Transplantation: platform to study recurrence of disease.

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.

Achalasia as an Unusual Cause of Acute Cellular Rejection of a Transplanted Heart.

A 68-year-old female with end-stage heart failure presented to the hospital for heart transplant. She was diagnosed with achalasia 14 months prior and treated with frequent botulinum toxin injections. She underwent orthotopic heart transplant on the day of admission and was extubated a few days later.

Benign course of residual inflammation at end of treatment of liver transplant recipients after sofosbuvir based therapy.

Background: Persistent inflammation on histology after successful hepatitis C (HCV) treatment has been reported. However, data regarding the long-term impact in liver transplant recipients is limited, particularly after using direct-acting antiviral (DAA) therapies.

Aim: To evaluate the impact of successful treatment with DAAs on histological changes and occult HCV and to describe the clinical course of residual inflammation in liver transplant recipients.

Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal.

Background: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial.

Human SLE variant -R90H promotes kidney damage and murine lupus through enhanced Tfh2 responses induced by defective efferocytosis of macrophages.

Objectives: We previously identified a hypomorphic variant, p.Arg90His (p.R90H) of neutrophil cytosolic factor 1 ( a regulatory subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 complex), as an putative causal variant for systemic lupus erythematosus (SLE), and established a knock-in (KI) H90 variant in the C57BL/6 background to study how this variant promotes lupus development.

Nonneoplastic Renal Parenchymal Changes in Renal Cell Carcinoma With Tumor Thrombus.

Introduction: Renal cell carcinoma may extend into the inferior vena cava (IVC) by the tumour thrombus (TT). Renal cell carcinoma with tumour thrombus (RCC/TT) could be associated with multiple collaterals making the surgery in cases of venous involvement very complex and challenging. The pathologic findings of non-neoplastic parenchymal changes in radical nephrectomy specimens of RCC/TT have not been well described.

Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma.

Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells.

Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial.

Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS.

Direct Actions of AT (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy.

Activation of AT (type 1 Ang) receptors stimulates cardiomyocyte hypertrophy in vitro. Accordingly, it has been suggested that regression of cardiac hypertrophy associated with renin-Ang system blockade is due to inhibition of cellular actions of Ang II in the heart, above and beyond their effects to reduce pressure overload. We generated 2 distinct mouse lines with cell-specific deletion of AT receptors, from cardiomyocytes.

Clostridium difficile infection mimics intestinal acute cellular rejection in pediatric multivisceral transplant-A case series.

Clostridium difficile infection (CDI) is the most common health care-associated infection in the United States. Thirty-nine percent of intestinal transplant recipients may develop CDI. Induction of rejection has been reported as a rare event.

Computed Tomography-Guided Kidney Transplant Biopsy Outcomes: A Single-Center Experience.

Objectives: Percutaneous kidney transplant biopsy is typically performed using ultrasonographic guidance; computed tomography is an alternative modality used to obtain kidney allografttissuewhen ultrasonographyguided percutaneous kidney transplant biopsy is technically challenging. Studies examining postbiopsy outcomes in kidney transplant patients using a computed tomography-guided approach are scarce. Our goal was to reportthe incidence of nonsevere and severe complications in computed tomographyguided percutaneous kidney transplant biopsies and the potential risk factors.

Quality control project of NGS HLA genotyping for the 17th International HLA and Immunogenetics Workshop.

The 17th International HLA and Immunogenetics Workshop (IHIW) organizers conducted a Pilot Study (PS) in which 13 laboratories (15 groups) participated to assess the performance of the various sequencing library preparation protocols, NGS platforms and software in use prior to the workshop. The organizers sent 50 cell lines to each of the 15 groups, scored the 15 independently generated sets of NGS HLA genotyping data, and generated "consensus" HLA genotypes for each of the 50 cell lines. Proficiency Testing (PT) was subsequently organized using four sets of 24 cell lines, selected from 48 of 50 PS cell lines, to validate the quality of NGS HLA typing data from the 34 participating IHIW laboratories.

Steroid-Free Immune Suppression Impairs Glycemic Control in a Healthy Cynomolgus Monkey.

The need for chronic immune suppression (IS) is one of the hurdles precluding widespread use of islet cell transplantation to restore glycemic control in patients with type 1 diabetes. We report the case of a healthy nonhuman primate (NHP) treated on and off for over 2.5 years with steroid-free IS, consisting of daclizumab induction and maintenance therapy with rapamycin and low dose tacrolimus.

Stable perfluorocarbon emulsions for the delivery of halogenated ether anesthetics.

Background: Research into injectable volatile anesthetics has been ongoing for approximately 40 years, with limited success, in an attempt to address the deficiencies of inhalational anesthesia. The purpose of this work was to formulate and optimize volatile anesthetic carrier emulsions based on our prior work in perfluorocarbon emulsions.

Methods: Perfluorocarbons were screened for their volatilty and emulsion stability.

Cardioprotective Effects of Paricalcitol Alone and in Combination With FGF23 Receptor Inhibition in Chronic Renal Failure: Experimental and Clinical Studies.

Background: In uremic animals, vitamin D receptor (VDR) agonists like paricalcitol (Pc) attenuate cardiac hypertrophy, but this effect has not been replicated consistently in humans with chronic kidney disease. Elevated fibroblast growth factor 23 (FGF23) levels cause cardiac hypertrophy with activation of the myocardial calcineurin/nuclear factor of activated T cell (NFAT) axis and may antagonize the cardioprotective effects of VDR agonist therapy. We hypothesized that the effectiveness of Pc may depend on the prevailing circulating levels of FGF23 and could be potentiated by the combined administration of a pan-FGF23 receptor (FGFR) blocker agent (PD173074).

Kidney-derived c-kit progenitor/stem cells contribute to podocyte recovery in a model of acute proteinuria.

Kidney-derived c-kit cells exhibit progenitor/stem cell properties and can regenerate epithelial tubular cells following ischemia-reperfusion injury in rats. We therefore investigated whether c-kit progenitor/stem cells contribute to podocyte repair in a rat model of acute proteinuria induced by puromycin aminonucleoside (PAN), the experimental prototype of human minimal change disease and early stages of focal and segmental glomerulosclerosis. We found that c-kit progenitor/stem cells accelerated kidney recovery by improving foot process effacement (foot process width was lower in c-kit group vs saline treated animals, P = 0.

Antibody-mediated rejection implies a poor prognosis in kidney transplantation: Results from a single center.

Two major barriers to achieving long-term graft survival include patient nonadherence in taking the prescribed immunosuppression and antibody-mediated rejection(AMR). We were therefore interested in determining the prognostic impact of developing an AMR component to rejection in a prospective randomized trial of 200 kidney transplant recipients who received dual induction therapy (rATG combined with either daclizumab or alemtuzumab) and planned early corticosteroid withdrawal. With a median follow-up of 96 months post-transplant, 40/200 developed a first BPAR; 9/200 developed a second BPAR.

Podocytes exhibit a specialized protein quality control employing derlin-2 in kidney disease.

Podocytes are terminally differentiated cells of the kidney filtration barrier with a limited proliferative capacity and are the primary glomerular target for various sources of cellular stress. Accordingly, it is particularly important for podocytes to cope with stress efficiently to circumvent cell death and avoid compromising renal function. Improperly folded proteins within the endoplasmic reticulum (ER) are associated with increased cellular injury and cell death.

E1841K Mutation Augments Proteinuria and Podocyte Injury and Migration.

Intronic variants of the gene that encodes the nonmuscle myosin heavy chain IIA are associated with diabetic nephropathy in European Americans and with sickle cell disease-associated nephropathy. However, the causal functional variants of have remained elusive. Rare missense mutations in cause macrothrombocytopenia and are occasionally associated with development of nephropathy.

Meeting Report of the XIV International Small Bowel Transplant Symposium: Summary of Presentations, Workshops, and Debates From a Comprehensive Meeting on Intestinal Failure, Rehabilitation, and Transplantation, Buenos Aires, Argentina, June 10-13, 2015.

The 2015 meeting of the Intestinal Transplant Association was held in Buenos Aires, Argentina. This was the 14th International Small Bowel Transplant Symposium, and it was the first meeting organized as a joint venture of the Transplantation Society, the Intestinal Transplant Association, and the Argentinean Transplant Society (Sociedad Argentina de Trasplantes). Innovative aspects of the classic meeting format included workshops sessions, debates, and multicenter studies.