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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.

The p53 family transcriptional factor p73 plays a pivotal role in development. Ablation of p73 results in severe neurodevelopmental defects, chronic infections, inflammation and infertility. In addition to this, Trp73(−\-) mice display severe alteration in the ciliated epithelial lining and the full-length N-terminal isoform TAp73 has been implicated in the control of multiciliogenesis transcriptional program. With our recently generated Trp73(Δ13/Δ13) mouse model, we interrogate the physiological role of p73 C-terminal isoforms in vivo. Trp73(Δ13/Δ13) mice lack exon 13 in Trp73 gene, producing an ectopic switch from the C-terminal isoforms p73α to p73β. Trp73(Δ13/Δ13) mice show a pattern of expression of TAp73 comparable to the wild-type littermates, indicating that the α to β switch does not significantly alter the expression of the gene in this cell type. Moreover, Trp73(Δ13/Δ13) do not display any significant alteration in the airway ciliated epithelium, suggesting that in this context p73β can fully substitute the function of the longer isoform p73α. Similarly, Trp73(Δ13/Δ13) ciliated epithelium of the brain ependyma also does appear defective. In this district however expression of TAp73 is not detectable, indicating that expression of the gene might be compensated by alternative mechanisms. Overall our work indicates that C-terminus p73 is dispensable for the multiciliogenesis program and suggests a possible tissue-specific effect of p73 alternative splicing.

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.

Authors observed three identity gaps (personal-relational, personal-enacted, and enacted-relational) as predictors of communication satisfaction and two identity gaps (personal-enacted and enacted-...

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

Breast cancer is the second leading cause of cancer-related deaths among women, largely due to the progression of a significant fraction of primary tumours to the metastatic stage. Here, we show that zinc-finger protein 750 (ZNF750) opposes the migration and invasion of breast cancer cells by repressing a prometastatic transcriptional programme, which includes genes involved in focal adhesion and extracellular matrix interactions, such as LAMB3 and CTNNAL1. Mechanistically, ZNF750 recruits the epigenetic modifiers KDM1A and HDAC1 to the promoter regions of LAMB3 and CTNNAL1, influencing histone marks and transactivating these genomic sites. Gene expression analysis in cancer patient datasets indicated that ZNF750 and its targets were negative prognostic factors in breast cancer. Together, our findings shed light on the molecular mechanism by which ZNF750 regulates cell migration and invasion, suggesting a role in breast cancer metastasis.

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.

p73 is a transcription factor belonging to the p53 tumour suppressor family. p73−/− mice exhibit a range of phenotypes including neurological, reproductive and inflammatory defects. Although the role of p73 in the control of genomic stability explains part of these phenotypes, a clear mechanism of how p73 participates in the inflammatory response is still elusive. Interleukin-1β (IL-1β) has a crucial role in mediating the inflammatory response. Because of its high potency to induce inflammation, the activation and secretion of IL-1β is tightly regulated by large protein complexes, named inflammasomes. Inflammasomes regulate activation of proinflammatory caspase-1, which in turn proteolytically processes its substrates, including pro-IL-1β. Caspase-1 gene transcription is strongly activated by p53 protein family members including p73. Here, we have addressed whether p73 might be directly involved in IL-1β regulation and therefore in the control of the inflammatory response. Our results show that TAp73β upregulates pro-IL-1β mRNA and processed IL-1β protein. In addition, analysis of breast and lung cancer patient cohorts demonstrated that interaction between p73 and IL-1β predicts a negative survival outcome in these human cancers., Highlights • The p53 family member p73 controls a wide a range of biological processes required for its tumour suppressor functions. • p73 regulates IL-1β expression, thus potentially affecting inflammasomes and inflammatory response. • p73/IL-1β axis correlates with poor prognosis in lung and breast cancer.

The most important function of the epidermis is to form a barrier against the environment by means of several layers of terminally differentiated, dead keratinocytes, the cornified envelope (CE). CEs consist of keratins enclosed within an insoluble amalgam of proteins and lipids. Transglutaminase enzymes catalyse the formation of characteristic crosslinks between structural proteins to form the protein part of the CE. Another form of cell death, that is, apoptosis, which has a completely different molecular mechanism and physiological significance, also occurs in the skin. Defects of apoptosis are related to the development of cancer, whereas CE abnormalities are associated with barrier abnormalities and ichthyosis. Key concepts: Keratinocyte apoptosis (occurring in basal layer) is an active and rapid, energy-dependent, gene-directed biochemical pathway of defensive cell death that does not require de novo protein synthesis and preserves plasma membrane. Cornification, the keratinocyte differentiation programme (occurring in upper layer), is a slow, coordinated process in space and time, which allows the formation of a layer of dead cells (corneocytes) to create a physical barrier for the skin. The stratum corneum is composed of tightly attached corneocytes with mostly keratin intermediate filaments (KIFs) embedded into a filaggrin matrix. The structural proteins of the CE, including involucrin, loricrin, trichohyalin and the class of small proline-rich proteins (SPRs), constitute about 7–10% of the mass of the epidermis. These structural proteins together with lipids (ceramides) form the complete barrier. Transglutaminase are Ca2+-dependent enzymes that catalyse the formation of Ne-(γ-glutamyl)lysine bonds between CE structural proteins to confer the characteristic resistance and insolubility to the skin. The junctions responsible for intercellular adhesion and for cohesion of the stratum corneum of the epidermis are of two types: (1) the adherence junctions (connecting the actin cytoskeleton of neighbouring cells) and (2) desmosomes (connecting the keratin filament cytoskeleton of adjacent cells). Proteases are involved in at least three processes in skin differentiation. First, certain cornified envelope precursors require proteolytic processing before cornified envelope formation occurs. Second, the loss of nuclei and mitochondria requires proteolytic processing. Third, desquamation requires proteolysis of the corneodesmosomes. Keywords: apoptosis; cornified envelope; cell death; transglutaminase; keratinocyte differentiation; cornification; keratinization

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.

Significance High-risk neuroblastomas (NBs) show undifferentiated/poorly differentiated morphology as a distinctive feature. We have identified the transcription factor ZNF281 as a factor that can counteract the neuronal differentiation of primary neurons in culture and NB cells. The expression of ZNF281 is inhibited by TAp73 and promoted by MYCN. In turn, ZNF281 inhibits the expression of GDNF and NRP2, two proteins associated with neuronal differentiation. In patients with NB, the expression of ZNF281 is higher in high-risk patients and is associated with worse prognosis. Understanding the molecular mechanisms that regulate neuronal differentiation is relevant for the identification of defects in this process that underlie the development of tumors such as NB, in which an aberrant differentiation arrest has occurred., Derangement of cellular differentiation because of mutation or inappropriate expression of specific genes is a common feature in tumors. Here, we show that the expression of ZNF281, a zinc finger factor involved in several cellular processes, decreases during terminal differentiation of murine cortical neurons and in retinoic acid-induced differentiation of neuroblastoma (NB) cells. The ectopic expression of ZNF281 inhibits the neuronal differentiation of murine cortical neurons and NB cells, whereas its silencing causes the opposite effect. Furthermore, TAp73 inhibits the expression of ZNF281 through miR34a. Conversely, MYCN promotes the expression of ZNF281 at least in part by inhibiting miR34a. These findings imply a functional network that includes p73, MYCN, and ZNF281 in NB cells, where ZNF281 acts by negatively affecting neuronal differentiation. Array analysis of NB cells silenced for ZNF281 expression identified GDNF and NRP2 as two transcriptional targets inhibited by ZNF281. Binding of ZNF281 to the promoters of these genes suggests a direct mechanism of repression. Bioinformatic analysis of NB datasets indicates that ZNF281 expression is higher in aggressive, undifferentiated stage 4 than in localized stage 1 tumors supporting a central role of ZNF281 in affecting the differentiation of NB. Furthermore, patients with NB with high expression of ZNF281 have a poor clinical outcome compared with low-expressors. These observations suggest that ZNF281 is a controller of neuronal differentiation that should be evaluated as a prognostic marker in NB.

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.

Glioblastoma Multiforme is one of the most highly metastatic cancers and constitutes 70% of all gliomas. Despite aggressive treatments these tumours have an exceptionally bad prognosis, mainly due to therapy resistance and tumour recurrence. Here we show that the transcription factor p73 confers an invasive phenotype by directly activating expression of POSTN (periostin, HGNC:16953) in glioblastoma cells. Knock down of endogenous p73 reduces invasiveness and chemo-resistance, and promotes differentiation in vitro. Using chromatin immunoprecipitation and reporter assays we demonstrate that POSTN, an integrin binding protein that has recently been shown to play a major role in metastasis, is a transcriptional target of TAp73. We further show that POSTN overexpression is sufficient to rescue the invasive phenotype of glioblastoma cells after p73 knock down. Additionally, bioinformatics analysis revealed that an intact p73/ POSTN axis, where POSTN and p73 expression is correlated, predicts bad prognosis in several cancer types. Taken together, our results support a novel role of TAp73 in controlling glioblastoma cell invasion by regulating the expression of the matricellular protein POSTN.

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.

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ?accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. "Regulated cell death" (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Nomenclature Committee on Cell Death. Equipe 11 Apoptose, Cancer et Immunité. Centre de Recherche des Cordeliers; Francia

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

$('.header-date').hide();$('#titleAuthors').hide(); $('#abstractHeader').hide(); Richard A. Knight 1 , Mikhail Gostev 2 , Sergei Ilisavskii 2 , Anne E. Willis 1 , Gerry Melino 1 , 2 , 3 , Alexey V. Antonov 1 1 Medical Research Council Toxicology Unit, Leicester LE1 9HN, UK 2 Molecular Pharmacology Laboratory, Technological University, St-Petersburg, Russia. 3 Department of Experimental Medicine & Surgery, University of Rome “Tor Vergata”, 00133 Rome, Italy Corresponding Author: Alexey V. Antonov, e-mail: aa668@le.ac.uk Received : November 12, 2013 Accepted : December 12, 2013 Published : January 21, 2014 Abstract Understanding therapeutic mechanisms of drug anticancer cytotoxicity represents a key challenge in preclinical testing. Here we have performed a meta-analysis of publicly available tumor cell line growth inhibition assays (~ 70 assays from 6 independent experimental groups covering ~ 500 000 molecules) with the primary goal of understanding molecular therapeutic mechanisms of cancer cytotoxicity. To implement this we have collected currently available information on protein targets for molecules that were tested in the assays. We used a statistical methodology to identify protein targets overrepresented among molecules exhibiting cancer cytotoxicity with the particular focus of identifying overrepresented patterns consisting of several proteins (i.e. proteins “A” and “B” and “C”). Our analysis demonstrates that targeting individual proteins can result in a significant increase (up to 50-fold) of the observed odds for a molecule to be an efficient inhibitor of tumour cell line growth. However, further insight into potential molecular mechanisms reveals a multi-target mode of action: targeting a pattern of several proteins drastically increases the observed odds (up to 500-fold) for a molecule to be tumour cytotoxic. In contrast, molecules targeting only one protein but not targeting an additional set of proteins tend to be nontoxic. Our findings support a poly-pharmacology drug discovery paradigm, demonstrating that anticancer cytotoxicity is a product, in most cases, of multi-target mode of drug action.

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.

Cells mount a transcriptional anti-oxidative stress (AOS) response program to scavenge reactive oxygen species (ROS) that arise from chemical, physical, and metabolic challenges. This protective program has been shown to reduce carcinogenesis triggered by chemical and physical insults. However, it is also hijacked by established cancers to thrive and proliferate within the hostile tumor microenvironment and to gain resistance against chemo- and radiotherapies. Therefore, targeting the AOS response proteins that are exploited by cancer cells is an attractive therapeutic strategy. In order to identify the AOS genes that are suspected to support cancer progression and resistance, we analyzed the expression patterns of 285 genes annotated for being involved in oxidative stress in 994 tumors and 353 normal tissues. Thereby we identified a signature of 116 genes that are highly overexpressed in multiple cancers while being only minimally expressed in normal tissues. To establish which of these genes are more likely to functionally drive cancer resistance and progression, we further identified those whose overexpression correlates with negative patient outcome in breast and lung carcinoma. Gene-set enrichment, gene ontology, network, and pathway analyses revealed that members of the thioredoxin and glutathione pathways are prominent components of this oncogenic signature and that activation of these pathways is common feature of many cancer entities. Interestingly, a large fraction of these AOS genes are downstream targets of the transcription factors NRF2, NF-kappaB, and FOXM1, and rely on NADPH for their enzymatic activities highlighting promising drug targets. We discuss these findings and propose therapeutic strategies that may be applied to overcome cancer resistance.

The amino acid Glutamine is converted into Glutamate by a deamidation reaction catalyzed by the enzyme Glutaminase (GLS). Two isoforms of this enzyme have been described, and the GLS2 isoform is regulated by the tumor suppressor gene p53. Here, we show that the p53 family member TAp73 also drives the expression of GLS2. Specifically, we demonstrate that TAp73 regulates GLS2 during retinoic acid-induced terminal neuronal differentiation of neuroblastoma cells, and overexpression or inhibition of GLS2 modulates neuronal differentiation and intracellular levels of ATP. Moreover, inhibition of GLS activity, by removing Glutamine from the growth medium, impairs in vitro differentiation of cortical neurons. Finally, expression of GLS2 increases during mouse cerebellar development. Although, p73 is dispensable for the in vivo expression of GLS2, TAp73 loss affects GABA and Glutamate levels in cortical neurons. Together, these findings suggest a role for GLS2 acting, at least in part, downstream of p73 in neuronal differentiation and highlight a possible role of p73 in regulating neurotransmitter synthesis.

Significance p73 is a tumor suppressor protein that also plays a central role in brain development. But how p73 modulates neurite outgrowth and neurite arborization is not clear. Neurotrophins are small molecules, which send signals between cells. Neurotrophins can induce cells to either apoptosis or survival. We show that TAp73 is a transcriptional activator of the p75 neurotrophin receptor (p75 NTR ). TAp73 knockout mice have reduced levels of p75 NTR and show peripheral nerve defect, including reduced myelin thickness and thermal sensitivity. p75 NTR is expressed most strongly in the peripheral nerve, where it is important for nerve development. Relatively limited information exists on p75 NTR gene regulation; by linking the p53/p73 gene family to p75 NTR transcription, we introduce possibly controversial mechanisms of regulation.

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.