Refusal of transplant organs for non-medical reasons including COVID-19 status.

Transplant centers and physicians in the United States have limited guidance on the information which they can and cannot provide to transplant candidates regarding donors of potential organs. Patients may refuse organs for a variety of reasons ranging from pernicious requests including racism to misinformation about emerging medicine as with the COVID-19 vaccine and infection. Patient autonomy, organ stewardship, and equity are often at odds in these cases, but precedent indeed exists to help address these challenges. This work uses such cases to highlight the urgent need for uniform, national policy prohibiting informational requests unrelated to well-established risks.

Teaching Third-Year Medical Students to Address Patients' Spiritual Needs in the Surgery/Anesthesiology Clerkship.

Introduction: Despite many patients wanting physicians to inquire about their religious/spiritual beliefs, most physicians do not make such inquiries. Among physicians who do, surgeons are less likely than family and general practitioners and psychiatrists to do so. Methods: To address this gap, we developed a 60-minute curriculum that follows the Kolb cycle of experiential learning for third-year medical students on their surgery/anesthesiology clerkship. The session includes definitions of religion/spirituality, an overview of the literature on spirituality in surgery, a review of the FICA Spiritual History Tool, discussion of the role of the chaplain and the process of initiating a chaplain consult, and three cases regarding the spiritual needs of surgical patients. Results: In total, 165 students participated in 10 sessions over 13 months. Of these, 120 students (73%) provided short-term feedback. Overall, 82% rated the session above average or excellent, and 72% stated the session was very relevant to patient care. To improve the session, students recommended assigning key readings, discussing more cases, role-playing various scenarios, inviting patients to speak, practicing mock interviews, and allowing for more self-reflection and discussion. Long-term feedback was provided by 105 students (64%) and indicated that the spirituality session impacted their attitudes about the role of religion/spirituality in medicine and their behaviors with patients. Discussion: We have designed a successful session on spirituality for third-year students on their surgery/anesthesiology clerkship. Students reported it to be a positive addition to the curriculum. The session can be modified for other surgical subspecialties and specialties outside of surgery.

Trends in management of the small renal mass in renal transplant recipient candidates: A multi-institutional survey analysis.

INTRODUCTION: Patients with end-stage renal disease are under increased risk for renal cell carcinoma development, and radical nephrectomy is the preferred treatment in this setting. Owing to the increased surgical morbidity and mortality, active surveillance (AS) may be a valid option for treatment of small renal masses (SRM). As there is a lack of high-level evidence for treatment recommendations, we performed a survey analysis to analyze the treatment patterns of transplant surgeons. MATERIAL AND METHODS: A 21-question online survey designed to analyze the practice patterns to treat SRM in renal transplant recipient candidates was sent to active transplant centers in the United States. The list of recipients to whom the survey was distributed was obtained with permission from the American Society of Transplant Surgeons. RESULTS: We received 62 responses. All regions of United Network of Organ Sharing were represented. Radical nephrectomy was the preferred treatment (59%, n = 61), followed by AS (21.3%, n = 13), partial nephrectomy (14.8%, n = 9), and focal ablative therapy (4.9%, n = 3). Among the responders whose institutions did not allow AS, 77.4% indicated that if presented with long-term data showing safety of AS, they would perform immediate transplantation and monitor SRM. Responders were more likely to allow immediate transplantation after radical nephrectomy (77.4%), as opposed to partial nephrectomy (58.1%) and focal ablation (45.2%). CONCLUSION: Though radical nephrectomy is the preferred treatment, most transplant surgeons would consider AS if long-term safety data were available.

Prostate-specific antigen screening and prostate cancer treatment in renal transplantation candidates: A survey of U.S. transplantation centers.

INTRODUCTION: Renal transplantation candidates are a highly screened population. There are currently no guidelines or consensus on prostate cancer (CaP) screening in these patients. In light of the recent United States Preventive Services Task Force recommendations against prostate-specific antigen (PSA) screening, we conducted a survey of transplantation surgeons to gain a better understanding of practice patterns among U.S. centers. MATERIALS AND METHODS: A 14-question multiple-choice online survey was e-mailed to 195 U.S. renal transplantation centers. The questionnaire assessed CaP screening and treatment practices. The survey also evaluated characteristics of the respondent's institution. Descriptive statistics were used for each of the responses, and associations were made with program characterization using logistic or linear regression models. RESULTS: A total of 90 surgeons responded, representing 65 of 195 programs (33% response rate). Overall, 89% of respondents reported routinely screening for CaP in renal transplantation candidates and 71% had set guidelines for PSA screening. The most common age to start PSA screening was 50 years (51%) and 79% of respondents reported no age limit to stop PSA screening. Definitive treatment of CaP was required before proceeding to transplantation in 45% of respondents. Active surveillance was a viable option in 67% of responders. Most respondents (73%) replied that the waiting time for eligibility after treatment depended on the CaP stage and risk. CONCLUSIONS: Although most programs have guidelines on PSA screening in renal transplantation candidates, there is still variation nationwide in screening and treatment practices. AS is a viable treatment option in most of the programs. Our results suggest a benefit of a consensus panel to recommend guidelines in this population.

Hepatitis C and renal transplantation.

Hepatitis C is a widespread problem, and the prevalence is higher in patients on hemodialysis than in the general population. In addition, hepatitis C reduces survival in dialysis patients and renal-transplant recipients. Kidney transplantation offers a survival advantage to those patients with chronic hepatitis C infection faced with the alternative of remaining on dialysis. Kidney transplantation should therefore be considered the treatment of choice for patients with end-stage renal disease and hepatitis C infection. However, these patients need to be chosen appropriately, and there are no well-established guidelines for the workup or selection of these of these patients. Liver biopsy is an essential tool to determine the degree of fibrosis in these patients and also will prove useful in the management of the patients after transplantation. Transplantation of kidneys from hepatitis C-positive donors to hepatitis C-positive recipients has been shown to be safe and confers a significant advantage in terms of waiting time in this population where death on the waiting list is significant. Treatment prior to transplantation should be considered by the hepatology team, although it is often more difficult to treat given the constraints of a patient in renal failure. Although interferon treatment in hepatitis C-positive kidney-transplant candidates is recommended, treatment posttransplant remains controversial. Simultaneous kidney/liver transplantation should be considered for those candidates with evidence of portal hypertension or decompensated cirrhosis.

Curing diabetes with transplantation?

Type 1 diabetes affects >1 million people in the United States, where it accounts for up to 10% of all diabetes cases. Glycemic control via the use of exogenous insulin injections in diabetic patients is incomplete, resulting in multiple long-term complications such as retinopathy, neuropathy, vasculopathy, and nephropathy. The goal of beta-cell replacement by whole-pancreas or islet transplantation is to achieve long-term insulin independence, and the proposed benefits are improved quality of life, prevention of recurrent diabetic nephropathy, stabilization or improvement in secondary complications, and improved mortality. No other regimen of insulin delivery can achieve this level of physiologic regulation.

Antibodies reactive to non-HLA antigens in transplant glomerulopathy.

Although T and B cell alloimmunity contribute to transplant injury, autoimmunity directed at kidney-expressed, non-HLA antigens may also participate. Because the specificity, prevalence, and importance of antibodies to non-HLA antigens in late allograft injury are poorly characterized, we used a protein microarray to compare antibody repertoires in pre- and post-transplant sera from several cohorts of patients with and without transplant glomerulopathy. Transplantation routinely induced changes in antibody repertoires, but we did not identify any de novo non-HLA antibodies common to patients with transplant glomerulopathy. The screening studies identified three reactivities present before transplantation that persisted after transplant and strongly associated with transplant glomerulopathy. ELISA confirmed that reactivity against peroxisomal-trans-2-enoyl-coA-reductase strongly associated with the development of transplant glomerulopathy in independent validation sets. In addition to providing insight into effects of transplantation on non-HLA antibody repertoires, these results suggest that pretransplant serum antibodies to peroxisomal-trans-2-enoyl-coA-reductase may predict prognosis in kidney transplantation.

Tubular expression of KIM-1 does not predict delayed function after transplantation.

Injured epithelial cells of the proximal tubule upregulate the glycoprotein kidney injury molecule 1 (KIM-1), suggesting its potential as a biomarker of incipient kidney allograft injury. It is unknown whether KIM-1 expression changes in kidney allografts with delayed graft function (DGF), which often follows ischemia-reperfusion injury. Here, we prospectively measured KIM-1 RNA and protein expression in preperfusion biopsies of 30 living- and 85 deceased-donor kidneys and correlated the results with histologic and clinical outcomes after transplantation. We detected KIM-1 expression in 62% of deceased-donor kidneys and only 13% of living-donor kidneys (P < 0.0001). The level of KIM-1 expression before reperfusion correlated inversely with renal function at the time of procurement and correlated directly with the degree of interstitial fibrosis. Surprising, however, we did not detect a significant correlation between KIM-1 staining intensity and the occurrence of DGF. Our findings are consistent with a role for KIM-1 as an early indicator of tubular injury but do not support tissue KIM-1 measurement before transplantation to identify kidneys at risk for DGF.

Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation.

While studies in animal models have linked Toll-like receptor (TLR) 4 signaling to kidney injury induced by ischemia and reperfusion, the relevance of TLR4 activation to allograft injury in human kidney transplants is unknown. Here we show that TLR4 is constitutively expressed within all donor kidneys but is significantly higher in deceased-, compared with living-donor organs. Tubules from deceased- but not living-donor kidneys also stained positively for high-mobility group box-1 (HMGB1), a known endogenous TLR4 ligand. In vitro stimulation of human tubular cells with HMGB1, in a TLR4-dependent system, confirmed that HMGB1 can stimulate proinflammatory responses through TLR4. To assess the functional significance of TLR4 in human kidney transplantation, we determined whether TLR4 mutations that confer diminished affinity for HMGB1 influence intragraft gene-expression profiles and immediate graft function. Compared with kidneys expressing WT alleles, kidneys with a TLR4 loss-of-function allele contained less TNFalpha, MCP-1, and more heme oxygenase 1 (HO-1), and exhibited a higher rate of immediate graft function. These results represent previously undetected evidence that donor TLR4 contributes to graft inflammation and sterile injury following cold preservation and transplantation in humans. Targeting TLR4 signaling may have value in preventing or treating postischemic acute kidney injury after transplantation.

Kidney and pancreas transplantation in type 1 diabetes mellitus.

Type 1 diabetes mellitus is characterized by autoimmune destruction of pancreatic beta cells, leading to a state of absolute insulin deficiency. Glycemic control via the use of exogenous insulin injections is often imperfect, resulting in multiple long-term complications, such as retinopathy, neuropathy, vasculopathy, and nephropathy. The Diabetes Control and Complications Trial has provided conclusive evidence that better glycemic control by intensive insulin treatment effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with insulin-dependent diabetes mellitus. At this moment, the only reliable option for achieving long-term insulin independence is whole-pancreas transplantation. The proposed benefits of pancreas transplantation are clear: improved quality of life, prevention of recurrent diabetic nephropathy, freedom from exogenous insulin with euglycemia and normalization of glycosylated hemoglobin, less stringent dietary restrictions, less frequent blood glucose monitoring, and stabilization of or improvement in secondary complications. The trade-offs to the patient are the operative risk, the need for chronic immunosuppression, and the inherent side effects of chronic immunosuppression.

Professionalism in medical education: the development and validation of a survey instrument to assess attitudes toward professionalism.

BACKGROUND AND AIM: This study examined attitudes toward professionalism in an academic medical center. The paper will describe the development and factorial validity of an instrument to measure attitudes toward professionalism in medical education among students, residents and faculty. METHODS: A factor analysis of the intercorrelations of responses to 36 items reflecting the American Board of Internal Medicine (ABIM) elements of professionalism for a sample of 765 medical students, residents and faculty was carried out. Data were collected during the spring of 2004. The study was conducted at the Penn State College of Medicine in Hershey, PA, USA. RESULTS: Main outcome measures include internal consistency reliability estimates (Cronbach's alpha) for each element of professionalism and a principal components analysis of the intercorrelations of responses to the 36 items in the questionnaire. Analysis of responses reveals seven identifiable factors of professionalism: accountability, altruism, duty, enrichment, equity, honor and integrity, and respect. CONCLUSIONS: The Penn State College of Medicine Professionalism Questionnaire is one of the first valid and reliable surveys of attitudes among medical students, residents, and faculty that reflects seven elements of professionalism.

Maturation of Thyriothecia of Schizothyrium pomi on the Reservoir Host Rubus allegheniensis.

Flyspeck disease caused by the Ascomycete fungus Schizothyrium pomi is a major component of a summer disease complex that has become an increasing problem on apple in the northeastern United States. This study describes the development of thyriothecia of S. pomi on one of its major reservoir hosts, wild blackberry, and suggests that temperature drives thyriothecium maturation. An empirical model relating thyriothecium maturity to degree-days from apple leaf budbreak in Massachusetts had a high coefficient of determination, R2 = 0.90. Ninety percent of thyriothecia matured between 540 and 1,625 degree-days from the budbreak biofix. S. pomi produced one generation of asci per year on blackberry. This discrete maturation period occurred well before signs of disease developed on apple fruit and before production of conidia. Considering that fungicide applications for scab management in commercial apple orchards also will protect fruit from flyspeck during early fruit development, it is unlikely that ascospores produced on reservoir hosts directly infect fruit. Instead, they probably initiate infections in reservoir hosts adjacent to commercial orchards, which produce conidia that are the inoculum which infects apple fruit in commercial production.

Excellent outcome in infants and small children with thrombophilias undergoing kidney transplantation.

One of the most common causes of early graft failure in children undergoing renal transplantation is vascular thrombosis. Numerous risk factors for graft thrombosis have been previously described. Children with various types of thrombophilias such as protein C, protein S and factor V Leiden deficiencies are at an increased risk for vascular thrombosis. Infants and small children with these disorders undergoing renal transplantation have not been well documented in the literature. We reviewed our experience in the diagnosis, peri-operative management and follow up of these patients at our institution. A retrospective analysis of all children undergoing renal transplantation at our institution, using data obtained from the Pediatric Transplant Registry at our institution since May 2000 was performed. The indications for renal transplant included focal segmental glomerulosclerosis, renal dysplasia and reflux nephropathy. One patient had factor V Leiden mutation and two patients had protein S deficiency. Patients were anticoagulated in the peri-operative and post-transplant period. All index transplants were performed with living donor kidneys. There were no adverse outcomes in children with thrombophilias despite having significantly lower weight at the time of transplant vs. children without thrombophilia. The incidence of graft thrombosis in the pediatric renal transplant recipients is high. We identify a potential cause of thrombosis in children not well documented in the literature. A high index of suspicion combined with preoperative screening and diagnosis of thrombophilias and an appropriate treatment plan may decrease the incidence of graft thrombosis in infants and small children undergoing renal transplantation.

Giant cavernous liver hemangiomas: effect of operative approach on outcome.

HYPOTHESIS: The choice of operative technique for resection of giant cavernous hepatic hemangiomas has an effect on outcome. DESIGN: Case series. SETTING: Tertiary hepatobiliary surgery-liver transplantation service. PATIENTS AND INTERVENTIONS: Fifty-two adult patients who underwent resection of symptomatic hepatic hemangiomas (38 [73%] in the right lobe; average diameter, 10.9 cm) by means of lobectomy or enucleation, with or without Pringle inflow occlusion. MAIN OUTCOME MEASURES: Blood transfusion, morbidity, mortality, and length of hospitalization. RESULTS: Patient age and sex and the size of hemangiomas were similar for patients who underwent lobectomy and enucleation. Right-lobe lesions were more often treated by enucleation, and inflow occlusion was used more frequently; transfusion requirements and length of hospitalization were similar for both techniques. Complications were more frequent after lobectomy. There were no deaths. In the latter years of the series, enucleation was used in 22 (63%) and inflow occlusion in 24 (69%) of 35 patients. CONCLUSIONS: Outcome is related to the operative approach used for resection of giant cavernous liver hemangiomas. Although lobectomy and enucleation are curative, enucleation offers greater preservation of normal hepatic parenchyma and fewer complications and is the preferred technique for suitable lesions.

Dual-kidney transplants: long-term results.

BACKGROUND: Dual-kidney transplantation, where two usually aged adult kidneys are placed into an adult recipient, is one way to help alleviate the continuing disparity between the number of patients on the kidney transplant waiting list and those who receive kidney transplants each year. The Dual Kidney Registry was developed to analyze donor and recipient data and outcomes at several centers. METHODS: Two hundred eighty-seven patients who have undergone transplantation since 1994 have been entered into the relational database. The patients were followed yearly after initial entry into the database. RESULTS: The mean donor age was 58+/-13 years and the mean terminal creatinine clearance was 77+/-40 mL/min. The mean glomerular sclerosis on procurement biopsy was 16+/-13%. Delayed graft function (DGF), defined as dialysis in the first 7 days after transplantation, was a predictor of poor outcome, and increased cold storage time was a predictor of DGF. The overall incidence of DGF was 27%. In recipients with prompt graft function (PGF), the mean cold storage time was 22+/-9 hr versus 29+/-10 hr in recipients with DGF (P<0.001). The overall 1- and 5-year graft survival was 86% and 69%, respectively. The 1- and 5-year graft survival rates were significantly better in recipients with PGF (90% and 74%) versus DGF (79% and 54%) (P<0.002). CONCLUSIONS: Cold storage time and DGF have a significant impact on the 1- and 5-year graft survival in recipients of dual-kidney transplants. The 5-year graft survival in recipients of dual-kidney transplants is excellent.