A randomized controlled trial of high volume simethicone to improve visualization during capsule endoscopy.

BACKGROUND: The optimal dose of simethicone before capsule endoscopy is unknown. Prior studies have reported inconsistent cleansing, with some showing improved visualization only in the proximal small intestine. We hypothesized a higher volume of simethicone may improve cleansing and diagnostic yield, especially in the distal small bowel. METHODS: A phase III randomized controlled trial was conducted comparing high volume (1125 mg simethicone in 750 ml water) versus standard volume (300 mg simethicone in 200 ml water) solutions, both at 1.5 mg/ml. The primary outcome was adequate bowel preparation, defined as a KOrea-CanaDA (KODA) score >2.25, overall and stratified by the proximal and distal half of the small bowel. Secondary outcomes included mean KODA score, diagnostic yield, completion rate, and adverse events. All analyses were intention-to-treat. RESULTS: A total of 167 patients were randomized (mean (SD) age 58.7 (15.7), 54% female) and the most common indication was obscure gastrointestinal bleeding (71.7%). Adequate cleansing was achieved in 39 (50%) patients in the high volume group and in 39 (48%) patients in the standard volume group (RR 1.04, 95% CI 0.76-1.43, p = 0.82), with no differences observed in the proximal half (71% vs 64%, p = 0.40) or the distal half -of the small bowel (36% vs. 37%, p = 0.88). There was no differences in the mean (SD) KODA score (2.20 (0.41) vs. 2.18 (0.44), p = 0.73), diagnostic yields (53% vs. 56%, p = 0.71), or completion rates (both 95%). One adverse event, nausea, occurred in the control group. CONCLUSION: High volume simethicone does not improve visualization during capsule endoscopy. CLINICAL TRIAL REGISTRATION: Clinical trial: NCT02334631.

The role of imaging in determining prognosis for primary sclerosing cholangitis: A systematic review.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is a chronic, progressive, fibrotic bile duct disease. Resultant complications include infection, progressive liver disease and cancer. While diagnosis relies extensively on imaging, the role of imaging in determining prognosis is unclear. The aim of this study was to systematically review existing imaging indices and features that predict PSC progression. MATERIALS AND METHODS: We performed a systematic review of imaging features that predict PSC progression. PubMed, EMBASE, MEDLINE, Clinicaltrials.gov and the Cochrane Library were searched from inception to November 2018 for relevant studies. Pertinent data were extracted and assessed. Study quality was evaluated using the Newcastle-Ottawa scale (NOS). RESULTS: The search returned 2504 results. Nine studies were included in the final review. Four studies evaluated the prognostic value of imaging features and five evaluated prognostic algorithms. The mean NOS score was 4.44 ± 0.98 on a scale of 0 to 9. Imaging features that were of prognostic value were degree of intrahepatic duct narrowing, the presence of a dominant biliary duct stricture and percentage of narrowed intraheptic ducts. Three imaging indices (one endoscopic retrograde cholangiopancreatography (ERCP)-based and two magnetic resonance-based) had been derived. The ERCP index was validated in a second cohort and subsequently updated to improve its predictive ability. The magnetic resonance cholangiopancreatography (MRCP) index was validated in two studies and was found to be predicative of transplant-free survival. A modified MRCP index (MRCP-risk score) was evaluated in a prospective multicenter study and was found to be predicative of PSC-related disease progression. CONCLUSION: In conclusion, ERCP and MRCP-based indices have short-term prognostic value in PSC. However, more studies are required to validate their predictability of disease-related progression, such as liver decompensation, ascending cholangitis, cholangiocarcinoma and liver transplantation.

Low dose naltrexone for induction of remission in Crohn's disease.

BACKGROUND: Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy. OBJECTIVES: The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease. SEARCH METHODS: A systematic search of MEDLINE, Embase, PubMed, CENTRAL, and the Cochrane IBD Group Specialized Register was performed from inception to 15 January 2018 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also screened. SELECTION CRITERIA: Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included. DATA COLLECTION AND ANALYSIS: Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.3.5). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of < 150 or a pediatric Crohn's disease activity index (PCDAI) of < 10. Secondary outcomes included clinical response (70- or 100-point decrease in CDAI from baseline), endoscopic remission or response, quality of life, and adverse events as defined by the included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. MAIN RESULTS: Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed eight weeks of LDN (0.1 mg/kg, maximum 4.5 mg/day) treatment compared to placebo in pediatric patients (N = 12). The primary purpose of the pediatric study was to assess safety and tolerability. Both studies were rated as having a low risk of bias. The study in adult patients reported that 30% (5/18) of LDN treated patients achieved clinical remission at 12 weeks compared to 18% (3/16) of placebo patients, a difference that was not statistically significant (RR 1.48, 95% CI 0.42 to 5.24). The study in children reported that 25% of LDN treated patients achieved clinical remission (PCDAI < 10) compared to none of the patients in the placebo group, although it was unclear if this result was for the randomized placebo-controlled trial or for the open label extension study. In the adult study 70-point clinical response rates were significantly higher in those treated with LDN than placebo. Eighty-three per cent (15/18) of LDN patients had a 70-point clinical response at week 12 compared to 38% (6/16) of placebo patients (RR 2.22, 95% CI 1.14 to 4.32). The effect of LDN on the proportion of adult patients who achieved a 100-point clinical response was uncertain. Sixty-one per cent (11/18) of LDN patients achieved a 100-point clinical response compared to 31% (5/16) of placebo patients (RR 1.96, 95% CI 0.87 to 4.42). The proportion of patients who achieved endoscopic response (CDEIS decline > 5 from baseline) was significantly higher in the LDN group compared to placebo. Seventy-two per cent (13/18) of LDN patients achieved an endoscopic response compared to 25% (4/16) of placebo patients (RR 2.89; 95% CI 1.18 to 7.08). However, there was no statistically significant difference in the proportion of patients who achieved endoscopic remission. Endoscopic remission (CDEIS < 3) was achieved in 22% (4/18) of the LDN group compared to 0% (0/16) of the placebo group (RR 8.05; 95% CI 0.47 to 138.87). Pooled data from both studies show no statistically significant differences in withdrawals due to adverse events or specific adverse events including sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue. No serious adverse events were reported in either study. GRADE analyses rated the overall quality of the evidence for the primary and secondary outcomes (i.e. clinical remission, clinical response, endoscopic response, and adverse events) as low due to serious imprecision (sparse data). AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to allow any firm conclusions regarding the efficacy and safety of LDN used to treat patients with active Crohn's disease. Data from one small study suggests that LDN may provide a benefit in terms of clinical and endoscopic response in adult patients with active Crohn's disease. Data from two small studies suggest that LDN does not increase the rate of specific adverse events relative to placebo. However, these results need to be interpreted with caution as they are based on very small numbers of patients and the overall quality of the evidence was rated as low due to serious imprecision. Further randomized controlled trials are required to assess the efficacy and safety of LDN therapy in active Crohn's disease in both adults and children.

Low dose naltrexone for induction of remission in Crohn's disease.

BACKGROUND: Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy. OBJECTIVES: The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease. SEARCH METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL, and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Specialized Register was performed from inception to February 2013 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also reviewed. SELECTION CRITERIA: Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included. DATA COLLECTION AND ANALYSIS: Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.2). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of < 150 or a pediatric Crohn's disease activity index (PCDAI) of < 10. Secondary outcomes included clinical response (70- or 100-point decrease in CDAI from baseline), endoscopic remission or response, quality of life, and adverse events as defined by the included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. MAIN RESULTS: Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed eight weeks of LDN (0.1 mg/kg, maximum 4.5 mg/day) treatment compared to placebo in pediatric patients (N = 12). The primary purpose of the pediatric study was to assess safety and tolerability. Both studies were rated as having a low risk of bias. The study in adult patients reported that 30% (5/18) of LDN treated patients achieved clinical remission at 12 weeks compared to 18% (3/16) of placebo patients, a difference that was not statistically significant (RR 1.48, 95% CI 0.42 to 5.24). The study in children reported that 25% of LDN treated patients achieved clinical remission (PCDAI < 10) compared to none of the patients in the placebo group, although it was unclear if this result was for the randomized placebo-controlled trial or for the open label extension study. In the adult study 70-point clinical response rates were significantly higher in those treated with LDN than placebo. Eighty-three per cent (15/18) of LDN patients had a 70-point clinical response at week 12 compared to 38% (6/16) of placebo patients (RR 2.22, 95% CI 1.14 to 4.32). The effect of LDN on the proportion of adult patients who achieved a 100-point clinical response was uncertain. Sixty-one per cent (11/18) of LDN patients achieved a 100-point clinical response compared to 31% (5/16) of placebo patients (RR 1.96, 95% CI 0.87 to 4.42). The proportion of patients who achieved endoscopic response (CDEIS decline > 5 from baseline) was significantly higher in the LDN group compared to placebo. Seventy-two per cent (13/18) of LDN patients achieved an endoscopic response compared to 25% (4/16) of placebo patients (RR 2.89; 95% CI 1.18 to 7.08). However, there was no statistically significant difference in the proportion of patients who achieved endoscopic remission. Endoscopic remission (CDEIS < 3) was achieved in 22% (4/18) of the LDN group compared to 0% (0/16) of the placebo group (RR 8.05; 95% CI 0.47 to 138.87). Pooled data from both studies show no statistically significant differences in withdrawals due to adverse events or specific adverse events including sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue. No serious adverse events were reported in either study. GRADE analyses rated the overall quality of the evidence for the primary and secondary outcomes (i.e. clinical remission, clinical response, endoscopic response, and adverse events) as low due to serious imprecision (sparse data). AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to allow any firm conclusions regarding the efficacy and safety of LDN used to treat patients with active Crohn's disease. Data from one small study suggests that LDN may provide a benefit in terms of clinical and endoscopic response in adult patients with active Crohn's disease. Data from two small studies suggest that LDN does not increase the rate of specific adverse events relative to placebo. However, these results need to be interpreted with caution as they are based on very small numbers of patients and the overall quality of the evidence was rated as low due to serious imprecision. Further randomized controlled trials are required to assess the efficacy and safety of LDN therapy in active Crohn's disease in both adults and children. One study is currently ongoing (NCT01810185).

Female donor to male recipient gender discordance results in inferior graft survival: a prospective study of 1,042 liver transplants.

BACKGROUND: The influence of donor-recipient gender mismatch on outcomes after liver transplantation (LT) is controversial. The aim of this study was to evaluate the effect of donor and recipient gender discordance on graft survival. METHODS: All patients who underwent primary LT from 1994-2012 at a single-center were identified prospectively. Clinico-demographic data were collected at the time of LT and last follow-up. Gender match included both male donor to male recipient (MM) and female donor to female recipient (FF), while gender mismatch included female donor to male recipient (FM) and male donor to female recipient (MF). Survival curves for graft survival were generated using Kaplan-Meier method and compared by log-rank test. Unadjusted and multivariate adjusted COX regression analyzing graft survival at up to 10 years post-transplant was performed. RESULTS: A total of 1,042 subjects fulfilled the criteria. Graft survival in patients receiving a donor-recipient gender match was better than those receiving a gender mismatch (P = 0.047). Female-to-male transplants had the worst graft survival of all combinations (P < 0.001); this difference was maintained in multivariate regression after adjustment for recipient and donor variables (hazards ratio 2.09, P = 0.013). CONCLUSION: Female-to-male liver transplants are associated with a statistically significant poorer graft survival as compared with other donor-recipient gender groups.

A case of tinea incognito.

Tinea incognito is a dermatophyte infection of the skin that presents atypically because it has previously been treated with imunnosuppresive medication. Herein we present a case of a middle-aged man who was initially clinically diagnosed to have plaque-type psoriasis on his arms. Over the course of two months of topical hydrocortisone and calciptriol treatment as well as phototherapy, the rash worsened. At the time of presentation to hospital the patient had a pruritic, widespread, sloughing, erythematous rash with areas of eschar. A punch biopsy skin confirmed dermatophyte fungal infection of the skin. Fungal culture was positive for Trichophyton Rubrum and the eruption resolved with systemic anti-fungal therapy. Patient specific risk factors for atypical presentation included poor hygiene and hepatatic disease.

The management of eosinophilic esophagitis in adults.

Eosinophilic esophagitis (EoE), typically a pediatric disease, is becoming more frequently recognized in adults. The optimal treatment of EoE in this population has not yet been established. This paper reviews the literature detailing the treatments for EoE in adults, and provides a treatment strategy. To accomplish this task a comprehensive literature search of Medline was undertaken for studies evaluating the treatment of EoE in adults. High-dose topical corticosteroids and specific elimination diets have been found to improve symptoms, reduce eosinophilic infiltrate in esophageal mucosa, and improve endoscopic markers of inflammation. Dilation therapy does improve symptoms but not underlying inflammation. Other treatments including leukotriene inhibitors and immunomodulatory drugs have been unsuccessful. An effective strategy for treating EoE in adults is using topical corticosteroids and elimination diets for inflammatory disease, and esophageal dilation for fibrotic disease. The conclusion that inflammatory and fibrotic components of EoE respond to different treatment modalities should be evaluated in future clinical trials.