Integrated decision strategies for skin sensitization hazard

One of the top priorities of the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) is the identification and evaluation of non‐animal alternatives for skin sensitization testing. Although skin sensitization is a complex process, the key biological events of the process have been well characterized in an adverse outcome pathway (AOP) proposed by the Organisation for Economic Co‐operation and Development (OECD). Accordingly, ICCVAM is working to develop integrated decision strategies based on the AOP using in vitro, in chemico and in silico information. Data were compiled for 120 substances tested in the murine local lymph node assay (LLNA), direct peptide reactivity assay (DPRA), human cell line activation test (h‐CLAT) and KeratinoSens assay. Data for six physicochemical properties, which may affect skin penetration, were also collected, and skin sensitization read‐across predictions were performed using OECD QSAR Toolbox. All data were combined into a variety of potential integrated decision strategies to predict LLNA outcomes using a training set of 94 substances and an external test set of 26 substances. Fifty‐four models were built using multiple combinations of machine learning approaches and predictor variables. The seven models with the highest accuracy (89–96% for the test set and 96–99% for the training set) for predicting LLNA outcomes used a support vector machine (SVM) approach with different combinations of predictor variables. The performance statistics of the SVM models were higher than any of the non‐animal tests alone and higher than simple test battery approaches using these methods. These data suggest that computational approaches are promising tools to effectively integrate data sources to identify potential skin sensitizers without animal testing. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA.     

Fluorescein angiography complication survey

This is a report on the results of a national survey designed to study the nature and frequency of moderate and severe complications of intravenous fluorescein angiography. In this survey, 2434 responding ophthalmologists reported on 221,781 fluorescein angiograms performed in the year 1984. Adverse reactions were classified as mild, moderate, severe, and death, depending on the duration of the effect, the necessity for medical intervention, the time required for its resolution, and the final outcome. The frequency rate for a moderate reaction was (1:63), for a severe reaction (1:1900), and for death (1:222,000). A review of previous studies on adverse reactions to the drug, a compilation of suggested methods for the amelioration and prevention of the complications, and a comparison of the responses of the general ophthalmic public to the members of The Macula Society are also reported.     

3D Cube FLAIR plus HyperSense compressed sensing is superior to 2D T2WI FLAIR scanning regarding image quality,spatial resolution,detection rate for cortical microinfarcts

3-dimention (3D) Cube isotropic volumetric magnetic resonance imaging (MRI) facilitates comprehensive recognition of microinfarcts while it takes long scanning time. HyperSense compressed sensing is an emerging technique for accelerating MRI acquisition to reduce scanning time, while its application along with 3D Cube MRI for microinfarcts is seldom reported. Therefore, this study aimed to investigate the efficiency of 3D Cube FLAIR plus HyperSense compressed sensing technique versus conventional 2-dimention (2D) FLAIR scanning in the detection of cortical microinfarcts (CMIs).Totally 59 patients with cerebrovascular disease were enrolled then scanned by 3D Cube FLAIR plus HyperSense compressed sensing and 2D T2WI FLAIR sequences. The image quality scores, signal-to-noise ratio (SNR) for gray matter (GM), SNR for white matter (WM), their contrast-to-noise ratio (WM-to-GM CNR), detected number of CMIs were evaluated.3D Cube FLAIR plus HyperSense showed a dramatically increased scores of uniformity, artifact, degree of lesion displacement, and overall image quality compared to 2D T2WI FLAIR. Meanwhile, it exhibited similar SNRwm and SNRgm, but a higher WM-to-GM contrast-to-noise ratio compared with 2D T2WI FLAIR. Furthermore, the scanning time of 3D Cube FLAIR plus HyperSense and 2D T2WI FLAIR were both set as 2.5 minutes. Encouragingly, 244 CMIs were detected by 3D Cube FLAIR plus HyperSense, which was higher compared to 2D T2WI FLAIR (106 detected CMIs).3D Cube FLAIR plus HyperSense compressed sensing is superior to 2D T2WI FLAIR scanning regarding image quality, spatial resolution, detection rate for CMIs; meanwhile, it does not increase the scanning time. These findings may contribute to early detection and treatment of stroke.     

原发性肝癌诊疗指南(2022年版)

  目的  探索经肝动脉化疗栓塞（transcatheter arterial chemoembolization, TACE）为基础的不同方案治疗不可切除肝细胞癌（unresectable hepatocellular carcinoma,uHCC）患者的疗效和安全性,以及TACE联合酪氨酸激酶抑制剂（tyrosine kinase inhibitors,TKIs）和免疫检査点抑制剂（immune checkpoint inhibitors,ICIs）的最佳时机。  方法  回顾性分析2016年4月至2021年12月期间在南方医科大学南方医院接受基于TACE治疗的555例uHCC患者资料。根据不同治疗方案分为：TACE组(n=317)、TACE+TKIs组(n=66)、TACE+ICIs组(n=33)、TACE+TKIs+ICIs组(n=139)。在亚组分析中,根据不同的联合时间将TACE+TKIs+ICIs组分为 “TACE前”和“TACE后”组。采用单因素、多因素Cox回归分析影响OS的预后因素。  结果  TACE+TKIs+ICIs组获得最长的OS(21.9个月,95% CI: 17.2～26.6,P=0.030)和PFS(8.3个月,95% CI: 7.3～9.3,P=0.004)。在亚组分析中,“TACE后”组比“TACE前”组获得更长的OS(26.8个月vs.19.2个月,P=0.011)。 TACE组、TACE+TKIs组、TACE+ICIs组、TACE+TKIs+ICIs组的ORR分别为32.8%、41.1%、42.4%、52.5%（P=0.001）,DCR分别为59.6%、71.2%、69.7%、82.7%（P<0.001）。不良反应事件与既往研究相似。Cox回归分析提示肿瘤数量、肝外转移及治疗方案是患者OS的独立预后因素（均P<0.05）。  结论  TKIs或ICIs可以提高TACE治疗uHCC患者的OS和PFS,TKIs+ICIs联合TACE生存获益更佳。首次TACE术后3个月内联合“TKIs+ICIs”治疗方案的总生存期获益更显著。     

Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure

Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neu^hi), but low levels of CD8⁺ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neu^hi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.     

Increased neutrophil count Is associated with the development of chronic kidney disease in patients with diabetes

BackgroundThis study aims to investigate the potential association of peripheral inflammatory blood cell parameters with the incidence and progression of chronic kidney disease (CKD) in patients with diabetes.MethodsThe cross‐sectional study included 1192 subjects with diabetes derived from one center. The cohort study included 2060 subjects with diabetes derived from another two centers followed up for 4 years. Logistic regression and Cox proportional hazards models were used to evaluate the association of peripheral inflammatory blood cell with CKD.ResultsIn the cross‐sectional study, neutrophil count performed best as an independent risk factor for CKD (odds ratio 2.556 [95% confidence interval 1.111, 5.879]) even after 1:1 case–control matching for age, gender, history of high blood pressure and duration of diabetes. Spline regression revealed a significant linear association of CKD incidence with continuous neutrophil count in excess of 3.6 × 10⁹/L. In the cohort study, subjects were grouped based on tertile of neutrophil count and neutrophil‐to‐lymphocyte ratio. Cox regression analysis results showed that only neutrophil count was independently associated with CKD progression (the highest group vs. the lowest group, hazard ratio 2.293 [95% confidence interval 1.260, 4.171]) after fully adjusting for potential confounders. The cumulative incidence of CKD progression in patients with diabetes gradually increased with increasing neutrophil count (53 (7.7%) subjects in the lowest group vs. 60 (8.2%) in the middle group vs. 78 (12.2%) in the highest group).ConclusionsThis study suggested that neutrophil count is an independent risk factor for progression of CKD in patients with diabetes.     

安庆市农村地区中老年男性原发性高血压人群代谢综合征的患病现况

目的：了解安徽省安庆农村地区中老年男性高血压人群代谢综合征及其相关疾病的患病情况。 方法：2005—08／2006—02在安徽省安庆市及其农村地区选择年龄在50～75周岁的中老年男性原发性高血压患者637例。569人完成了4周随访。利用569人的基线资料，分析代谢综合征及其相关疾病的患病情况。 结果：①安庆市农村地区，中老年男性高血压人群代谢综合征的检出率为7．7％。②其主要组分的检出率分别为：肥胖11．1％、高血糖9．5％、高三酰甘油10．4％、低高密度脂蛋白胆固醇3．9％。③经分层分析发现，随着体质量指数、腰围、腰臀比的增加，代谢综合征、高空腹血糖、高三酰甘油、低高密度脂蛋白的检出率均明显增高，差异有统计学意义（P〈0．01）。 结论：安庆市农村地区中老年男性高血压人群中患有代谢综合征比例较高。     

Effects of Internet-Based Nutrition and Exercise Interventions on the Prevention and Treatment of Sarcopenia in the Elderly

Effective nutrition and exercise interventions may improve sarcopenia in the elderly. The purpose of our study was to investigate the effectiveness of Internet-based nutrition and exercise interventions in the elderly with sarcopenia. Participants were divided into 4 groups: control, nutrition, exercise, and comprehensive (nutrition plus exercise) groups; there was at least 50 participants in each group. Our trial lasted 12 weeks. We conducted dietary and exercise interventions through an app and collected feedback from the participants every three weeks. Information on the diet, skeletal muscle mass, and muscle function was collected before and after the interventions. The comprehensive group had higher high-quality protein intake than the control (p = 0.017) and exercise (p = 0.012) groups. After the interventions, we obtained differences in skeletal muscle mass, skeletal muscle mass/height², skeletal muscle mass/weight, muscle mass/BMI, and skeletal muscle mass/body fat percentage (p < 0.05). Changes in average daily energy and total daily protein intakes were not significantly different; however, there was an overall improvement in the intervention groups relative to baseline data. There were no changes in the average daily time of moderate physical activity. The Internet was an effective tool of nutrition intervention in the elderly with sarcopenia. The Internet-based nutrition intervention improved high-quality protein intake and skeletal muscle mass in the elderly with sarcopenia.     

Development and Validation of Global Leadership Initiative on Malnutrition for Prognostic Prediction in Patients Who Underwent Cardiac Surgery

The Global Leadership Initiative on Malnutrition (GLIM) has achieved a consensus for the diagnosis of malnutrition in recent years. This study aims to determine the prognostic effect of the GLIM after cardiac surgery. A total of 603 patients in the training cohort and 258 patients in the validation cohort were enrolled in this study. Perioperative characteristics and follow-up data were collected. A nomogram based on independent prognostic predictors was developed for survival prediction. In total, 114 (18.9%) and 48 (18.6%) patients were defined as being malnourished according to the GLIM criteria in the two cohorts, respectively. Multivariate regression analysis showed that GLIM-defined malnutrition was an independent risk factor of total complication (OR 1.661, 95% CI: 1.063–2.594) and overall survival (HR 2.339, 95% CI: 1.504–3.637). The c-index was 0.72 (95% CI: 0.66–0.79) and AUC were 0.800, 0.798, and 0.780 for 1-, 2-, and 3-year survival prediction, respectively. The calibration curves of the nomogram fit well. In conclusion, GLIM criteria can efficiently identify malnutrition and has a prognostic effect on clinical outcomes after cardiac surgery. GLIM-based nomogram has favorable performance in survival prediction.     

血液透析患者动静脉内瘘自我护理行为现状及影响因素研究

目的 调查血液透析患者动静脉内瘘自我护理行为现状并分析其影响因素,为临床护理干预提供理论依据.方法 采用便利抽样法,选取湖州市某三级甲等医院血液透析行动静脉内瘘患者118例为调查对象,采用一般资料调查表及血液透析患者动静脉内痿自我护理行为量表进行调查,运用单因素分析及多元线性回归分析其自我护理行为影响因素.结果 血液透...