Missed opportunities?: an evaluation of potentially preventable poisoning deaths**

Introduction: Although most poisoning deaths are not preventable with current medical technology, in some cases different management decisions may have prevented fatal outcomes. Objective: This study aims to review reported poisoning-related deaths for preventability to provide insight to improve future care. Methods: Fatality abstracts published in the US National Poison Data System (NPDS) Annual Reports (2008–2012) were analyzed. Preventability was graded using a Likert scale of 1 (definitely non-preventable) to 6 (definitely preventable). Two medical toxicologists screened all cases. Cases deemed definitely not preventable (score 1) by both reviewers were excluded from further review and considered to be “non-preventable”. All cases considered at least possibly preventable by either screener were reviewed by a multidisciplinary panel of 5 physicians for preventability scoring. Differences were resolved by consensus. Cases determined to be “preventable” (scores 4–6) were characterized by type of improvement issue involved (diagnosis, treatment, monitoring, other) and recurring scenarios. Results: Of 390 published abstracts, 78 (20.0%) deaths were considered at least possibly preventable by at least one screener. Of these, 34 (8.7%) deaths were determined to be “preventable” by the panel. Inter-observer agreement by weighted kappa analysis was 0.58 for screening, 0.24 for preventability, and 0.44 for specific aspects of care. The most common toxicants were salicylates (n?=?9), opioids (n?=?4), toxic alcohols (n?=?3), fluoride containing product (n?=?3), and bupropion (n?=?3). The most common improvement opportunities involved treatment and monitoring. Discussion: Most of the ingested substances in preventable deaths have delayed GI absorption or require metabolic activation to produce a delayed effect (such as salicylates, opioids, and toxic alcohols), and therefore provide an opportunity for early recognition and successful interventions. Most improvement opportunities are clearly described in the literature but may be not recognized. Conclusions: Based on an analysis of published NPDS data, a considerable number of poisoning-related deaths reaching medical attention may be preventable. The most common scenarios involved in potentially preventable poisoning fatalities related to monitoring and treatment. Salicylates and opioids were the most common agents involved in preventable deaths.     

甲颏高度对喉镜暴露困难的评估

目的 评价甲颏高度对评估国人喉镜暴露困难的准确性.方法 选取拟择期行气管插管全身麻醉的患者120例,术前分别采用改良Mallampati分级、甲颏间距、身高/甲颏距离、甲颏高度对所有患者气道分级进行评估.再根据插管时实际声门暴露情况按照Cormack' s-Lehane法对气道进行分级.计算4种方法的敏感性、特异性、阳性预测值及阴性预测值.结果 喉镜暴露困难率4.2％,困难插管率1.7％,无插管失败患者.4种方法的特异性由高到低依次是身高/甲颏距离(91.3％)、甲颏间距(85.2％)、甲颏高度(89.6％)、改良Mallampati分级(48.7％).与改良Mal-lampati分级比较,甲颏间距、身高/甲颏距离、甲颏高度的特异性明显增高(P＜0.01);4种评估方法的敏感性、阳性预测值和阴性预测值的差异均无统计学意义.结论 甲颏高度在评估国人困难气道方面与甲颏距离及身高/甲颏距离有相近的敏感性、特异性、阳性预测值和阴性预测值,可作为独立危险因素应用于喉镜暴露困难的评估.     

Implementation of Constant Dose Rate and Constant Angular Spacing Intensity-modulated Arc Therapy for Cervical Cancer by Using a Conventional Linear Accelerator

Background:

Volumetric-modulated arc therapy (VMAT) can only be implemented on the new generation linacs such as the Varian Trilogy^® and Elekta Synergy^®. This prevents most existing linacs from delivering VMAT. The purpose of this study was to investigate the feasibility of using a conventional linear accelerator delivering constant dose rate and constant angular spacing intensity-modulated arc therapy (CDR-CAS-IMAT) for treating cervical cancer.

Methods:

Twenty patients with cervical cancer previously treated with intensity-modulated radiation therapy (IMRT) using Varian Clinical 23EX were retreated using CDR-CAS-IMAT. The planning target volume (PTV) was set as 50.4 Gy in 28 fractions. Plans were evaluated based on the ability to meet the dose volume histogram. The homogeneity index (HI), target volume conformity index (CI), the dose to organs at risk, radiation delivery time, and monitor units (MUs) were also compared. The paired t-test was used to analyze the two data sets. All statistical analyses were performed using SPSS 19.0 software.

Results:

Compared to the IMRT group, the CDR-CAS-IMAT group showed better PTV CI (0.85 ± 0.03 vs. 0.81 ± 0.03, P = 0.001), clinical target volume CI (0.46 ± 0.05 vs. 0.43 ± 0.05, P = 0.001), HI (0.09±0.02 vs. 0.11 ± 0.02, P = 0.005) and D95 (5196.33 ± 28.24 cGy vs. 5162.63 ± 31.12 cGy, P = 0.000), and cord D2 (3743.8 ± 118.7 cGy vs. 3806.2 ± 98.7 cGy, P = 0.017) and rectum V40 (41.9 ± 6.1% vs. 44.2 ± 4.8%, P = 0.026). Treatment time (422.7 ± 46.7 s vs. 84.6 ± 7.8 s, P = 0.000) and the total plan Mus (927.4 ± 79.1 vs. 787.5 ± 78.5, P = 0.000) decreased by a factor of 0.8 and 0.15, respectively. The IMRT group plans were superior to the CDR-CAS-IMAT group plans considering decreasing bladder V50 (17.4 ± 4.5% vs. 16.6 ± 4.2%, P = 0.049), bowel V30 (39.6 ± 6.5% vs. 36.6 ± 7.5%, P = 0.008), and low-dose irradiation volume; there were no significant differences in other statistical indexes.

Conclusions:

Patients with cervical cancer treated with CDR-CAS-IMAT using Varian Clinical 23EX can get equivalent or superior dose distribution compared to those treated with IMRT. CDR-CAS-IMAT has a less treatment time and MU, which can reduce the uncertainty factor and patient discomfort in treatment.     

直肠肛管恶性肿瘤腹会阴联合切除术中两种途径腹膜外乙状结肠造口的比较

目的探讨直肠肛管恶性肿瘤腹会阴联合切除术中两种途径腹膜外乙状结肠造口的临床应用价值。方法将行腹会阴联合切除术的67例直肠肛管恶性肿瘤患者,按腹膜外乙状结肠造口方式分为两组,其中A组34例（经腹内斜肌腹膜外造口）,B组33例（经腹直肌外缘腹膜外造口),比较两组围手术期指标（手术时间、造口水肿、造口回缩塌陷、造口坏死、造口梗阻）和术后远期指标（腹胀感受、排便感觉、控便能力、造口旁疝、造口脱垂）的差异。结果两组均未发生造口回缩塌陷、造口梗阻、造口脱垂;在造口手术时间、造口水肿、造口坏死、排便感觉、腹胀感受和造口旁疝等方面比较,差异均无统计学意义（P＞0.05）;在控便能力方面A组明显优于B组（P＜0.05）。结论两种腹膜外乙状结肠造口方式均安全可行,A种术式在预防造口旁疝方面可能有一定优势,适合普通患者;对于肠管较粗、系膜过于肥厚者适合B种术式。     

钙黏蛋白E、桥粒芯糖蛋白2、磷酸化Akt和转录因子Snail在侵袭性前列腺癌中的作用

目的  探讨钙黏蛋白E（E-cadherin）、桥粒芯糖蛋白（2DSG2）、磷酸化Akt（pAkt）和转录因子Snail在前列腺癌发病进程中的作用;阐明E-cadherin、DSG2、pAkt和Snail对前列腺癌发病进程的影响及在临床预后中的作用。方法  组织芯片法检测E-cadherin、DSG2、pAkt和Snail在前列腺癌组织中的表达情况。结果  前列腺癌组织中E-cadherin表达明显低于正常前列腺组织,细胞质和细胞核中均可观察到pAkt表达,且在肿瘤高分化区和低分化区内均有较高表达。E-cadherin和DSG2表达呈显著正相关。E-cadherin和DSG2表达下降提示前列腺癌患者血清前列腺特异性抗原（PSA）浓度含量增加,Gleason评分较高及病理分期更高。结论  前列腺癌低分化细胞中钙黏蛋白表达降低,钙黏蛋白低表达提示肿瘤细胞侵袭性更强,转移发生率高。钙黏蛋白在前列腺癌发展中发挥关键作用,E-cadherin和DSG2有望成为侵袭性前列腺癌的预后因子。

     

Protective role of Bacillus anthracis exosporium in macrophage-mediated killing by nitric oxide

The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis to survive in activated macrophages is key to its germination and survival. In a previous publication, we discovered that exposure of primary murine macrophages to B. anthracis endospores upregulated NOS 2 concomitant with an .NO-dependent bactericidal response. Since NOS 2 also generates O(2).(-), experiments were designed to determine whether NOS 2 formed peroxynitrite (ONOO(-)) from the reaction of .NO with O(2).(-) and if so, was ONOO(-) microbicidal toward B. anthracis. Our findings suggest that ONOO(-) was formed upon macrophage infection by B. anthracis endospores; however, ONOO(-) does not appear to exhibit microbicidal activity toward this bacterium. In contrast, the exosporium of B. anthracis, which exhibits arginase activity, protected B. anthracis from macrophage-mediated killing by decreasing .NO levels in the macrophage. Thus, the ability of B. anthracis to subvert .NO production has important implications in the control of B. anthracis-induced infection.     

Activation of ASK1 during reperfusion of ischemic spinal cord

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK), which plays a pivotal role in cell apoptosis. To determine the mechanism of ASK1 induction during reperfusion of ischemic spinal tissue, we used a model of rabbit spinal cord ischemia and reperfusion. To assess the role of ASK1 in spinal cord ischemia-reperfusion injuries, we examined alterations in spinal tissue morphology, protein-protein interactions, and activation of key members of the ASK1-mediated signaling pathway. Changes in spinal cord morphology were observed with hematoxylin and eosin (H&E) staining and electron microscopy. The phosphorylation levels of ASK1, JNK, and p38 were assessed by immunoblotting proteins from animals that received 30 min of ischemia followed by 1 or 24h of reperfusion. We observed increased phosphorylation of ASK1, JNK, and p38 after reperfusing ischemic spinal cords. Immunohistochemical studies were performed to determine the cellular localization of phosphorylated ASK1 (pASK1) and 14-3-3. Following reperfusion for 24h, we observed increased cytoplasmic localization of pASK1 and decreased cytoplasmic localization of 14-3-3. Immunoprecipitation analyses suggested that 14-3-3 dissociates from ASK1 during reperfusion of ischemic spinal cords. These results indicate that activation of ASK1 may play an important role in the apoptotic signaling mechanisms that occur in reperfused spinal cord injuries.     

Synthesis of glutathione C60 derivative and its protective effect on hydrogen peroxide-induced apoptosis in rat pheochromocytoma cells

Oxidized glutathione C(60) derivative has been synthesized and characterized in our research. As a novel derivative of C(60), the glutathione C(60) derivative is soluble in dimethylsulfoxide, dimethylformamide and dimethylacetamide. Rat pheochromocytoma (PC12) cells are treated with hydrogen peroxide and underwent cytotoxicity; apoptotic death is determined by MTT assay, flow cytometry analysis, PI/Hoechst 33342 staining and glutathione assay. The results suggest that glutathione C(60) derivative has the potential to prevent oxidative stress-induced cell death without evident toxicity.     

Clioquinol and vitamin B12 (cobalamin) synergistically rescue the lead-induced impairments of synaptic plasticity in hippocampal dentate gyrus area of the anesthetized rats in vivo

Lead (Pb(2+)) exposure in development induces impairments of synaptic plasticity in the hippocampal dentate gyrus (DG) area of the anesthetized rats in vivo. The common chelating agents have many adverse effects and are incapable of alleviating lead-induced neurotoxicity. Recently, CQ, clioquinol (5-chloro-7-iodo-8-hydroxy-quinoline), which is a transition metal ion chelator and/or ionophore with low affinity for metal ions, has yielded some promising results in animal models and clinical trials related to dysfunctions of metal ions. In addition, CQ-associated side effects are believed to be overcome with vitamin B12 (VB12) supplementation. To determine whether CQ treatment could rescue impairments of synaptic plasticity induced by chronic Pb(2+) exposure, we investigated the input/output functions (I/Os), paired-pulse reactions (PPRs) and long-term potentiation (LTP) of different treatment groups in hippocampal DG area of the anesthetized rat in vivo by recording field potentials and measured hippocampal Pb(2+) concentrations of different treatment groups by PlasmaQuad 3 inductive coupled plasma mass spectroscopy. The results show: CQ alone does not rescue the lead-induced impairments of synaptic plasticity in hippocampal DG area of the anesthetized rats in vivo; VB12 alone partly rescues the lead-induced impairments of LTP; however the co-administration of CQ and VB12 totally rescues these impairments of synaptic plasticity and moreover, the effects of CQ and VB12 co-administration are specific to the lead-exposed animals.