Using blood transcriptome analysis for Alzheimer's disease diagnosis and patient stratification.

INTRODUCTION: Blood protein biomarkers demonstrate potential for Alzheimer's disease (AD) diagnosis. Limited studies examine the molecular changes in AD blood cells. METHODS: Bulk RNA-sequencing of blood cells was performed on AD patients of Chinese descent (n = 214 and 26 in the discovery and validation cohorts, respectively) with normal controls (n = 208 and 38 in the discovery and validation cohorts, respectively). Weighted gene co-expression network analysis (WGCNA) and deconvolution analysis identified AD-associated gene modules and blood cell types. Regression and unsupervised clustering analysis identified AD-associated genes, gene modules, cell types, and established AD classification models. RESULTS: WGCNA on differentially expressed genes revealed 15 gene modules, with 6 accurately classifying AD (areas under the receiver operating characteristics curve [auROCs] > 0.90). These modules stratified AD patients into subgroups with distinct disease states. Cell-type deconvolution analysis identified specific blood cell types potentially associated with AD pathogenesis. DISCUSSION: This study highlights the potential of blood transcriptome for AD diagnosis, patient stratification, and mechanistic studies. HIGHLIGHTS: We comprehensively analyze the blood transcriptomes of a well-characterized Alzheimer's disease cohort to identify genes, gene modules, pathways, and specific blood cells associated with the disease. Blood transcriptome analysis accurately classifies and stratifies patients with Alzheimer's disease, with some gene modules achieving classification accuracy comparable to that of the plasma ATN biomarkers. Immune-associated pathways and immune cells, such as neutrophils, have potential roles in the pathogenesis and progression of Alzheimer's disease.

A blood-based multi-pathway biomarker assay for early detection and staging of Alzheimer's disease across ethnic groups.

INTRODUCTION: Existing blood-based biomarkers for Alzheimer's disease (AD) mainly focus on its pathological features. However, studies on blood-based biomarkers associated with other biological processes for a comprehensive evaluation of AD status are limited. METHODS: We developed a blood-based, multiplex biomarker assay for AD that measures the levels of 21 proteins involved in multiple biological pathways. We evaluated the assay's performance for classifying AD and indicating AD-related endophenotypes in three independent cohorts from Chinese or European-descent populations. RESULTS: The 21-protein assay accurately classified AD (area under the receiver operating characteristic curve [AUC] = 0.9407 to 0.9867) and mild cognitive impairment (MCI; AUC = 0.8434 to 0.8945) while also indicating brain amyloid pathology. Moreover, the assay simultaneously evaluated the changes of five biological processes in individuals and revealed the ethnic-specific dysregulations of biological processes upon AD progression. DISCUSSION: This study demonstrated the utility of a blood-based, multi-pathway biomarker assay for early screening and staging of AD, providing insights for patient stratification and precision medicine. HIGHLIGHTS: The authors developed a blood-based biomarker assay for Alzheimer's disease. The 21-protein assay classifies AD/MCI and indicates brain amyloid pathology. The 21-protein assay can simultaneously assess activities of five biological processes. Ethnic-specific dysregulations of biological processes in AD were revealed.

The gut microbiome: an overview of current trends and risks for paediatric populations.

PURPOSE OF REVIEW: Gut health is an increasingly popular topic of discussion among scientists and the general population alike. As interest surrounding the gut microbiome grows, the accessibility to misinformation and unfounded gut health trends to youth is likely to emerge as a public health concern. The purpose of this review is to provide paediatricians with current information about the gut microbiome, as well as explanations and possible risks of the multitude of gut health trends that adolescents may be exposed to. RECENT FINDINGS: The gut microbiome is implicated in overall health by playing roles in digestion, immunity and mental health. Novel microbiome-related therapies, such as faecal microbiota transplants, and the gut-brain link show the therapeutic potential of the gut microbiome. However, unproven dietary fads and trends on social media are rampant as well, such as ginger juice shots. In addition, paediatric supplements meant to target gut health are unregulated, yet are highly marketed. Improperly applying these trends and diets may result in risks of malnutrition and body image issues for impressionable children. SUMMARY: Increased familiarity regarding the types of gut health trends and diets among young people will allow paediatricians to more effectively advise their patients about potential risks and good gut health practices. Paediatricians and caregivers serve as role models and educators with regard to children's perceptions and management of their gut and overall health.

Clinical characteristics and outcomes of PTLD following intestinal transplantation.

Post-transplant lymphoproliferative disease (PTLD) has the highest incidence following intestinal transplantation (ITx). Our center has seen a recent increase in PTLD. Our aim was to review a single-center PTLD experience with a focus on clinical characteristics and outcomes. We completed a retrospective review of biopsy-proven PTLD cases using a prospectively maintained database of 115 ITx recipients transplanted between 1991 and 2014. Nineteen (17%) ITx recipients developed 25 PTLD cases during a median follow-up time of 6.4 (1.6-14.6) years. The incidence of early PTLD was 6% (n = 7). There was a trend toward increased risk of PTLD in children compared with adults (P = .11) and a significantly increased risk of PTLD in re-ITx compared with primary ITx recipients (P = .03). Most PTLD cases were diagnosed between 2010 and 2014 (n = 14). All early PTLD cases were EBV+ on in situ hybridization. Overall graft and patient survival are 68% and 74%, respectively. Second episodes of PTLD were diagnosed in 43% of surviving pediatric patients. Our program has a low incidence of early PTLD with overall excellent graft and patient survival following diagnosis. However, we have also seen a rising incidence of late PTLD. The cause of the increase is unknown as no major changes in immunosuppression protocols have occurred since 1999.

Obliterative portal venopathy: A histopathologic finding associated with chronic antibody-mediated rejection in pediatric liver allografts.

The significance of post-transplant HLA DSA and chronic AMR in LT is an emerging field of study. Although OPV has previously been described as a histopathologic finding in DSA-positive adult LT recipients, it was not included in the recent Banff criteria for chronic AMR. Our aim was to describe the association between OPV and chronic AMR in pediatric LT recipients. A retrospective review of 67 liver biopsies performed between November 2014 and April 2016 in 45 pediatric LT recipients identified four patients with OPV. Clinical status, liver biochemistry, the presence of DSA, and available non-HLA antibody testing, as well as histopathologic features of chronic AMR, were assessed. All four patients with OPV had class II DSA and histopathologic features of chronic AMR based on the Banff criteria. Two patients were noted to have non-HLA antibodies. Three patients are undergoing treatment with IVIG but have persistent DSA. Two patients have graft failure and are awaiting retransplantation. In conclusion, OPV is a histopathologic finding associated with chronic AMR in pediatric LT recipients. Further studies are needed to elucidate whether OPV is reversible and/or amenable to medical therapy.

Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer's disease.

Alzheimer's disease (AD), characterized by cognitive decline, has emerged as a disease of synaptic failure. The present study reveals an unanticipated role of erythropoietin-producing hepatocellular A4 (EphA4) in mediating hippocampal synaptic dysfunctions in AD and demonstrates that blockade of the ligand-binding domain of EphA4 reverses synaptic impairment in AD mouse models. Enhanced EphA4 signaling was observed in the hippocampus of amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mouse model of AD, whereas soluble amyloid-ß oligomers (Aß), which contribute to synaptic loss in AD, induced EphA4 activation in rat hippocampal slices. EphA4 depletion in the CA1 region or interference with EphA4 function reversed the suppression of hippocampal long-term potentiation in APP/PS1 transgenic mice, suggesting that the postsynaptic EphA4 is responsible for mediating synaptic plasticity impairment in AD. Importantly, we identified a small-molecule rhynchophylline as a novel EphA4 inhibitor based on molecular docking studies. Rhynchophylline effectively blocked the EphA4-dependent signaling in hippocampal neurons, and oral administration of rhynchophylline reduced the EphA4 activity effectively in the hippocampus of APP/PS1 transgenic mice. More importantly, rhynchophylline administration restored the impaired long-term potentiation in transgenic mouse models of AD. These findings reveal a previously unidentified role of EphA4 in mediating AD-associated synaptic dysfunctions, suggesting that it is a new therapeutic target for this disease.

The impact of antibodies and virtual crossmatching on intestinal transplant outcomes.

PURPOSE OF REVIEW: Sensitization to human leukocyte antigens (HLAs) limits access to potential donors and contributes to inferior graft survival after transplantation. In this article, we will review the effects of HLA-specific antibodies on intestinal transplant outcomes, and discuss considerations in the monitoring and treatment of anti-HLA antibodies. RECENT FINDINGS: Only a handful of studies has investigated the effects of donor-specific anti-HLA antibodies (DSAs) on intestinal allograft outcomes. Most have reported associations between DSA presence and rejection-related graft failure. The evolution of antibody detection methods and improvements in crossmatch testing have allowed for a systematic approach to the broadly sensitized transplant candidate, and facilitated the identification of compatible organ donors. The virtual crossmatch can be used to aid in organ allocation and avoid transplantation across preformed DSA. However, much remains unknown about the mechanisms of antibody-mediated injury in the intestinal graft, and the effectiveness of current therapies against DSA has yet to be established. SUMMARY: On the basis of available data, we will provide recommendations for the testing and management of DSA among intestinal transplant recipients. The precise management protocol should be tailored to each individual based on immunologic risk as well as clinical status.

Neuroprotective effect of a novel Chinese herbal decoction on cultured neurons and cerebral ischemic rats.

BACKGROUND: Historically, traditional Chinese medicine has been widely used to treat stroke. Based on the theory of Chinese medicine and the modern pharmacological knowledge of herbal medicines, we have designed a neuroprotective formula called Post-Stroke Rehabilitation (PSR), comprising seven herbs - Astragalus membranaceus (Fisch.) Bunge, Salvia miltiorrhiza Bunge, Paeonia lactiflora Pall., Cassia obtusifolia L., Ligusticum chuanxiong Hort., Angelica sinensis (Oliv.) Diels, and Glycyrrhiza uralensis Fisch. We aim to examine the neuroprotective activity of PSR in vitro and in vivo, and to explore the underlying molecular mechanisms, to better understand its therapeutic effect and to further optimize its efficacy. METHODS: PSR extract or vehicle was applied to primary rat neurons to examine their survival effects against N-methyl-D-aspartate (NMDA)-elicited excitotoxicity. Whole-cell patch-clamp recording was conducted to examine the NMDA-induced current in the presence of PSR. ERK- and CREB-activation were revealed by western blot analysis. Furthermore, PSR was tested for CRE promoter activation in neurons transfected with a luciferase reporter. The protective effect of PSR was then studied in the rat middle cerebral artery occlusion (MCAO) model. MCAO rats were either treated with PSR extract or vehicle, and their neurobehavioral deficit and cerebral infarct were evaluated. Statistical differences were analyzed by ANOVA or t-test. RESULTS: PSR prominently reduced the death of cultured neurons caused by NMDA excitotoxicity in a dose-dependent manner, indicating its neuroprotective property. Furthermore, PSR significantly reduced NMDA-evoked current reversibly and activated phosphorylation of ERK and CREB with distinct time courses, with the latter's kinetics slower. PSR also triggered CRE-promoter activity as revealed by the increased expression of luciferase reporter in transfected neurons. PSR effectively reduced cerebral infarct and deficit in neurological behavior in MCAO rats when PSR decoction was administered starting either 6 days before or 6 h after onset of ischemia. CONCLUSIONS: PSR is neuroprotective both in vitro and in vivo - it protects cultured neurons against NMDA excitotoxicity, and effectively reduces ischemic injury and neurobehavioral deficit in MCAO rats in both the pre- and post-treatment regimens. The underlying neuroprotective mechanisms may involve inhibition of NMDA receptor current and activation of ERK and CREB. This study provides important preclinical data necessary for the further development of PSR for stroke treatment.

Melanocortin-4 receptor regulates hippocampal synaptic plasticity through a protein kinase A-dependent mechanism.

Learning and memory require orchestrated regulation of both structural and functional synaptic plasticity in the hippocampus. While a neuropeptide alpha-melanocyte-stimulating hormone, α-MSH, has been implicated in memory acquisition and retention, the functional role of its cognate receptor, melanocortin-4 receptor (MC4R), in hippocampal-dependent synaptic plasticity has not been explored. In this study, we report that activation of MC4R enhances synaptic plasticity through the regulation of dendritic spine morphology and abundance of AMPA receptors. We show that activation of postsynaptic MC4R increases the number of mature dendritic spines and enhances surface expression of AMPA receptor subunit GluA1, resulting in synaptic accumulation of GluA1-containing AMPA receptors. Moreover, MC4R stimulates surface GluA1 trafficking through phosphorylation of GluA1 at Ser845 in a Gα(s)-cAMP/PKA-dependent manner. Blockade of protein kinase A (PKA) signaling abolishes the MC4R-mediated enhancement of neurotransmission and hippocampal long-term potentiation. Importantly, in vivo application of MC4R agonists increases LTP in the mouse hippocampal CA1 region. These findings reveal that MC4R in the hippocampus plays a critical role in the regulation of structural and functional plasticity.

Renal allograft outcomes following early corticosteroid withdrawal in Hispanic transplant recipients.

BACKGROUND: Renal transplant outcomes in Hispanics have been conflicting regarding acute rejection (AR) and allograft survival. Additionally, the feasibility of early corticosteroid withdrawal (ECW) regimens among Hispanics has not been adequately addressed. The purpose of this study is to report outcomes following ECW among Hispanic renal transplant recipients. METHODS: We retrospectively reviewed 498 consecutive renal transplants performed at our institution between July 2005 and October 2007, including 73 Hispanic and 146 white recipients who had ECW (median follow-up 49 months). Demographics, transplant data, and outcomes of Hispanic and white recipients (WR) were analyzed. RESULTS: Hispanics had a higher incidence of diabetes mellitus and hypertension (p = 0.007), a higher proportion of blood type O (p = 0.006), and a higher serum panel reactive antibody at the time of transplantation (p = 0.02) compared with WR. Additionally, Hispanics were on dialysis longer than WR prior to transplantation (p = 0.03). Nevertheless, the incidence of AR, patient, and graft survival rates was similar (p > 0.05) between Hispanics and WR. Ethnicity was not an independent predictor of inferior patient and graft outcomes in multivariate analyses. CONCLUSION: Our single-center experience indicates that ECW can be performed in Hispanic renal transplant recipients, with patient and allograft outcomes comparable with those observed in WR.

Neonatal Hypocalcemia: Common, Uncommon, and Rare Etiologies.

Calcium homeostasis in the neonatal period is a reflection of the transition from placental regulation to hormonal maturation in the newborn. Hypocalcemia occurring within the first 72 hours after birth, termed early-onset hypocalcemia (EOH), is more common and often asymptomatic. Hypocalcemia occurring beyond 72 hours of age is termed late-onset hypocalcemia (LOH). LOH is less common than EOH, and affected patients are more likely to be symptomatic. To prevent and treat hypocalcemia in the newborn, neonatal clinicians should be familiar with the common, uncommon, and rare etiologies of EOH and LOH, as summarized in this review.

Cecal diverticulitis as a continuing diagnostic and management dilemma: a report of two cases in children.

Right-sided diverticulitis remains an exceedingly rare condition in the pediatric population. The clinical presentation mimics acute appendicitis, and the correct diagnosis is often difficult to make prior to operative exploration. We report two cases of cecal diverticulitis, and discuss the diagnosis and management of this disease, with a review of the literature.

Integrated analysis of tumor samples sheds light on tumor heterogeneity.

The heterogeneity of tumor samples is a major challenge in the analysis of high-throughput profiling of tumor biopsies and cell lines. The measured aggregate signals of multigenerational progenies often represent an average of several tumor subclones with varying genomic aberrations and different gene expression levels. The goal of the present study was to integrate copy number analyses from SNP-arrays and karyotyping, gene expression profiling, and pathway analyses to detect heterogeneity, identify driver mutations, and explore possible mechanisms of tumor evolution. We showed the heterogeneity of the studied samples, characterized the global copy number alteration profiles, and identified genes whose copy number status and expression levels were aberrant. In particular, we identified a recurrent association between two BRAF(V600E) and BRAF(V600K) mutations and changes in DKK1 gene expression levels, which might indicate an association between the BRAF and WNT pathways. These findings show that the integrated approaches used in the present study can robustly address the challenging issue of tumor heterogeneity in high-throughput profiling.

Evaluation of intraperitoneal vancomycin in peritoneal dialysis-associated peritonitis.

BACKGROUND: Intraperitoneal (IP) vancomycin is recommended as one of the treatment options for gram-positive coverage in the management of peritoneal dialysis (PD)-associated peritonitis. There is a lack of literature supporting the optimal dose and approach to vancomycin therapeutic drug-level monitoring. METHODS: A retrospective chart review was conducted using the BC Renal Agency PROMIS Database and our hospital records from 1 June 2011 to 1 July 2019. Adult patients with PD-associated peritonitis who received IP vancomycin and had at least one serum vancomycin level drawn were included. All patients received a loading dose of 30 mg/kg, which was repeated every 3-5 days depending on PD modality. Serum vancomycin levels were drawn prior to the second vancomycin dose, then at the discretion of the prescriber. The primary end point was the rate of therapeutic serum vancomycin levels ≥15 mg/L. RESULTS: Twenty-three episodes of PD-associated peritonitis in 20 patients met the eligibility criteria. Only 15/23 serum vancomycin levels were drawn appropriately after the first dose. Sixty per cent of these levels were subtherapeutic at <15 mg/L. All subsequent serum vancomycin levels were above the therapeutic target. Most peritonitis episodes (78%) achieved resolution of infection. Residual kidney function was not significantly correlated with serum vancomycin levels (p = 0.19). CONCLUSIONS: An IP vancomycin regimen of 30 mg/kg every 3-5 days resulted in subtherapeutic serum vancomycin levels in most patients following the loading dose but therapeutic levels thereafter. A large percentage of vancomycin levels were drawn inappropriately due to misalignment of outpatient follow-up visits and timing of blood work.

Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies.

BACKGROUND: Genomic aberrations can be used to determine cancer diagnosis and prognosis. Clinically relevant novel aberrations can be discovered using high-throughput assays such as Single Nucleotide Polymorphism (SNP) arrays and next-generation sequencing, which typically provide aggregate signals of many cells at once. However, heterogeneity of tumor subclones dramatically complicates the task of detecting aberrations. RESULTS: The aggregate signal of a population of subclones can be described as a linear system of equations. We employed a measure of allelic imbalance and total amount of DNA to characterize each locus by the copy number status (gain, loss or neither) of the strongest subclonal component. We designed simulated data to compare our measure to existing approaches and we analyzed SNP-arrays from 30 melanoma samples and transcriptome sequencing (RNA-Seq) from one melanoma sample.We showed that any system describing aggregate subclonal signals is underdetermined, leading to non-unique solutions for the exact copy number profile of subclones. For this reason, our illustrative measure was more robust than existing Hidden Markov Model (HMM) based tools in inferring the aberration status, as indicated by tests on simulated data. This higher robustness contributed in identifying numerous aberrations in several loci of melanoma samples. We validated the heterogeneity and aberration status within single biopsies by fluorescent in situ hybridization of four affected and transcriptionally up-regulated genes E2F8, ETV4, EZH2 and FAM84B in 11 melanoma cell lines. Heterogeneity was further demonstrated in the analysis of allelic imbalance changes along single exons from melanoma RNA-Seq. CONCLUSIONS: These studies demonstrate how subclonal heterogeneity, prevalent in tumor samples, is reflected in aggregate signals measured by high-throughput techniques. Our proposed approach yields high robustness in detecting copy number alterations using high-throughput technologies and has the potential to identify specific subclonal markers from next-generation sequencing data.

Perforated Carcinoid Tumor of the Appendix: Need for Guidelines for Management With Respect to Prognostic Factors.

Carcinoid tumors, one of the most common malignant lesions involving the appendix, are typically found incidentally during routine appendectomies. While up to 20% of acute appendicitis cases present with perforation, the incidence of perforation among patients with undiagnosed carcinoid tumors of the appendix is unknown. In addition, there is no consensus on the management of carcinoid tumors in the perforated appendix or its impact on prognosis. We present a case of a 42-year-old woman presented with perforated appendicitis. Final pathology demonstrated the presence of a 1.1 cm, well-differentiated grade 1 neuroendocrine tumor at the tip of the appendix extending into the subserosa, without evidence for lymphovascular invasion. Given the depth of tumor invasion and the relatively young age of the patient, the decision was made to perform an interval completion right hemicolectomy for lymph node sampling. Only a few cases have been reported in the available literature, and it remains unclear whether appendiceal perforation represents an independent negative prognostic factor for patient survival. Additional data from cohort studies are needed to determine the true incidence, prognosis, and optimal management of newly diagnosed carcinoid tumors in the perforated appendix. Furthermore, clear consensus guidelines are needed to identify the subgroup of patients who would benefit from interval or primary right hemicolectomy.

Patient experiences of sleep in dialysis: systematic review of qualitative studies.

RATIONALE AND OBJECTIVE: Sleep problems affect more than half of patients receiving dialysis and are associated with increased risk of mortality, cardiovascular events, depression and impaired functioning and quality of life. Symptoms such as fatigue and exhaustion may be attributed to sleep problems or sleep disorders, as well as the burden of kidney disease and treatment. This study aims to describe the patient perspectives on the reasons, impact and management of sleep problems in dialysis. STUDY DESIGN: Systematic review and thematic synthesis of qualitative studies that report patient experience and perspectives on sleep in dialysis. SETTING AND POPULATION: Patients receiving dialysis. SEARCH STRATEGY AND SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, reference lists and PhD dissertations were searched from inception to August 2019. DATA EXTRACTION: All text from the results/conclusion of the primary studies. ANALYTICAL APPROACH: Thematic synthesis. RESULTS: We included 48 studies involving 1156 participants from 16 countries. We identified six themes: dominating demands of treatment (with subthemes of: demanding and relentless schedule, regret for wasted time); scheduling and control (managing sleep routines, napping and nocturnal sleep disruption, meditative aids); disruptions due to dialysis (unsettled sleep, hypervigilance and worry); symptoms depriving sleep (difficulty falling asleep, constant waking); overwhelmed and without choice (futility of sleep, uncontrollable exhaustion, restlessness is irrepressible); and as a coping mechanism (avoiding anxiety, alleviating symptoms, combating boredom). LIMITATIONS: Most studies were conducted in high-income, English-speaking countries. CONCLUSION: The treatment and symptom burden of dialysis disrupts and deprives patients of sleep, which leads to overwhelming and uncontrollable exhaustion. Better management of symptoms and effective strategies to manage sleep routines may improve sleep quality for better overall health in patients receiving dialysis.

Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032.

Activating mutations in BRAF kinase are common in melanomas. Clinical trials with PLX4032, the mutant-BRAF inhibitor, show promising preliminary results in patients selected for the presence of V600E mutation. However, activating V600K mutation is the other most common mutation, yet patients with this variant are currently excluded from the PLX4032 trials. Here we present evidence that a patient bearing the BRAF V600K mutation responded remarkably to PLX4032, suggesting that clinical trials should include all patients with activating BRAF V600E/K mutations.

Outcomes of laparoscopic donor nephrectomy without intraoperative systemic heparinization.

PURPOSE: Intravenous heparin has traditionally been given during living donor laparoscopic nephrectomy despite the paucity of evidence supporting its use. We present the results of our experience with laparoscopic donor nephrectomy done without intraoperative systemic heparinization. MATERIALS AND METHODS: We retrospectively reviewed the records of 167 consecutive laparoscopic donor nephrectomies done without intravenous heparin from July 2005 to October 2007 at our institution. We evaluated preoperative donor characteristics, intraoperative and postoperative complications, recipient renal function and graft outcomes. RESULTS: All 138 left nephrectomies were done using a conventional laparoscopic approach while 25 of 29 right nephrectomies were done using the hand assisted technique. Warm ischemia time was approximately 3.0 minutes in each group. Mean +/- SE estimated blood loss was 183 +/- 29 ml for left and 115 +/- 16 ml for right nephrectomy. Postoperatively hematocrit decreased an average of 4.5%. There were no intraoperative complications or open conversion requirements. The postoperative complication rate was 4.8%, including 2 patients (1.2%) in whom retroperitoneal hematoma developed. Only 1 of these patients (0.6%) required blood transfusion. Two grafts (1.2%) were lost due to vascular thrombosis in the immediate postoperative period and another 2 recipients experienced delayed graft function. Average 6, 12 and 24-month serum creatinine was 1.5, 1.5 and 1.6 mg/dl, respectively. Renal allograft survival was 97% 2 years after transplantation. CONCLUSIONS: Results indicate that laparoscopic donor nephrectomy can be successfully done without systemic heparinization with few donor complications, and excellent recipient graft survival and renal function up to 2 years after transplantation.

Emergent toxicities associated with the use of mTOR inhibitors in patients with advanced renal carcinoma.

The inhibitors of the mammalian target of rapamycin (mTOR) improve outcomes in patients with advanced renal cell carcinoma. These agents are associated with unusual class-adverse events that represent a challenge to the clinician, making it critical to recognize and treat them appropriately. This study aims to highlight the clinical management of these toxicities by presenting evidence from the literature and suggesting treatment recommendations. A critical review of the literature is performed and a summary of the most relevant emergent toxicities and their management is presented. Treatment recommendations of metabolic disturbances induced by mTOR inhibitors, such as hypophosphatemia, hyperglycemia, and hyperlipidemia along with the management of drug-induced pneumonitis and possible pharmacological interactions are presented. Most of these toxicities, if recognized and treated accordingly, should resolve with minimal impact on patients' quality of life and in the efficacy of this anticancer therapy. Oncologists should be familiar with the recognition and appropriate medical management of these clinical scenarios.