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Telemedicine has shown promising results in the follow up of patients with inflammatory bowel disease. This study compared quality of life and disease activity in patients with inflammatory bowel d...

Background We aim to show the endoscopic placement of a T-tube to treat a persistent large gastro-cutaneous fistula after OAGB. Methods We present the case of a 46-year-old woman with BMI of 48 kg/m2, who underwent OAGB and was re-operated on the 2nd postoperative day (POD) for leakage. Washing and drainage of the abdominal cavity was performed, and no fistulous orifice was identified. An upper gastrointestinal (GI) endoscopy was performed at POD 20 for the persistence of leakage of 150 ml/day by the drain and a gastric fistulous orifice of 2 cm was detected. Results At POD 22, under general anesthesia, upper GI endoscopy was performed and a T-tube was placed in the fistulous orifice with a “rendez-vous” technique (as demonstrated in the Video), placing the T branch in the digestive lumen pressed against the wall and the long part of the T exiting at the cutaneous orifice. The T-tube was clamped after 3 days and the patient could be gradually re-fed. The patient was discharged 8 days after the procedure, with perfect clinical tolerance and no complications. The ablation of the tube one was performed on POD 84. No relapse occurred during a follow-up of 48 months. Conclusion Persistent large gastro-cutaneous fistulas with an orifice bigger than 1 cm in diameter are difficult to manage. The endoscopic placement of a T-tube seems a useful option, which may facilitate the healing of the fistula. Further studies are needed to better define the role of this procedure.

Purpose Post-bariatric surgery gastrocutaneous fistula is a chronic leak with an incidence of 1.7 to 4.0% and no standardized management. A large gastrocutaneous fistula (LGCF) is not indicated for treatment with pigtail drains. We aimed to evaluate results of a novel treatment using endoscopic Kehr’s T-tube placement. Methods Only patients with a postoperative LGCF duration of > 10 days and a flow rate of > 50 cc by external drainage after revisional surgery for sepsis were included. Endoscopic placement of Kehr’s T-tube was performed. Patients had been reoperated with wash and drainage for severe sepsis after initial bariatric surgery in which no fistula had been discovered. Patients not reoperated, or with a fistula requiring intraoperative Kehr’s T-tube placement, or a pigtail drain were excluded. Primary outcomes were endoscopic characteristics and results (LGCF closure rate, Kehr T-tube retention time, etc.). Results The study group included 12 women, 2 men; body mass index 43.1 ± 4.5 kg/m2. Interventions were SG (7), RYGB (2), OAGB (4), and SADI-S (1). Endoscopic assessment was carried out after a mean of 33.2 ± 44.3 days after the bariatric procedure. The mean fistula orifice diameter was 2.0 ± 0.9 cm. Kehr’s T-tube was positioned at a mean 51.5 ± 54.8 days after the bariatric procedure. T-tube tolerance was excellent. Mean additional days: hospitalization, 34.4 ± 27.0; T-tube retention, 86.4 ± 73.1; fistula healing, 139.9 ± 111.5, LGCF closure rate, 92.9%. Complications: 1 pulmonary embolism, 2 T-tube migrations,1 drain-path bleed, 1 skin abscess. No mortality. Conclusions Endoscopic Kehr’s T-tube placement was successful in closing persistent post-bariatric surgery LGCF in 92.9% of patients. Graphical abstract

Summary Objectives Combination therapy using peginterferon alfa-2a (40 kD) plus ribavirin achieves viral eradication in nearly 60% of patients with chronic hepatitis C viral infection. However, because of the numerous side effects, use of the combination regimen might be restricted for patients consulting private practitioners specialized in hepatogastroenterology. Patients and method Conducted in this specific context, this prospective clinical trial investigated the safety and efficacy of combination therapy in 197 patients. Therapy was given in compliance with the recommendations of the French consensus conference on hepatitis C treatment. Results Commonly reported adverse effects were noted in 90% of patients, most occurring during the first three months, with a stable prevalence thereafter and resolution after treatment end. The most frequent adverse events were asthenia (35 to 37.5% according to the treatment group pruritus (25 to 26.3%) and flu-like syndrome (19 to 21.7%). A depressive syndrome was reported in 20 to 21% of patients. Grade 4 neutropenia was exceptional and never led to severe infections. At intent-to-treat analysis, the rate of sustained virological response was 54.8% for the entire population. It was 71.1% for patients with genotypes 2 or 3 (mainly treated for 24 weeks) and 44.6% for patients with genotype 1 (all treated 48 weeks). Conclusion The characteristic features of combination therapy observed in the context of private hepatogastroenterology consultations are similar to those observed in randomized clinical trials.

AIM: To assess, in a routine practice setting, the sustained virologic response (SVR) to telaprevir (TPV) or boceprevir (BOC) in hepatitis C virus (HCV) null-responders or relapsers with severe liver fibrosis. METHODS: One hundred twenty-five patients were treated prospectively for 48 wk with TPV or BOC + pegylated-interferon (peg-INF) α2a + ribavirin (PR) according to standard treatment schedules without randomization. These patients were treated in routine practice settings in 10 public or private health care centers, and the data were prospectively collected. Only patients with severe liver fibrosis (Metavir scores of F3 or F4 upon liver biopsy or liver stiffness assessed by elastography), genotype 1 HCV and who were null-responders or relapsers to prior PR combination therapy were included in this study. RESULTS: The Metavir fibrosis scores were F3 in 35 (28%) and F4 in 90 (72%) of the patients. In total, 62.9% of the patients were null-responders and 37.1% relapsers to the previous PR therapy. The overall SVR rate at 24 wk post-treatment withdrawal was 59.8%. The SVR was 65.9% in the TPV group and 44.1% in the BOC group. Independent predictive factors of an SVR included a response to previous treatment, relapsers vs null-responders [OR = 3.9; (1.4, 10.6), P = 0.0084], a rapid virological response (RVR) [OR 6.9 (2.6, 18.2), P = 0.001] and liver stiffness lower than 21.3 kPa [OR = 8.2 (2.3, 29.5), P = 0.001]. During treatment, 63 patients (50.8%) had at least one severe adverse event (SAE) of grade 3 or 4. A multivariate analysis identified two factors associated with SAEs: female gender [OR = 2.4 (1.1, 5.6), P = 0.037] and a platelet count below 150 × 103/ mm3 [OR = 5.3 (2.3, 12.4), P ≤ 0.001]. CONCLUSION: More than half of these difficult-to-treat patients achieved an SVR and had SAEs in an actual practice setting. The SVR rate was influenced by the response to previous PR treatment, the RVR and liver stiffness.

Backgroundl Aim: Fifty percent of patients infected with hepatitis C virus (HCV) show no response to α-interferon, and no alternative therapy has thus far proven to be effective. Therapeutic combination with ribavirin and α-interferon has shown promising results in naive patients and in relapsers, but based on limited series, it was reported to be inefficient in non-responders. The aim of our study was therefore to explore and compare, in a randomized trial, the tolerance and potential efficacy of α-interferon alone with a sequential combination of ribavirin and the same α-interferon regimen in those patients. Methods: Sixty-four non-responder patients were randomized in the α2b-interferon group (a 6-month course at a dosage of 6 MU followed by a 6-month course of 3 MU three times weekly subcutaneously) and 62 in the "combination" group (sequential combination of the same α2b-interferon therapy preceded by a 2-month course of ribavirin which was then associated for 2 months with α2b-interferon at a daily dosage of 1.0 or 1.2 g). Results: Treatment withdrawal was necessary for six patients from the α-interferon and eight patients from the combination group. Normalization of aminotransferase activities was significantly more frequent after the 4-month course of ribavirin with 2 months of interferon than after 2 months of interferon alone (52.8 vs . 26.2%, p vs . 7.7%, p =0.02), but did not differ 6 months after the end of therapy (9.8 and 8.3%, respectively). The long-term response was not associated with liver status (cirrhosis vs . absence of cirrhosis) or genotype. Mean viremia was significantly lower in long-term responders than in non-responders or relapsers in both groups ( p p vs . 35.9%, p

The purpose of this study is to compare a combination of interferon (IFN)-alpha2a (Roferon) + Tenoxicam with IFN-alpha2a alone in the treatment of chronic hepatitis C. This prospective, randomized double-blind study included 149 patients, all of whom were diagnosed with active chronic hepatitis C but non-cirrhotic (ALT > or = 1.5 upper limit of normal, anti-hepatitis C virus (HCV) positive by enzyme-linked immunosorbant assay2 and RIBA3). The patients were randomized in two groups, as follows: G1 (n = 76): IFNalpha2a 3 million units times per week during 6 months + placebo; and G2 (n = 73): IFNalpha2a 3 million units three times per week + Tenoxicam (20 mg/day) during 6 months. Alanine aminotransferase (ALT) and HCV RNA were determined before and at months 6 and 12 of treatment. 2'5' oligoadenylate synthetase activity (2'5' AS) was dosed in mononuclear cells before and at 3-month treatment intervals in 28 patients. Liver biopsy was performed before and 6 months after the end of therapy. Parameters were similar before therapy for both groups. Biochemical and virological responses were similar for both groups at month 6 (49.3% vs. 42.9% and 43.3% vs. 38.3%, respectively) and month 12 (28.3% vs. 23.8% and 17.2% vs. 17.5%, respectively). HCV RNA level significantly decreased in both groups at month 6, with no difference whatever the therapy; however, the HCV RNA level returned to initial values at month 12 and was the only significant prognostic factor of a sustained response. No peak of 2'5' AS activity was observed during treatment in patients with dual therapy. A histological improvement was also noted in both groups without difference, regardless of therapy. The percentage of adverse events was identical for both groups. Paracetamol intake, assessed in 80 patients, was 49.1 g per 6 months in the G1 group and 22.5 g per 6 months in the G2 group (not significant). In conclusion, the non-steroid anti-inflammatory drug, Tenoxicam, does not increase IFNalpha efficacy in the treatment of chronic hepatitis C. This combination is well tolerated and partially lowers Paracetamol intake, but not preexisting alpha-IFN adverse events.

International audience; New factors that influence the viral response in HCV non-genotype 2/3 patients must be identified in order to optimize anti-HCV treatment. This multicenter prospective study evaluates the influence of HCV variability and pharmacological parameters on the virological response of these patients to pegylated interferon α2a (peg-IFN-α2a: 180 µg/week) and ribavirin (800-1200 mg/day) for 48 weeks. HCV subtypes were identified by sequencing the NS5B region. Serum ribavirin and peg-IFN-α2a concentrations were measured at weeks 4 and 12. The 115 patients (67 men; median age=49, range [31-76]) included 64 who had never been treated and 27 co-infected with HIV. The mean baseline HCV RNA was 6.30 ± 0.06 log IU/mL and the HCV genotypes were: G1 (n=93) with 1a (n=37) and 1b (n=50), G4 (n=20) and G5 (n=2). Most patients (79/108; 73%) had an early virological response. Independent predictors of an early virological response were interferon naive patients (OR=2.98 [1.15; 7.72]) and ribavirin of > 2,200 ng/mL at week 12 (OR=3.41 [1.31; 8.90]). Forty of 104 patients (38%) had a sustained virological response. The only independent predictors of a sustained virological response were subtype 1b (OR=6.82 [1.7; 26.8]), and HCV RNA 2,200 ng/mL was associated with an early virological response and patients infected with HCV subtype 1b had a better chance of a sustained virological response than did those infected with subtype 1a.

Molsidomine, a long-acting vasodilator mainly used as an antianginal agent, was reported to decrease the portohepatic venous pressure gradient in patients with alcoholic cirrhosis. This study investigated the effects of linsidomine, the active metabolite of molsidomine, on systemic and splanchnic hemodynamics in rats with CCl4-induced cirrhosis using the microsphere technique. Compared with placebo-treated rats, linsidomine-treated animals were found to have a significant decrease in portal venous pressure (-18%, p less than 0.01) and in mean arterial pressure (-16%, p less than 0.01), smaller peripheral resistances (p less than 0.01), greater portal venous inflow (p less than 0.05), smaller splanchnic arteriolar resistances (p less than 0.01) and smaller protocol-lateral resistances (p less than 0.05). Cardiac output, hepatic arterial blood flow, portal blood flow and estimated hepatic blood flow were not significantly different between the two groups of animals. Linsidomine-treated rats exhibited a trend toward greater collateral blood flow compared with controls, but this difference was not significant. We conclude that linsidomine decreases portal venous pressure by reducing portocollateral resistances without affecting liver blood flow. These effects should be beneficial for patients with cirrhosis and portal hypertension.

Organic nitrates were reported to reduce portohepatic venous pressure gradient in patients with cirrhosis. However, these drugs lower arterial pressure and are well known to induce tolerance. The aim of the present study was to assess the hemodynamic effects of molsidomine, an antianginal agent, which does not induce tolerance and has little effect on arterial pressure in patients with normal liver, in 13 patients with alcoholic cirrhosis. Wedged hepatic vein pressure (-11%, p less than 0.01), portohepatic venous pressure gradient (-15%, p less than 0.005), hepatic blood flow (-17.4%, p less than 0.005), mean arterial pressure (-13.5%, p less than 0.01) and cardiac output (-17%, p less than 0.001) were significantly reduced by molsidomine. Free hepatic vein pressure, intrinsic hepatic clearance indocyanine green, heart rate and systemic vascular resistances were not significantly modified. There was no correlation between the decrease in portohepatic venous pressure gradient and the reduction in mean arterial pressure on one hand and the decrease in cardiac output on the other hand. We therefore conclude that in patients with cirrhosis, molsidomine has effects similar to nitrates on systemic and splanchnic hemodynamics.

To study Quality of Life during chronic hepatitis C infection in patients recruited by hospital-based- or private hepatologists and to assess the effect of antiviral therapy.A self-administered quality of life questionnaire (SF36) was proposed before, during, and 6 months after the end of treatment. The quality of life scales were assessed according to treatment response.599 patients filled in the questionnaire before treatment and 168 patients 6 months after the end of treatment. After 6 months of therapy, patients with treatment response (n=54) showed increased scores in all SF-36 scales, this increase reaching more than 25% for "Role Physical", "General Health Perception" and "Vitality" scores. Non-responders (n=70) had an impairment of physical scores but a general improvement of Mental Health.This study confirms that sustained virological response is associated with an improved quality of life in hepatitis C patients. However, non-responders still have a positive "General Health Perception". Together with the development of new therapies, these observations could help to convince reluctant patients to be treated.

Propranolol and molsidomine have both been shown to decrease the hepatic venous pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of the combination of these two drugs on splanchnic and systemic haemodynamics of cirrhotic patients. Fifteen patients with biopsy proven alcoholic cirrhosis had haemodynamic measurements under basal conditions, 60 min after oral administration of 4 mg molsidomine then 15 min after intravenous administration of 15 mg propranolol. As compared with baseline values, molsidomine was found to decrease mean arterial pressure (-7.9%, (P < 0.01), cardiac output (-7.3%, P < 0.01), pulmonary wedged pressure (-45.8%, (P < 0.05) and hepatic venous pressure gradient (-11.7%, P < 0.01). Propranolol decreased heart rate (-21%, P < 0.01), further decreased cardiac output (-20.6%, (P < 0.01) and hepatic venous pressure gradient (-10.5%, P < 0.01). As a whole, molsidomine plus propranolol decreased mean arterial pressure (-8%, P < 0.01), heart rate (-19%, P < 0.01), cardiac output (-26.5%, P < 0.01) and hepatic venous pressure gradient (-21%, P < 0.01). Pulmonary wedged pressure, liver blood flow and hepatic intrinsic clearance of indocyanine green were not significantly changed by the association of molsidomine and propranolol. We conclude that in patients with cirrhosis, molsidomine and propranolol potentiate their effects on hepatic venous pressure gradient. Such a combination could therefore prove useful in the treatment of portal hypertension.

In patients treated with sclerotherapy, most rebleeding episodes are observed before variceal obliteration. This prospective randomized study aimed to assess if propranolol together with sclerotherapy could reduce the rebleeding rate before variceal obliteration. Seventy-five patients (59 male, 16 female; mean age, 54 +/- 15 years) with cirrhosis (from alcohol abuse in 91%) admitted with upper gastrointestinal bleeding, which was endoscopically proven to originate from ruptured esophageal varices, were included. After initial control of bleeding, the patients were randomized into the following two groups: group 1 treated with sclerotherapy alone (36 patients) and group 2 treated with sclerotherapy plus propranolol (39 patients). They were followed up to variceal obliteration. In group 2, 7 patients rebled as compared with 14 patients treated with sclerotherapy alone (P less than 0.005). When considering only rebleedings from esophageal varices, 4 patients rebled in group 2 vs. 10 in group 1 (P less than 0.10). The total number of rebleeding episodes was lower in group 2 than in group 1 whether considering all causes (8 vs. 17; P less than 0.07) or variceal rebleedings alone (4 vs. 13; P less than 0.01). Mean total blood requirement per patient was lower in group 2 than in group 1 (1.4 +/- 3.4 vs. 2.79 +/- 6.4 units of blood, respectively; P less than 0.01). Mortality was similar in both groups of patients (14% vs. 13% in groups 1 and 2, respectively, NS). It is concluded that patients treated with sclerotherapy should be given propranolol before variceal obliteration.

Introduction Les parametres pharmacologiques peuvent influencer la reponse virologique au cours de l’hepatite virale C (HVC). Le but de cette etude prospective etait d’evaluer l’influence de la concentration plasmatique de Peginterferon alpha 2a (PEG-IFNα 2a) et de la ribavirine (RBV) sur la reponse virologique precoce (RVP) chez les patients infectes par un genotype 1 ou 4. Patients et Methodes Les criteres d’inclusions etaient : HCV genotype 1 ou 4 traites par PEG-IFNα 2a (180 μg/sem) and RBV (800-1 200 mg/j, ajuste au poids). La RVP etait definie par une diminution de l’ARN ≥ 2 log IU/mL ou Resultats 106 patients (58 % hommes, âge moyen de 52 ans) ont ete inclus. 24 % etaient coinfectes par le VIH et 21 etaient sous traitement antiretroviral. Le METAVIR etait F0 (n = 5), F1 (n = 12), F2 (n = 37), F3 (n = 15), F4 (n = 28). L’ARN etait a 6,30 ± 0,06 log IU/mL, la distribution des genotypes etait genotype 1 (n = 87, 82 %) et 4 (n = 19, 18 %). La RVP etait observee chez 76 patients (72 %). A la semaine 12, la concentration plasmatique moyenne de PEG-IFNα 2a etait de 101 ± 11 ng/mL (extremes : 4-538) et celle de RBV etait de 2 345 ± 91 ng/mL (extremes : 290-6 169). Aucune difference de concentrations plasmatiques de RBV et de PEG-IFNα 2a etait observee entre les monoinfectes HCV et les HIV-HCV coinfectes. Le taux moyen d’hemoglobine a la semaine 12 diminuait de 2,95 g/dL et etait inversement proportionnel a la Ribavirinemie (r = -0,26, p 2 200 ng/mL, la RVP etait de 84 %. Conclusion Nos resultats montrent que pour les patients avec HCV de genotype 1 ou 4, il existe une correlation entre Ribavirinemie et RVP a la semaine 12 alors que les concentrations plasmatiques de PEG-IFNα 2a n’influencent pas la RVP. Le suivi de ces patients dans les prochains mois nous permettra de determiner l’influence de ces parametres sur l’eradication virale. Remerciements, financements, autres Natalia Kharlova, Laboratoire Roche.

1-Naphthyl N-methyl carbamate (carbaryl), potent carbamate insecticide with anticholinesterase activity, was tested for its ability to affect mouse peritoneal macrophages in particular arachidonic acid (AA) metabolism and oxidative burst. Carbaryl inhibited in a dose-related manner the reactive oxygen intermediate dependent chemiluminescence (CL) induced by opsonized zymosan (OZ), 12-O-tetradecanoyl phorbol-13-acetate (TPA) and calcium ionophore (A23187); this carbamate did not affect CL-mediated by AA. The intracellular and extracellular concentrations of prostaglandins (PGs) and 5-hydroxyeicosatetraenoic (5-HETE) generated in macrophages stimulated with OZ has been investigated for various periods. Carbaryl effect displayed two successive phases on AA metabolism stimulation. In a first phase (up to 2-15 min), carbaryl did not alter the rapid AA metabolite synthesis (total amount of intra- and extracellular metabolites) but it increased intracellular concentration of PGE2, PGA2, PGF2 alpha and decreased 5-HETE intracellular concentration. In a second phase (after 2-15 min), carbaryl inhibited AA metabolite synthesis. The release of cyclooxygenase (CO) and lipoxygenase (LO) metabolites decreased, in particular PGF2 alpha and PGD2 which in addition seemed to be submit to a cellular retention; the inhibition of other metabolite release appeared essentially related to the inhibition of their synthesis since the intracellular amount did not augment. The inhibition by carbaryl of the NADPH-oxidase dependent CL induced by OZ may be related to the alteration of the intra- and extracellular concentrations of AA metabolites.

This study aimed to assess the effects of verapamil, a calcium-channel blocker, on porto-hepatic pressure gradient and on hepatic function as measured by the intrinsic hepatic clearance of indocyanine green (ICG) in patients with biopsy proven alcoholic cirrhosis. Hepatic venous pressures and hepatic extraction of ICG were measured before and 60 min after intravenous injection of 10 mg of verapamil in 19 consecutive patients. Hepatic blood flow and intrinsic hepatic clearance of ICG were calculated in the 10 patients whose hepatic extraction fraction was higher than 10%. No significant difference was observed when comparing porto-hepatic pressure gradient (17.72 ± 4.79 vs. 17.77 ± 4.43 mmHg), hepatic blood flow (13.47 ± 4.75 vs. 16.13 ± 7.88 ml.min −1 - · kg −1 ) and intrinsic hepatic clearance of ICG (1.99 ± 0.54 vs. 1.97 ± 0.45 ml · min −1 · kg −1 ) before and after verapamil injection. We conclude that verapamil has no beneficial effect in patients with alcoholic cirrhosis.