Citations

Background and Aims Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. Approach and Results We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow‐up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow‐up after LT was 3 years (interquartile range 1.1‐6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy‐proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid‐refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). Conclusions The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune‐reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.

Background and Aims Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. Approach and Results We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty‐four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention‐to‐treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma‐glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5‐year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. Conclusions We presented the largest‐ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end‐stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo‐controlled treatment trials are needed to identify effective treatments for pediatric PSC.

Abstract Background Modern-day penile prostheses use infection retardant coating to decrease rates of postoperative infection, subsequently reducing explantation and revision rates as well. The Coloplast Titan models are dipped into antimicrobial solutions right before implantation, and the components used for dipping can be tailored toward the patient. Aim To compare infection, explantation, and revision rates among different dipping solutions used before implantation for patients with diabetes receiving a Coloplast Titan implant. Methods We systematically reviewed 932 patients with diabetes receiving a primary penile implant across 18 different centers from the period April 2003 to August 2018. Of those patients, 473 received a Coloplast device, whereas 459 received an AMS device. Data regarding the type of antimicrobial solution used before implantation were recorded for 468 patients receiving a Coloplast Titan, including whether or not they suffered a postoperative infection and if they underwent explantation and/or revision. Outcome rates were compared using Fisher’s exact and Pearson’s chi-square tests, and logistic regression modeling was performed to account for covariates. Outcomes The main outcome measures of this study were postoperative infection, explantation, and revision rates. Results Of the total 932 patients reviewed, 33 suffered a postoperative infection. Of 468 patients receiving Coloplast implants, there was a 3.4% infection rate. The most commonly used antibiotic combination before dipping was vancomycin + gentamicin (59.0%). There was a significantly lower rate of postoperative infection, explantation, and revision when vancomycin + gentamicin was used than those associated with the use of all other dipping solutions ([1.4% vs 6.4%; P = .004], [1.1% vs 8.3%; P &lt; .001], and [2.5% vs 12.5; P &lt; .001], respectively). After adjusting for age, body mass index, preoperative blood glucose level, and hemoglobin A1c, the use of other dips was an independent predictor of postoperative infection (odds ratio: 0.191; P = .049). The inclusion of rifampin in the dipping solution trended toward being a significant risk factor for infection (P = .057). Including antifungals in the dipping solution did not affect infection (P = .414), explantation (P = .421), or revision (P = .328) rates. Clinical Implications Vancomycin + gentamicin was the most efficacious combination of antibiotics used for dipping in terms of preventing postoperative infection and subsequent explantation and revision. Strengths and Limitations Data were sampled across multiple institutions providing a large sample that may be more representative of the population of interest. A key limitation of the study was its retrospective nature, which prevented us from controlling certain variables. Conclusion The use of rifampin did not provide the same type of protection, possibly representing a shift in resistance patterns of common bacteria responsible for device infection.