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Introduction: The safety and liver utilization with prerecovery liver biopsy (PLB) in extended criteria liver donors are unclear. Methods: We conducted a retrospective cohort study in 1323 brain death donors (PLB=496) from three organ procurement organizations (OPOs). Outcomes were complications, preemption of liver recovery (PLR) and livers transplanted (LT). Additional analyses included liver only and propensity score-matched multiorgan donor subgroups. Results: PLB donors were older (57yrs vs 53yrs, p

Animal models and observational human data indicate that complement, including C5a, pathogenically participates in ischemia reperfusion (IR) injury that manifests as delayed graft function (DGF) following deceased donor kidney transplantation. We report on the safety/efficacy of anti-C5 monoclonal antibody eculizumab (Ecu) administered in the operating room prior to reperfusion, to prevent DGF in recipients of deceased donor kidney transplants in two related, investigator-sponsored, randomized controlled trials. Eight recipients from a single center were enrolled in a pilot study that led to a 19-subject multicenter trial. Together, 27 deceased donor kidney transplant recipients, 16 Ecu-treated and 11 controls, were treated with rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil with or without glucocorticoids, and followed for 6 months. Data analysis showed no epidemiological or transplant-related differences between study arms. Ecu was well tolerated with a similar severe adverse event incidence between groups. The DGF rate did not differ between Ecu-treated (44%) and control (45%, P = 1.0) subjects. Serum creatinine reduction in the first week after transplantation, and graft function up to 180-days post-transplant, were also similar. Ecu administration was safe but did not reduce the rate of DGF in a high-risk population of deceased donor recipients.

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)

Hemodialysis access options become complex in long-term treatment for patients with renal disease, while awaiting renal transplantation (RT). Once upper extremity sites are exhausted, lower extremities are used. RT is preferably in the contralateral iliac fossa, rarely ipsilateral. In current literature, RT dysfunction secondary to the hemodynamic effects of an ipsilateral femoral arteriovenous graft (AVG) has been rarely described. To our knowledge, AVG ligation is the only published technique for hemodynamic correction of an ipsilateral AVG. We present a simple, potentially reversible endovascular approach to manage the hemodynamic effects of an AVG, without potentially permanently losing future AVG access.

BACKGROUND Recent cases of donor-derived infections raise the question of how best to screen donors without excessive restriction of the donor pool. METHODS The New York Organ Donor Network (NYODN) established an Infectious Diseases Working Group (IDWG) in 2008, which established an on-call schedule of voluntary transplant infectious disease physicians to provide remote evaluations for donors at increased risk for disease transmission. RESULTS Data were reviewed from 40 available IDWG evaluations from 2008 to 2011. Eighteen cases (45%) were considered to be at unacceptable risk for infection transmission. Sixteen of these cases were excluded from donation secondary to IDWG recommendation; there was limited recipient center interest in the remaining two cases. Approximately 22 (55%) cases were categorized by the IDWG as acceptable, with 14 proceeding to recovery of 49 organs. IDWG physician recommendations were conveyed to recipient centers, and screening guidelines for donors were revised based on the IDWG experiences. CONCLUSION Establishment of a donation service area disease transmission evaluation service is a valuable program for donor screening and may promote dissemination of more detailed donor information to recipient centers.

Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multicenter study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.28) and 1.33 (1.02-1.72), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.

Background and objectives The influence of deceased-donor AKI on post-transplant outcomes is poorly understood. The few published studies about deceased-donor preimplant biopsy have reported conflicting results regarding associations between AKI and recipient outcomes. Design, setting, participants, & measurements This multicenter study aimed to evaluate associations between deceased-donor biopsy reports of acute tubular necrosis (ATN) and delayed graft function (DGF), and secondarily for death-censored graft failure, first adjusting for the kidney donor risk index and then stratifying by donation after cardiac death (DCD) status. Results Between March 2010 and April 2012, 651 kidneys (369 donors, 4 organ procurement organizations) were biopsied and subsequently transplanted, with ATN reported in 110 (17%). There were 262 recipients (40%) who experienced DGF and 38 (6%) who experienced graft failure. DGF occurred in 45% of kidneys with reported ATN compared with 39% without ATN ( P =0.31) resulting in a relative risk (RR) of 1.13 (95% confidence interval [95% CI], 0.9 to 1.43) and a kidney donor risk index–adjusted RR of 1.11 (95% CI, 0.88 to 1.41). There was no significant difference in graft failure for kidneys with versus without ATN (8% versus 5%). In stratified analyses, the adjusted RR for DGF with ATN was 0.97 (95% CI, 0.7 to 1.34) for non-DCD kidneys and 1.59 (95% CI, 1.23 to 2.06) for DCD kidneys ( P =0.02 for the interaction between ATN and DCD on the development of DGF). Conclusions Despite a modest association with DGF for DCD kidneys, this study reveals no significant associations overall between preimplant biopsy-reported ATN and the outcomes of DGF or graft failure. The potential benefit of more rigorous ATN reporting is unclear, but these findings provide little evidence to suggest that current ATN reports are useful for predicting graft outcomes or deciding to accept or reject allograft offers.

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 Alc 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 Alc 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 Alc testing, pancreas utilization rates were 21% and 18%, respectively. In 2008, 2009, and 2010, after hemoglobin Alc 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 Alc testing. Conclusion Hemoglobin Alc testing may increase utilization of ideal and expanded criteria pancreata.

This study examined whether patient symptoms and relatives' affective behavior, when expressed during directly observed family interactions, are associated with the short-term course of bipolar disorder. Twenty-seven bipolar patients and their relatives participated in two 10-minute family interactions when patients were discharged after a manic episode. Results indicated that patients who showed high levels of odd and grandiose thinking during the interactions were more likely to relapse during a 9-month followup period than patients who did not show these symptoms during the family discussions. Relapse was also associated with high rates of harshly critical and directly supportive statements by relatives. Patients' odd thinking and relatives' harsh criticism were significantly more likely to be correlated when patients relapsed (r = .53) than when they did not relapse (r = .12). Results suggest that bipolar patients who show increased signs of residual symptomatology during family transactions during the post-hospital period are at increased relapse risk. The data also suggest that relatives of relapsing patients cope with these symptoms by increasing both positive and negative affective behaviors. Moreover, a bidirectional, interactional relationship between patients' symptoms and relatives' coping style seems to capture best the role of the family in predicting relapse in bipolar disorder.

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.

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.

Hypothermic machine perfusion (HMP) is widely used to preserve kidneys for transplantation with improved results over cold storage (CS). To date, successful transplantation of livers preserved with HMP has been reported only in animal models. In this, the first prospective liver HMP study, 20 adults received HMP-preserved livers and were compared to a matched group transplanted with CS livers. HMP was performed for 3-7 h using centrifugal perfusion with Vasosol solution at 4-6 degrees C. There were no cases of primary nonfunction in either group. Early allograft dysfunction rates were 5% in the HMP group versus 25% in controls (p = 0.08). At 12 months, there were two deaths in each group, all unrelated to preservation or graft function. There were no vascular complications in HMP livers. Two biliary complications were observed in HMP livers compared with four in the CS group. Serum injury markers were significantly lower in the HMP group. Mean hospital stay was shorter in the HMP group (10.9 +/- 4.7 days vs. 15.3 +/- 4.9 days in the CS group, p = 0.006). HMP of donor livers provided safe and reliable preservation in this pilot case-controlled series. Further multicenter HMP trials are now warranted.

We report a case of Strongyloides stercoralis hyperinfection syndrome in a renal transplant recipient complicated by septic shock, acute respiratory distress syndrome, and Klebsiella pneumoniae superinfection. The patient was treated successfully with drotrecogin alfa (activated), parenteral ivermectin, albendazole, and piperacillin/tazobactam. This outcome suggests that drotrecogin alfa (activated) may be useful therapy for transplant recipients who develop severe sepsis or septic shock secondary to potentially lethal opportunistic infections.

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.

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.

In current practice, human immunodeficiency virus-infected (HIV(+) ) candidates with CD4 >200 cells/mm(3) are eligible for kidney transplantation; however, the optimal pretransplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and

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.

ationally, student interest in pursuit of a general surgery resdency steadily dropped from the early 1980s through the first art of this decade. General surgery was the first-choice resiency for 10.7% of U.S. senior medical students in 1984, but nly 4.7% in 2002. This diminishing interest finally maniested itself in the National Resident Matching Program in 001, when 68 (6.5%) general surgery residency positions went nfilled. In 2002, U.S. graduates comprised less than 80% of all atched applicants for the first time and 58 (5.5%) positions ere unfilled. Analysis of these data led to projections of further eclines in the number and quality of U.S. students matching o general surgery residencies, with serious implications for the ation. Published data suggest that, given an aging population, he United States will face an absolute shortage of general sureons as soon as 2010, with difficulty in attracting and retaining urgeons in some regions of the country already apparent. The past decade has seen many publications about medical tudent career preferences and the decline of interest in general urgery. Data demonstrate that perceived resident and attendng surgeon lifestyle are the major deterrents to medical stuents considering surgery as a career option. Students specifcally associate general surgery with irregular schedules, limited amily and leisure time, and high levels of stress. They cite anageable work hours as more important than income, and hey identify “controllable lifestyle” as their highest priority. his evolving attitude, combined with perceptions of surgery as particularly demanding field, underlie the decline of interest n general surgery residency programs.

The term thrombotic microangiopathy (TMA) hasbeenapplied toa diversegroup of conditionsthat sharethe common pathomechanism of endothelial damage.TMA is a recognized complication of solid organtransplantation.ThemajorityofcasesrepresentdenovoTMA, which occurs in 02.8–3.5% of renal transplantrecipients and is associated with a 22% rate of graftloss [1]. The rate of graft loss is strongly influencedby whether the TMA is systemic or renal limited (38vs 0% graft loss, respectively) [1].Treatment with calcineurin inhibitors (CNIs) is awell-established risk factor for the development of denovoTMA.Arecent,largeanalysisoftheUnitedStatesRenal Data System (USRDS) and Medicare claimsidentified multiple additional risk factors includingyounger recipient age, older donor age, female genderof the recipient, longer duration of dialysis before tran-splantation, previous renal transplant, delayed graftfunction (DGF), allograft rejection, increased peakpanel-reactive antibody, and treatment with sirolimus(SRL) [2]. Anti-cardiolipin antibody seropositivity,often in the setting of chronic hepatitis C virus infec-tion, is an additional risk factor for de novo TMA [3].SRL (rapamycin) is an immunosuppressive agentcommonly administered to renal transplant recipients.SRL may be used in combination with a CNI or as analternative agent. A recent, large trial has shown thatSRL facilitates early CNI withdrawal and that thisregimen is associated with less long-term nephrotox-icity [4]. The most frequently reported side effects ofSRL are thrombocytopenia, leukopenia, hypertriglyc-eridaemia and hypercholesterolaemia [5].SRL has a similar mechanism of action to the CNIs.Cyclosporin (CSA), tacrolimus (TAC) and SRL allproduce their immunosuppressive effect by binding tocytoplasmic proteins called immunophilins that modifyimmune function. CSA binds cyclophilin, and TACbinds FK-binding protein 12 (FKBP12); these com-plexes in turn inhibit calcineurin, a calcium-dependentphosphatase required for interleukin-2 production andprogression of T cells from the G to G

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.

Hepatic ischemia/reperfusion (I/R) injury associated with liver transplantation and hepatic resection is characterized by hepatocellular damage and a deleterious inflammatory response. In this study, we examined whether receptor for advanced glycation end product (RAGE) activation is linked to mechanisms accentuating inflammation on I/R in a murine model of total hepatic ischemia. Animals treated with soluble RAGE (sRAGE), the extracellular ligand-binding domain of RAGE, displayed increased survival after total hepatic I/R compared with vehicle treatment. TUNEL assay and histologic analysis revealed that blockade of RAGE was highly protective against hepatocellular death and necrosis on I/R; in parallel, proliferating cell nuclear antigen was enhanced in livers of mice treated with sRAGE. Rapid activation of p38, p44/42, stress-activated protein kinase and c-Jun N-terminal kinase mitogen-activated protein kinases, signal transducer and activator of transcription-3, and nuclear translocation of activator protein-1 was evident at early times on I/R. In the remnants of sRAGE-treated livers, however, activation of each of these signaling and transcription factor pathways was strikingly decreased. sRAGE-treated remnants displayed enhanced activation of nuclear factor kappaB, in parallel with increased transcripts for the proregenerative cytokine, tumor necrosis factor-alpha. In conclusion, these data suggest that RAGE modulates hepatic I/R injury, at least in part by activation of key signaling pathways linked to proinflammatory and cell death-promoting responses. We propose that blockade of this pathway may represent a novel strategy to attenuate injury in hepatic I/R and to facilitate regeneration.

Over the past decade we have reported excellent outcomes in pediatric living-donor liver transplantation (LDLT) with recipient survival exceeding 90%. Principles established in these patients were extended to LDLT in adults. To compare outcomes in donors and recipients between adult and pediatric LDLT in a single center, we reviewed patient records of 45 LDLT performed between 1/98 and 2/01: 23 adult LDLT (54 +/- 6.5 yr) and 22 pediatric LDLT (33.7 +/- 53.5 months). Preoperative liver function was worse in adults (International Normalized Ratio [INR] 1.5 +/- 0.4 vs. INR 1.2 +/- 0.5; p = 0.032). 4 adults (17%) met criteria for status 1 or 2A. Only 1 child was transplanted urgently. Analysis included descriptive statistics and Kaplan-Meier estimation. Donor mortality was 0% with 1 re-exploration, 2.4%. Median hospital stay (LOS) was 6.0 days (range, 4-12 days). Donor morbidity and LOS did not differ by sex, extent of hepatectomy, or adult and pediatric LDLT ( p = 0.49). In contrast, recipient outcomes were worse for adults. Adult 1 year graft survival was 65% (3 retransplants [ReTx], 5 deaths) vs. 91% for children (1 ReTx, 1 death) p = 0.02. Graft losses in adults were due to sepsis (n = 3), small for size (n = 2), suicide, and hepatic artery thrombosis (HAT), whereas in children graft losses were due to portal thrombosis and total parenteral nutrition (TPN) liver failure. Biliary leaks occurred in 22% of adults and 9% of children. Hepatic vein obstruction occurred in 17% of adults and in none of the children. Median LOS was comparable (adult, 16.5 days (range, 7-149 days); child, 17 days (range, 10-56 days), p = 0.2). Graft function (total bilirubin (TBili) < 5mg/dl, INR < 1.2, aspartate aminotransferase (AST) < 100 U/l) normalizing by day 4 in children and by day 14 in adults. Adults fared worse, with an array of problems not seen in children, in particular, hepatic vein obstruction and small-for-size syndrome. Biliary leaks were diagnosed later in adults and were lethal in 3 cases; this was later avoided with biliary drainage in adult recipients. Finally, use of LDLT in decompensated adults led to death in 3 of 4 patients, and should be restricted to elective use.

Recently hospitalized bipolar, manic patients (N = 53) were randomly assigned to a 9-month, manual-based, family-focused psychoeducational therapy (n = 28) or to an individually focused patient treatment (n = 25). All patients received concurrent treatment with mood-stabilizing medications. Structured follow-up assessments were conducted at 3-month intervals for a 1-year period ofactive treatment and a 1-year period of posttreatment follow-up. Compared with patients in individual therapy, those in family-focused treatment were less likely to be rehospitalized during the 2-year study period. Patients in family treatment also experienced fewer mood disorder relapses over the 2 years, although they did not differ from patients in individual treatment in their likelihood of a first relapse. Results suggest that family psychoeducational treatment is a useful adjunct to pharmacotherapy in decreasing the risk of relapse and hospitalization frequently associated with bipolar disorder.

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.

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. 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. 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). Less-than-expected post-NODAT risk for graft loss and death may exist in the current climate of tighter glucose monitoring post transplant.

Intramuscular endocrine gland transplantation has been well described as it pertains to parathyroid autotransplantation; however, transplantation of the adrenal gland is less well characterized. While adrenal autotransplantation in the setting of Cushing's disease has been described, intramuscular adrenal allotransplantation as a cure for adrenal insufficiency to our knowledge has not been previously carried out. Current treatment for adrenal insufficiency leaves patients without diurnal variation in cortisol release and susceptible to the detrimental effects of chronic hypercortisolism. We describe here the case of a 5-year-old girl with renal failure who had adrenal insufficiency following fulminant meningococcemia that led to requirements for both stress-dose steroid and mineralocorticoid replacement. Ten months after the onset of her disease, she received a simultaneous renal and adrenal gland transplant from her mother. The adrenal gland allograft was morselized into 1 mm(3) segments and implanted into three 2 cm pockets created in her rectus abdominis muscle. Three years after surgery, her allograft remains fully functional, responding well to adrenocorticotropin hormone stimulation and the patient does not require any steroid or mineral-corticoid supplementation. We believe this case represents the first description of successful functional intramuscular adrenal allograft transplantation with long-term follow up as a cure for adrenal insufficiency.

In a sample of 35 family members of patients with recent-onset schizophrenia, attributions of control and the content of critical comments were compared for 2 relatives of the same household who held discrepant expressed emotion (EE) attitudes (1 high and 1 low) toward their mentally ill family member. Attributions and the content of critical comments were also compared for low-EE relatives from low-EE homes versus low-EE relatives from high-EE homes. Our results indicate that high-EE relatives tend to attribute more control over behavior to patients than do low-EE relatives of the same patient. In addition, low-EE relatives from high-EE homes attribute more behavioral control to patients than do low-EE relatives from low-EE homes. These findings suggest that EE status is linked to attributions of control over behaviors, but additional patient factors or influences among family members may also affect EE attitudes.

Culture is widely thought to influence the form, content, and extent of symptoms experienced and expressed by the mentally ill. However, little is known about how specific cultural groups differ in their symptomatic presentation of mental illness. Using data derived from the Present State Exam, the current study compared 63 Anglo-American and 53 Mexican-American patients with schizophrenia on ten psychiatric symptoms. A series of logistic regressions offered several interesting findings. For instance, as hypothesized, Mexican-American patients were more likely to report physical symptoms than their Anglo-American counterparts. Also in line with expectations, Anglo-American patients reported experiencing a greater frequency of several psychiatric symptoms such as persecutory delusions, nervous tension, and blunted affect. Results from this study suggest that the presentation of even a very biologically determined disorder such as schizophrenia can be shaped by sociocultural factors. Specific aspects of Anglo-American and Latino cultures that may influence symptom patterns in patients suffering from schizophrenia are discussed.

This pilot study sought to follow up on indications that patients from households with high levels of expressed emotion (EE) differ from those from households with low levels of EE in ways not assessed in typical symptom rating profiles. We examined how patients appraised and coped with a prominent societal stressor. Soon after the start of the Gulf War, 22 patients with recent-onset schizophrenia living in Los Angeles appraised the stressor and completed a coping questionnaire. Results indicated that patients from high-EE homes were likely to use emotion-based confrontational methods to cope with the crisis, while patients from low-EE environments were likely to use avoidance and denial. Patients from high-EE homes thus coped with this non-familial, societal stressor in a way similar to the way in which they have been observed to cope with family conflict: they more readily expressed their anger and frustration than patients from low-EE homes. These pilot data suggest that increased attention should be d...

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.

Using a sample of 40 Anglo American family members of schizophrenic patients, the present study replicates and lends cross-cultural support for an attribution-affect model of expressed emotion (EE). Consistent with attribution theory, the authors found that highly critical relatives (high-EE) viewed the illness and associated symptoms as residing more within the patient's personal control as compared with less critical relatives (low-EE). A content analysis classified the types of behaviors and symptoms most frequently criticized by relatives. Symptoms reflecting behavioral deficits (e.g., poor hygiene) were found to be criticized more often than symptoms reflecting behavioral excesses (e.g., hallucinations). In line with an attribution-affect framework, relatives may be less tolerant of behavioral deficits because they are viewed as intentional, whereas behavioral excesses are easily recognized as core symptoms of mental illness.

During the course of schizophrenia, symptoms tend to increase at the highest rate during the first 5 years of the disease. Moreover, 10% of suicides by schizophrenic patients occur within the first 10 years of schizophrenia being diagnosed. These facts emphasize the importance of early intervention to improve the course of the disease before further deterioration. The use of psychosocial interventions and drug management programmes, in addition to maintenance antipsychotic medication, reduces the risk of psychotic relapse. Continuity of care from inpatient to outpatient treatment also significantly improves outcome, largely as a result of better drug compliance. It appears, however, that the addition of a behavioural family intervention alone to a standard programme offers little additional benefit. The benefits of intervention programmes last only as long as the programme, and patients should continue with such intensive treatment strategies for at least the duration of the critical phase. Under these circumstances, very mild psychotic complaints may be recognized at an early stage so that treatment can begin even earlier, further increasing the chance of an optimal long-term outcome. Further studies of early intervention and relapse prevention are required to support these findings.

Prevention of relapse is the main purpose of intervention in schizophrenia. Early studies found that antipsychotic medication protected patients against relapse. Subsequent research showed that family intervention therapy in combination with pharmacotherapy was superior to pharmacotherapy alone and to individual therapy in combination with pharmacotherapy. More recent research has focused on expressed-emotion (EE) status and has tried to determine what type of family intervention best suits patients from particular family types. The Amsterdam relapse prevention study investigated the effectiveness of a family behavioral management approach combined with standard individual therapy in comparison with standard individual therapy alone in young, recent-onset, first- or second-episode schizophrenic patients whose families had been taken through a supportive psychoeducational program while the patient was in hospital. The standard individual therapy was highly effective, and further benefit of family intervention could not be demonstrated. Patients in high-EE families were most at risk of relapse; cannabis abuse was the second most important risk factor. Among low-EE families, the relapse rate in the combination intervention group was higher (13%) than in patients given standard individual therapy alone (0%); this suggests that psychosocial intervention approaches need to be tailored to suit family type. Since intensive intervention has a short duration in relation to the length of the disorder in most patients, strategies must be developed for continuity of care. Involving family members in the continuity of care programs may be a crucial step in the delay or remission of psychotic relapse, combined with maintenance of atypical antipsychotic medication.

This study examined the relation between the presence of depressive symptoms in schizophrenic patients with a recent first psychotic episode and affective disorders among their relatives.Data on depressive symptoms in 70 patients with schizophrenia diagnosed according to the DSM-III-R criteria, who had had a recent first psychotic episode, and psychiatric diagnostic information on 293 of their first-degree and 674 of their second-degree relatives were collected. Depressive symptoms in the schizophrenic probands were examined at the index psychotic episode (at study entry) and systematically over a 1-year follow-through period. The majority of first-degree family members were interviewed in person with the use of semistructured diagnostic interviews.The linear regression findings confirmed the hypothesis that depressive symptoms in the early course of schizophrenia are associated with a family history of unipolar affective illness.Because depression in the patients was associated with a family history of depression, this suggests that depression in schizophrenia is not solely either a reaction to having had a psychotic episode or part of the recovery process. The findings are consistent with a model in which a familial genetic liability to affective disorder, when present, is viewed a s exerting a modifying influence on the patient's schizophrenic illness to increase expression of depressive symptoms.

BackgroundPrevious research has generally found that variations in relatives' affective attitudes (expressed emotion; EE) towards a schizophrenic family member could not be accounted for by differences in the severity or form of the patient's symptomatology. These findings have been based on clinicians' ratings of psychopathology in patients.MethodTo approach the question from a different perspective, videotaped interactions between a patient and family members, obtained four to five weeks after hospital discharge, were coded for subclinical signs of psychopathology expressed by the patient. The Behavioral Subclinical Rating Scale (BSRS) was developed to compare subclinical levels of non-verbal and paralinguistic symptoms expressed by patients from both high- and low-EE families.ResultsHighly significant differences were found in the BSRS data. Patients from high-EE families showed more hostile and unusual behaviour with relatives than those from low-EE homes, who, in contrast, showed more anxious behaviour.ConclusionThese data suggest that a complex transactional model is necessary to understand how family attitudes evolve during the course of a relatives' schizophrenic disorder.

An interview designed to assess a respondent's experience with erotic material in photographs, films, and books, during adolescence and adulthood, was administered to convicted male rapists, pedophiles, homosexuals, transsexuals, heavy pornography users, and two nondeviant contrast groups. One nondeviant group was composed of whites matched for the sex offender group; the other was composed of ghetto and middle-class blacks. Adolescent exposure to erotica was significantly less for all deviant and offender groups compared to the nondeviants. During adulthood, the sex offenders and transsexuals continued to report less exposure to erotic stimuli than controls. The homosexuals and users, however, both report greater exposure during adulthood. As adolescents, the control group, rapists, and heavy users were excited to masturbate by the erotic materials more than the other groups. As adults, the controls and rapists showed a sharp decrease in being excited to masturbate to erotica while the users' rate remained high and the homosexuals' rate rose. Less than a quarter of the respondents in any group imitated sexual behavior seen in the erotic material immediately or shortly after its viewing. The hypothesis that extent of exposure during adolescence to erotica is positively associated with the later emergence of sexual pathology is not borne out by this study. The nondeviant, non-sex-offender groups sampled had had significantly greater exposure to erotic materials during adolescence than the deviants, convicted sex offenders, or heavy adult users of pornography.

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.To compare pancreas utilization rates before and after implementation of hemoglobin A1c testing.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.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.Hemoglobin A1c testing may increase utilization of ideal and expanded criteria pancreata.

Hepatic inflow clamping during hepatectomy introduces ischemia-reperfusion (I/R) injury, and many authors regard the addition of caval occlusion as adding increased risk. Ischemic preconditioning (IPC) is one of the protective strategies employed to reduce I/R injury in animal experiments and limited clinical series. The aim of the present study was to determine the impact of systematic adoption of IPC in patients undergoing complex hepatectomy under total hepatic vascular exclusion (TVE) based on outcomes review.The records of 93 patients who underwent major hepatectomy involving TVE at our center from February 1998 to December 2008 were reviewed. These patients were divided into two groups: group 1 (n = 55, TVE alone) and group 2 (n = 38, TVE with IPC). IPC was performed by portal triad clamping for 10 min followed by 3-5 min of reperfusion prior to TVE and resection.The two groups were comparable regarding demographics, underlying liver diseases, indications for hepatectomy, duration of TVE, and preoperative liver and kidney function tests. Overall postoperative laboratory results of liver function tests were not significantly different between the two groups. Creatinine levels and prothrombin times were not significantly different between the groups. The use of IPC had no impact on the duration of the operation, blood loss, or hospital stay. The morbidity rates were 37.5 and 34.2 %, respectively.Our adoption of IPC as a protective strategy against I/R injury under TVE did not affect operative or laboratory parameters and clinical outcomes when compared to continuous clamping for comparable ischemic periods.

Whereas verbal interactional behaviors have been repeatedly found to distinguish the families of persons with and without major psychiatric disorders, there has been comparatively little examination of the discriminative value of nonverbal interactional behaviors. We developed the Nonverbal Interactional Coding System to measure "affiliative" and "distancing" nonverbal behaviors in 18 schizophrenic and 18 bipolar patients and their parents during 10-minute interactions conducted during a posthospital period. Bipolar patients and their parents displayed affiliative nonverbal behaviors ("illustrator gestures" or "prosocial behaviors") for longer durations than schizophrenic patients and their parents. In contrast, parents of schizophrenic patients displayed distancing nonverbal behaviors (looking away) for longer durations than those of bipolar patients. The nonverbal interactional data added to the statistical strength of patients' and parents' verbal interactional data in distinguishing between these diagnostic groups. Nonverbal interactional behaviors are important variables to consider in interventions aimed at improving the communication skills of families coping with psychiatric disorders.

A review of the literature on family psychoeducational interventions in schizophrenic disorders revealed two generations of studies. The first generation compared the clinical efficacy of psychoeducational family treatments and medication to medication only or routine care. A second generation of studies used more complex experimental designs that often narrowed the differences between the experimental treatment and comparison conditions. The results of the first generation of studies are unequivocal in demonstrating the superiority of family intervention plus medication over medication alone in delaying psychotic relapses. The second-generation studies had more equivocal results; they suggest that the efficacy of family intervention as an adjunct to medication in schizophrenia is in part a function of the type and format of the intervention being delivered, the treatment setting, and other variables.

There have been repeated demonstrations [1] that measures of a relative's affective attitudes toward a schizophrenic patient convey important prognostic information. However, the mechanisms linking these attitudes, termed high or low Expressed Emotion (EE), to the recurrence of a patient's disorder have not been clearly specified in these studies. The research carried out by our group at the University of California, Los Angeles (UCLA), has been designed to shed some light on this issue and to clarify the interface between attitudes expressed to clinicians in the course of a semistructured interview and the actual interactions observed in direct family transactions. Our studies are based on the hypothesis that attitudes impact on patient status because they are predictors of how relatives are likely to behave with patients on a day-to-day basis. In order to test this hypothesis, we developed a method for sampling family interaction within our laboratory setting that was designed to highlight difficult problems in daily living that might elicit interpersonal analogues of highor lowEE attitudes. Generally, these interactional measurements have been obtained a few weeks after a patient, either schizophrenic or bipolarmanic (in our more recent research), was discharged from the hospital following an acute episode of his or her disorder. Inasmuch as the Camberwell Family Interview (CFI), the main method used to assess relatives' EE status in our studies, was typically administered at an

The present study examined the effectiveness of 2 types of intervention (contingent monetary reinforcement and enhanced instruction) on span of apprehension performance. Forty chronic schizophrenia inpatients (26 men, 14 women) received a 3- and 12-letter array version of the span of apprehension task 4 times: baseline, intervention, immediate posttest, and 1-week follow-up. All patients were randomly assigned to 1 of 4 groups that differed according to method of intervention: repeat administration, monetary reinforcement only, instruction only, and monetary reinforcement plus instruction. The combination of monetary reinforcement plus instruction yielded significantly greater improvement in span accuracy than the other methods of intervention. These findings suggest that performance on this putative vulnerability indicator can be modified through certain interventions. Language: en

The authors examined whether young, recently discharged schizophrenic patients from high (n = 34) and low (n = 14) expressed emotion (EE) families differ in their level of subclinical symptomatology during a direct interaction task. Compared with patients from low-EE homes, patients from high-EE home showed significantly more odd and disruptive behavior with family members. High-EE relatives were more likely than low-EE relatives to respond with criticism to the first unusual thought verbalized by the patient; when this occurred, the probability of a second unusual thought was augmented. Results suggest that high-EE family members may display negative attitudes toward patients in part because they are exposed to higher levels of unusual or disruptive behavior than low-EE relatives. The data also support a bidirectional, transactional model of the relationship between relatives' EE and patients psychopathology.