Abnormal time-zero histology is predictive of kidney transplant outcomes.

INTRODUCTION: Time-zero biopsies can detect donor-derived lesions at the time of kidney transplantation, but their utility in predicting long-term outcomes is unclear under the updated Kidney Allocation System. METHODS: We conducted a single-center retrospective cohort study of 272 consecutive post-reperfusion time-zero biopsies. We tested the hypothesis that abnormal time-zero histology is a strong indicator of donor quality that increases the precision of the kidney donor profile index (KDPI) score to predict long-term outcomes. RESULTS: We detected abnormal biopsies in 42% of the cohort, which were independently associated with a 1.2-fold increased hazard for a composite of acute rejection, allograft failure, and death after adjusting for clinical characteristics including KDPI. By Kaplan-Meier analysis, the relationship between abnormal time-zero histology and the composite endpoint was only significant in the subgroup of deceased donor kidney transplants with KDPI scores >35. Abnormal time-zero histology, particularly vascular intimal fibrosis and arteriolar hyalinosis scores, was independently associated with lower 12-month estimated GFR. CONCLUSION: In conclusion, abnormal time-zero histology is relatively common and identifies a group of kidney recipients at increased risk for worse long-term outcomes. Further studies are needed to determine the optimal patient population in which to deploy time-zero biopsies as an additional surveillance tool.

The potential of genetically engineered pig heart transplantation in infants with complex congenital heart disease.

Despite advances in surgical and medical techniques, complex congenital heart disease in neonates and infants continues to be associated with significant mortality and morbidity. More than 500 infants in the USA are placed on the cardiac transplantation wait-list annually. However, there remains a critical shortage of deceased human donor organs for transplantation with a median wait-time of 4 months. Hence, infant mortality on the heart transplant wait-list in the USA is higher than for any other solid organ transplant group. Orthotopic transplantation of a pig heart as a bridge to allotransplantation might offer the best prospect of long-term survival of these patients. In recent years, there have been several advances in genetic engineering of pigs to mitigate the vigorous antibody-mediated rejection of a pig heart transplanted into a nonhuman primate. In this review, we briefly highlight (i) the history of clinical heart xenotransplantation, (ii) current advances and techniques of genetically engineering pigs, (iii) the current status of pig orthotopic cardiac graft survival in nonhuman primates, and (iv) progress toward pursuing clinical trials of cardiac xenotransplantation. Ultimately, we argue that pig heart xenotransplantation should initially be used as a bridge to cardiac allotransplantation in neonates and infants.

Initial experimental experience of triple-knockout pig red blood cells as potential sources for transfusion in alloimmunized patients with sickle cell disease.

BACKGROUND: Blood transfusion remains important in the treatment of patients with sickle cell disease (SCD). However, alloimmunization after blood transfusion is associated with patient morbidity and mortality. Triple-knockout (TKO) pigs (i.e., pigs in which the three known xenoantigens to which humans have anti-pig antibodies have been deleted) may be an alternative source of RBCs for these patients because many humans have no preformed antibodies to TKO pig RBCs (pRBCs). METHODS AND MATERIALS: In an in vitro study, plasma from alloimmunized (n = 12) or non-alloimmunized (n = 12) SCD patients was used to determine IgM/IgG binding to, and CDC of, TKO pRBCs. In an in vivo study, after an estimated 25% of blood volume was withdrawn from two capuchin monkeys, CFSE-labeled TKO pRBCs were transfused. Loss of TKO pRBCs was monitored by flow cytometry, and 7 weeks later, 25% of blood was withdrawn, and CFSE-labeled monkey RBCs were transfused. RESULTS: The in vitro study demonstrated that plasma from neither alloimmunized nor non-alloimmunized SCD patients bound IgM/IgG to, or induced CDC of, TKO pRBCs. In the in vivo study, survival of TKO pRBCs in the two capuchin monkeys was of 5 and 7 days, respectively, whereas after allotransfusion, survival was >28 days. CONCLUSIONS: In conclusion, (1) in the present limited study, no antibodies were detected that cross-reacted with TKO pRBCs, and (2) TKO pigs may possibly be an alternate source of RBCs in an emergency if no human RBCs are available.

Case report: Facilitating right heart recovery after durable LVAD implantation through repair of atrioventricular valves and RVAD implantation using tunneled Dacron grafts.

Right ventricular assist device (RVAD) weaning is often an important goal for durable left ventricular assist device support. This may be facilitated by mitral and tricuspid repair as well as by minimizing the trauma of RVAD decannulation by using Dacron grafts.

Cannulation strategies for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a type of extracorporeal life support (ECLS) in which the function of the heart and/or lungs is partially or completely replaced by a portable system that provides prolonged support to critically ill patients with respiratory or cardiac failure. There are two major variants of ECMO: veno-venous (VV) ECMO and veno-arterial (VA) ECMO. VV ECMO replaces the function of the lung in which it uses a cannula to remove venous blood and oxygenates it using the extracorporeal system, and returns the blood to the right atrium to be pumped to the body. VA ECMO is slightly different in that it replaces the function of the heart and lungs by returning oxygenated blood to the aorta. As a therapy for respiratory failure, ECMO minimizes hypoxia, diminishes lung stress and strain, and allows lung protective mechanical ventilation. As a support for acute and terminal heart failure, ECMO reduces preload, increases aortic flow, and allows for end-organ perfusion. Due to its physiological support and advantages, it is used for a variety of chronic and acute support purposes such as bridge therapy for heart/lung transplant, durable ventricular assist devices, and intermediate-term mechanical support postoperatively. Our review gives a broad overview of the two main types of ECMO strategies and their clinical indications, cannulation strategies, unique clinical utility, and their limitations.

Analysis of Applicants' Perspectives of Cardiothoracic Surgery Fellowship Program Websites.

BACKGROUND: Cardiothoracic (CT) surgery fellowship websites help applicants determine where they apply and/or accept an interview. However, relevant information from programs is not communicated in a standardized way. METHODS: We used Fellow and Residency Electronic Interactive Database Access (FREIDA) Online to identify residency programs with traditional CT fellowships. Program-specific variables included presence or absence of tracks, track duration, and annual cardiac and thoracic cases. Resident-specific variables included number of resident(s) a program accepts and case numbers per fellow. Current CT residents completed an online survey in which they rated how important they deemed the presence of these variables in program websites. RESULTS: According to FREIDA Online, 74 traditional CT surgery fellowship websites were analyzed. Among the websites listed on FREIDA, only 16 (22%) linked directly to the CT fellowship page. Surveys were sent to all trainees enrolled in the 74 programs, and 24 responded. There were marked deficiencies in the availability of information on program websites that was highly valued by trainees. Only 31% of websites reported annual program volume, and 14% reported resident case numbers, while this data was highly valued by >60% of respondents. Similarly, 11% of program websites described their education curriculum, while 81% of respondents highly valued this information. One-quarter of respondents were dissatisfied with the overall information provided by program websites. CONCLUSIONS: CT fellowship program websites lack crucial content that is deemed highly valued by applicants. This study suggests the possible need for a single comprehensive data repository or a standardized method for communicating information through program websites.

Resuscitative Endovascular Balloon Occlusion of the Aorta in the Management of a Gunshot Wound and Rupture of the Uterus.

Trauma is the leading cause of non-obstetrical maternal death. A 19-year-old woman at 20 weeks' gestation was brought to the emergency room after suffering a gunshot wound to the lower abdomen. Upon arrival, she was hemodynamically stable and imaging was obtained. CT revealed a rupture of the uterus with a partially extrauterine fetus, and the patient was immediately taken for an explorative laparotomy. Prior to the surgical start, the patient's blood pressure declined and, subsequently, a resuscitative endovascular balloon occlusion of the aorta (REBOA) was placed. The fetus and placenta were delivered and both uterine arteries and the inferior epigastric artery were ligated. Following an unremarkable postoperative course, she was discharged on hospital day 17. The mainstay approach to trauma in pregnancy should be to utilize focused imaging techniques to assess extent of trauma and provide adequate circulation to vital organs. Aortic balloon occlusion may be considered as a viable strategy to enhance resuscitation.

Will previous palliative surgery for congenital heart disease be detrimental to subsequent pig heart xenotransplantation?

INTRODUCTION: Pig heart xenotransplantation might act as a bridge in infants with complex congenital heart disease (CHD) until a deceased human donor heart becomes available. Infants develop antibodies to wild-type (WT, i.e., genetically-unmodified) pig cells, but rarely to cells in which expression of the 3 known carbohydrate xenoantigens has been deleted by genetic engineering (triple-knockout [TKO] pigs). Our objective was to test sera from children who had undergone palliative surgery for complex CHD (and who potentially might need a pig heart transplant) to determine whether they had serum cytotoxic antibodies against TKO pig cells. METHODS: Sera were obtained from children with CHD undergoing Glenn or Fontan operation (n = 14) and healthy adults (n = 8, as controls). All of the children had complex CHD and had undergone some form of cardiac surgery. Seven had received human blood transfusions and 3 bovine pericardial patch grafts. IgM and IgG binding to WT and TKO pig red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry, and killing of PBMCs by a complement-dependent cytotoxicity assay. RESULTS: Almost all children and adults demonstrated relatively high IgM/IgG binding to WT RBCs, but minimal binding to TKO RBCs (p < 0.0001 vs WT), although IgG binding was greater in children than adults (p < 0.01). All sera showed IgM/IgG binding to WT PBMCs, but this was much lower to TKO PBMCs (p < 0.0001 vs WT) and was greater in children than in adults (p < 0.05). Binding to both WT and TKO PBMCs was greater than to RBCs. Mean serum cytotoxicity to WT PBMCs was 90% in both children and adults, whereas to TKO PBMCs it was only 20% and < 5%, respectively. The sera from 6/14 (43%) children were cytotoxic to TKO PBMCs, but no adult sera were cytotoxic. CONCLUSIONS: Although no children had high levels of antibodies to TKO RBCs, 13/14 demonstrated antibodies to TKO PBMCs, in 6 of these showed mild cytotoxicity. As no adults had cytotoxic antibodies to TKO PBMCs, the higher incidence in children may possibly be associated with their exposure to previous cardiac surgery and biological products. However, the numbers were too small to determine the influence of such past exposures. Before considering pig heart xenotransplantation for children with CHD, testing for antibody binding may be warranted.

Mechanical or chemical and mechanical pleurodesis for spontaneous pneumothorax: what is the most effective approach in preventing recurrence? A systematic review and meta-analysis.

OBJECTIVES: Surgical management of spontaneous pneumothorax typically involves wedge resection and mechanical pleurodesis. It is unclear whether combining mechanical and chemical pleurodesis can further reduce the recurrence rate. We have performed a meta-analysis of studies comparing the combined approach with mechanical pleurodesis alone. METHODS: A comprehensive search of the existing literature was performed using PubMed, EMBASE and Web of Science for all types of studies that compared combined pleurodesis to a single approach. We used the Cochrane Risk of Bias Tool and Strengthening The Reporting of OBservational Studies in Epidemiology (STROBE) to assess the quality of the studies. Relative risk of pneumothorax recurrence was calculated, and the differences between the studies were examined. The primary outcome was the recurrence of pneumothorax. RESULTS: Of 2301 eligible studies, 5 studies were included. Five hundred sixty-one patients who received combined pleurodesis were compared to 286 patients who received mechanical pleurodesis only. Patients treated with combined intervention had a 63% lower risk of developing a recurrent pneumothorax compared to single intervention [relative risk 0.37, 95% confidence interval (CI) 0.18-0.76; P = 0.006]. There were no statistically significant differences in the length of stay (standardized mean difference -0.17, 95% CI -0.39 to 0.05, P = 0.138), the duration of postoperative air leak (standardized mean difference 0.17, 95% CI -1.14 to 1.47, P = 0.804) or the duration of postoperative chest tube drainage (standardized mean difference -0.07, 95% CI -0.27 to 0.12, P = 0.471). CONCLUSIONS: This meta-analysis demonstrated that combined intervention with mechanical and chemical pleurodesis for spontaneous pneumothorax may be more effective in preventing recurrence than mechanical pleurodesis alone. These findings will provide some guidance to surgeons in the decision-making process.

Evidence for GTKO/ß4GalNT2KO Pigs as the Preferred Organ-source for Old World Nonhuman Primates as a Preclinical Model of Xenotransplantation.

BACKGROUND: Triple-knockout (TKO) pigs (in which expression of the 3 known pig carbohydrate xenoantigens has been deleted) are likely to be an optimal source of organs for transplantation into human recipients, many of whom do not have natural antibodies against TKO pig cells. However, old world monkeys, for example, baboons, have natural antibodies directed to TKO cells (to a "fourth" xenoantigen that is exposed after TKO). METHODS: We measured (1) anti-pig IgM/IgG binding, and (2) complement-dependent cytotoxicity (CDC), by flow cytometry to α1,3-galactosyltransfearse gene-knockout (GTKO), GTKO/ß4GalNT2KO (that do not express the "fourth" xenoantigen), and TKO pig peripheral blood mononuclear cells (PBMCs) using 72 baboon sera (30 specific pathogen-free [SPF], and 42 non-SPF baboons). RESULTS: Mean IgM antibody binding to GTKO/ß4GalNT2KO pig PBMCs was significantly lower than to GTKO or TKO pig PBMCs (P < 0.01). Mean IgG antibody binding to GTKO/ß4GalNT2KO pig PBMCs was significantly lower than to TKO PBMCs (P < 0.01). Mean CDC of GTKO/ß4GalNT2KO pig PBMCs was significantly lower than of GTKO or TKO pig PBMCs (P < 0.01). SPF baboon serum IgM and IgG binding to, and CDC of, GTKO/ß4GalNT2KO or TKO PBMCs were significantly lower than non-SPF baboon sera (P < 0.01). CONCLUSIONS: Although TKO pigs form the basis for proposed clinical trials of xenotransplantation, it is difficult to identify baboons with a low or negative CDC to TKO pigs. For pig-to-baboon organ transplantation, the use of GTKO/ß4GalNT2KO pigs would be preferable. The use of SPF baboons as recipients might be a minor advantage.