Risk Factors for Development of Acute Renal Failure After Liver Transplantation

Background.?Acute renal failure (ARF) is a common complication after liver transplantation (LTx). Identification of risk factors may prevent the development and attenuate the impact of ARF on patients outcome after LTX. Methods.?Retrospective analysis of variables in the pre, intra, and postoperative periods of 92 patients submitted to LTx was performed in order to identify risk factors for development of ARF after LTx. ARF was defined as serum creatinine ≥2.0 mg/dL in the first 30 days after LTx. Univariate and multivariate analysis by logistic regression were performed. Results.?ARF group comprised 56 patients (61%). Preoperative serum creatinine was higher in ARF group. During the intraoperative period, ARF group required more blood transfusions, developed more episodes of hypotension and presented longer anesthesia time. In the postoperative period, ARF group presented higher serum bilirubin and more episodes of hypotension. Dialysis was required in 10 patients (11%). The identified risk factors for development of ARF were: preoperative serum creatinine >1.0 mg/dL, more than five blood transfusions in the intraoperative period, hypotension during intra and postoperative periods. The identified mortality risk factors were hypotension in the postoperative period and no recovery of renal function after 30 days. Conclusions.?Several factors are involved in the pathogenesis of ARF after LTx and may influence patients outcome and mortality. Pretransplant renal function and hemodynamic conditions in the operative and postoperative periods were identified as risk factors for development of ARF after LTx. Nonrenal function recovery and postoperative hypotension were identified as mortality risk factors after LTx.     

Fungal infections in solid organ transplantation: An update on diagnosis and treatment

Invasive fungal infections constitute an important cause of morbidity and mortality in solid organ transplantation recipients. Since solid organ transplantation is an effective therapy for many patients with end-stage organ failure, prevention and treatment of fungal infections are of vital importance. Diagnosis and management of these infections, however, remain difficult due to the variety of clinical symptoms in addition to the lack of accurate diagnostic methods. The use of fungal biomarkers can lead to an increased diagnostic accuracy, resulting in improved clinical outcomes. The evidence for optimal prophylactic approaches remains inconclusive, which results in considerable variation in the administration of prophylaxis. The implementation of a standard protocol for prophylaxis remains difficult as previous treatment regimens, which can alter the distribution of different pathogens, affect the outcome of antifungal susceptibility testing. Furthermore, the increasing use of antifungals also contributes to incremental costs and the risk of development of drug resistance. This review will highlight risk factors, clinical manifestations and timing of fungal infections and will focus predominately on the current evidence for diagnosis and management of fungal infections.     

Evolution of Functional Exercise Capacity in Lung Transplant Patients With and Without Bronchiolitis Obliterans Syndrome: A Longitudinal Case–Control Study

Introduction

Bronchiolitis Obliterans Syndrome (BOS) is a debilitating disease with limited treatment options that threatens both the quality of life and long-term survival of lung transplant (LTx) recipients. This retrospective longitudinal case–control study was performed to compare the long-term functional evolution of LTx recipients with and without BOS.

The effect of alpha-latrotoxin on the neurosecretory PC12 cells differentiated by treatment with nerve growth factor

Neurosecretory PC12 cells differentiated in vitro by prolonged (at least 2 weeks) treatment with nerve growth factor were exposed to alpha-latrotoxin and studied by morphological and biochemical techniques. Cell monolayers or suspensions responded to the toxin with a prompt and massive release of neurotransmitter. The dose dependency (Km approximately 5 X 10(-10)M) and the maximum release effect (approximately 60% of the stored [3H]dopamine released within 8 min) were not appreciably different from the values found in non-differentiated PC12 cells. Moreover, the concentration dependency of the release was found to correspond closely to that of the [125I]alpha-latrotoxin binding to its specific sites (the alpha-latrotoxin receptors). The number of these receptors was over two-fold higher in differentiated than in undifferentiated cells. Since, however, differentiation implies a large increase in cell size and surface area, the receptor density (number/unit area) remained virtually unchanged. By radioautography the alpha-latrotoxin receptors were found to remain diffusely distributed at the entire surface of differentiated cells even when these were allowed to form synapses with myotubes. This situation is at variance with that demonstrated recently at the frog neuromuscular junction, where alpha-latrotoxin receptors are exclusively localized at the nerve terminal plasmalemma. Scanning and transmission electron microscopy revealed that the enlargements of neurites where dense granules are preferentially accumulated--the varicosities and terminals--underwent swelling and extensive disorganization within a few minutes after the application of alpha-latrotoxin, whereas the cell bodies and the tracts of neurites occupied primarily by microtubules were less severely affected. The greater sensitivity of varicosities and terminals with respect to the other parts of the differentiated cells, rather than the consequence of a specific addressing of the toxin to these structures, might be due to their vulnerability by toxin-induced events, such as the uncontrolled activation of ion fluxes.     

The effect of alpha-latrotoxin on the neurosecretory PC12 cell line: studies on toxin binding and stimulation of transmitter release

alpha-Latrotoxin of black widow spider venom was found to bind with high affinity (KA = 1.8 X 10(9)M-1) to specific sites present in discrete number (approximately 6300/cell, approximately 12/micron2) at the surface membrane of PC12 cells. This binding correlated with (and therefore, probably caused) the secretory response produced by the toxin. Binding was enhanced (approximately 2-fold) in the presence of mM concentrations of various divalent cations (Ca2+, Mn2+ and Co2+) while Ba2+ and Sr2+ had a smaller effect and Mg2+ was inactive. Hypertonicity, concanavalin A and trypsin pretreatment of the cells blocked the binding interaction. The alpha-latrotoxin-induced stimulation of 3H-dopamine release was massive and occurred very rapidly when cells were exposed to the toxin in a Ca2+-containing Krebs-Ringer medium, whereas it occurred at a much slower rate in a Ca2+-free, Mg2+-containing Ringer. Introduction of Ca2+ into the latter medium resulted in a shift of the release rate from slow to fast. In contrast, in divalent cation-free medium the response was abolished. The toxin-induced secretory response was unaffected by Na+ and Ca2+ channel blockers (tetrodotoxin and D600) as well as by calmodulin inhibitors (calmidazolium and trifluoperazine). The effects of Ca2+ and Mg2+ were found to be concentration-dependent, with half maximal responses occurring at approximately 0.3 and 1.5 mM for the two divalent cations, respectively. Other divalent cations could substitute for Ca2+ and Mg2+, the relative efficacy being Sr2+ greater than Ca2+ greater than Ba2+ much greater than Mn2+ greater than Mg2+ greater than Co2+. Moreover, the response occurring at suboptimal concentration of Ca2+ (0.4 mM) was potentiated by the concomitant addition of either Mg2+, Mn2+ or Co2+. The effect(s) of divalent cations in supporting the alpha-latrotoxin-induced release response seem(s) to occur primarily at step(s) beyond toxin binding because (a) the stimulatory effects of the various cations on release were not matched by parallel effects on binding, and (b) Ca2+ maintained its ability to stimulate fast release even when toxin binding had occurred in a Ca2+-free medium. Delays in the release responses were observed when cells were exposed to alpha LTx in Na+-free, glucosamine or methylamine-based media, or depolarized with high K+ (in the presence of D600) before toxin treatment. Moreover, in these two conditions the ability of Mg2+ to support the alpha LTx response was considerably decreased.(ABSTRACT TRUNCATED AT 400 WORDS)     

Intraoperative support during lung transplantation

The role of intraoperative mechanical support during lung transplantation (LTx) is essential to provide a safe hemodynamic and ventilatory status during critical intraoperative events. This hemodynamic and ventilatory stability is vital to minimize the odds of suboptimal outcomes, especially considering that, due to the scarcity of donors and the fact that more and more patients with significant comorbidities are being considered for this therapy, a more aggressive approach is often needed by the transplant centers. Hence, the attenuation of any potential injury that can happen during this complex event is paramount. While a thorough assessment of the donor and optimization of postoperative care is pursued, certainly protective intraoperative management would also contribute to better outcomes. Understanding each patient’s underlying anatomy and cardiopulmonary physiology, associated with awareness of critical events during a complicated procedure like LTx, is essential for a precise indication and safe use of support. Cardiopulmonary bypass (CPB) and veno-arterial extracorporeal membrane oxygenation (VA ECMO) have been the most common approaches used, with the latter gaining popularity more recently and we have used VA ECMO exclusively for the last decade. New technologies certainly contributed to more liberal use of VA ECMO intraoperatively, enabling a protecting and physiologic environment for the newly implanted grafts. In this setting, potential prophylactic use for lung protection during a critical period is also considered.