoscopic examination. The capsule technique has some limitations: costs are higher than conventional pH monitoring, misplacement may occur, and the sampling rate is lower. Finally, compared with pH-impedance monitoring, only acid reflux events can be evaluated.

Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators.

BACKGROUND: Growing evidence suggests that patients with irritable bowel syndrome (IBS) have increased intestinal permeability. In addition, mucosal soluble mediators are involved in the pathophysiology of pain in IBS. We aimed to investigate (1) paracellular permeability in colonic biopsies of patients with IBS; and (2) the ability of soluble factors from colonic biopsies to reproduce these alterations in vitro. METHODS: Paracellular permeability in colonic biopsies of healthy subjects and patients with IBS was measured by mounting the biopsies in Ussing chambers. Cleared supernatant (SUP) of the culture from colonic biopsies was collected and applied to Caco-2 cells for 48 h. Paracellular permeability and transepithelial resistance (TER) were evaluated. mRNA expression of the tight junction proteins, zonula occludens (ZO)-1 and occludin, was assessed in colonic biopsies. Abdominal pain was assessed using a validated questionnaire. RESULTS: Permeability of colonic biopsies was significantly higher in patients with IBS compared to healthy subjects. These changes were associated with significantly lower expression of ZO-1 mRNA in biopsies of IBS as compared to healthy subjects. Compared to healthy subjects, SUP of IBS markedly reduced TER and significantly increased permeability in Caco-2 cells. SUP of IBS patients induced a significant decrease of ZO-1 mRNA in Caco-2 as compared to healthy subjects. SUP-induced increased paracellular permeability correlated with the severity of abdominal pain. CONCLUSIONS: Our study shows that colonic soluble mediators are able to reproduce functional (permeability) and molecular (ZO-1 mRNA expression) alterations observed in IBS patients. These findings might pave the way both to identify novel biomarkers as well as new therapeutic targets in IBS.

Hypotonic Low Esophageal Sphincter Is Not Predictive of Gastroesophageal Reflux Disease After Sleeve Gastrectomy.

BACKGROUND: Sleeve gastrectomy is the most commonly performed bariatric surgery these days but is associated with de novo reflux. OBJECTIVE: We aimed to study the influence of hypotonic lower esophageal sphincter (LES) on postoperative gastroesophageal reflux disease (GERD). METHODS: Patients with pre- and postoperative esophageal high-resolution manometry (HRM) and 24-h pH monitoring (pHM) were included retrospectively in our study. Preoperative hypotonic LES was defined by a mean residual pressure of the lower esophageal sphincter < 4 mmHg. Postoperative GERD was defined by a DeMeester's score > 14.72. We also evaluated postoperative manometric changes at the esophageal-gastric junction. RESULTS: Sixty-nine patients (54 females and 15 males) had pre- and postoperative HRM and pHM. The mean age was 45.9 ± 9.8 years. The mean body mass index (BMI) was 47.5 ± 7.5 kg/m2. Hypotonic LES concerned 21 patients (30.4%) before sleeve gastrectomy. The mean time between the two esophageal monitorings was 32.1 ± 24.1 months. The sensitivity, specificity, positive predictive value, and negative predictive value of hypotonic LES to predict GERD were 31, 70, 52, and 48% respectively. The LES minimal residual pressure was not statistically decreased after sleeve gastrectomy (p = 0.24). Only the wave speed, esophageal length, and LES length were significantly reduced after SG (p = 0.029, 3.8 × 10-7 and 0.00032). CONCLUSION: Hypotonic LES has a poor predictive value on postoperative GERD. The LES's length is significantly reduced after SG and this could be a factor explaining de novo reflux.

Expectations of IBS patients concerning disease and healthcare providers: Results of a prospective survey among members of a French patients' association.

BACKGROUND AND AIMS: IBS patients have an impaired quality of life (QoL) and feel dissatisfaction with medical care. We aim to describe the expectations of members of the French Association of IBS patients (APSSII) concerning health care providers (HCPs) and a patients' organization. PATIENTS AND METHODS: From January to June 2013, APSSII members were asked to answer questionnaires on their expectations and experiences concerning IBS and HCP. RESULTS: 222/330 (67%) responded (women: 68.5%, 46.5±17.7 years, disease duration: 8.8±0.7 years, IBS-D 33.6%, IBS-C 26.7%, IBS-M 38.2%. IBS-SSS>300 in 53% and HAD score>19 in 45%). QoL impairment was correlated with disease severity and HAD score (r=-0.707 and r=-0.484, P<0.001 respectively), but not with IBS subtype. Expectations for IBS were "improved health", "better information on causes and treatments" (94%) and "better disease recognition" (86%). A significant gap was observed between expectations and experiences with HCPs. Better information, less isolation, recognition of the disease and a decrease in medical expenses were the main expectations for joining a patients' organization. CONCLUSIONS: French IBS patients have a severe disease with a significant psychological impact and impaired QoL in half of the patients, certain unsatisfied expectations concerning HCP and high expectations in joining a patients' organization.

[Irritable bowel syndrome: outcome aspects]. / Syndrome de l'intestin irritable : aspects évolutifs.

Irritable bowel syndrome is a chronic relapsing disorder. In most patients, symptom severity and clinical characteristics change frequently. Nonetheless, broad progressive trends can be defined. Over the very short term, symptoms occur over short sequences appearing sequentially and are interrupted by short remission periods. Over the medium term (3 months), early recovery from symptoms is observed in 20%-40% of patients. No good clinical predictors of IBS progression seem to exist even if clinical improvement at 3 months seems related to a better prognosis after a 1-year follow-up. Over the long term (several years), symptoms are still present in 60%-70% of patients. Symptom turnover is high in these patients from either transitioning into other irritable bowel syndrome subgroups or overlapping with dyspeptic symptoms. Psychiatric comorbidities appear to be of primary importance in the clinical course of patients with irritable bowel syndrome.

Modulation of VIPergic phenotype of enteric neurons by colonic biopsy supernatants from patients with inflammatory bowel diseases: Involvement of IL-6 in Crohn's disease.

BACKGROUND: Neuroplastic changes in the enteric nervous system (ENS) observed during IBD might participate in physiopathological processes. Vasoactive intestinal polypeptide has been shown to be involved in intestinal inflammation and barrier functions. We aimed to investigate the modulation of VIP expression in colonic biopsies of IBD patient, the ability of soluble factors from biopsies to reproduce in vitro these modulations and identify soluble factors responsible. METHODS: VIP and cytokines mRNA expressions were assessed in colonic biopsies of healthy subjects (HS) and IBD patients from inflamed (I) and non-inflamed areas (NI). Supernatants (SUP) of biopsies were applied to primary culture of ENS and VIP and cytokines mRNA expressions were assessed. The role of cytokines in SUP induced changes in VIP expression was evaluated. KEY RESULTS: VIP mRNA expression was lower in biopsies of patients with Crohn's disease (CD) than Ulcerative Colitis (UC) but unchanged as compared to HS. VIP mRNA and protein expression were lower in primary culture of ENS incubated with SUP-CD than with SUP-UC. Furthermore, in CD but not UC, SUP-I reduced VIP expression in the ENS as compared to SUP-NI. Next, IL-6 but not IL-5, IL-10, IL-17, IFN-γ or TNF-α reduced VIP expression in the ENS. Finally, in CD, SUP-I incubated with anti-IL-6 antibody increased VIP expression as compared to SUP-I alone. CONCLUSIONS & INFERENCES: Mucosal soluble factors from IBD induce VIP neuroplastic changes in the ENS. IL-6 was identified as a putative soluble factor responsible in part for changes in VIP expression in CD.

Glioplasticity in irritable bowel syndrome.

BACKGROUND: Growing evidence indicates a wide array of cellular remodeling in the mucosal microenvironment during irritable bowel syndrome (IBS), which possibly contributes to pathophysiology and symptom generation. Here, we investigated whether enteric glial cells (EGC) may be altered, and which factors/mechanisms lead to these changes. METHODS: Colonic mucosal biopsies of IBS patients (13 IBS-Constipation [IBS-C]; 10 IBS-Diarrhea [IBS-D]; 11 IBS-Mixed [IBS-M]) and 24 healthy controls (HC) were analyzed. Expression of S100ß and GFAP was measured. Cultured rat EGC were incubated with supernatants from mucosal biopsies, then proliferation and Ca2+ response to ATP were analyzed using flow cytometry and Ca2+ imaging. Histamine and histamine 1-receptor (H1R) involvement in the effects of supernatant upon EGC was analyzed. KEY RESULTS: Compared to HC, the mucosal area immunoreactive for S100ß was significantly reduced in biopsies of IBS patients, independently of the IBS subtype. IBS-C supernatants reduced EGC proliferation and IBS-D and IBS-M supernatants reduced Ca2+ response to ATP in EGC. EGC expressed H1R and the effects of supernatant upon Ca2+ response to ATP in EGC were blocked by pyrilamine and reproduced by histamine via H1R. IBS supernatants reduced mRNA expression of connexin-43. The S100ß-stained area was negatively correlated with the frequency and intensity of pain and bloating. CONCLUSION AND INFERENCES: Changes in EGC occur in IBS, involving mucosal soluble factors. Histamine, via activation of H1R-dependent pathways, partly mediates altered Ca2+ response to ATP in EGC. These changes may contribute to the pathophysiology and the perception of pain and bloating in patients with IBS.

Acute exacerbation of pain in irritable bowel syndrome: efficacy of phloroglucinol/trimethylphloroglucinol. A randomized, double-blind, placebo-controlled study.

BACKGROUND: Abdominal pain is the predominant symptom in irritable bowel syndrome patients. Phloroglucinol and its methylated derivative are antispasmodic agents acting on smooth muscle. AIM: To evaluate the efficacy of phloroglucinol/trimethylphloroglucinol on pain intensity during an acute exacerbation of pain of irritable bowel syndrome over a 1-week period treatment. METHODS: Irritable bowel syndrome Rome II patients seeking medical advice for an acute exacerbation of abdominal pain were randomized to phloroglucinol/trimethylphloroglucinol (62.2 mg P + 80 mg TMP) two pills three times daily or placebo for 7 days. Patients were included if they had a pain with a minimal intensity of 40 on a 100-mm visual analogue scale, and if pain occurred at least 2 days during the week previous inclusion. RESULTS: Three hundred and seven patients were included by 78 general practitioners. The intent-to-treat population included 300 patients, aged of 46.9 +/- 14.8 years (73% female). The relative decrease of pain intensity at day 7 was 57.8 +/- 31.7% vs. 46.3 +/- 34.7% (Delta = 11.5 +/- 3.8%, [CI(95%): 4.0 ; 19.1], P = 0.0029) and the percentage of patients with at least a 50% decrease of pain intensity was 62% vs. 47% (Delta = 15.3 +/- 5.7%, [CI(95%): 4.1 ; 26.5], P = 0.0078) in phloroglucinol/trimethylphloroglucinol and placebo groups, respectively. CONCLUSIONS: A 1-week phloroglucinol/trimethylphloroglucinol treatment significantly reduces pain intensity in irritable bowel syndrome patients consulting their general practitioners for pain exacerbation.

The selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056) reduces the incidence of reflux episodes in dogs and patients with moderate to severe gastroesophageal reflux disease.

BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) induced by gastric distension are modulated by the metabotropic glutamate receptor 5 (mGluR5) that influences the vagal reflex loop. We therefore aimed to examine the effects of the selective mGluR5 antagonist mavoglurant (AFQ056) on the number of TLESRs in dogs and reflux episodes in patients with gastroesophageal reflux disease (GERD). METHODS: In a dog model, the number of meal-induced TLESRs was determined after intravenous (0.03, 0.1, 0.3, and 1 mg kg-1 ) and oral (1, 3, and 10 mg kg-1 ) doses of mavoglurant with reference to vehicle. In a multicenter, randomized, double-blind, placebo-controlled, three-period crossover study, the incidence of meal-induced reflux episodes was assessed by esophageal impedance monitoring after single, oral doses of mavoglurant (50 and 400 mg) or baclofen (40 mg) in 30 patients with moderate to severe GERD. KEY RESULTS: In dogs, mavoglurant reduced the number of TLESRs after intravenous and oral administration. In patients with GERD, the incidence of postprandial reflux episodes was significantly lower at a dose of 400 mg mavoglurant (-37.5% ; 90% confidence interval [CI]: -57.8, -17.2), whereas there was no significant difference at 50 mg of mavoglurant compared to placebo. A significantly lower incidence of reflux episodes was also noted with the active comparator baclofen (-50.3%; 90% CI: -66.2, -34.3), thereby validating this study. CONCLUSIONS AND INFERENCES: These data suggest a potential clinical benefit of mGluR5 antagonists such as mavoglurant in patients with GERD, particularly in those with persisting symptoms despite treatment with proton pump inhibitors.

Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome.

BACKGROUND: Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. AIM: To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS. METHODS: We conducted a pilot, 12-week, randomised, double-blind, placebo-controlled, multicentre study assessing the effect of palmithoylethanolamide/polydatin 200 mg/20 mg or placebo b.d. on low-grade immune activation, endocannabinoid system and symptoms in IBS patients. Biopsy samples, obtained at screening visit and at the end of the study, were analysed by immunohistochemistry, enzyme-linked immunoassay, liquid chromatography and Western blot. RESULTS: A total of 54 patients with IBS and 12 healthy controls were enrolled from five European centres. Compared with controls, IBS patients showed higher mucosal mast cell counts (3.2 ± 1.3 vs. 5.3 ± 2.7%, P = 0.013), reduced fatty acid amide oleoylethanolamide (12.7 ± 9.8 vs. 45.8 ± 55.6 pmol/mg, P = 0.002) and increased expression of cannabinoid receptor 2 (0.7 ± 0.1 vs. 1.0 ± 0.8, P = 0.012). The treatment did not significantly modify IBS biological profile, including mast cell count. Compared with placebo, palmithoylethanolamide/polydatin markedly improved abdominal pain severity (P < 0.05). CONCLUSIONS: The marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition. Further studies are now required to elucidate the mechanism of action of palmithoylethanolamide/polydatin in IBS. ClinicalTrials.gov number, NCT01370720.

Validation of criteria for the definition of transient lower esophageal sphincter relaxations using high-resolution manometry.

BACKGROUND: Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well-defined for Dentsleeve manometry. As high-resolution manometry (HRM) is now the gold standard to assess esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM. METHODS: Postprandial esophageal HRM combined with impedance was performed in 10 patients with gastroesophageal reflux disease. Transient lower esophageal sphincter relaxations identification was performed by 17 experts using a Delphi process. Four investigators then characterized TLESR candidates that achieved 100% agreement (TLESR events) and those that achieved less than 25% agreement (non-events) after the third round. Logistic regression and decision tree analysis were used to define optimal diagnostic criteria. KEY RESULTS: All diagnostic criteria were more frequently encountered in the 57 TLESR events than in the 52 non-events. Crural diaphragm (CD) inhibition and LES relaxation duration >10 seconds had the highest predictive value to identify TLESR. Based on decision tree analysis, reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis were alternate diagnostic criteria. CONCLUSION & INFERENCES: Using HRM, TLESR might be defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with CD inhibition.

Antireflux surgery for non-erosive and erosive reflux disease in community practice.

BACKGROUND: Antireflux surgery has been mainly evaluated in tertiary referral centres. Data regarding post-operative outcome in non-erosive reflux disease are lacking. AIM: To assess long-term outcome after antireflux surgery performed in a community practice setting. METHODS: We selected consecutively 60 non-erosive reflux disease patients and 61 erosive oesophagitis patients with symptomatic gastro-oesophageal reflux disease. After surgery, each subject answered a validated disease-specific health-related quality of life questionnaire and another questionnaire focusing on symptoms, late morbidity and drug use. RESULTS: After a 43-month median follow-up, an excellent outcome was reported by less than two-thirds of patients. Quality of life scores were lower in the non-erosive reflux disease group, especially in female patients. Non-erosive reflux disease patients reported more daily symptoms and more reflux-related symptoms (P = 0.04). Proton-pump inhibitor use was higher in non-erosive reflux disease patients (P < 0.005). Multivariate analysis identified four independent predictive factors associated with better outcome, namely male gender, abnormal preoperative acid exposure, a long duration of symptoms and surgical expertise. CONCLUSIONS: In community practice, the results of antireflux surgery are inferior to those reported by tertiary centres. Outcome seems poorer in non-erosive reflux disease especially in female patients. Nearly one-third of the non-erosive reflux disease patients continue to take proton-pump inhibitors. These results highlight the need for careful selection of patients before antireflux surgery.

Ambulatory 24-h oesophageal impedance-pH recordings: reliability of automatic analysis for gastro-oesophageal reflux assessment.

Oesophageal pH-impedance monitoring allows detection of acid and non-acid gastro-oesophageal reflux (GOR) events. Visual analysis of impedance recording requires expertise. Our aim was to evaluate the efficacy of an automated analysis for GOR assessment. Seventy-three patients with suspected GORD underwent 24-h oesophageal pH-impedance monitoring. Recordings analysis was performed visually (V) and automatically using Autoscan function (AS) of Bioview software. A symptom index (SI) > or =50% was considered for a significant association between symptoms and reflux events. AS analysis detected more reflux events, especially non-acid, liquid, pure gas and proximal events. Detection of oesophageal acid exposure and acid reflux events was similar with both analyses. Agreement between V and AS analysis was good (Kendall's coefficient W > 0.750, P < 0.01) for all parameters. During pH-impedance studies, 65 patients reported symptoms. As compared to visual analysis, the sensitivity and specificity of a positive SI determined by AS were respectively 85.7% and 80% for all reflux events, 100% and 98% for acid reflux and 33% and 87.5% for non-acid reflux. Despite good agreement with visual analysis, automatic analysis overestimates the number of non-acid reflux events. Visual analysis remains the gold standard to detect an association between symptoms and non-acid reflux events.

Community-acquired Clostridium difficile infections.

OBJECTIVE: To describe the management and treatment of community-acquired C. difficile infections (CDI) and to evaluate family physicians' (FP) knowledge and practice. PATIENTS AND METHODS: Observational study from December 2013 to June 2014. All community-acquired CDI case patients diagnosed in the community or at the University Hospital of Nantes were prospectively included. A questionnaire was mailed to 150 FPs of the area of Nantes. RESULTS: A total of 27 community-acquired CDI case patients were included (incidence: 7.7 case patients/100,000 inhabitants). Mean age was higher among case patients diagnosed at hospital (69years) compared with those diagnosed in the community (44years). Fifteen patients were treated at home (55%) and 22 received a first-line treatment with metronidazole. Only one patient did not receive any prior antibiotic treatment. Amoxicillin-clavulanic acid was mainly prescribed (68%) for respiratory and ENT infections (40%). Twenty-three patients were cured on Day 7 and three had complications (two deaths). Thirty-one of 47 FPs reported to have already managed CDI patients. Twenty-two FPs reported to usually treat patients with uncomplicated CDI at home, 21 to refer patients to a specialist, and three to hospital. Forty-one FPs reported to prescribe a CD toxin test only after recent antibiotic exposure and 30 when patients are at risk of CDI. CONCLUSION: The incidence and impact of community-acquired CDIs may be underestimated and the unjustified use of antibiotics may promote their emergence. FPs are not used to treat CDIs as more than 50% prefer referring patients to hospital or to a specialist.

A comparative study of the early effects of tenatoprazole 40 mg and esomeprazole 40 mg on intragastric pH in healthy volunteers.

BACKGROUND: Tenatoprazole is a novel proton pump inhibitor with a seven-hour plasma half-life. AIM: To compare the effects of tenatoprazole 40 mg and esomeprazole 40 mg on intragastric acidity during the first 48 h in healthy volunteers. METHODS: This randomized two-period crossover study included 24 Helicobacter Pylori-negative subjects; tenatoprazole 40 mg or esomeprazole 40 mg daily were given before breakfast for two consecutive days, with a 2-week wash-out between the administration periods. Intragastric pH was monitored for 48 h. RESULTS: Over 48 h, tenatoprazole 40 mg exerted a more potent acid inhibition than esomeprazole 40 mg (median pH: 4.3 vs. 3.9, P < 0.08; per cent of time above pH 4: 57% vs. 49%, P < 0.03; proportion of subjects with at least half of the time above pH 4: 71% vs. 46%). These differences resulted from better night-time acid control with tenatoprazole 40 mg than esomeprazole 40 mg (first night median pH: 4.2 vs. 2.9, P < 0.0001; second night: 4.5 vs. 3.2, P < 0.0001). The duration of nocturnal acid breakthroughs was significantly reduced during both nights. In contrast, no significant difference was detected during the daytime periods between both regimens. CONCLUSION: Over the first 48 h, tenatoprazole 40 mg achieves a better overall and night-time control of gastric pH than esomeprazole 40 mg. The translation of better early control of acidity into clinical benefits deserves further studies.

[Gastro-esophageal reflux and chronic respiratory diseases]. / Reflux gastro-œsophagien et pathologies respiratoires chroniques.

Gastroesophageal reflux disease (GERD) frequently occurs in association with chronic respiratory diseases although the casual link is not always clear. Several pathophysiological and experimental factors are considered to support a role for GERD in respiratory disease. Conversely, respiratory diseases and bronchodilator treatment can themselves exacerbate GERD. When cough or severe asthma is being investigated, GERD does not need to be systematically looked for and a therapeutic test with proton pump inhibitors is not always recommended. pH impedance monitoring is now the reference diagnostic tool to detect non acid reflux, a form of reflux for which proton pump inhibitor treatment is ineffective. Recent data have shown a potential role of GERD in idiopathic pulmonary fibrosis and bronchiolitis obliterans following lung transplantation, leading to discussions about the place of surgery in this context. However, studies using pH impedance monitoring are still needed to better understand and manage the association between GERD and chronic respiratory diseases.

Chemotherapy-driven dysbiosis in the intestinal microbiome.

BACKGROUND: Chemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation (HSCT). Chemotherapy leads to several side effects, with gastrointestinal (GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome. AIM: To identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high-throughput DNA-sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy. METHODS: We amplified and sequenced 16S rRNA genes from faecal samples before and after chemotherapy in 28 patients with non-Hodgkin's lymphoma who received the same myeloablative conditioning regimen and no other concomitant therapy such as antibiotics. RESULTS: We found that faecal samples collected after chemotherapy exhibited significant decreases in abundances of Firmicutes (P = 0.0002) and Actinobacteria (P = 0.002) and significant increases in abundances of Proteobacteria (P = 0.0002) compared to samples collected before chemotherapy. Following chemotherapy, patients had reduced capacity for nucleotide metabolism (P = 0.0001), energy metabolism (P = 0.001), metabolism of cofactors and vitamins (P = 0.006), and increased capacity for glycan metabolism (P = 0.0002), signal transduction (P = 0.0002) and xenobiotics biodegradation (P = 0.002). CONCLUSIONS: Our study identifies a severe compositional and functional imbalance in the gut microbial community associated with chemotherapy-induced GI mucositis. The functional pathways implicated in our analysis suggest potential directions for the development of intestinal microbiome-targeted interventions in cancer patients.