Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project

Background and aimThe URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes.Methods and resultsThe URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up.A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04–1.47) and CV mortality (HR:1.31, 95%CI:1.03–1.66), than those with SUA <5.6 mg/dl. Increased all-cause mortality risk was shown in participants with SUA ≥4.7 mg/dl vs SUA below 4.7 mg/dl, but not statistically significant after adjustment for all confounders.ConclusionsSUA thresholds previously proposed by the URRAH study group are predictive of total and CV mortality also in people with diabetes. The threshold of 5.6 mg/dl can predict both total and CV mortality, and so is candidate to be a clinical cut-off for the definition of hyperuricemia in patients with diabetes.     

Effect of intravenous ethanol on pancreatic secretion in the conscious rat

To study whether the secretory state of thein vivo pancreas affects its response to ethanol, we administered ethanol intravenously to conscious rats in the presence and absence of exogenous secretin. In the absence of secretin when pancreatic secretion was maintained at basal levels, intravenous ethanol produced a significant stimulation of the flow rate, bicarbonate concentration, and protein concentration. This response persisted despite elimination of gastric acid production by infusion of the H2 receptor antagonist cimetidine. In contrast, intravenous ethanol inhibited the flow rate and bicarbonate concentration when pancreatic secretion was augmented by the infusion of GIH secretin. Thus, the rat pancreas responds differently to intravenous ethanol in the basal and secretin-stimulated states. These results may account for the lack of agreement regarding the pancreatic effects of systemic ethanol.This work was supported by USPHS grant AA-03508.     

The misleading nature of in vitro and ex vivo findings in studying the impact of stress hormones on NK cell cytotoxicity

In vitro and ex vivo studies assessing the impact of stress hormones on immune competence commonly replace the natural milieu of leukocytes with an artificial medium, excluding plasma factors, hormones, and cytokines. Given prevalent inconsistencies between in vitro, ex vivo, and in vivo findings, we studied whether such procedures could yield misleading outcomes regarding the impact of stress hormones on NK cell cytotoxicity (NKCC), using fresh human whole blood samples. We found that in the presence of plasma 10–30-fold higher concentrations of cortisol, epinephrine, and prostaglandin-E2 (PGE2) were required to reach suppression levels evident in the context of artificial medium. Importantly, whereas the NK suppressive effects of PGE2 occurred immediately and remained stable upon prolonged exposure, the suppressive effects of cortisol slowly increased over time. Last, to simulate the exclusion of stress factors in the ex vivo approach, we subjected whole blood to stress hormones (as occurs in vivo), and abruptly removed them. We found that the effects of epinephrine and PGE2 quickly disappeared, while the effects of cortisol persisted. Overall, these findings demonstrate the potential misleading nature of in vitro and ex vivo procedures, and specifically suggest that (i) the common in vitro findings of profound suppression of NKCC by stress hormones are overestimation of their direct effects expected in vivo; and (ii) the common ex vivo approach cannot reflect the direct in vivo suppressive effects of epinephrine and PGE2 on NKCC, while inflating the effects of glucocorticoids. Some of these fallacies may be circumvented by using non-delayed whole blood NKCC assays in humans.     

12例肝淀粉样变性患者临床特征分析

目的分析肝淀粉样变性患者的临床特点。方法收集2011年1月-2016年12月于解放军第三〇二医院肝病科住院治疗的12例确诊为肝淀粉样变性患者的临床资料,观察患者的一般资料、临床症状、体征、实验室检查结果、影像学特点、病理特点等。结果 12例肝淀粉样变性患者中,男11例(91.7%),女1例(8.3%);年龄40~67岁,平均(53.0±8.5)岁,其中AA型肝淀粉样变性2例(16.7%),AL型肝淀粉样变性10例(83.3%)。临床症状主要表现为乏力7例(58.3%),纳差5例(41.7%),肝区不适疼痛9例(75.0%),蛋白尿8例(66.7%)。影像学检查肝硬化12例(100%),肝大12例(100%),脾大8例(66.7%)。实验室检查Alb水平下降8例(66.7%),肝功能异常11例(91.7%),TBil水平升高7例(58.3%),GGT水平升高12例(100%),ALP水平升高11例(91.7%)。结论肝淀粉样变性多发于中年男性,临床出现肝硬化、肝大、蛋白尿、肝功能异常、ALP及GGT水平升高时,需高度警惕肝淀粉样变性可能,进行活组织病理检查可确诊。目前该病无有效的特异性治疗方法,但早期诊断、早期干预,及时处理相关并发症,可对患者预后起到一定的改善作用。     

射频凝固肝组织的酶组织化学研究

目的比较分析研究NADH（nieotinamide adenine dinucleotide）和HE（hematoxylin and eosin）染色评价射频治疗后即刻肝组织损伤。方法应用RF2000型射频治疗仪及LeVeen电极针,对5只实验猪肝脏进行射频消融,治疗后即刻取肝脏,分别行NADH和HE染色,评价肝组织坏死程度。结果HE染色射频消融中央区表现为核浓缩、胞浆红染,而核碎裂、核消失少见,肝细胞索完整,其细胞核形态和排列较消融前无明显改变。周边带表现为肝窦充血、出血。消融中央区、周边出血带和正常区之间界限模糊,难以准确评价射频消融的组织坏死程度,而NADH染色见消融中央区肝细胞完全失去活力,周边充血出血带肝细胞尚有活力,与正常区呈色截然不同,境界清晰,可准确、快速地对射频消融的肝组织坏死程度作出判断。结论射频是一种有效的肝癌治疗方法,HE染色不能准确评价射频消融对肝组织的即刻灭活效应,酶组织化学NADH染色判定细胞活力简易、直观、准确。     

Pretransplant serum BAFF levels are associated with pretransplant HLA immunization and renal allograft survival

BackgroundThe essential function of B cell–activating factor (BAFF) is regulating the survival and differentiation of B cells. The link between pretransplant BAFF levels and pretransplant alloimmunization and its value to predict subsequent acute antibody-mediated rejection (AMR) and outcome after renal transplantation is not fully understood.MethodsObjective of our retrospective single-center study was to determine, by ELISA analysis of pretransplant serum BAFF levels in 249 patients undergoing renal transplantation, association between preformed anti-human leukocyte antigen (HLA) antibodies, occurrence of acute antibody mediated rejection (AMR) and renal allograft survival.ResultsPretransplant serum BAFF levels were significantly higher in presensitized recipients with anti-HLA antibodies (3262 ± 2796 pg/ml) than in recipients without occurrence of anti-HLA antibodies (2252 ± 1425 pg/ml; p < 0.0001). In addition, pretransplant BAFF levels correlated with cumulative MFI values of anti-HLA antibodies (r = 0.2966, p = 0.0025). Patients with high pretransplant BAFF levels (≥ 2137 pg/ml) experienced significantly lower allograft survival rates compared to low pretransplant BAFF levels (80% vs. 91%; p = 0.01). Coexistence of high pretransplant BAFF levels and posttransplant AMR was associated with the worst allograft survival rates (56%). Relative risk (RR) for allograft loss was associated with high serum BAFF levels (RR 2.3; p = 0.02), presence of anti-HLA antibodies (RR 2.5; p = 0.007) or anti-HLA -donor-specific antibodies (DSAs) (RR 2.6; p = 0.003) before transplant and AMR post transplant (RR 2.5; p = 0.007). AMR was the strongest independent risk factor for allograft failure (RR 2.6; p = 0.03).ConclusionElevated pretransplant serum BAFF levels negatively affect renal allograft survival and represent a risk factor for allosensitization and subsequent AMR.