Trends in the Management and Outcomes of Kidney Transplantation for Autosomal Dominant Polycystic Kidney Disease

Background. Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure. The objective of this study was to evaluate a longitudinal experience of kidney transplantation for ADPKD. Methods. A single center retrospective review of patients undergoing kidney transplantation was conducted, with comparisons across two time periods: early (02/2000–04/2007, n = 66) and late (04/2007–08/2012, n = 67). Results. Over the 13.5-year study period, 133 patients underwent transplantation for ADPKD. Overall, no significant difference between the early and late group with regard to intraoperative complications, need for reoperation, readmissions within 30 days, delayed graft function, and mortality was noted. There was a trend towards increase in one-year graft survival (early 93.1% versus late 100%, P = 0.05). In the early group, 67% of recipients had undergone aneurysm screening, compared to 91% of recipients in the late group (P < 0.001). Conclusions. This study demonstrates consistent clinical care with a trend towards improved rates of one-year graft survival. Interestingly, we also note a significantly higher use of cerebral imaging over time, with the majority that were detected requiring surgical intervention which may justify the current practice of nonselective radiological screening until improved screening criteria are developed

Olivine formation processes and fluid pathways in subducted serpentinites revealed by in-situ oxygen isotope analysis (Zermatt-Saas, Switzerland)

Dehydration of serpentinites plays a crucial role in mass transfer into the Earth's interior by releasing aqueous fluids and forming new minerals. These minerals, such as metamorphic olivine, can serve as tracers of fluid-related processes. High-pressure (HP) antigorite, metamorphic olivine, and coexisting magnetite in serpentinites from a continuous, km-scale outcrop within the Zermatt-Saas HP ophiolite were analyzed in situ for trace elements and oxygen isotopes to identify differences in the initial serpentinization conditions and to investigate fluid pathways during subduction-related metamorphism. The oxygen isotopic composition, and As and Sb concentrations in antigorite reveal two distinct serpentinization conditions within the studied region: i) high As and Sb (1–25 μg/g and 0.5–5 μg/g, respectively), coupled with δ18O of +6 to +7 ‰, suggesting serpentinization at relatively low temperatures near the seafloor, and ii) low As and Sb (0.03–5 μg/g and ≤ 0.1 μg/g, respectively), coupled with mostly lower δ18O of +4 to +6 ‰, suggesting serpentinization at higher temperatures by interaction with fluids deeper below the seafloor. Olivine produced in situ by the brucite + antigorite dehydration reaction during subduction shows isotopic equilibrium with antigorite, and coexisting magnetite with ∆18OAtg-Ol of +1.5–2.5 ‰ and ∆18OOl-Mt of ∼+3 ‰ at reaction temperature conditions of 550–600 °C. The obtained isotopic signatures of metamorphic olivine with δ18O values of +1 to +2 ‰ and + 4 to +5 ‰ correspond to two different isotopic compositions of the released fluid of +5 to +6 ‰ and + 8 to +9 ‰ at these temperature conditions. This suggests that fluids released from subducted serpentinites may have variable δ18O under forearc conditions. The presence of fluids with variable δ18O can cause olivine in structures associated with fluid flow (e.g., shear bands, shear zones and veins) to be in isotopic equilibrium with magnetite, but in either isotopic equilibrium or disequilibrium with antigorite. Isotopic equilibrium with antigorite is achieved when the fluid responsible for olivine crystallization is internally derived. Isotopic disequilibrium is due to an externally derived fluid released by dehydration of serpentinite with a different isotopic composition than the serpentinite with which the fluid interacts. The restricted occurrence of non-equilibrated olivine only in shear bands and nearly pure Ol-veins indicates channelized fluid flow in subduction zone settings and demonstrates that isotopic disequilibrium can be used as a tracer for fluid infiltration

Live Donor Partial Hepatectomy for Liver Transplantation: Is There a Learning Curve?

Background: Donor safety is the first priority in living donor liver transplantation (LDLT). Objective: To determine the characteristics and outcome of live liver donors who underwent donor hepatectomy from January, 1997 to May, 2007 at Massachusetts General Hospital. Methods: 30 patients underwent LDLT between January, 1997 and May, 2007 at our institution. Results: The type of graft was the right lobe (segments 5-8) in 14, left lobe (segments 2-4) in 4, and left lateral sector (segments 2 and 3) in 12 patients. The mean donor age was 36 (range: 26-57) years. The mean follow-up was 48 (range: 18-120) months. No deaths occurred. Overall, 8 (26.6%) patients experienced a total of 14 post-operative complications. Donor complications based on graft type were as follows: left lateral sector (16.7%), left lobe (25%), and right lobe (35.7%). The experience was divided into two periods 1997-2001 (n=15) and 2002-2007 (n=15). Overall complications during 2 periods were 40% and 13.3%, respectively (p<0.001). The incidence of grade III complication also significantly decreased; 66.7% vs 33.3% (p<0.01). Conclusion: Partial hepatectomy in living donors has a learning curve which appears to be approximately 15 cases. This learning curve is not restricted to the surgeons performing the procedure but involves all aspects of patient care

Induction with Rabbit Antithymocyte Globulin following Orthotopic Liver Transplantation for Hepatitis C

Background: Hepatitis C (HCV) is the most common indication for liver transplantation in the US. Objective: Since steroids are the major stimulus of viral replication, we postulated that steroid-free immunosuppression might be a safer approach. Methods: From January 1995 to October 2002, we used steroid plus calcineurin inhibitor (CNI) immunosuppression after liver transplantation for HCV (steroid group, n=81). From October 2002 to June 2007, rabbit antithymocyte globulin (RATG) induction, followed by CNI and azathioprine (RATG group, n=73) was utilized. Results: There were no differences in 1- and 3-year patient/allograft survival rates. The incidence of acute rejection rate (19% vs. 28%), of biopsy-proven HCV recurrence (70% vs. 75%), and chronic rejection (6% vs. 9%) were comparable. The mean time to develop recurrent HCV was significantly longer in the RATG group (16.2 vs. 9.2 months, p=0.008). The incidence of severe portal fibrosis appears to be lower in RATG group compared to the steroid group; 14% vs. 4% (p=0.07). Conclusions: RATG induction is safe and effective after liver transplantation for HCV, but has no impact on the incidence of HCV recurrence and patient/allograft survival. However, a significant delay in time to HCV recurrence and a trend toward less rejection and portal fibrosis was observed

Heat Stroke as a Cause of Liver Failure and Evaluation of Liver Transplant

Heat stroke is a multiple organ dysfunction syndrome of poorly understood pathogenesis. Exertional heat stroke with acute liver failure is a rarely reported condition. Liver transplant has been recommended as treatment in cases of severe liver dysfunction; however, there are only 5 described cases of long-term survival after this procedure in patients with heat stroke. Here, we present 2 cases of young athletes who developed heat stroke. Both patients developed acute liver failure and were listed for liver transplant. Liver function tests of one patient improved, and he was discharged on postoperative day 13. The other patient showed no signs of improvement and liver biopsy showed massive necrosis. The patient underwent combined kidney-liver transplant and was discharged on postoperative day 17. After a follow-up of longer than 6 years, both patients are doing well with normal liver function and no neurologic sequelae. We also reviewed all published cases of hepatic failure associated with heat stroke and found 9 published cases of liver transplant for heat stroke in the English literature. Conservative management appears to be justified in heat stroke-associated liver failure, even in the presence of accepted criteria for emergency liver transplant

Heat Stroke as a Cause of Liver Failure and Evaluation of Liver Transplant

Heat stroke is a multiple organ dysfunction syndrome of poorly understood pathogenesis. Exertional heat stroke with acute liver failure is a rarely reported condition. Liver transplant has been recommended as treatment in cases of severe liver dysfunction; however, there are only 5 described cases of long-term survival after this procedure in patients with heat stroke. Here, we present 2 cases of young athletes who developed heat stroke. Both patients developed acute liver failure and were listed for liver transplant. Liver function tests of one patient improved, and he was discharged on postoperative day 13. The other patient showed no signs of improvement and liver biopsy showed massive necrosis. The patient underwent combined kidney-liver transplant and was discharged on postoperative day 17. After a follow-up of longer than 6 years, both patients are doing well with normal liver function and no neurologic sequelae. We also reviewed all published cases of hepatic failure associated with heat stroke and found 9 published cases of liver transplant for heat stroke in the English literature. Conservative management appears to be justified in heat stroke-associated liver failure, even in the presence of accepted criteria for emergency liver transplant

Convalescent Plasma Therapy in Four Critically Ill Pediatric Patients With Coronavirus Disease 2019: A Case Series

Background: Coronavirus disease 2019 is a pandemic with no specific therapeutic agents or vaccination. Small published case series on critically ill adults suggest improvements in clinical status with minimal adverse events when patients receive coronavirus disease 2019 convalescent plasma, but data on critically ill pediatric patients are lacking. We report a series of four critically ill pediatric patients with acute respiratory failure who received coronavirus disease 2019 convalescent plasma as a treatment strategy for severe disease. Case Summary:  Patients ranged in age from 5 to 16 years old. All patients received coronavirus disease 2019 convalescent plasma within the first 26 hours of hospitalization. Additional disease modifying agents were also used. All patients made a full recovery and were discharged home off of oxygen support. No adverse events occurred from the coronavirus disease 2019 convalescent plasma transfusions. Conclusion: Coronavirus disease 2019 convalescent plasma is a feasible therapy for critically ill pediatric patients infected with severe acute respiratory syndrome coronavirus 2. Well-designed clinical trials are necessary to determine overall safety and efficacy of coronavirus disease 2019 convalescent plasma and additional treatment modalities in pediatric patients

Leveraging the tolerogenic potential of TNF-α and regulatory B cells in organ transplantation

A subset of B-cells with tolerogenic functions, termed B-regulatory cells or Bregs, is characterized by the expression of anti-inflammatory/tolerogenic cytokines, namely IL-10, TGF-β, and IL-35, that contribute to their regulatory functions. Breg regulation favors graft acceptance within a tolerogenic milieu. As organ transplantation invariably triggers inflammation, new insights into the crosstalk between cytokines with dual properties and the inflamed milieu are needed to tailor their function toward tolerance. Using TNF-α as a proxy of dual-function cytokines involved in immune-related diseases and transplantation settings, the current review highlights the multifaceted role of TNF-α. It focuses on therapeutic approaches that have revealed the complexity of TNF-α properties tested in clinical settings where total TNF-α inhibition has proven ineffective and often detrimental to clinical outcomes. To improve the efficacy of current TNF-α inhibiting therapeutics, we propose a three-prong strategy to upregulate the tolerogenic pathway engaging the TNFR2 receptor while simultaneously inhibiting the inflammatory mechanisms associated with TNFR1 engagement. When combined with additional administrations of Bregs-TLR that activate Tregs, this approach may become a potential therapeutic in overcoming transplant rejection and promoting graft tolerance