Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:In December of 2014, the Organ Procurement and Transplant Network implemented a new Kidney Allocation System (KAS) for deceased donor transplant, with increased priority for highly sensitized candidates (calculated panel-reactive antibody [cPRA] >99%). We used a modified version of the new KAS to address issues of access and equity for these candidates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:In a simulation, 10,988 deceased donor kidneys transplanted into waitlisted recipients in 2010 were instead allocated to candidates with cPRA≥80% (n=18,004). Each candidate's unacceptable donor HLA antigens had been entered into the allocation system by the transplant center. In simulated match runs, kidneys were allocated sequentially to adult ABO identical or permissible candidates with cPRA 100%, 99%, 98%, etc. to 80%. Allocations were restricted to donor/recipient pairs with negative virtual crossmatches. RESULTS:The simulation indicated that 2111 of 10,988 kidneys (19.2%) would have been allocated to patients with cPRA 100% versus 74 of 10,988 (0.7%) that were actually transplanted. Of cPRA 100% candidates, 74% were predicted to be compatible with an average of six deceased donors; the remaining 26% seemed to be incompatible with every deceased donor organ that entered the system. Of kidneys actually allocated to cPRA 100% candidates in 2010, 66% (49 of 74) were six-antigen HLA matched/zero-antigen mismatched (HLA-A, -B, and -DR) with their recipients versus only 11% (237 of 2111) in the simulation. The simulation predicted that 10,356 of 14,433 (72%) candidates with cPRA 90%-100% could be allocated an organ compared with 7.3% who actually underwent transplant. CONCLUSIONS:Data in this simulation are consistent with early results of the new KAS; specifically, nearly 20% of deceased donor kidneys were (virtually) compatible with cPRA 100% candidates. Although most of these candidates were predicted to be compatible with multiple donors, approximately one-quarter are unlikely to receive a single offer.

According to the United States census bureau 20% of Americans will be older than 65 years in 2030 and half of them will need an operation - equating to about 36 million older surgical patients. Older adults are prone to complications during gastrointestinal cancer treatment and therefore may need to undergo special pretreatment assessments that incorporate frailty and sarcopenia assessments. A focused, structured literature review on PubMed and Google Scholar was performed to identify primary research articles, review articles, as well as practice guidelines on frailty and sarcopenia among patients undergoing gastrointestinal surgery. The initial search identified 450 articles; after eliminating duplicates, reports that did not include surgical patients, case series, as well as case reports, 42 publications on the impact of frailty and/or sarcopenia on outcome of patients undergoing gastrointestinal surgery were included. Frailty is defined as a clinically recognizable state of increased vulnerability to physiologic stressors resulting from aging. Frailty is associated with a decline in physiologic reserve and function across multiple physiologic systems. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Unlike cachexia, which is typically associated with weight loss due to chemotherapy or a general malignancy-related cachexia syndrome, sarcopenia relates to muscle mass rather than simply weight. As such, while weight reflects nutritional status, sarcopenia - the loss of muscle mass - is a more accurate and quantitative global marker of frailty. While chronologic age is an important element in assessing a patient's peri-operative risk, physiologic age is a more important determinant of outcomes. Geriatric assessment tools are important components of the pre-operative work-up and can help identify patients who suffer from frailty. Such data are important, as frailty and sarcopenia have repeatedly been demonstrated among the strongest predictors of both short- and long-term outcome following complicated surgical procedures such as esophageal, gastric, colorectal, and hepato-pancreatico-biliary resections.

Earlier studies reported inferior outcomes among black compared with white kidney transplant (KT) recipients. We examined whether this disparity improved in recent decades. Using the Scientific Registry of Transplant Recipients and Cox regression models, we compared all-cause graft loss among 63,910 black and 145,482 white adults who received a first-time live donor KT (LDKT) or deceased donor KT (DDKT) in 1990-2012. Over this period, 5-year graft loss after DDKT improved from 51.4% to 30.6% for blacks and from 37.3% to 25.0% for whites; 5-year graft loss after LDKT improved from 37.4% to 22.2% for blacks and from 20.8% to 13.9% for whites. Among DDKT recipients in the earliest cohort, blacks were 39% more likely than whites to experience 5-year graft loss (adjusted hazard ratio [aHR], 1.39; 95% confidence interval [95% CI], 1.32 to 1.47; P<0.001), but this disparity narrowed in the most recent cohort (aHR, 1.10; 95% CI, 1.03 to 1.18; P=0.01). Among LDKT recipients in the earliest cohort, blacks were 53% more likely than whites to experience 5-year graft loss (aHR, 1.53; 95% CI, 1.27 to 1.83; P<0.001), but this disparity also narrowed in the most recent cohort (aHR, 1.37; 95% CI, 1.17 to 1.61; P<0.001). Analyses revealed no statistically significant differences in 1-year or 3-year graft loss after LDKT or DDKT in the most recent cohorts. Our findings of reduced disparities over the last 22 years driven by more markedly improved outcomes for blacks may encourage nephrologists and patients to aggressively promote access to transplantation in the black community.

OBJECTIVE:To characterize the risk of liver-related events and death in hepatitis B virus (HBV)-exposed liver transplantation (LT) recipients. METHODS:Retrospective review was performed in all adults who underwent LT between January 1995 through December 2010 at the Johns Hopkins Hospital. Recipients with graft failure or death within 14 d of LT or missing HBV status were excluded, leaving 575 individuals for analysis. Patients were classified according to HBV exposure status: Unexposed, Resolved HBV, Chronic HBV, or hepatitis B core antibody (anti-HBc) seropositive liver donor. RESULTS:Compared with HBV-unexposed patients, the relative hazard of combined liver-related events (rejection, cirrhosis, re-transplantation) and death after LT was not increased in patients with a baseline history of resolved HBV infection or chronic hepatitis B. Using anti-HBc seropositive donors also did not increase the risk of liver-related events, death, or composite events (all p ≥ 0.05). However, hepatitis C was associated with liver-related events [adjusted hazard ratio (aHR), 1.59; 95% confidence interval (CI), 1.00-2.52], and blacks had a higher risk of death (aHR, 1.50; 95% CI, 1.01-2.22). CONCLUSION/CONCLUSIONS:LT of patients with prior HBV exposure or use of anti-HBc seropositive donors is not associated with increased risk of liver-related events or death.

BACKGROUND:Midodrine is prescribed to prevent symptomatic hypotension and decrease complications associated with hypotension during dialysis. We hypothesized that midodrine use before kidney transplantation may be a novel marker for posttransplant risk. METHODS:We analyzed integrated national US transplant registry, pharmacy records, and Medicare claims data for 16 308 kidney transplant recipients transplanted 2006 to 2008, of whom 308 (1.9%) had filled midodrine prescriptions in the year before transplantation. Delayed graft function (DGF), graft failure, and patient death were ascertained from the registry. Posttransplant cardiovascular complications were identified using diagnosis codes on Medicare billing claims. Adjusted associations of pretransplant midodrine use with complications at 3 and 12 months posttransplant were quantified by multivariate Cox or logistic regression, including propensity for midodrine exposure. RESULTS:At 3 months, patients who used midodrine pretransplant had significantly (P < 0.05) higher rates of DGF, 32% versus 19%; hypotension, 14% versus 4%; acute myocardial infarction, 4% versus 2%; cardiac arrest, 2% versus 0.9%, graft failure, 5% versus 2%; and death, 4% versus 1% than nonusers. After multivariate adjustment including recipient and donor factors, as well as for the propensity of midodrine exposure, pretransplant midodrine use was independently associated with risks of DGF (adjusted odds ratio, 1.78; 95% confidence interval [CI], 1.36-2.32), and 3 month death-censored graft failure (adjusted hazard ratio, 2.0; 95% CI, 1.18-3.39), and death (adjusted hazard ratio, 3.49; 95% CI, 1.95-6.24). Patterns were similar at 12 months. CONCLUSIONS:Although associations may in part reflect underlying conditions, the need for midodrine before kidney transplantation is a risk marker for complications including DGF, graft failure, and death.

The HIV Organ Policy Equity (HOPE) Act now allows transplantation of organs from HIV-positive living and deceased donors to HIV-positive individuals with end-stage organ disease in the United States. Although clinical experience with such transplants is limited to a small number of deceased-donor kidney transplants from HIV-positive to HIV-positive persons in South Africa, unprecedented HIV-positive-to-HIV-positive liver transplantations and living-donor kidney transplantations are also now on the horizon. Initially, all HIV-positive-to-HIV-positive transplantations will occur under research protocols with safeguards and criteria mandated by the National Institutes of Health. Nevertheless, this historic change brings ethical opportunities and challenges. For HIV-positive individuals needing an organ transplant, issues of access, risk, and consent must be considered. For potential HIV-positive donors, there are additional ethical challenges of privacy, fairness, and the right to donate. Careful consideration of the ethical issues involved is critical to the safe and appropriate evaluation of this novel approach to transplantation.

BACKGROUND:Patients who require hemodialysis are historically excluded from randomized studies of carotid artery stenting (CAS) due to perceived poor outcomes. Observational studies of outcomes after CAS in hemodialysis patients are mostly limited to small, single-institution series. OBJECTIVE:This study evaluated long-term outcomes after CAS in a large nationally representative cohort of hemodialysis patients. METHODS:We studied all patients who underwent CAS in the United States Renal Disease System database between January 2006 and December 2011. Patient outcomes were determined by matching with the Medicare database. Univariable and multivariable logistic and Cox regression were used to compare perioperative (stroke, death, myocardial infarction) and long-term (stroke, death) outcomes after CAS. RESULTS:The cohort included 1109 patients who underwent CAS. Median follow-up was 2.5 years (interquartile range, 1.30-3.71; maximum, 4.97 years). Mean age was 67 (standard deviation, 9.9) years, and 61% of patients were male, 75% were white, and 83% were asymptomatic. Overall, 30-day perioperative stroke, myocardial infarction, and death rates were 5.5%, 5.5%, and 3.1%, respectively. Long-term freedom from stroke was 90% at 1 year, 85% at 2 years, and 76% at 4 years. Patient survival was 73% at 1 year and 29% at 4 years. Symptomatic status was the only significant predictor of stroke in a long-term period of 4 years (hazard ratio, 1.92; 95% confidence interval, 1.12-3.29; P < .05). CONCLUSIONS:This study, which is the largest population-based study of outcomes after CAS in hemodialysis patients, demonstrates relatively poor long-term survival and prohibitive operative stroke and death risk. We recommend avoidance of CAS in asymptomatic dialysis patients and cautious consideration when planning CAS in symptomatic patients.

BACKGROUND & AIMS:Treatment of Crohn's disease (CD) may require multiple bowel resections that lead to short bowel syndrome. Intestinal transplantation is an effective treatment for short bowel syndrome, but limited data are available on long-term outcomes in CD. We aimed to characterize the long-term risk of rejection, graft failure, and death among patients with CD after intestinal transplantation, and compare their outcomes with those of patients without CD. METHODS:We performed a retrospective study of adults in the Scientific Registry of Transplant Recipients who received intestinal transplants in the United States from May 1990 through June 2014. Outcomes data were collected at 3 months, 6 months, 1 year, and every year after the procedure. We compared risks of rejection at 1 year after transplantation between patients with and without CD using the chi-square test and logistic regression. Longitudinal risks of graft failure and death were compared between patients with and without CD using the Kaplan-Meier method and Cox proportional hazards. Multivariable analyses adjusted for recipient, donor, and institutional characteristics. RESULTS:Of 1115 cases of intestinal transplantation, 142 were performed for CD and 973 for non-CD indications. One year after the procedure, the transplant was rejected in 36.9% of patients with CD and 33.3% of patients without CD (P = .48). For patients with CD, the actuarial risk of graft failure at 1, 5, and 10 years after intestinal transplantation was 18.6%, 38.7%, and 49.2%; the risk of death was 22.5%, 50.3%, and 59.7%, respectively. The risk of graft failure was greater for patients with CD (adjusted hazard ratio [aHR], 1.48; 95% CI, 1.03-2.13; P = .04), but patients with versus without CD had similar risks of death (aHR, 0.88; 95% CI, 0.64-1.20; P = .41). In subgroup analyses, the risk of graft failure was increased among patients with CD undergoing transplantation between 1990 and 2000 (aHR, 3.49; 95% CI, 1.23-9.92; P = .02), but not after 2000 (aHR, 1.37; 95% CI, 0.92-2.04; P = .12). CONCLUSIONS:In an analysis of patients who received intestinal transplants, the risks of graft rejection or death were similar between patients with versus without CD. Before year 2000, patients with CD had an increased risk of graft failure, but not thereafter. Changes in posttransplant immunosuppression around the same time might be analyzed to learn more about the mechanisms and management strategies to reduce graft failure in CD.

Under the Physician Payments Sunshine Act, "payments or transfers of value" by biomedical companies to physicians must be disclosed through the Open Payments Program. Designed to provide transparency of financial transactions between medication and device manufacturers and health care providers, the Open Payments Program shows financial relationships between industry and health care providers. Awareness of this program is crucial because its interpretation or misinterpretation by patients, physicians, and the general public can affect patient care, clinical practice, and research. This study evaluated nonresearch payments by industry to orthopedic surgeons. A retrospective cross-sectional review of the first wave of Physician Payments Sunshine Act data (August through December 2013) was performed to characterize industry payments to orthopedic surgeons by subspecialty, amount, type, origin, and geographic distribution. During this 5-month period, orthopedic surgeons (n=14,828) received $107,666,826, which included 3% of those listed in the Open Payments Program and 23% of the total amount paid. Of orthopedic surgeons who received payment, 45% received less than $100 and 1% received $100,000 or more. Median payment (interquartile range) was $119 ($34-$636), and mean payment was $7261±95,887. The largest payment to an individual orthopedic surgeon was $7,849,711. The 2 largest payment categories were royalty or license fees (68%) and consulting fees (13%). During the study period, orthopedic surgeons had substantial financial ties to industry. Of orthopedic surgeons who received payments, the largest proportion (45%) received less than $100 and only 1% received large payments (≥$100,000). The Open Payments Program offers insight into industry payments to orthopedic surgeons. [Orthopedics. 2016; 39(6):e1058-e1062.].

We examined integrated national transplant registry, pharmacy fill, and medical claims data for Medicare-insured kidney transplant recipients in 2000-2011 (n = 45 164) from the United States Renal Data System to assess the efficacy and safety endpoints associated with seven early (first 90 days) immunosuppression (ISx) regimens. Risks of clinical complications over 3 years according to IS regimens were assessed with multivariate regression analysis, including the adjustment for covariates and propensity for receipt of a nonreference ISx regimen. Compared with the reference ISx (thymoglobulin induction with tacrolimus, mycophenolate, and prednisone maintenance), sirolimus-based ISx was associated with significantly higher three-year risks of pneumonia (adjusted hazard ratio, aHR 1.45; P < 0.0001), sepsis (aHR 1.40; P < 0.0001), diabetes (aHR 1.21; P < 0.0001), acute rejection (AR; adjusted odds ratio, aOR 1.33; P < 0.0001), graft failure (aHR 1.78; P < 0.0001), and patient death (aHR 1.40; P < 0.0001), but reduced skin cancer risk (aHR 0.71; P < 0.001). Cyclosporine-based IS was associated with increased risks of pneumonia (aHR 1.17; P < 0.001), sepsis (aHR 1.16; P < 0.001), AR (aOR 1.43; P < 0.001), and graft failure (aHR 1.39; P < 0.001), but less diabetes (aHR 0.83; P < 0.001). Steroid-free ISx was associated with the reduced risk of pneumonia (aHR 0.89; P = 0.002), sepsis (aHR 0.80; P < 0.001), and diabetes (aHR 0.77; P < 0.001), but higher graft failure (aHR 1.35; P < 0.001). Impacts of ISx over time warrant further study to better guide ISx tailoring to balance the efficacy and morbidity.