CMV-associated collapsing focal segmental glomerulosclerosis after kidney transplant in a pediatric patient.

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity among immunocompromised patients who have undergone kidney transplantation and is known to rarely induce collapsing focal segmental glomerulosclerosis (FSGS) among adults. METHODS: We present the first reported case of CMV-induced collapsing FSGS in a pediatric patient after kidney transplant. RESULTS: Our patient underwent a deceased donor kidney transplant due to end-stage renal disease secondary to lupus nephritis. Approximately 4 months after transplantation, he developed signs of worsening kidney function in the setting of CMV viremia and was found to have collapsing features of FSGS on kidney transplant biopsy. He was managed with a prompt escalation of antiviral therapy along with a reduction of immunosuppression and recovered without significant complication. At follow-up, he continued to have undetectable CMV titers, creatinine within normal limits, and no significant proteinuria. CONCLUSION: This report demonstrates CMV as a cause of collapsing FSGS and should be considered among pediatric transplant recipients who present with acute kidney injury, as should early assessment of APOL1 genetic status in both donor and recipient.

Liver biopsy in assessment of extended criteria donors.

The safety and liver utilization with prerecovery liver biopsy (PLB) in extended criteria liver donors are unclear. We conducted a retrospective cohort study in 1323 brain death donors (PLB = 496) from 3 organ procurement organizations (OPOs). Outcomes were complications, preempted liver recovery (PLR), and liver transplantation (LT). Additional analyses included liver-only and propensity score-matched multiorgan donor subgroups. PLB donors were older (57 versus 53 years; P < 0.001). Hepatitis C antibody positivity (14.3% versus 9.6%, P = 0.01) and liver-only donors (42.6% versus 17.5%; P < 0.001) were more prevalent. The PLB cohort had fewer complications (31.9% versus 42.3%; P < 0.001). In the PLB cohort, PLR was significantly higher (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.42-4.92) and LT lower (OR, 0.69; 95% CI, 0.52-0.91). In liver-only and propensity score-matched multiorgan donor subgroups, PLR was significantly higher (OR, 1.76; 95% CI, 1.06-2.94 and OR, 2.29; 95% CI, 1.37-3.82, respectively) without a decrease in LT (OR, 0.71; 95% CI, 0.43-1.18 and OR, 0.91; 95% CI, 0.63-1.33, respectively) in PLB subgroups. In conclusion, in extended criteria liver donors, PLB is safe and decreases futile liver recovery without decreasing LT. Increased use of PLB, especially in liver-only donors, is likely to save costs to OPOs and transplant centers and improve efficiencies in organ allocation. Liver Transplantation 24 182-191 2018 AASLD.

Lesson From the New York City Out-of-Hospital Uncontrolled Donation After Circulatory Determination of Death Program.

STUDY OBJECTIVE: In 2006, the Institute of Medicine emphasized substantial potential to expand organ donation opportunities through uncontrolled donation after circulatory determination of death (uDCDD). We pilot an out-of-hospital uDCDD kidney program for New York City in partnership with communities that it was intended to benefit. We evaluate protocol process and outcomes while identifying barriers to success and means for improvement. METHODS: We conducted a prospective, participatory action research study in Manhattan from December 2010 to May 2011. Daily from 4 to 12 pm, our organ preservation unit monitored emergency medical services (EMS) frequencies for cardiac arrests occurring in private locations. After EMS providers independently ordered termination of resuscitation, organ preservation unit staff determined clinical eligibility and donor status. Authorized parties, persons authorized to make organ donation decisions, were approached about in vivo preservation. The study population included organ preservation unit staff, authorized parties, passersby, and other New York City agency personnel. Organ preservation unit staff independently documented shift activities with daily operations notes and teleconference summaries that we analyzed with mixed qualitative and quantitative methods. RESULTS: The organ preservation unit entered 9 private locations; all the deceased lacked previous registration, although 4 met clinical screening eligibility. No kidneys were recovered. We collected 837 notes from 35 organ preservation unit staff. Despite frequently recounting protocol breaches, most responses from passersby including New York City agencies were favorable. No authorized parties were offended by preservation requests, yielding a Bayesian posterior median 98% (95% credible interval 76% to 100%). CONCLUSION: In summary, the New York City out-of-hospital uDCDD program was not feasible. There were frequent protocol breaches and confusion in determining clinical eligibility. In the small sample of authorized persons we encountered during the immediate grieving period, negative reactions were infrequent.

Lower tacrolimus trough levels are associated with subsequently higher acute rejection risk during the first 12 months after kidney transplantation.

The premise that lower TAC trough levels are associated with subsequently higher first BPAR risk during the first 12 mo post-transplant was recently questioned. Using our prospectively followed cohort of 528 adult, primary kidney transplant recipients (pooled across four randomized trials) who received reduced TAC dosing plus an IMPDH inhibitor, TAC trough levels measured at seven time points, 7, 14 days, 1, 2, 3, 6 and 9 months post-transplant, were utilized along with Cox's model to determine the multivariable significance of TAC level(t) (a continuous time-dependent covariate equaling the most recently measured TAC level prior to time t) on the hazard rate of developing first BPAR during the first 12 months post-transplant. The percentage developing BPAR during the first 12 months post-transplant was 10.2% (54/528). In univariable analysis, lower TAC level(t) was associated with a significantly higher BPAR rate (P = 0.00006), and its significance was maintained even after controlling for 2 significant baseline predictors (African-American/Hispanic Recipient and Developed DGF) in Cox's model (multivariable P = 0.0003). Use of a cutpoint, TAC level(t) <4.0 vs. ≥4.0 ng/ml, yielded an even greater association with BPAR rate (univariable and multivariable P < 0.000001), with an estimated hazard ratio of 6.33. These results suggest that TAC levels <4.0 ng/ml should be avoided during the first 12 months post-transplant when TAC is used in combination with fixed-dose mycophenolate with or without corticosteroids and induction therapy.

Single-centre study of 628 adult, primary kidney transplant recipients showing no unfavourable effect of new-onset diabetes after transplant.

AIMS/HYPOTHESIS: To better understand the implications of new-onset diabetes after transplant (NODAT), we used our prospectively followed cohort of 628 adult primary kidney transplant recipients to determine the prognostic impact of pretransplant diabetes and NODAT. METHODS: The study cohort consisted of all participants in four randomised immunosuppression trials performed at our centre since May 2000. For each cause-specific hazard analysed, Cox stepwise regression was used to determine a multivariable model of significant baseline predictors; the multivariable influence of having pretransplant diabetes and NODAT (t) (the latter defined as a zero-one, time-dependent covariate) was subsequently tested. Similar analyses of estimated glomerular filtration rate (eGFR) at 36 and 60 months post transplant were performed using stepwise linear regression. Finally, a repeated measures analysis of mean HbA1c as a function of diabetes category (pretransplant diabetes vs NODAT) and randomised trial (first to fourth) was performed. RESULTS: Median follow-up was 56 months post transplant. Patients with pretransplant diabetes comprised 23.4% (147/628), and 22.5% (108/481) of the remaining patients developed NODAT. Pretransplant diabetes had no prognostic influence on first biopsy-proven acute rejection and death-censored graft failure hazard rates, nor on eGFR, but was associated with significantly higher rates of death with a functioning graft (DWFG) (p = 0.003), DWFG due to a cardiovascular event (p = 0.005) and infection that required hospitalisation (p = 0.03). NODAT (t) had no unfavourable impact on any of these hazard rates nor on eGFR, with actuarial freedom from DWFG remaining at over 90% among patients in pre- and post-NODAT states at 72 months post transplant/NODAT. Mean HbA1c for patients in the first to fourth randomised trials, averaged across diabetes category, decreased by trial (7.28%, 6.92%, 6.87% and 6.64% [56.1, 52.1, 51.6 and 49.1 mmol/mol], respectively; p = 0.02). CONCLUSIONS/INTERPRETATION: Less-than-expected post-NODAT risk for graft loss and death may exist in the current climate of tighter glucose monitoring post transplant.

Multivariable risk of developing new onset diabetes after transplant-results from a single-center study of 481 adult, primary kidney transplant recipients.

BACKGROUND: Understanding the relative contributions of baseline demographics and immunosuppressive therapy on NODAT risk may help in developing preventive strategies. METHODS: Using our prospectively followed cohort of 481 adult, primary kidney transplant recipients without pre-transplant diabetes, we determined the significant baseline predictors for the hazard rate of developing NODAT via Cox stepwise regression. The multivariable influence of first BPAR (defined as a time-dependent covariate) was also tested. RESULTS: Median follow-up was 57 mo post-transplant; the overall percentage who developed NODAT was 22.5% (108/481). Four baseline predictors of a greater NODAT hazard rate were found (by order of selection): higher BMI (p < 0.000001), planned maintenance with SRL (p = 0.0003), non-white recipient (p = 0.0004), and older recipient age (p = 0.0004). Approximately one-half of the 106 patients in the highest demographic risk category (BMI ≥25 kg/m(2) , non-white race, and age at transplant ≥40 yr) developed NODAT; actuarial NODAT risk ranged from 10% to 30% in the lower demographic risk categories. First BPAR was also associated with significantly higher NODAT in multivariable analysis (p = 0.02)-the highly elevated NODAT rate observed during the first few months post-transplant and following first BPAR appears to demonstrate the diabetogenic effect of using high-dose (intravenous) corticosteroids. CONCLUSIONS: The disturbingly high NODAT rate found among patients having multiple demographic risk factors is still an important problem that awaits a better solution.

Hemoglobin A1c testing is associated with improved pancreas utilization for transplant.

CONTEXT: Aging, higher prevalence of diabetes, worsening obesity, and hyperglycemia among potential donors increase the likelihood that pancreata will be declined by transplant centers. Hemoglobin A1c testing, also known as glycated hemoglobin testing, identifies a donor's average blood glucose concentration for the preceding 2 to 3 months and is the standard test for identifying prolonged periods of hyperglycemia. OBJECTIVE: To compare pancreas utilization rates before and after implementation of hemoglobin A1c testing. DESIGN: A retrospective study of data from the New York Organ Donor Network was conducted. Potential donors were defined as standard criteria donors who had no history of diabetes and were not seropositive for hepatitis B or C. Criteria for "ideal" potential pancreas donors were based on age, body mass index, lipase level, and terminal creatinine level. Potential donors who did not meet the criteria for ideal donors were considered "expanded" potential pancreas donors. Pancreas utilization rate was defined as the number of pancreata transplanted divided by the number of potential pancreas donors. RESULTS: Of 779 standard criteria donors, 691 (89%) were potential pancreas donors: 251 ideal (36%) and 440 expanded (64%) donors. In 2005 and 2006, before hemoglobin A1c testing, pancreas utilization rates were 21% and 18%, respectively. In 2008, 2009, and 2010, after hemoglobin A1c testing was incorporated, utilization rates were 27%, 28%, and 32%, respectively. Utilization of ideal donors increased from 33% to 51% (P= .003), and utilization of expanded donors increased from 11% to 17% (P= .05). Pancreas utilization increased 51.0%, and pancreas discards decreased 50.8% with the implementation of hemoglobin A1c testing. CONCLUSION: Hemoglobin A1c testing may increase utilization of ideal and expanded criteria pancreata.

The impact of race on organ donation authorization discussed in the context of liver transplantation.

Inadequate organ donation limits transplantation for many in need of a life-saving organ. Race of donor families and requesting coordinators may impact the authorization rate for organ donation. We evaluated authorization rates for organ donation within the New York Organ Donor Network by race during 2009 and 2010. The donation authorization rate varied considerably according to the race of the donor. The authorization rate was 57% for Hispanic, 53% for Caucasian, 48% for African-American, and 23% for Asian donor families. Fifty-five percent of donor families agreed to donation when there was racial concordance between coordinator and donor. Donation authorization was 49% when a racial mis-match existed. When adjusted for coordinator training and experience, racial discordance had a lesser impact on authorization rates. Our findings suggest the need for education and communication strategies to overcome racial-associated perception during the organ donation process.

Identifying risk factors in renal allografts before transplant: machine-measured renal resistance and posttransplant allograft survival.

Enhancement of renal allograft function and survival in an era where expanded criteria donors are increasingly used requires validated selection criteria. The goal of this retrospective study was to evaluate the significance of pretransplant donor and allograft parameters to identify risk factors that can be used in a model to predict 1-year allograft outcomes. Donor demographic factors, donor type, and allograft parameters such as biopsy results and machine-measured renal resistance were correlated with 1-year graft outcome. The Kaplan-Meier method was used to estimate graft survival using the categorical predictors of donor type, donor age, and machine measured renal resistance at 1.5, 3, and 5 hours. The log-rank test was used to test the difference in survival curves between cohorts. The Cox regression analysis was used to estimate hazard ratios for machine-measured renal resistance, donor age, donor terminal creatinine level, donor's estimated glomerular filtration rate, cold ischemia time, and percent glomerulosclerosis. The data show that machine-measured renal resistance at 3 and 5 hours has a statistically significant inverse relationship to 1-year graft survival. All other risk factors had no correlation with 1-year graft survival. The machine-measured renal resistance at 3 hours is the earliest significant predictor of 1-year allograft outcome.

Digital imaging of extended criteria donor livers to facilitate placement and utilization.

The disparity between organ supply and demand has necessitated more aggressive use of livers from extended criteria donors. Organ sharing between donor service areas and transplant centers in other regions is common. Confidence in the graft quality is greatly improved with a digital image taken in conjunction with the recovery surgeon's report and biopsy data. Three cases in which digital images of various levels of quality allowed the recipient's surgery to proceed, minimized the cold ischemia time, and yielded excellent outcomes are described. Another case in which a picture was not available and the liver was discarded after importation is also presented for comparison.

Intravenous leiomyomatosis with intracardiac extension: a single-institution experience.

OBJECTIVE: The aim of this study was to outline the surgical management and outcomes for patients diagnosed with intravenous leiomyomatosis with intracardiac extension at a single institution. STUDY DESIGN: This was a retrospective review of patients diagnosed with intravenous leiomyomatosis with intracardiac extension between 2002-2008. RESULTS: Four patients were identified. The surgical approach in 3 (75%) patients was a single-stage operation. Four (100%) patients presented with cardiac symptoms: 3 (75%) with syncope and 1 (25%) with an abnormal electrocardiogram. Mean age at presentation was 48 years (range, 42-58 years). Complete resection of tumor was obtained in 1 (25%) patient and 3 (75%) patients experienced incomplete resection. Mean follow-up, including surveillance imaging, was 25.5 months (range, 8-57 months) and all 4 patients (100%) are currently free of recurrence. CONCLUSION: Surgical excision remains an effective therapy for treating patients with benign metastasizing leiomyomatosis. Incomplete surgical resection may result in favorable response.

Immune suppression leading to hepatitis C virus re-emergence after sustained virological response.

Sustained virological response SVR is defined as undetectable HCV RNA in plasma 6 months after therapy has been discontinued. Relapse or re-emergence of viremia after SVR is rare. We report two patients that relapsed when immune suppressive therapy was given within a few weeks of achieving SVR. Patient 1 received prednisone for bronchitis and patient 2 relapsed soon after immune suppression was started post renal transplantation. These data suggest that the early phase of SVR might be associated with incomplete protective immunity. They suggest that sterilizing immunity with complete elimination of virus is unlikely. The cases also caution against the use of immune suppressive therapy in the immediate aftermath of SVR.

Critical care management of the liver transplant recipient.

Liver transplantation is an acceptable treatment modality for complications of end-stage liver disease from chronic and acute liver failure. In the United States, 16 377 people are currently awaiting liver transplant but only 6492 transplantations were performed in 2007. All options for liver transplantation including Model for End stage Liver Disease allocated, expanded criteria deceased donors, and live donor liver transplantation should be discussed with potential recipients on the waitlist to create an early access plan for safe and expeditious transplantation. After transplantation, careful management to avoid complications and intervene early is necessary. Common postoperative complications include graft dysfunction, vascular thrombosis, biliary tract complications, infection, rejection, neurologic injury, electrolyte imbalances, and drug interactions. A multidisciplinary approach to care including the critical care nurse is necessary for successful long-term outcomes.

Remission of aseptic inflammatory ascites after nephrectomy of a failed allograft.

There are multiple possible causes of ascites in patients with end-stage renal disease on hemodialysis therapy. In this report, we describe a patient with chronic hepatitis C infection who presented with refractory inflammatory ascites, along with cachexia, hypoalbuminemia, and erythropoietin resistance associated with the chronic inflammatory state induced by a failed kidney transplant. Evaluation showed only mild hepatic fibrosis, absence of portal hypertension, and no other identifiable cause of the ascites. Furthermore, the inflammatory ascites did not respond to antibiotic therapy, but promptly resolved, along with the other manifestations of the chronic inflammatory state, after transplant nephrectomy. This report describes a novel cause for refractory inflammatory ascites in a patient with a failed kidney transplant and emphasizes the importance of transplant nephrectomy.

Work Hours Assessment and Monitoring Initiative (WHAMI) under resident direction: a strategy for working within limitations.

PURPOSE: A review of surgical residents' duty-hours prompted a Work Hours Assessment and Monitoring Initiative (WHAMI) that preemptively limits residents from violating "duty-hours rules." METHODS: Work hours data for the Department of Surgery were reviewed over 8-months at New York Presbyterian Hospital-Columbia Campus. This ongoing review is performed by a work-hours monitoring team, which supervises residents' hours for the initial 5-days of each week. As residents approach work-hours limits for the week, they are dismissed from duty for appropriate time periods in the remaining 2 days of the week. RESULTS: The work-hours data entry compliance for 52 residents was increased from 93% to 99% after creation of the WHAMI. Before the new system, a mean of 9.5 residents per month (19%) worked an average of 7.3 +/- 6.4 hours over the 80-hour limit. Averaged monthly compliance with the 80-hour work limit was increased to 98% with introduction of the WHAMI. A review of on-call duty hours revealed a mean of 7 (14%) residents per month who worked an average of 2.4 hours beyond 24-hour call limitations including "sign-out" time imposed by the ACGME. New monitoring procedures have improved compliance to 100% with 24-hour call limitations imposed by the ACGME. Compliance with the more stringent New York State (NYS) guidelines has approached 94% with noncompliant residents extending on-call hours by an average of 1.5 hours over the 24-hour limitations, most on "off General Surgery" rotations or out-of-state rotations. Review of mandatory rest periods contributed to an increase in mean "time off" between work periods, thereby increasing compliance with ACGME guidelines and NYS regulations from 75% to 88%, and 90% to 98%, respectively. Residents reporting less than 10 hours rest reported increased "time off" from 6.2 +/- 2.0 to 7.9 +/- 1.3 hours (p < 0.001). CONCLUSIONS: Internal review of surgical resident's duty-hours at a large university hospital revealed that despite strict scheduling and the requirement of mandatory duty-hours entry, achieving the goals of meeting the duty-hours requirements and of ongoing data entry required the creation of a resident enforced, real-time Work Hours Assessment and Monitoring Initiative.

Are communication deviance and expressed emotion related to family history of psychiatric disorders in schizophrenia?

Studies have reported that certain measures of intrafamilial transactions are associated with an increased risk both for the initial onset of schizophrenia and for its recurrence following the initial episode of disorder. Two of the most studied of these are communication deviance (CD), a measure of subclinical thought disorder expressed in speech, and expressed emotion (EE), defined as notable attitudes of criticism and/or emotional overinvolvement manifested in a semistructured interview. A previous study (Goldstein et al. 1992) examined whether these two measures were associated with the presence of a diagnosable psychiatric disorder in the biological parents of recent-onset schizophrenia patients. In general, they were not. The present study went one step further. It examined whether these same measures were correlated with family history of schizophrenia or affective disorder in the biological parents and siblings of these same parents. High EE was not associated with a greater family history of schizophrenia spectrum disorders among the parent's parents and siblings but was unexpectedly found to be inversely associated with familial affective disorders. In contrast, CD was associated with a family history of schizophrenia spectrum disorders among the parent's parents and siblings. The findings are consistent with the possibility that CD may be an indicator of a genetic vulnerability factor for schizophrenia.

Pancreaticogastrostomy: a novel application after central pancreatectomy.

BACKGROUND: Limited middle segment pancreatectomy, or central pancreatectomy, has been described for sparing normal pancreatic tissue during resection of benign neoplasms of the pancreatic neck. Anatomic reconstruction after central pancreatectomy has been reported in other series with creation of a Roux-en-Y loop of jejunum for a mucosa-to-mucosa pancreaticojejunostomy. STUDY DESIGN: Hospital charts and outpatient records were reviewed for 12 consecutive patients undergoing central pancreatectomy from August 1999 to November 2002. RESULTS: We performed central pancreatectomy with pancreaticogastrostomy in 12 patients: 5 with serous cystadenomas, 6 with mucinous cystadenomas, and 1 with neuroendocrine tumor. All tumors were located in the body or neck of the pancreas, measuring a mean +/- standard deviation (SD) of 2.5 +/- 1.2 cm. Median postoperative hospital stay was 6.5 days (range 5 to 15 days). There were no intraoperative complications. Perioperative complications included two urinary tract infections and one readmission for acute pancreatitis. There were no pancreatic leaks or fistulas in this series. Two of the 12 patients experienced endocrine insufficiency with elevated glycosylated hemoglobin levels during outpatient followup. None of the 12 patients experienced exocrine insufficiency. CONCLUSIONS: Central pancreatectomy with pancreaticogastrostomy reconstruction is safe and technically advantageous over Roux-en-Y pancreaticojejunostomy, and should be considered a safe reconstruction technique after central pancreatectomy for benign disease.