Current and Evolving Indications for Simultaneous Liver Kidney Transplantation.

This review will discuss the etiologies of kidney disease in liver transplant candidates, provide a historical background of the prior evolution of simultaneous liver-kidney (SLK) transplant indications, discuss the current indications for SLK including Organ Procurement and Transplantation Network policies and Model for End Stage Liver Disease exception points, as well as provide an overview of the safety net kidney transplant policy. Finally, the authors explore unanswered questions and future research needed in SLK transplantation.

Thrombocytopenia in Chronic Liver Disease: New Management Strategies.

Thrombocytopenia is common in advanced liver disease, and such patients frequently need invasive procedures. Numerous mechanisms for thrombocytopenia exist, including splenic sequestration and reduction of levels of the platelet growth factor thrombopoietin. Traditionally, platelet transfusions have been used to increase platelet counts before elective procedures, usually to a threshold of greater than or equal to 50,000/µL, but levels vary by provider, procedure, and specific patient. Recently, the thrombopoietin receptor agonists avatrombopag and lusutrombopag were studied and found efficacious for increasing platelet count in the outpatient setting for select patients with advanced liver disease who need a procedure.

Donor-Specific Antibodies in Liver Transplantation.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-1-reading-nilles a video presentation of this article Answer questions and earn https://www.wileyhealthlearning.com/Activity/7025330/disclaimerspopup.aspx.

Solid organ donation after death in the United States: Data-driven messaging to encourage potential donors.

US deceased donor solid organ transplantation (dd-SOT) depends upon an individual's/family's altruistic willingness to donate organs after death; however, there is a shortage of deceased organ donors in the United States. Informing individuals of their own lifetime risk of needing dd-SOT could reframe the decision-making around organ donation after death. Using United Network for Organ Sharing (UNOS) data (2007-2016), this cross-sectional study identified (1) deceased organ donors, (2) individuals waitlisted for dd-SOT (liver, kidney, pancreas, heart, lung, intestine), and (3) dd-SOT recipients. Using US population projections, life tables, and mortality estimates, we quantified probabilities (Pr) of (1) becoming deceased organ donors, (2) needing dd-SOT, and (3) receiving dd-SOT. Lifetime Pr (per 100 000 US population) for males and females of becoming deceased organ donors were 212 and 146, respectively, and of needing dd-SOT were 1323 and 803, respectively. Lifetime Pr of receiving dd-SOT was 50% for males, 48% for females. Over a lifetime, males were 6.2 and females 5.5 times more likely to need dd-SOT than to become deceased organ donors. Organ donation is traditionally contextualized in terms of charity toward others. Our analyses yield a new tool, in the form of quantifying an individual's own likelihood of needing dd-SOT, which may assist with reframing motivations toward deceased donor organ donation.

Thrombocytopenia and Procedural Prophylaxis in the Era of Thrombopoietin Receptor Agonists.

Thrombocytopenia is common in patients with advanced liver disease. These patients frequently require invasive diagnostic or therapeutic procedures in the setting of thrombocytopenia. A common platelet goal before such procedures is ≥50,000/µL, but target levels vary by provider and the procedure. Platelet transfusion has disadvantages, including safety and cost. No other short-term options for ameliorating thrombocytopenia before procedures were available until the thrombopoietin receptor agonists were recently approved. Avatrombopag and lusutrombopag can be used in certain patients with thrombocytopenia due to advanced liver disease undergoing elective invasive procedures; these new agents are highly effective in carefully selected patients, and real world data of safety and efficacy are awaited.

Donor-derived Viral Infections in Liver Transplantation.

Donor-derived infections are defined as any infection present in the donor that is transmitted to 1 or more recipients. Donor-derived infections can be categorized into 2 groups: "expected" and "unexpected" infections. Expected transmissions occur when the donor is known to have an infection, such as positive serology for cytomegalovirus, Epstein Barr virus, or hepatitis B core antibody, at the time of donation. Unexpected transmissions occur when a donor has no known infection before donation, but 1 or more transplant recipients develop an infection derived from the common donor. Unexpected infections are estimated to occur in far less than 1% of solid organ transplant recipients. We will review the epidemiology, risk factors, and approaches to prevention and management of donor-derived viral infectious disease transmission in liver transplantation.

Incidence and impact of rejection following simultaneous liver-kidney transplantation.

BACKGROUND & AIMS: Due to hepatic immunoregulation, simultaneous liver-kidney recipients are presumed to be reasonably protected from kidney rejection and typically receive less immunosuppression compared to kidney transplants alone. However, data to support these conclusions and practices are sparse. METHODS: We characterized the incidence and types of rejection, graft function, and graft and patient survival in a large population of simultaneous liver-kidney recipients (n=140) with long-term follow-up at our centre (1998-2010). RESULTS: Acute cellular, antibody-mediated, and chronic kidney rejection was diagnosed in 9 (6.4%), 2 (1.4%), and 1 (0.7%) patient, respectively. Borderline acute kidney rejection was diagnosed in another 16 patients (11.4%). Acute cellular liver rejection occurred in 16 (11.4%) and chronic liver rejection in 4 (2.9%). One-, three-, and five-year patient survival was 86.4%, 78.0%, and 74.0%, respectively, and did not significantly differ by presence or absence of kidney or liver rejection. However, kidney rejection was associated with decreased renal function by lower serum GFR over time (p=0.003). CONCLUSIONS: Various forms of kidney rejection occurred in ∼20% of our simultaneous liver-kidney recipients and were associated with deterioration in graft function, indicating that the liver may not confer complete protective allo-immunity. More stringent graft monitoring and management strategies, perhaps more akin to kidney transplant alone, should be prospectively studied in simultaneous liver-kidney recipients.

Knockin animal models of inherited arrhythmogenic diseases: what have we learned from them?

Mouse models are becoming an increasingly accepted method of studying human diseases. Knockin and knockout techniques have several advantages over traditional transgenic overexpression, and the versatility of the knockin mouse allows the study of both gain of function mutations through targeted mutagenesis, as well as the replacement of one gene by another functional gene. Here, we will review the methods available to generate knockin mice; provide an overview of the techniques used to study electrophysiology in the mice at the cellular, organ, and whole animal level; and highlight knockin mice that have implications for inherited arrhythmias. Specifically, we will focus on models that used knockin mice to clarify gene expression, identify similarities and differences between related genes, and model human arrhythmia syndromes. Our goal is to provide the reader with a general understanding of studies done on knockin mouse models of inherited arrhythmias as well as ideas for future directions.

Tunnel expansion after anterior cruciate ligament reconstruction with autogenous hamstrings: a comparison of the medial portal and transtibial techniques.

PURPOSE: The purpose of this study was to evaluate the effects of 2 techniques of drilling the femoral tunnel in anterior cruciate ligament (ACL) reconstruction (medial portal v transtibial) on tunnel expansion. METHODS: Autogenous hamstring ACL reconstructions performed by the senior author between July 1998 and July 2004, with a minimum 6-month radiographic follow-up, using the transtibial technique (41 patients) and the medial portal technique (34 patients), were evaluated. All procedures were performed via an endoscopic technique with identical postoperative rehabilitation and graft fixation. Lateral and 45 degrees posteroanterior (PA) radiographs were obtained for each patient at a minimum of 6 months postoperatively. The sclerotic margins of the femoral and tibial tunnels were measured at the widest dimension of the tunnel by 2 physicians and were compared with the initially drilled tunnel size after correction for radiographic magnification. Statistical analysis was performed to compare the 2 groups by use of the independent-samples t test, with significance set at .05. RESULTS: The mean percentage increase in the femoral tunnel was 38.20% +/- 17.76% for the medial portal technique and 53.96% +/- 21.72% for the transtibial technique on the PA view and 23.80% +/- 16.50% for the medial portal technique and 50.07% +/- 26.98% for the transtibial technique on the lateral view. This difference was statistically significant on both PA and lateral views. The mean percentage increase in the tibial tunnel was 31.81% +/- 14.39% for the medial portal technique and 36.31% +/- 17.81% for the transtibial technique on the PA view and 27.70% +/- 15.25% for the medial portal technique and 30.11% +/- 18.98% for the transtibial technique on the lateral view; however, these increases failed to reach statistical significance on either view. CONCLUSIONS: Femoral tunnel expansion for hamstring autologous ACL reconstructions is significantly lower for the medial portal technique when compared with the conventional transtibial technique. LEVEL OF EVIDENCE: Level III, retrospective, comparative therapeutic study.