A Rare Complication of Peritoneal Dialysis (PD) Catheter: Perforation of Sigmoid Colon by Migrating Tip of Peritoneal Dialysis Catheter.

BACKGROUND Peritoneal dialysis (PD) has benefits over hemodialysis (HD), including the ability of daily performance at home without interfering with important activities such as school attendance in children. However, there are risks and complications associated with it. This is the third pediatric case report of a dormant PD catheter tip perforating the colon and protruding through the anus, but without peritonitis, as would be highly expected. CASE REPORT A 12-year-old male with ESRD secondary to obstructive uropathy received a pre-emptive deceased donor kidney transplant that failed within a few days due to thrombosis secondary to factor V Leiden deficiency. Transplant nephrectomy was performed and several months later he was started on PD. Subsequently, due to multiple episodes of catheter drain failure, the modality was switched to HD with a plan to remove the PD catheter later. Two months after discontinuing PD, he presented to the Emergency Department with the catheter tip protruding through the anus and he was asymptomatic. Abdominal X-ray (AXR) and CT scans were performed. The PD catheter was removed and the colon was repaired by proctosigmoidoscopy and laparotomy. Five years later, he continues to be on HD by preference, with arteriovenous fistula (AVF), without any complications of perforation. CONCLUSIONS There are 2 cases previously reported in children with colonic perforation by the tip of a PD catheter without signs and symptoms of peritonitis, but those patients were on immunosuppression after kidney transplant. Our patient is unique because he was not on immunosuppression.

Comparison of standard of care treatment with a low steroid and mycophenolate mofetil regimen for lupus nephritis in the ALMS and AURA studies.

Lupus nephritis is the most common organ-threatening manifestation of systemic lupus erythematosus. The current standard of care for patients is treatment with a combination of steroids plus either mycophenolate mofetil (MMF) or cyclophosphamide. However, these medications are associated with considerable toxicity and suboptimal efficacy. This retrospective propensity analysis of data from 63 matched patients enrolled in two of the largest active lupus nephritis controlled trials, ALMS and AURA, suggests that the high dose regimen of MMF and steroids as described in the 2012 American College of Rheumatology lupus nephritis guidelines may not be necessary in all lupus nephritis patients. A lower dose regimen may result in better long-term safety, including a reduction in lymphoproliferative disorders, skin cancers and steroid related side effects, without compromising efficacy. An ongoing randomized controlled double-blind phase 3 study, AURORA (NCT03021499), is investigating renal response in 358 patients randomized to receive a low dose regimen containing voclosporin, MMF and steroid therapy as used in the AURA trial. It is anticipated that the AURORA study and its blinded two-year extension will provide important long-term outcome data.

Socioeconomic Factors Associated with Readmission after Deceased Donor Renal Transplantation.

Early hospital readmissions after kidney transplantation pose a significant financial burden and hardship for patients and health-care institutions alike. We sought to identify the risk factors associated with increased likelihood of readmission after transplantation, and examined to determine whether patient socioeconomic demographics impacted the likelihood of perioperative readmissions. We evaluated all deceased donor renal transplants performed at our institution between August 2011 and December 2015. In a cohort of 325 transplant operations that met our inclusion criteria, 117 (36%) were readmitted to the hospital within 90 days of discharge. In univariable analyses, length of stay and pretransplant disabled status were associated with increased likelihood of readmission within 90 days of transplant. When placed into multivariable models, there was a suggestion association with length of stay and disability status. Kidney donor profile index, estimated posttransplant survival, employment, race, age, and payor status were not associated with readmission. In conclusion, the factors associated with posttransplant readmission are not necessarily influenced by socioeconomic factors in our study population. The data collected in this single center study indicate that the factors associated with increased rates of readmission are likely clinical in nature.

Hepatitis E in post-liver transplantation: is it time to routinely consider it?

Hepatitis E, although commonly recognized in the Eastern Hemisphere, is less well recognized in the West. Particularly owing to this disease's grave impact on outcomes after liver transplantation, greater consideration of hepatitis E is necessary in the context of abnormal liver tests. Here, we review the most recent data on detecting and managing hepatitis E, both pre- and post-liver transplantation, discuss major detection assay limitations, consider future directions, and propose an algorithm for the diagnosis and management of pre-and post-transplantation hepatitis E.

Comparison of Nanoscale Focused Ion Beam and Electrochemical Lithiation in ß-Sn Microspheres.

The development of Li focused ion beams (Li-FIB) enables controlled Li ion insertion into materials with nanoscale resolution. We take the first step toward establishing the relevance of the Li-FIB for studies of ion dynamics in electrochemically active materials by comparing FIB lithiation with conventional electrochemical lithiation of isolated ß-Sn microspheres. Samples are characterized by cross-sectioning with Ga FIB and imaging via electron microscopy. The Li-FIB and electrochemical lithiated Sn exhibit similarities that suggest that the Li-FIB can be a powerful tool for exploring dynamical Li ion-material interactions at the nanoscale in a range of battery materials.

Hepatocyte autophagy is linked to C/EBP-homologous protein, Bcl2-interacting mediator of cell death, and BH3-interacting domain death agonist gene expression.

BACKGROUND: Endoplasmic reticulum (ER) stress and autophagy each play important roles in hepatocyte cell injury. We hypothesized that gene expression of C/EBP-homologous protein (CHOP) and the BH3 proteins Bcl2-interacting mediator of cell death (BIM) and BH3-interacting domain death agonist (BID) are involved in a complex interplay that regulates ER stress-induced autophagy and cell death. MATERIALS AND METHODS: Hepatocytes were cultured from lean Zucker rats. Confluent hepatocytes were incubated with single or combined small interfering RNA for CHOP, BIM, and/or BID for 24 h providing gene inhibition. Incubation with tunicamycin (TM) for another 24 h stimulated ER stress. Quantitative real-time polymerase chain reaction determined the expression levels of CHOP, BIM, and BID. Immunostaining with microtubule-associated protein 1 light chain 3 measured autophagy activity. Trypan blue exclusion determined the cell viability. RESULTS: TM treatment increased the messenger RNA levels of CHOP and BIM but decreased the messenger RNA levels of BID. TM increased autophagy and decreased cell viability. Individual inhibition of CHOP, BIM, or BID protected against autophagy and cell death. However, simultaneous treatment with any combination of CHOP, BIM, and BID small interfering RNAs reduced autophagy activity but increased cell death independent of ER stress induction. CONCLUSIONS: Autophagy in hepatocytes results from acute ER stress and involves interplay, at the gene expression level, of CHOP, BIM, and BID. Inhibition of any one of these individual genes during acute ER stress is protective against cell death. Conversely, inhibition of any two of the three genes results in increased nonautophagic cell death independent of ER stress induction. This study suggests interplay between CHOP, BIM, and BID expression that can be leveraged for protection against ER stress-related cell death. However, disruption of the CHOP/BH3 gene expression homeostasis is detrimental to cell survival independent of other cellular stress.

Hepatocellular carcinoma: resection versus transplantation.

Hepatic resection and transplantation remain the standard curative therapies for hepatocellular carcinoma. These treatments are limited to either patients with early-stage tumors in the case of transplantation or patients with preserved liver function in the case of resection. Currently, patients with early-stage tumors and advanced liver disease are best served by transplant evaluation; however, the best treatment strategy for patients with well-preserved liver function, absence of portal hypertension, and early-stage HCC is debated. Numerous retrospective studies have documented better disease-free survival with transplantation, although the benefit on overall survival is less clear. This effect is likely due to the availability of effective liver-directed therapies for recurrence postresection and the effect of immunosuppression on tumor progression following posttransplant recurrence. Survival studies based on intention-to-treat principle incorporating patients listed for transplantation, but did not undergo the procedure due to waitlist dropoff have also suggested that overall survival rates may not be different despite high recurrence rates following resection. Transplantation has been shown to offer a survival advantage beyond 5-years; however, improvements in adjuvant therapies may narrow this gap. Determining optimal therapy for an individual patient requires consideration of numerous factors including tumor stage, severity of liver disease, and comorbidities as well as geographic and logistical factors that may affect transplant availability.

Small bowel obstruction after pediatric liver transplantation: the unusual is the usual.

BACKGROUND: Intestinal obstruction is a rare but serious complication after liver transplantation. Adhesions are the most common cause of obstruction in the nontransplantation setting; however, after pediatric liver transplantation unusual causes must be considered. STUDY DESIGN: A prospectively maintained institutional database was analyzed for all reoperations for intestinal obstruction on pediatric liver allograft recipients from 1990 to 2009. RESULTS: During the study period, 181 pediatric patients underwent liver transplantation at the study center. The most common indication for transplantation was biliary atresia. Seven patients required reoperation for intestinal obstruction. All 7 patients had abdominal operations before transplantation and 5 of 7 received reduced-size grafts. No patients had adhesive small bowel obstruction. The cause was right-sided diaphragmatic hernia in 4 and post-transplantation lymphoproliferative disorder (PTLD) in 3. Diaphragmatic hernia was demonstrated by chest radiograph in 3 of 4 patients. The fourth was taken to surgery with a presumptive diagnosis of intestinal obstruction and a diaphragmatic hernia was found at exploration. In patients with PTLD causing obstruction, 2 presented with an obstructing mass and the third presented with intussusception. Mean time to reoperation was 29 months after liver transplantation. Patients with diaphragmatic hernia presented earlier post-transplantation than those with PTLD (4.2 ± 2.4 months versus 59.3 ± 54.6 months, respectively; p = 0.0003, Fisher's exact test). Six patients are alive at a median follow-up of 5.8 years. One patient succumbed to recurrent B-cell lymphoma. CONCLUSIONS: Intestinal obstruction after pediatric liver transplantation is commonly related to what would conventionally be considered unusual causes. A high index of suspicion must be maintained and early operative therapy considered as obstruction because causes such as diaphragmatic hernia and PTLD are unlikely to resolve with conservative measures.

Cyclosporine sparing with mycophenolate mofetil, daclizumab and corticosteroids in renal allograft recipients: the CAESAR Study.

Although the calcineurin inhibitors (CNI) cyclosporine (CsA) and tacrolimus are highly effective immunosuppressants, they are associated with serious side effects. There is great interest in immunosuppressive regimens that permit reduction or elimination of CNIs, while maintaining adequate immunosuppression and acceptable acute rejection rates. Patients (n = 536) receiving their first renal allograft were randomized to one of three immunosuppressant regimens: daclizumab, mycophenolate mofetil (MMF), corticosteroids (CS) and low-dose CsA (target trough levels of 50-100 ng/mL), weaned from month 4 and withdrawn by month 6; daclizumab, MMF, CS and low-dose CsA; or MMF, CS and standard-dose CsA. Mean GFR 12 months after transplantation (primary end point) was not statistically different in the CsA withdrawal and low-dose CsA groups (both 50.9 mL/min/1.73 m(2)) vs. the standard-dose CsA group (48.6 mL/min/1.73 m(2)). At 12 months, the incidence of biopsy-proven acute rejection was significantly higher in the CsA withdrawal group (38%) vs. the low- or standard-dose CsA groups (25.4% and 27.5%, respectively; p < 0.05). In summary, a regimen of continuous low-dose CsA with MMF, CS and daclizumab induction is a clinically safe and effective immunosuppressive regimen in renal transplant recipients.

Daclizumab induction/tacrolimus sparing: a randomized prospective trial in renal transplantation.

Tacrolimus inhibits lymphocyte responses by blocking calcium-dependent signalling pathways important in IL-2 generation. Daclizumab, a humanized monoclonal antibody, binds with high affinity to the Tac subunit of the IL-2 receptor complex. We reasoned therefore that the absence of IL-2R should permit lower doses of tacrolimus and thereby less toxicity. Twenty-eight patients were randomized and followed for 6 months: Group 1, high dose (HD) tacrolimus (trough 12-17 ng/mL; n = 13); Group 2, low dose (LD) tacrolimus (trough 5-10 ng/mL; n = 15). All patients received daclizumab induction (2 mg/kg) on days 0 and 14, mycophenolate mofetil (2 g/d except for one patient who received 1 g) and rapid prednisone taper. Serious infections were minimal in both groups. Hospitalizations, for various reasons, were HD (n = 12) and LD (n = 6). All patients and grafts survived for the 6-month study period. There was one rejection episode in a non-compliant patient at 101 d. LD tacrolimus appears equally effective as HD tacrolimus in preventing rejection episodes and may be associated with fewer adverse events.