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To describe and compare differences in peri-operative outcomes of robot-assisted (RA-RPLND) and open (O-RPLND) retroperitoneal lymph node dissection performed by a single surgeon where chemotherapy is the standard initial treatment for Stage 2 or greater non-seminomatous germ cell tumour. Review of a prospective database of all RA-RPLNDs (28 patients) and O-RPLNDs (72 patients) performed by a single surgeon from 2014 to 2020. Peri-operative outcomes were compared for patients having RA-RPLND to all O-RPLNDs and a matched cohort of patients having O-RPLND (20 patients). Further comparison was performed between all patients in the RA-RPLND group (21 patients) and matched O-RPLND group (18 patients) who had previous chemotherapy. RA-RPLND was performed for patients suitable for a unilateral template dissection. O-RPLND was performed prior to the introduction of RA-RPLND and for patients not suitable for RA-RPLND after its introduction. RA-RPLND showed improved peri-operative outcomes compared to the matched cohort of O-RPLND—median blood loss (50 versus 400 ml, p

Kidney fibrosis constitutes the shared final pathway of nearly all chronic nephropathies, but biomarkers for the non-invasive assessment of kidney fibrosis are currently not available. To address this, we characterize five candidate biomarkers of kidney fibrosis: Cadherin-11 (CDH11), Sparc-related modular calcium binding protein-2 (SMOC2), Pigment epithelium-derived factor (PEDF), Matrix-Gla protein, and Thrombospondin-2. Gene expression profiles in single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets from rodent models of fibrosis and human chronic kidney disease (CKD) were explored, and Luminex-based assays for each biomarker were developed. Plasma and urine biomarker levels were measured using independent prospective cohorts of CKD: the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semiquantitative assessment of kidney fibrosis, and the Seattle Kidney Study, a cohort of patients with common forms of CKD. Ordinal logistic regression and Cox proportional hazards regression models were used to test associations of biomarkers with interstitial fibrosis and tubular atrophy and progression to end-stage kidney disease and death, respectively. Sc/snRNA-seq data confirmed cell-specific expression of biomarker genes in fibroblasts. After multivariable adjustment, higher levels of plasma CDH11, SMOC2, and PEDF and urinary CDH11 and PEDF were significantly associated with increasing severity of interstitial fibrosis and tubular atrophy in the Boston Kidney Biopsy Cohort. In both cohorts, higher levels of plasma and urinary SMOC2 and urinary CDH11 were independently associated with progression to end-stage kidney disease. Higher levels of urinary PEDF associated with end-stage kidney disease in the Seattle Kidney Study, with a similar signal in the Boston Kidney Biopsy Cohort, although the latter narrowly missed statistical significance. Thus, we identified CDH11, SMOC2, and PEDF as promising non-invasive biomarkers of kidney fibrosis.

Background Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. Methods A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. Results A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). Conclusions Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.

Background. Orthostatic hypotension (OH) is a poorly understood complication of simultaneous pancreas–kidney (SPK) transplantation. We sought to determine the incidence, timing, and relationship of OH to rapid glycemic control in the early posttransplant period. Methods. This was a nonrandomized retrospective single-center review of 75 SPK and 19 kidney-alone (KA) recipients with type 1 diabetes (DM). Results. OH occurred in 57 (76%) SPK versus 2 (10%) KA recipients (odds ratio [OR] 61.72, 95% confidence interval [CI], 9.69-393.01; P < 0.001). The median onset of OH was 12 (interquartile range [IQR] 9–18) days posttransplant and resolved in 85% of SPK recipients after a median of 2.5 (IQR 1.2–6.3) months. Among SPK recipients, independent risk factors for OH were a shorter duration of DM (OR 0.85, 95% CI, 0.73-0.98; P = 0.03) and rapid glycemic control in the early posttransplant period (OR 1.13, 95% CI, 1.01-1.27; P = 0.04), as evidenced by a larger percent change in hemoglobin A1c (HbA1c) from transplant to month 3. OH patients had a higher median baseline HbA1c [8.3% (IQR 7.2–10.0) versus 7.1% (IQR 6.8–8.3); P = 0.07], lower median 3-month HbA1c [4.8% (IQR 4.6–5.2) versus 5.2% (IQR 5.0–5.4); P = 0.02], and a larger reduction in HbA1c over time as compared to recipients without OH (P < 0.01). Conclusions. Our results show that OH is more likely to occur following SPK versus KA transplantation and is strongly associated with rapid glucose normalization within the early posttransplant period.

We hope that at the point that readers see this CJASN article, they will have already read the three accompanying CJASN articles on patient preference information and patient-centered innovation in KRT ([1][1][⇓][2]–[3][3]). These four articles represent a combined effort to chronicle the

Objectives: To determine the vascular access modalities used for hemodialysis, the reasons for choosing them, and determinants of satisfaction with vascular access among patients with end-stage renal disease. Methods: The American Association of Kidney Patients Center for Patient Research and Education used the American Association of Kidney Patients patient engagement database to identify eligible adult hemodialysis patients. Participants completed an online survey consisting of 34 demographic, medical history, and hemodialysis history questions to determine which vascular access modalities were preferred and the reasons for these preferences. Results: Among 150 respondents (mean age 54 years, 53% females), hemodialysis was most frequently initiated with central venous catheter (64%) while the most common currently used vascular access was arteriovenous fistula (66%). Most (86%) patients previously received an arteriovenous fistula, among whom 77% currently used the arteriovenous fistula for vascular access. Older patients and males were more likely to initiate hemodialysis with an arteriovenous fistula. The factors most frequently reported as important in influencing the selection of vascular access modality included infection risk (87%), physician recommendation (84%), vascular access durability (78%), risk of complications involving surgery (76%), and impact on daily activities (73%); these factors were influenced by patient age, sex, and race. Satisfaction with current vascular access was 90% with arteriovenous fistula, 79% with arteriovenous graft, and 67% with central venous catheter. Conclusion: Most end-stage renal disease patients continue to initiate hemodialysis with central venous catheter despite being associated with the lowest satisfaction rates. While arteriovenous fistula was associated with the highest satisfaction rate, there are significant barriers to adoption that vary based on patient demographics and perception of procedure invasiveness.

In kidney transplantation, BK virus infection has historically resulted in high rates of graft dysfunction and graft loss. Unlike other opportunistic infections, no therapies have been shown to prevent BK. The purpose of the current study was to evaluate the safety and efficacy of ciprofloxacin for the prevention of BK viremia in kidney transplant recipients. Two hundred kidney transplant recipients were enrolled in a prospective, randomized, double-blind, placebo-controlled trial comparing a 3-month course of ciprofloxacin (n = 133) vs placebo (n = 67) for the prevention of BK viremia. The primary endpoint of BK viremia at month 6 posttransplant occurred in 25 (18.8%) patients in the ciprofloxacin group and 5 (7.5%) in the placebo group (P = .03). Higher rates of BK viremia (23.3% vs 11.9%; P = .06) and BK nephropathy (5.8% vs 1.5%; P = .26) remained at 12 months in the ciprofloxacin group. Ciprofloxacin use was associated with a significantly higher rate of fluoroquinolone-resistant gram-negative infections (83.3% vs 50%; P = .04). A 3-month course of ciprofloxacin was ineffective at preventing BK viremia in kidney transplant recipients and was associated with an increased risk of fluoroquinolone-resistant infections. Clinical trial registration number: NCT01789203.

Background TruGraf v1 is a well-validated DNA microarray-based test that analyzes blood gene expression profiles as an indicator of immune status in kidney transplant recipients with stable renal function. Methods In this study, investigators assessed clinical utility of the TruGraf test in patient management. In a retrospective study, simultaneous blood tests and clinical assessments were performed in 192 patients at 7 transplant centers, and in a prospective observational study they were performed in 45 subjects at 5 transplant centers. Results When queried regarding whether or not the TruGraf test result impacted their decision regarding patient management, in 168 of 192 (87.5%) cases the investigator responded affirmatively. The prospective study indicated that TruGraf results supported physicians' decisions on patient management 87% (39/45) of the time, and in 93% of cases physicians indicated that they would use serial TruGraf testing in future patient management. A total of 21 of 39 (54%) reported results confirmed their decision that no intervention was needed, and 17 of 39 (44%) reported that results specifically informed them that a decision not to perform a surveillance biopsy was correct. Conclusions TruGraf is the first and only noninvasive test to be evaluated for clinical utility in determining rejection status of patients with stable renal function and shows promise of providing support for clinical decisions to avoid unnecessary surveillance biopsies with a high degree of confidence. TruGraf is an invaluable addition to the transplant physician's tool kit for managing patient health by avoiding painful and invasive biopsies, reducing health care costs, and enabling frequent assessment of patients with stable renal function to confirm immune quiescence.

TruGraf v1 is a laboratory-developed DNA microarray-based gene expression blood test to enable proactive noninvasive serial assessment of kidney transplant recipients with stable renal function. It has been previously validated in patients identified as Transplant eXcellence (TX: stable serum creatinine, normal biopsy results, indicative of immune quiescence), and not-TX (renal dysfunction and/or rejection on biopsy results). TruGraf v1 is intended for use in subjects with stable renal function to measure the immune status as an alternative to invasive, expensive, and risky surveillance biopsies. Materials and Methods In this study, simultaneous blood tests and clinical assessments were performed in 192 patients from 7 transplant centers to evaluate TruGraf v1. The molecular testing laboratory was blinded to renal function and biopsy results. Results Overall, TruGraf v1 accuracy (concordance between TruGraf v1 result and clinical and/or histologic assessment) was 74% (142/192), and a result of TX was accurate in 116 of 125 (93%). The negative predictive value for TruGraf v1 was 90%, with a sensitivity 74% and specificity of 73%. Results did not significantly differ in patients with a biopsy-confirmed diagnosis vs those without a biopsy. Conclusions TruGraf v1 can potentially support a clinical decision enabling unnecessary surveillance biopsies with high confidence, making it an invaluable addition to the transplant physician's tool kit for managing patients. TruGraf v1 testing can potentially avoid painful and risky invasive biopsies, reduce health care costs, and enable frequent assessment of patients with stable renal function to confirm the presence of immune quiescence in the peripheral blood.

Deceased organ donor intervention research aims to increase organ quality and quantity for transplantation. We assessed the proportion of kidney transplant candidates who would accept "intervention organs," participate in organ intervention research, and factors influencing acceptance. Kidney transplant candidates were presented 12 hypothetical scenarios, which varied three attributes, donor age, predicted waiting time to receive another organ offer, and research risk to the organ. Candidates were also randomly assigned to one of two conditions varying recipient risk. For each scenario, candidates agreed to accept the intervention organ or remain waitlisted. We fit a multivariable logit model to determine the association between scenario attributes and the acceptance decision. Of 249 participants, most (96%) accepted intervention organs under some or all conditions. Factors independently associated with candidates' greater likelihood of accepting an intervention organ included: low risk to the kidney from the intervention (OR 20.53 [95% Confidence Interval (CI), 13.91-30.29]); younger donor age (OR 3.72 [95% CI, 2.83-4.89]), longer time until the next organ offer (OR 3.48 [95% CI, 2.65-4.57]), and greater trust in their transplant physician (OR 1.03 [95% CI, 1.00-1.06]). Candidates with a lower likelihood of acceptance had been waitlisted longer (OR 0.97 per month [95% CI, 0.96-0.99]) and were Black (OR 0.21 [95% CI, 0.08-0.55]). Most candidates would accept an intervention organ, which should encourage transplant leaders to conduct deceased donor organ intervention trials.

Background Renal allograft survival is negatively affected by the development of de novo posttransplant donor-specific antibodies (dnDSA). We sought to determine whether treatment with intravenous immunoglobulin (IVIG) could remove or reduce the intensity of dnDSA. Methods A single-center study of 12 recipients with dnDSA and stable function who received IVIG 1 g/kg monthly for 6 months were compared with a contemporaneous cohort of 24 recipients with dnDSA who did not receive IVIG. Results The median time to first dnDSA was 6 months (interquartile range [IQR], 1-12), and follow-up was 83 months (IQR, 58-94) posttransplant. Resolution of dnDSA occurred in 27% of IVIG vs 46% of control recipients (P = .48). Fifty-eight percent of recipients in both cohorts demonstrated a reduction in the intensity of the dominant DSA at last follow-up (P =1.0). A reduction in the number of dnDSAs occurred in 58% vs 62% of the IVIG and control cohorts, respectively (P = .81). Post-dnDSA, acute rejection occurred in 8% of the IVIG vs 42% in the control group (P = .06). Forty-two percent of IVIG-treated vs 49% of control recipients had a deterioration in function from first dnDSA until most recent follow-up (P = .81). Actuarial graft survivals were equivalent between groups. Conclusions IVIG treatment of dnDSA in recipients with stable graft function had no impact on DSA clearance or MFI reduction, but this outcome may also be owing to sample size. Larger studies or alternate dosing regimens may be required to determine if there is any role for the use of IVIG as a treatment for dnDSA.

The novel coronavirus SARS-CoV-2 [coronavirus disease 2019 (COVID-19)] is a highly contagious and devastating virus that has currently infected over 2.5 million people worldwide and resulted in 177 641 deaths as of April 2020.1 Although most people diagnosed with COVID-19 exhibit mild-to-moderate symptoms, early reports from China described vulnerable patient populations, such as the elderly and those with chronic underlying medical conditions including the immunosuppressed, having more severe COVID-19-related illness compared to the general population.2,3 Solid organ transplant (SOT) recipients are one of the largest cohorts of immunosuppressed patients, yet little is known about their risk of contracting the virus, postinfection outcomes, and effect of immunosuppression on the clinical course of the disease. Unique challenges, such as immunosuppression management and interpretation of laboratory data, also exist. Current treatment strategies borrow upon prior experience from other pandemics, such as severe acute respiratory syndrome (SARS) and influenza A virus subtype.4 SARS-CoV-2 primarily affects the respiratory tract, progressing from pneumonia to acute respiratory distress syndrome in severe cases.5 In these cases, there is a recognized cytokine release syndrome (CRS) that when occurs results in multiorgan dysfunction and failure.6 The role of immunosuppression in mounting such inflammatory response is unclear. Inflammatory markers, such as C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer, may reflect disease progression and/or severity.7 Lymphopenia is reported as a common presentation among COVID-19 positive patients.8,9 Treatment options are limited. Antivirals such as hydroxychloroquine (HCQ) with or without azithromycin are widely used empiric options. Remdesivir, an RNA polymerase inhibitor, has shown in vitro activity against SARS-CoV-2 and is currently under phase 3 trial.10 Investigational agents to combat the cytokine response, such as tocilizumab, an interleukin 6 (IL-6) receptor inhibitor, are being studied. Although the exact role of immunosuppression on the progression of COVID-19 is unknown, early case reports of kidney transplant recipients suggest minimizing immunosuppression while continuing steroidal therapy.11 Evaluation of clinical symptoms, utility of biomarkers, and progression of disease are important to understand for optimizing the management in COVID-19 positive SOT recipients. The effect of COVID-19 on the heart, lung, liver, pancreas, and kidney transplant organ systems is not well described. Herein, we present our experience with 21 consecutive SOT recipients diagnosed with COVID-19 at the Houston Methodist J.C. Walter Transplant Center followed to April 22, 2020.

BACKGROUND Although originally described as a survival mechanism, it is unknown whether and to what extent autophagy is implicated in the terminal stages of heart failure. Here, we studied magnitude and evolution of autophagy in patients with intractable heart failure. MATERIAL AND METHODS Myocardial samples were obtained from 22 patients with ischemic cardiomyopathy and idiopathic dilated cardiomyopathy who were undergoing cardiac transplantation. Hearts from 11 patients who died from non-cardiac causes were used as control samples. Autophagy was evaluated by immunostaining with a monoclonal microtubule associated protein light chain 3 (LC3)-II antibody, while the relationship of autophagy with apoptosis and oncosis was assessed by double staining with TUNEL (terminal deoxynucleotidyl transferase - mediated deoxyuridine triphosphate nick end labeling) assay and complement 9 (C9) immunological staining, respectively. In addition, several necroptotic markers, including RIP1 and RIP3 (receptor interacting protein kinase 1 and 3), anti-C3 (cleaved-caspase-3), and anti-NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) were assessed by immunohistochemistry. RESULTS Anti-LC3-II staining was detected in 8.7±1.6% of the heart failure patient heart samples and in 1.2±0.3% of control patient heart samples. Vacuole formation started at one nuclear pole, before becoming bipolar and involving the cytosol. Subsequently, the autophagic process extended also to the nuclei, which underwent a progressive vacuolization and disintegration, assuming a peculiar "strawberry like appearance". Myocytes with extensive vacuole formation exhibited nuclear degeneration, which was associated with TUNEL, C3, C9, RIP1, and RIP3 positive staining. Conversely, myocytes with less extensive vacuole formation showed RIP1 and NF-κB positive staining, though not positivity for other cell death markers. CONCLUSIONS Autophagy was extensively detected in end-stage heart failure and its progression, resulted in secondary cell death, with occurrence of oncosis and necroptosis exceeding that of apoptosis. Conversely, activation of the RIP1/NF-κB pathway was associated with cell survival.

Living with chronic kidney disease (CKD) is associated with hardships for patients and their care-partners. Empowering patients and their care-partners, including family members or friends involved in their care, may help minimize the burden and consequences of CKD-related symptoms to enable life participation. There is a need to broaden the focus on living well with kidney disease and re-engagement in life, including an emphasis on patients being in control. The World Kidney Day (WKD) Joint Steering Committee has declared 2021 the year of "Living Well with Kidney Disease" in an effort to increase education and awareness on the important goal of patient empowerment and life participation. This calls for the development and implementation of validated patient-reported outcome measures to assess and address areas of life participation in routine care. It could be supported by regulatory agencies as a metric for quality care or to support labeling claims for medicines and devices. Funding agencies could establish targeted calls for research that address the priorities of patients. Patients with kidney disease and their care-partners should feel supported to live well through concerted efforts by kidney care communities including during pandemics. In the overall wellness program for kidney disease patients, the need for prevention should be reiterated. Early detection with a prolonged course of wellness despite kidney disease, after effective secondary and tertiary prevention programs, should be promoted. WKD 2021 continues to call for increased awareness of the importance of preventive measures throughout populations, professionals, and policy makers, applicable to both developed and developing countries.

PURPOSE OF REVIEW BK virus is a significant risk factor for kidney allograft dysfunction and loss among renal transplant recipients. Currently, there is no proven effective treatment except for the reduction of immunosuppression. In this review, we discuss diagnostic challenges and current treatment options for BK in kidney transplant recipients. RECENT FINDINGS Antiviral and antibiotic therapies have been employed for BK viraemia with variable efficacy. In addition, novel therapeutic regimens such as adoptive transfer of targeted T cells have been described as possible treatment options for recipients with BK nephropathy. BK can also be seen in the native kidneys of pancreas, heart, lung and liver transplant recipients, suggesting that BK screening measures should be employed to other solid organ transplant recipients. SUMMARY Early screening for BK combined with reduction of immunosuppression remains the mainstay of treatment for BK viraemia. New therapeutic advances demonstrate promise in vitro; however, the in-vivo efficacy will be demonstrated by future studies.

Review of cochlear implant (CI) outcomes in patients with Neurofibromatosis Type 2 (NF2), implanted in the presence of an ipsilateral vestibular schwannoma (VS). Hearing restoration was combined in some cases with a Bevacizumab regime.Retrospective review of 12 patients, managed over the period 2009-2016, at a tertiary referral multidisciplinary NF2 clinic. The patients are grouped by hearing outcomes to explore likely protective factors, and to generate a proposed decision-making tool for the selection of either CI or Auditory Brainstem Implant (ABI).Four of the 12 patients achieved speech discrimination without lip-reading. In these individuals there is reason to think that the mechanism of their hearing loss was cochlear dysfunction. A further four patients received benefit to lip-reading and awareness of environmental sound. For such patients their hearing loss may have been due to both cochlear and neural dysfunction. Two patients gained access to environmental sound only from their CI. Two patients derived no benefit from their CIs, which were subsequently explanted. Both these latter patients had had prior ipsilateral tumour surgery, one just before the CI insertion.Cochlear implantation can lead to open set speech discrimination in patients with NF2 in the presence of a stable VS. Use of promontory stimulation and intraoperative electrically evoked auditory brainstem response testing, along with case history, can inform the decision whether to implant an ABI or CI.

BACKGROUND Excessive weight (EW) gain is common after solid organ transplantation, but there is little information concerning obesity after pancreas transplantation. The study goal was to characterize EW gain after kidney-pancreas (KP) transplantation. METHODS This was a retrospective single-center review of 100 KP recipients transplanted between September 2007 and June 2015. RESULTS The median percent weight gain for all recipients at 1 year posttransplant was 10% (interquartile range, 2.7%-19.3%) of baseline weight. EW gain, defined as greater than or equal to a 19% 1-year increase in weight, included all recipients (n = 26) above the upper limit of interquartile range for weight gain at 1 year. In multivariate analysis, recipient age

Spontaneous rupture of a continent urinary reservoir is a rare, but clinically important event. The diagnosis of reservoir rupture should be considered in any patient with peritonitis and a history of continent urinary diversion. A pouchogram may confirm the diagnosis, but ultimately a laparotomy is mandatory in the setting of peritonitis and sepsis. Catheter drainage alone has been reportedly successful for patients who meet certain criteria. This case highlights the key steps in evaluation and management of a ruptured continent urinary reservoir.

Locally advanced urothelial carcinoma of the renal collecting system presents a unique challenge to the urologist performing nephroureterectomy, particularly if the tumor invades the renal vein or the IVC. Preoperative planning and a multidisciplinary approach are important to optimize the outcomes for these patients. The use of robotic assistance for laparoscopic nephroureterectomy has become common, but a simultaneous robotic assisted IVC excision has yet to be reported. This case report describes a robotic assisted laparoscopic right nephroureterectomy with IVC resection and retroperitoneal lymphadenectomy for locally advanced urothelial carcinoma. For a patient with locally advanced urothelial carcinoma of the renal collecting system which obliterates the renal vein, robotic assisted surgery provides a minimally invasive alternative to open surgery.

Modern-day treatment regimens for human immunodeficiency virus (HIV) are not only highly effective, but are now more often available as convenient fixed-dose combination products. Furthermore, as medication adherence is of utmost importance in this setting, national guidelines endorse the use of such products. Transplant providers of HIV-infected patients will undoubtedly encounter these products, some of which contain medications known to drastically alter the metabolism of certain immunosuppressants. Herein, we describe an instance of drug interaction-induced calcineurin inhibitor (CNI) nephrotoxicity in a renal transplant recipient being started on a cobicistat-containing combination product for HIV. CNI toxicity, in turn, was resolved with the aid of phenytoin as an inducer of drug metabolism. This case underscores the importance of familiarity with newer combination products on the market and constant communication with HIV-positive transplant recipients and their providers.

ObjectivesThe objective of this study was to assess vitamin D status of US non-pregnant adults using a standardised assay across 15 mL/min/1.73 m2increments of kidney function, report the use of dietary supplements containing vitamin D and assess relationships between vitamin D and markers of bone resorption.DesignThis study is a cross-sectional evaluation.SettingThe study is from the US National Health and Nutrition Evaluation Survey in 2001–2012.ParticipantsThe participants were non-institutionalised, non-pregnant adults, age ≥20 years.Primary and secondary outcome measuresThe primary outcome measure was serum 25OHD evaluated using liquid chromatography-tandem mass spectroscopy traceable to international reference standards. Secondary outcome measures were use of dietary supplements containing vitamin D and the serum intact parathyroid hormone and bone-specific alkaline phosphatase in a subset of participants.ResultsThe median 25OHD concentration in 27 543 US non-pregnant adults was 25.7 ng/mL (range, 2.2–150.0 ng/mL). Vitamin D supplements were used by 38.0%; mean (SE)=757 (43) international units/day. The range of 25OHD concentration across groups, stratified by kidney function, was 23.0–28.1 ng/mL. The lowest concentration of 25OHD observed was in people with higher kidney function (23.0 ng/mL for estimated glomerular filtration rate >105 mL/min/1.73 m2). Only 24% of people not taking a dietary supplement had a 25OHD concentration >30 ng/mL. Serum intact parathyroid hormone inversely correlated with 25OHD within all kidney function groups. Bone-specific alkaline phosphatase was also negatively associated with 25OHD concentration.ConclusionsThese data indicate that 25OHD concentrations and supplement use may be suboptimal in a significant proportion of the population, across all kidney function levels. The response of bone resorption markers further suggests that 25OHD levels could be improved. Together, these data support a re-evaluation of the 25OHD concentration associated with health in adults.

Background IL-17A and IL-17F are pro-inflammatory cytokines which induce the expression of several cytokines, chemokines and matrix metalloproteinases (MMPs) in target cells. IL-17 cytokines have recently attracted huge interest due to their pathogenic role in diseases such as arthritis and inflammatory bowel disease although a role for IL-17 cytokines in myocardial infarction (MI) has not previously been described. Methods In vivo MI was performed by coronary artery occlusion in the absence or presence of a neutralizing IL-17 antibody for blocking IL-17 actions in vivo. IL-17 signaling was also assessed in isolated primary cardiomyocytes by Western blot, mRNA expression and immunostaining. Results Expression of IL-17A, IL-17F and the IL-17 receptor (IL-17RA) were all increased following MI. Expression of several IL-17 target genes, including Cxcl1, Cxcl2, IL-1β, iNOS and IL-6 was also upregulated following MI. In addition, IL-17A promoted the expression of Cxcl1 and IL-6 in isolated cardiomyocytes in a MAPK and PI(3)K-dependent manner. IL-17A and ischaemia/reperfusion (I/R) injury were found to have an additive effect on Cxcl1 expression, suggesting that IL-17 may enhance myocardial neutrophil recruitment during MI. Moreover, protein levels of both IL-17R and IL-17A were enhanced following in vivo MI. Finally, blocking IL-17 signaling in vivo reduced the levels of apoptotic cell death markers following in vivo MI. Conclusions These data imply that the expression of IL-17 cytokines and their receptor are elevated during myocardial I/R injury and may play a fundamental role in post infarct inflammatory and apoptotic responses.

Background We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. Methods In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. Results At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conclusion Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function.

In many cases, individuality in metabolism of a drug is a reliable predictor of the drug efficacy/safety. Modern high-throughput metabolomics is an ideal instrument to track drug metabolism in an individual after treatment. Productivity and low cost of the metabolomics are sufficient to analyse a large cohort of patients to explore individual variations in drug metabolism and to discover drug metabolic biomarkers indicative of drug efficacy/safety. The only potential disadvantage of metabolomics becoming a routine clinical procedure is a need to treat the patient once before making a prognosis. However, in many clinical applications this would not be a limitation. Here, we explore current opportunities and challenges for translating high-throughput metabolomics into the platform for personalized medicine.

Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compare outcomes to single-kidney transplant (SKT) recipients.Methods. A retrospective single-center comparison of DKT and SKT performed between February 2007 and July 2013.Results. Of 516 deceased donor kidney transplants, 29 were DKT and 487 were SKT. Mean follow-up was 43 ± 67 months. DKT recipients were older and more likely than SKT recipients to receive an extended criteria graft (p<0.001). For DKT versus SKT, the rates of delayed graft function (10.3 versus 9.2%) and acute rejection (20.7 versus 22.4%) were equivalent (p= ns). A higher than expected urologic complication rate in the DKT cohort (14 versus 2%,p<0.01) was reduced through modification of the ureteral anastomosis. Graft survival was equivalent between DKT and SKT groups (p= ns) with actuarial 3-year DKT patient and graft survivals of 100% and 93%. At 3 years, the groups had similar renal function (p= ns).Conclusions. By utilizing extended criteria donor organs as DKT, the donor pool was enlarged while providing excellent patient and graft survival. The DKT urologic complication rate was reduced by modification of the ureteral anastomosis.

Background De novo donor-specific antibodies (dnDSA) after renal transplant are associated with acute rejection (AR) and graft loss, yet most recipients with dnDSA have stable function and no AR. We assessed whether the persistence of dnDSA increased the risk of a detrimental outcome. Methods A single-center review of renal transplant recipients monitored for dnDSA at multiple time points post-transplant. An Isolated dnDSA was defined as one positive dnDSA and no additional positive tests, whereas ≥2 positive dnDSA was defined as persistent dnDSA. Results Of 708 recipients, 22% developed dnDSA, of whom 64% had persistent dnDSA. At median follow-up of 35 (range 12-74) months, there were fewer episodes of AR in the isolated dnDSA vs the persistent dnDSA group (2% vs 22%; P

ObjectivesThe present study investigated the cardioprotective role of urocortin (Ucn) and its relationship with protein kinase C (PKC)ε and PKCδ in patients with (DMPs) and without (NDMPs) diabetes mellitus after on-pump cardiac surgery (OPCS). The molecular mechanisms responsible for the reported worse outcomes of DMP after OPCS remain unknown.MethodsTwo sequential biopsy specimens were obtained from the right atrium of 27 DMPs and 22 NDMPs before and after cardiopulmonary bypass.ResultsPostcardioplegic induction of Ucn in NDMPs (P

The development of therapies that lead to the regeneration or functional repair of compromised cardiac tissue is the most important challenge facing translational cardiovascular research today. During the last 25 years huge efforts have been made towards restoring the physiologic functions of the heart by means of delivering cell implants into the insulted heart, initially through 'naked cell' injections and more recently through the principle of cardiac tissue engineering and the use of elaborate delivery systems and priming mechanisms that include scaffolds, bioreactors or ex vivo manipulations of cells and support structures. In this review we summarise various approaches towards cardiac repair and highlight advances in the field of tissue engineering, ranging from a review of cell types used, to advances that attempt to address mechanistic and functional elements that are critical for successful restoration of the heart, including the maintenance of the extracellular matrix through scaffoldless cardiac sheets, strategies that promote neovascularisation and the precise micro-delivery of cell populations to form three-dimensional structures through bioengineering methods such as microfabrication.

This study aimed to assess kidney dysfunction in general surgical patients and examine the effect on postoperative mortality and morbidity.An estimated 13% of the US population has chronic kidney disease (CKD), but awareness among patients and caregivers is lacking.The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data sets for 2005-2007 were analyzed. Preoperative kidney function was assessed by the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate (eGFR) and staged according to National Kidney Foundation. Cross-sectional analyses were performed for 30-day mortality (Cox proportional hazard) and incidence of major complications (nominal logistic regression). A case-control cohort of colectomy cases was analyzed comparing patients in the stage 4 CKD group and the no CKD group (no-CKD).Sixty-four percent of evaluable patients had reduced eGFR, but eGFR was not evaluable in 28% of the surgical cases. In the 260,352 evaluable cases, adjusted hazard ratio for 30-day mortality was 2.30 [95% confidence interval (CI), 2.11-2.51] for stage 3 CKD; 3.37 (95% CI, 3.01-3.76) for stage 4 CKD; and 3.05 (95% CI, 2.68-3.47) for stage 5 CKD compared with no-CKD (P0.0001). CKD was an independent risk factor for having major complications postsurgery [stage 3, odds ratio (OR) = 1.24 (95% CI, 1.19-1.29); stage 4, OR = 1.65 (95% CI, 1.52-1.78); and stage 5 CKD, OR = 1.40 (95% CI, 1.30-1.51); P0.0001]. The case-control for colectomy was confirmatory: increased 30-day mortality in stage 4 CKD versus no-CKD (hazard ratio = 2.58, 95% CI, 1.13-5.92; P = 0.025).Renal insufficiency may be underrecognized in the general and vascular (noncardiac) surgery population, is a leading independent predictor of poor early postoperative outcomes, and should be routinely assessed in the preoperative setting.

BACKGROUND This study reviewed the outcomes of a screening protocol for BK viremia to determine if early diagnosis, followed by immunosuppression minimization, would prevent progression to nephropathy and graft loss. METHODS This review included 369 renal transplant recipients tested for BK virus at serial time points after transplantation. Management included immunosuppression minimization plus cidofovir treatment for BK nephropathy. RESULTS Recipients received tacrolimus-based immunosuppression, with 8% prednisone-free and 6% who received desensitization. With a mean follow-up of 22 ± 10 months, 16% (n = 57) of recipients became BK viremia positive. The median (range) time to diagnosis was 3 (1-17) months. Because renal biopsy was performed selectively, 59% of recipients underwent biopsy, with 47% showing BK nephropathy. Seventy-four percent of recipients cleared the virus at a median (range) time of 9 (3-33) months, with four grafts lost to BK nephropathy. Cidofovir-treated recipients displayed a higher viral load at diagnosis but showed equivalent renal function at last evaluation. In multivariate analysis, recipient age, Asian ethnicity, deceased donor, and prednisone use were factors independently associated with BK viremia. Actuarial survival of BK-positive grafts was worse than that of BK-negative grafts (P

What's known on the subject? and What does the study add? Most transplant centres harvest living donor kidneys via a conventional laparoscopic surgical approach. Laparoendoscopic single-site donor nephrectomy (LESS-DN) is a relatively novel minimally invasive approach that allows the surgery to be performed via a single incision. This technique may be advantageous in decreasing surgical morbidity and improving cosmetic outcomes, thus plausibly reducing the barriers to kidney donation. The study demonstrates the safety and feasibility of LESS-DN in a large consecutive series of kidney donors. Comparative analysis between LDN and LESS-DN showed that there was a significant decrease in intra-operative blood loss and allograft warm ischaemia time in the LESS-DN group, but also a significant increase in operating time. Other peri-operative outcomes were similar between the two approaches. Evaluation of the LESS-DN cases alone revealed that, the operating times did not significantly change through the course of the series. Using this outcome as a surrogate for technical difficulty suggests a relatively shallow learning curve for LESS-DN. Objective To present a comparative analysis of peri-operative outcomes for >200 cases of conventional laparoscopic donor nephrectomy (LDN) and laparoendoscopic single site donor nephrectomy (LESS-DN). Patients and Methods From 2006 to 2011, 213 donor nephrectomies were performed by two surgeons (R.E.L and W.A.M.) at a tertiary transplant centre. The approach changed from conventional LDN to LESS-DN over the course of the series. The two approaches were compared retrospectively and evaluated for differences in peri-operative outcomes. Statistical significance was assessed using Student's t-test and chi-squared analysis. Results A total of 111 patients underwent LDN and 102 patients underwent LESS-DN. Total operating time was significantly longer in the LESS-DN group (206.1 vs 181.9 min, P < 0.001), but LESS-DN resulted in less intra-operative blood loss (61.5 mL vs 85.9 mL, P < 0.001) and shorter warm ischaemia times (4.4 vs 5.0 min, P = 0.01). There were no significant differences in analgesic requirements, subjective pain scores, length of hospital stay, postoperative graft function, or donor's postoperative glomerular filtration rate between the two approaches. Complication rates were low regardless of the approach, and there were no major complications (>grade II) in the LESS-DN group. Conclusions In experienced hands, LESS-DN results in peri-operative outcomes similar to those of conventional LDN without compromising donor safety, while providing a desirable cosmetic result. For surgeons familiar with LDN, transitioning to the LESS approach using this technique appears to have a relatively short learning curve.

Background IL-17A and IL-17F are pro-inflammatory cytokines which induce the expression of several cytokines, chemokines and matrix metalloproteinases (MMPs) in target cells. IL-17 cytokines have recently attracted huge interest due to their pathogenic role in diseases such as arthritis and inflammatory bowel disease although a role for IL-17 cytokines in myocardial infarction (MI) has not previously been described.

Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups.

Increasing evidence suggests a detrimental effect of donor-specific antibodies directed against the human leukocyte antigen (HLA)-A, -B, and -DR loci on renal allograft outcomes. Limited data exist on the impact of de novo HLA-DQ antibodies. Over a 3-year period, we prospectively monitored 347 renal transplant recipients without pre-transplant donor-specific antibodies for their development de novo . After 26 months of follow-up, 62 patients developed donor-specific antibodies, of which 48 had a HLA-DQ antibody either alone (33 patients) or in combination with an HLA-A, -B, or -DR antibody (15 patients). Only 14 patients developed a donor-specific HLA-A, -B, or -DR antibody without a HLA-DQ antibody present. Acute rejection occurred in 21% of the HLA-DQ–only patients, insignificant when compared with 11% of patients without donor-specific antibodies. At the last follow-up, the mean serum creatinine and the fraction of patients with proteinuria were significantly higher in those that developed only HLA-DQ than those without antibodies. The 3-year graft survival was significantly worse when HLA-DQ antibodies were combined with non-DQ antibodies (52%) compared with HLA-DQ alone, non-DQ antibodies alone, or no antibodies (92–94%). Thus, our prospective monitoring study found that donor-specific HLA-DQ antibodies were the most common type detected and these antibodies may contribute to inferior graft outcomes. Ongoing surveillance is necessary to determine the long-term outcome of patients developing HLA-DQ donor-specific antibodies.

Objectives To report our approach to the surgical management of vestibular schwannomas (VSs) and hearing rehabilitation in neurofibromatosis Type 2 (NF2). Design Retrospective cohort study. Setting Tertiary referral NF2 unit. Patients Between 1981 and 2011, seventy-five patients were managed in our NF2 unit, of which, 58 patients are under current review. Main outcome measures Patients who underwent VS excision were evaluated for tumor size, surgical approach, and outcomes of hearing and facial nerve function. All current patients were evaluated for NF2 mutation, hearing, and auditory implantation outcomes. Results Forty-four patients underwent resection of 50 VS in our unit, of which, 14% had facial neuroma excision and reinnervation during the same operation. At 12 months after surgery, facial nerve outcomes were House-Brackmann (HB) 1 in 33%, HB2 in 21%, and HB3 in 30%. Total VS resection was achieved in 78% of patients using a translabyrinthine approach. Seventy-two percent of the current patients have American Association of Otolaryngology-Head and Neck Surgery class A to C hearing (maximum speech discrimination score over 50%) in the better hearing ear, and a further 14% are full-time users of cochlear implants or auditory brainstem implants. The remaining patients have been assessed for auditory implantation. Conclusion By following a policy of treating VS in NF2 patients where tumor growth is observed, complete tumor resection can be achieved through a translabyrinthine approach while achieving comparable facial nerve outcomes to published series. We advocate proactive hearing rehabilitation in all patients with timely assessment for auditory implantation to maintain quality of life.

Previous studies have shown that the transcription factor signal transducer and activator of transcription 1 (STAT1) activation is increased in primary cardiac myocytes exposed to simulated ischaemia/reperfusion injury. This promotes apoptotic cell death by enhancing the expression of pro-apoptotic proteins. Autophagy has been demonstrated to play a cardioprotective role in the heart following myocardial infarction (MI). We therefore investigated the role of STAT1 in the intact heart subjected to MI and examined the contribution of autophagy in modulating the protective effect of STAT1 after MI injury. STAT1-deficient hearts had significantly smaller infarcts than wild-type hearts and this correlated with increased levels of autophagy shown by light chain 3 (LC3)-I/LC3-II conversion, and up-regulation of Atg12 and Beclin 1. Moreover, pre-treatment with the autophagy inhibitor 3-methyladenine reversed the cardioprotection observed in the STAT1-deficient hearts. These results reveal a new function of STAT1 in the control of autophagy and indicate a cross-talk between the cardioprotective versus the damaging effects of STAT1 in the intact heart exposed to MI injury.

All seven STAT proteins are expressed in the heart, and in this review we will focus on their contribution to cardiac physiology and to ischemic heart disease and its consequences. A substantial literature has focused on the roles of STAT1 and STAT3 in ischemic heart disease, where, at least in the acute phase, they appear to have a yin-yang relationship. STAT1 contributes to the loss of irreplaceable cardiac myocytes both by increasing apoptosis and by reducing cardioprotective autophagy. In contrast, STAT3 is cardioprotective, since STAT3-deficient mice have larger infarcts following ischemic injury, and a number of cardioprotective agents have been shown to act, at least partly, through STAT3 activation. STAT3 is also absolutely required for preconditioning-a process where periods of brief ischemia protect against a subsequent or previous prolonged ischemic episode. Prolonged activation of STAT3, however, is strongly implicated in the post-infarction remodeling of the heart which leads to heart failure, where, possibly together with STAT5, it augments activation of the renin-angiotensin system.

Beef and Beyond: Paying for Ecosystem Services on Western US Rangelands DOI:10.2458/azu_rangelands_v33i5_goldstein

Gainer SM, Patel SJ, Seethamraju H, Moore LW, Knight RJ, Gaber AO. Increased mortality of solid organ transplant recipients with H1N1 infection: a single center experience. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01443.x. © 2011 John Wiley & Sons A/S. Abstract: Immunosuppressed solid organ transplant recipients are included in the cohort at increased risk for complications of viral infections such as the newly encountered H1N1. A retrospective review was performed to collect data on patients hospitalized during a recent H1N1 epidemic. H1N1 was suspected based on symptoms and real-time reverse-transcriptase-polymerase-chain-reaction assay confirmed the diagnosis. From August through October of 2009, 89 patients were admitted to The Methodist Hospital, Houston, Texas, with H1N1. Eighteen were solid organ transplant recipients with an age range of 34–69 yr. This group included nine kidney, five lung, one kidney-pancreas, one liver, and two heart recipients. Severe cardiac or pulmonary comorbidities existed in over half of non-transplant patients, while only eight of these non-transplant patients were otherwise healthy. Eighty-nine percent of transplant patients presented with fever or chills, 72% with cough, and 56% with gastrointestinal distress. Symptoms were similar to non-transplant patients. All transplant patients were treated with oseltamivir. Two non-transplant patients and three transplant patients died. Thirty-day survival was 97% in non-transplant and 83% in transplant patients (p = 0.02). In the context of an initial epidemic of H1N1, infection was associated with increased risk of complications and mortality in solid organ transplant recipients.

Patel SJ, Knight RJ, Suki WN, Abdellatif A, Duhart BT, Krauss AG, Mannan S, Nezakatgoo N, Gaber AO. Rabbit antithymocyte induction and dosing in deceased donor renal transplant recipients over 60 yr of age. Clin Transplant 2011: 25: E250–E256. © 2011 John Wiley & Sons A/S. Abstract: Background: Antithymocyte globulin (rATG) is a commonly used induction agent in renal transplantation; however, data in older kidney recipients are limited. Methods: We reviewed charts of 301 deceased donor renal transplants who received a protocol consisting of 3–7 doses of rATG and triple maintenance therapy. Outcomes of patients >60 yr of age (n = 45) were compared to those aged 18–59 yr (n = 256). Results: Older recipients had more diabetics, were more likely to receive expanded criteria donor kidneys (p 60 received less cumulative rATG (4.6 vs. 5.1 mg/kg; p 60 group (2% vs. 16%, p 60 group at three yr was lower (80% vs. 95%; p = 0.02). Specifically, patients >60 with delayed graft function and rATG cumulative dosing >6 mg/kg had a survival of 6 mg/kg. These data suggest that when used, lower cumulative dosages of rATG are preferable in the older recipient.

The Rocky Mountain West is experiencing rapid land use change in the form of residential development. Public land managers, like the U.S. Forest Service, Bureau of Land Management, and National Park Service are increasingly concerned with ecological and management implications of private land use adjacent to public lands. Using fine-grain land use data, collected from high resolution aerial photographs, we quantify human land use composition, patterns, and trends at the interface of public and private land in the Southern Rocky Mountain Ecoregion (SRE) of Colorado. We developed two metrics for assessing land use impacts. The first quantifies the amount of land cover modified (HM c ) by human land use and the second estimates the amount of wildlife habitat that is functionally modified (HM fd ). In 2005, we estimate that human land use modifies 8% of the total land cover in the Colorado SRE and that 13% of the study area was functionally modified. Agriculture had the greatest impact in terms of area of modified land cover (282,305 ha). Residential (exurban) land use had a smaller footprint (HM c ) but the close proximity to public lands, dispersed spatial pattern (high HM fd ), and rapid increase in rural and exurban housing density observed in the SRE have important implications. This research demonstrates how fine scale land cover data can be used to examine land use pattern and composition as well as track land use change.

Background Fever occurs frequently early after pancreas transplant, however, the exact cause is often undetermined. Limited data are available on pancreas recipients experiencing unexplained, noninfectious fever. This study aims to characterize unexplained fever (UF) in pancreas recipients and its effect on patient and graft outcomes. Methods We performed a retrospective cohort study of UF among consecutive pancreas or simultaneous pancreas-kidney transplant recipients from 1 January 2011 to 31 August 2015. Classification of UF was based on the absence of positive cultures, radiologic findings, and other diagnostic features of infection or rejection. Results Twenty-three of 92 (25%) patients experienced UF. The UF episode first occurred at a mean of 31 ± 17 days post-transplant and accounted for 34 admissions with an average length of stay of 5.1 ± 3.4 days. Intravenous corticosteroid was administered following confirmation of negative diagnostic tests in 77% of patients, with fever resolution occurring in all. No differences were seen in rates of biopsy-proven rejection, graft loss, death, or documented infections compared to UF-free patients during the first-year post-transplant. Conclusion UF is a common cause for readmission following pancreas transplantation. While the etiology of UF remains difficult to identify, UF occurrence was not associated with adverse outcomes during the first-year post-transplant.

Renal transplantation remains the definitive treatment for end-stage renal disease (ESRD). The shorter renal vein in right donor nephrectomies is associated with higher incidence of technical failure. We present here our experience with autologous internal jugular vein (IJV) conduits to facilitate living-donor transplants. Six patients underwent right, living-donor kidney transplant with simultaneous IJV harvest over a 1-year period. All had bilateral jugular duplex scans preoperatively and were placed on aspirin 81 mg postoperatively. Patient demographics, comorbidities, and laboratories were retrospectively queried. Postoperative follow-up and examination were performed per institutional protocol. The mean age and BMI were 51 ± 4.6 years and 30 ± 1.4 kg/m2 , respectively. An average 4.5 ± 0.5 cm of IJV was taken, and anastomosed exsitu, end to end to the renal vein. One patient developed a perinephric hematoma requiring reexploration and another expired during follow-up from septic shock of unknown etiology; there were no harvest site complications or deep vein thrombosis. All had immediate and stable graft function at 3.8 ± 1.7 (range: 0.7-11.3) months follow-up. Mean serum creatinine and estimated glomerular filtration rate were 1.3 ± 0.1 mg/dL and 55 ± 2.4 mL/min/1.73 m2 , respectively. Internal jugular vein extension of short right renal veins for kidney transplant is a viable technique for ESRD patients with promising results.

Sirolimus is an antiproliferative immunosuppressive agent that inhibits the mammalian target of rapamycin. It is highly effective in preventing acute renal allograft rejection and can be used with either calcineurin inhibitors, antimetabolites or corticosteroids. Early studies in renal transplantation have provided insight into optimal dosing strategies of sirolimus and of concomitant immunosuppressive agents. Familiarity with the adverse effect profile of sirolimus and pharmacokinetic and dynamic interactions with other immunosuppressive agents allows for earlier recognition and better management of sirolimus-related complications. The role of sirolimus in preserving long-term renal function, post-transplant malignancies and in prevention of atherosclerosis is currently being considered.

Of 25 simultaneous pancreas-kidney transplant (SPK) recipients treated with thymoglobulin induction, sirolimus and reduced-dose cyclosporine (CsA), 18 low-immune responders (non-African-Americans, PRA < 30%) were withdrawn from prednisone on post-transplant day 5, whereas seven high-immune responders continued on prednisone. Most high- and low-immune responder recipients were converted from CsA to mycophenolic acid (MPA) at six months post-transplantation. At a mean follow-up of 28 +/- 10 months, two pancreas grafts were lost to pancreatitis. There were no patient or kidney graft losses, but one acute rejection episode. At 28 +/- 11 months, all 18 low-responder recipients remain steroid-free. Twenty recipients (14 low and six high-immune responders) were converted from CsA to MPA. During conversion, immune response was monitored by Flow-PRA and T-cell stimulation (Cylex) assays. Nineteen of 20 recipients displayed a post-conversion PRA of 0%, whereas one highly sensitized patient expressed a post-conversion PRA of 67%. Fifty-eight percent of individual T-cell stimulation scores were in the hypo-responsive range. Twelve of 18 low-immune responders are both steroid and CsA-free at a mean follow-up of 17 +/- 13 months, whereas five of seven high-immune responders remain CsA-free at a mean follow-up of 11 +/- 10 months. These data suggest that thymoglobulin induction with combined sirolimus and CsA maintenance therapy permits immunosuppression minimization in selected SPK recipients.

The super boiler was developed to reduce emissions and increase efficiency, thus lessening the environmental impact of steam generation. It achieves high efficiency by two approaches: a staged combustion technique which allows lower excess air in combustion, and a novel heat recovery system that recovers both sensible and latent heat from the flue gas stream as well as the water vapor itself. At the current stage of development, up to 94 percent fuel-to-steam efficiency on a higher heating value (HHV) basis can be achieved. The super boiler has the potential to save U.S. industry $4 billion annually in fuel and facility costs while preventing over 140,000 tons of NOx and 20 million tons of greenhouse gases per year. A 300-horsepower (10,000-lb/h steam) boiler is being demonstrated at a manufacturing site in Alabama, and another 300-horsepower boiler field demonstration is scheduled to begin in November, 2007, at a food processing site in California.