高尔基体糖蛋白73在启东地区人群中的分布与随访

目的 探讨高尔基体糖蛋白73 (GP73)在不同人群中的检测水平和范围. 方法 在启东某社区35 ～ 69岁人群中,用HBsAg检测筛查12378人,随机抽取其中十分之一(受检者检测号末尾为“0”者)组成“自然人群组”(1227人);12378人中的所有HBsAg携带者组成“阳性组”(1025人);在HBsAg非携带者中随机抽取十分之一组成“阴性组”(1132人).采用ELISA法检测以上各组血清GP73与AFP,评价其分布以及中位值(50％百分位数)和95％临界值.对HBsAg携带者及非携带者人群进行了2年的随访并观察肝癌发生率的差别.采用stata软件进行检测水平分布的偏度系数(Skewness)和峰度系数(Kurtosis)检验,并进行率差异的显著性检验. 结果 GP73水平在HBsAg携带者、HBsAg非携带者和自然人群中的分布均为正偏态分布,50％百分位值(中位值)分别为67μg/L、54 μg/L及55 μg/L,95％百分位值分别为174 μg/L、108μg/L及114μg/L.HBsAg携带者中GP73高于均值者的AFP阳性率为7.23％ (37/512),低于均值者的AFP阳性率为0.78％ (4/513),差异有统计学意义(P＜0.01).经2年的随访,HBsAg携带者中GP73≥67μg/L的512例中,23例发生肝癌(4.49％),而＜67μg/L的513例中1例发生肝癌(0.19％),RR=23.6.但在HBsAg非携带者中,不管GP73水平高低,未见肝癌的发生. 结论 GP73在HBsAg携带者中的检出水平较高;用GP73作为标志物对HBsAg携带者人群进行随访,可能有助于肝癌的早期发现.     

血清甲胎蛋白、γ-谷氨酰转肽酶Ⅱ、高尔基体蛋白73检测在原发性肝癌早期诊断中的价值

目的探讨血清甲胎蛋白(AFP)、γ-谷氨酰转肽酶(GGT)Ⅱ、高尔基体蛋白73(GP73)对于原发性肝癌患者的早期诊断价值。方法抽取2013年2月至2014年2月在南通市第三人民医院进行治疗的100例肝病患者(50例肝炎及肝硬化患者为肝脏良性病变组,50例原发性肝癌患者为原发性肝癌组)和50例正常体检者血清,分别利用电化学发光法、特异免疫膜吸附法、酶联免疫吸附法检测血清中的AFP、GGTⅡ、GP73水平。计量资料多组间比较采用方差分析,两两比较采用q检验;对单项及联合检测结果作图绘成受试者工作特征曲线(ROC曲线),计算曲线下面积(AUC),观察AFP、GGTⅡ、GP73单独和联合检测的AUC、敏感度、特异度。结果血清GGTⅡ水平在对照组或肝脏良性病变组、原发性肝癌组的两两比较中差异均有统计学意义(P值均0.05),但是对照组与肝脏良性病变组差异没有统计学意义(P值均0.05)。AFP和GP73水平在原发性肝癌组、肝脏良性病变组,对照组的两两比较中差异均有统计学意义(P值均0.05)。单独检测时GP73的特异度为69%,敏感度为92%;GGTⅡ的特异度为64%,敏感度为84%;AFP的特异度为51%,敏感度为76%。联合检测特异度为94.6%,敏感度为98.8%。结论单独检测时GP73指标最好,3个指标联合检测,诊断原发性肝癌的特异度及灵敏度均提高。     

血清AFP和GP73在慢性乙型肝炎患者中的表达

目的检测不同程度的慢性乙型肝炎(chronic hepatitis B,CHB)患者的血清甲胎蛋白(AFP)和高尔基体蛋白73(GP73),研究CHB病情对AFP和GP73表达的影响。方法收集146例住院CHB患者血清,其中CHB轻度、中度、重度、肝硬化患者各30例,慢加亚急性肝衰竭患者26例,同时选取30名健康对照者,分别检测血清AFP、GP73。结果 AFP在CHB轻度组与对照组比较,差异无统计学意义(P=0.361);而在CHB其他各组中均较对照组升高,在CHB重度组最高(P0.05)。GP73在各组患者血清中表达均较对照组升高(P0.05);GP73在肝衰竭组中表达最高,依次为CHB重度组、肝硬化组、CHB中度组、轻度组,肝硬化组与CHB重度组差异无统计学意义(P=0.752),在CHB轻度组、CHB中度组中表达差异无统计学意义(P=0.584)。以20 ng/ml为cut-off值,AFP在所有CHB分组中均有阳性表现,CHB重度组(70.0%)及肝衰竭组(53.8%)阳性率最高,其他依次为肝硬化组(26.7%)、CHB中度组(23.3%)、CHB轻度组(3.3%)和对照组(0);以150μg/L为cut-off值,GP73在CHB轻度组与CHB中度组中阳性率分别为30.0%、36.7%,在CHB重度组、肝衰竭组及肝硬化组中稍高,分别为80.0%、61.5%、70.0%。结论 AFP和GP73在不同程度CHB患者血清中均可见升高,但受影响程度不一致,它们在用于肝癌诊断标志物时应排除不同程度肝脏炎症的影响。     

高尔基体蛋白73和透明质酸对HBV相关慢性肝病进展的诊断价值

目的探讨高尔基体蛋白73(GP73)与透明质酸(HA)在HBV相关慢性肝病进展中的临床应用价值。方法收集2016年12月-2017年4月就诊于青岛大学附属医院的患者142例,其中伴有肝硬化的肝细胞癌(HCC)36例(HCC组),乙型肝炎肝硬化66例(肝硬化组),慢性乙型肝炎(CHB)40例(CHB组)。另选取同一时期健康体检者30例作为对照。ELISA法检测血清中GP73浓度,化学发光法检测HA浓度。正态分布的计量资料多组间比较单因素方差分析;非正态分布的计量资料多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Mann-Whitney U检验。曲线分析比较GP73和HA单独或联合应用的临床诊断价值。受试者工作特征曲线下面积(AUC)比较采用Z检验,性别比、敏感度及特异度比较采用χ~2检验。结果 CHB组、肝硬化组及HCC组患者血清GP73和HA水平均高于对照组(P值均0.05)。肝硬化组、HCC组患者GP73和HA水平均明显高于CHB组(U值分别为677、637、291、193,P值均0.05)。肝硬化组内比较,失代偿期患者GP73与HA水平均显著高于代偿期患者(U值分别为171、212,P值均0.05)。对于CHB患者,GP73与HA联合检测的AUC及敏感度均高于GP73单独检测(0.950 vs 0.790,Z=2.32,P0.05;91.70%vs 72.20%,χ~2=5.14,P0.05)。预测肝硬化时GP73的诊断敏感度高于HA(87.90%vs 69.70%,χ~2=6.05,P0.05);二者联合应用较HA单独应用特异度降低(62.30%vs 86.80%,χ~2=14.60,P0.05),敏感度提高(93.90%vs69.70%,χ~2=11.80,P0.05)。诊断失代偿期肝硬化时GP73、HA联合应用敏感度高于HA单独应用(83.80%vs 67.60%,χ~2=4.17,P0.05)。GP73、HA和AFP诊断HCC的AUC分别为0.549、0.525、0.807,GP73与HA对HCC的诊断价值不如AFP(Z值分别为3.49、3.80,P值均0.05)。结论 GP73和HA均可作为监测HBV相关慢性肝病进展的辅助指标,联合应用对诊断肝硬化及肝硬化代偿情况具有重要的临床应用价值。     

GP73联合AFP-L3检测在低浓度甲胎蛋白肝癌患者诊断中的应用

目的研究高尔基体蛋白73(GP73)联合甲胎蛋白异质体(AFP-L3)检测在低浓度甲胎蛋白(AFP)肝癌患者诊断中的临床应用效果。方法选择2015年6月至2017年10月在我院诊治的125例低浓度AFP肝病患者,根据患者的肝病种类分为肝炎组(n=31例),肝硬化组(n=40例)以及肝癌组(n=54例),并选择同期在我院进行体检的60名健康者作为对照组。检测所有研究对象的血清GP73以及AFP-L3水平。结果肝癌组患者的血清GP73、AFP-L3水平和阳性率均明显高于肝炎组、肝硬化组以及对照组(P0.05);GP73以及AFP-L3联合检测肝癌患者的诊断特异度、灵敏度及准确度均明显高于单独检测GP73、AFP-L3(P0.05)。结论 GP73以及AFP-L3均可作为诊断低浓度AFP肝癌患者的血清标记物,二者联合检测具有更高的特异度、灵敏度及准确度。     

血清甲胎蛋白和高尔基体糖蛋白73联合检测对肝细胞癌的早期诊断价值

目的探讨血清甲胎蛋白(AFP)和高尔基体糖蛋白73(GP73)联合检测对肝细胞癌(HCC)的诊断价值,为早期诊断和鉴别诊断HCC提供依据。方法收集2012年6月-2013年5月住院患者标本共408例,其中HCC患者142例(HCC组),慢性肝炎患者156例(慢性肝炎组),肝硬化患者110例(肝硬化组)。分别采用电化学发光法和酶联免疫吸附试验(ELISA)双抗体夹心法测定3组患者的血清AFP和GP73的浓度,检测结果组间比较采用方差分析,率的比较采用χ2检验。并使用MedCalc统计学软件计算2项指标联合检测对HCC诊断的敏感度和特异度。结果 HCC组血清AFP和GP73的浓度显著高于肝硬化组和慢性肝炎组,差异具有统计学意义(P0.05);肝硬化组血清AFP和GP73的浓度显著高于慢性肝炎组,其差异亦有统计学意义(P0.05)。二者联合检测肝细胞癌的敏感度为95.8%,特异度为98.6%,较单项检测差异具有统计学意义(P0.05)。结论血清AFP和GP73联合检测对HCC具有较高的诊断价值和临床意义,可作为HCC早期的诊断和鉴别诊断指标,值得在临床上推广。     

AFP、AFP-L3％、GP73在肝硬化、肝癌患者血清中的表达及鉴别诊断价值

目的：探讨不同血清肿瘤标志物在肝硬化和肝癌的鉴别诊断中的临床价值。方法回顾性分析146例肝硬化患者、50例原发性肝癌患者的临床资料,并选取50例健康体检者作为对照,分别检测血清AFP、甲胎蛋白异质体（AFP-L3）和高尔基体糖蛋白73（GP73）含量,并计算 AFP-L3％。结果146例肝硬化患者的 AFP 阳性率为平均25．3％,低于肝癌组的72％（χ2＝34．69,P＜0．01）;AFP-L3％在不同病因肝硬化组中阳性率均较低,平均8．9％,低于肝癌组的58％（χ2＝53．32,P＜0．01）,也低于肝硬化组中AFP 的阳性率（χ2＝13．90,P＝0．0002）;GP73在不同病因肝硬化组、肝癌组阳性率均较高,在肝硬化组中平均阳性率为74．7％,高于AFP 及AFP-L3％在肝硬化组中的阳性率（χ2＝71．01,P＜0．01）,与GP73在肝癌组中的阳性率比较差异无统计学意义（χ2＝0．84,P＝0．36）。AFP、AFP-L3％的敏感性、特异性均较GP73好,联合诊断不能提高鉴别准确性。结论血清肿瘤标志物AFP 在乙型肝炎肝硬化及隐源性肝硬化患者中阳性率较高,AFP-L3％在各种病因肝硬化患者中均较低,AFP、AFP-L3％可有效区分肝癌和肝硬化;GP73在不同病因肝硬化组中均高,不能用于区分肝硬化和肝癌。     

血清甲胎蛋白、γ-谷氨酰基转肽酶Ⅱ、高尔基体蛋白73检测在原发性肝癌早期诊断中的价值

目的：探讨血清甲胎蛋白（AFP）、γ-谷氨酰转肽酶（GGT）Ⅱ、高尔基体蛋白73（GP73）对于原发性肝癌患者的早期诊断价值。方法抽取2013年2月至2014年2月在南通市第三人民医院进行治疗的100例肝病患者（50例肝炎及肝硬化患者为肝脏良性病变组,50例原发性肝癌患者为原发性肝癌组）和50例正常体检者血清,分别利用电化学发光法、特异免疫膜吸附法、酶联免疫吸附法检测血清中的 AFP、GGTⅡ、GP73水平。计量资料多组间比较采用方差分析,两两比较采用 q 检验;对单项及联合检测结果作图绘成受试者工作特征曲线（ROC 曲线）,计算曲线下面积（AUC）,观察 AFP、GGTⅡ、GP73单独和联合检测的 AUC、敏感度、特异度。结果血清 GGTⅡ水平在对照组或肝脏良性病变组、原发性肝癌组的两两比较中差异均有统计学意义（P 值均＜0．05）,但是对照组与肝脏良性病变组差异没有统计学意义（P 值均＞0．05）。AFP 和 GP73水平在原发性肝癌组、肝脏良性病变组,对照组的两两比较中差异均有统计学意义（P 值均＜0．05）。单独检测时 GP73的特异度为69％,敏感度为92％;GGTⅡ的特异度为64％,敏感度为84％;AFP 的特异度为51％,敏感度为76％。联合检测特异度为94．6％,敏感度为98．8％。结论单独检测时 GP73指标最好,3个指标联合检测,诊断原发性肝癌的特异度及灵敏度均提高。     

血清高尔基蛋白73、甲胎蛋白异质体3、甲胎蛋白和α-L-岩藻糖苷酶水平诊断原发性肝癌的效能分析

目的探讨应用血清高尔基蛋白体73(GP73)、甲胎蛋白异质体3(AFP-L3)、AFP和α-L-岩藻糖苷酶(AFU)水平诊断原发性肝癌(PLC)患者的效能。方法 2015年1月～2017年3月我院诊治的PLC患者261例,乙型肝炎肝硬化患者201例,慢性乙型肝炎患者238例和体检健康人200例,采用酶联免疫吸附试验法检测血清GP73水平,采用亲和吸附离心管法检测血清AFP-L3,采用全自动化学发光仪检测血清AFP,采用商用试剂盒检测血清AFU水平。绘制血清GP73、AFP-L3、AFP和AFU诊断PLC的ROC曲线,确定截断点(cut-off-value),计算ROC曲线下面积(AUC),判断它们的诊断效能。结果肝癌组血清GP73水平显著低于慢性肝炎组和肝硬化组,差异有统计学意义(P0.05),血清AFP-L3显著高于其他3组,差异有统计学意义(P0.05),血清AFU水平显著高于健康人和肝硬化组,但低于慢性肝炎组,差异有统计学意义(P0.05);以非肝癌人群为对照,血清GP73、AFP-L3、AFP和AFU诊断肝癌的ROC曲线下面积分别为0.564 (95%CI:0.485～0.636)、0.724 (95%CI:0.555～0.786)、0.745(95%CI:0.654～0.806)和0.571(95%CI:0.385～0.536),血清AFP-L3联合AFP诊断肝癌的截断点分别为8.25%和49.25 ng/ml,其灵敏度(Se)为55.5%,特异度(Sp)为85.0%,正确性(Ac)为80.1%,显著高于血清AFP-L3诊断的55.5%、85.0%和76.4%或AFP诊断的57.1%、82.7%和75.2%(P0.05);在261例肝癌患者中,血清AFP9.6 ng/ml者71例(27.2%),其中PG73106.5 ng/ml者30例(42.3%),提示GP73对AFP阴性肝癌有一定的诊断价值;在201例肝硬化患者中,血清AFP9.6 ng/ml者98例(48.8%),其中PG73106.5 ng/ml者52例(53.1%),提示血清GP73水平容易受到肝硬化的影响。结论应用血清AFP联合AFP-L3检测能够提高诊断肝癌的效能,但它们的灵敏度都还不够高,影响因素较多。临床医生需结合病史、影像学检查和动态血清学检测才能做出更为科学的结论。     

血清高尔基体糖蛋白73、甲胎蛋白及甲胎蛋白异质体3在肝癌诊断及射频消融术后复发监测中的应用价值

目的探讨高尔基体糖蛋白73(GP73)、甲胎蛋白(AFP)及甲胎蛋白异质体3(AFP-L3)3种血清肿瘤标志物在肝癌诊断及射频消融术后复发监测中的应用价值。方法收集2012年7月-2013年10月吉林大学白求恩第一医院住院患者及体检中心健康者174例,其中初诊肝癌患者86例,肝硬化患者39例,肝炎患者29例,健康对照20例,并对初诊肝癌的37例患者进行射频消融术后3个月的复诊。分别采用酶联免疫法、电化学发光法、亲和吸附层析法检测血清GP73、AFP、AFP-L3的水平。各组血清标本检测数据呈偏态分布,采用非参数检验,总体比较检验采用Kruskal-Wallis H检验,组间两两比较采用Mann-Whitney U检验,配对秩和检验采用Wilcoxon Signed Ranks检验,计数资料采用χ2检验。结果肝癌组GP73、AFP、AFP-L3表达水平均显著高于其他组(P值均<0.05);肝癌组中GP73和AFP-L3阳性率显著高于其他组(P值均<0.05),而肝癌患者中GP73和AFP-L3阳性率显著高于AFP(P值均<0.05);初诊肝癌的37例患者进行术后3个月复查,AFP-L3复发组术前显著高于未复发组术前(P<0.05)。结论血清GP73、AFP、AFP-L3在肝癌诊断中有重要价值,AFP-L3可以作为鉴别肝病良恶性以及肝癌射频消融术后复发监测的指标。     

Interplay between interferon-mediated innate immunity and porcine reproductive and respiratory syndrome virus

Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non-structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp's are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS.     

Control of intraabdominal hemorrhage and shock: a comparison of fluid resuscitation, MAST, and balloon occlusion

Our study examined the efficacy of four treatment modalities in controlling hemorrhage and achieving hemodynamic stabilization in hemorrhagic shock: intravenous fluid replacement (IV); military antishock trousers used concomitantly with fluids (MAST); balloon occlusion at the level of the diaphragm with concomitant fluid replacement (balloon); and a combination of MAST inflation, balloon occlusion, and fluid resuscitation (MAST and balloon). Twenty-eight mongrel dogs were anesthetized, and the spleen was exposed and completely crushed. The abdomen was closed, and treatment was initiated and continued for four hours or until the dog died. For all conditions the hematocrit dropped during the course of the experiment; balloon occlusion was effective at slowing this drop (P less than .0001), but MAST had no statistically significant effect. Animals with balloons bled more slowly into the abdominal cavity than did animals in the other two groups (P less than .0001). MAST also were effective at slowing the bleeding (P less than .05). Of the balloon and the MAST and balloon dogs, all except one survived the entire four hours; this difference between balloon and nonballoon dogs is significant (P = .002). MAST did not have a statistically significant effect on survival. Perfusion pressure (PP) declined during the course of the experiment, and the balloon was effective at slowing this decline (P less than .0001); none of the other comparisons was statistically significant.     

Disease Pandemics and Major Epidemics Arising From New Encounters between Indigenous Viruses and Introduced Crops

Virus disease pandemics and epidemics that occur in the world’s staple food crops pose a major threat to global food security, especially in developing countries with tropical or subtropical climates. Moreover, this threat is escalating rapidly due to increasing difficulties in controlling virus diseases as climate change accelerates and the need to feed the burgeoning global population escalates. One of the main causes of these pandemics and epidemics is the introduction to a new continent of food crops domesticated elsewhere, and their subsequent invasion by damaging virus diseases they never encountered before. This review focusses on providing historical and up-to-date information about pandemics and major epidemics initiated by spillover of indigenous viruses from infected alternative hosts into introduced crops. This spillover requires new encounters at the managed and natural vegetation interface. The principal virus disease pandemic examples described are two (cassava mosaic, cassava brown streak) that threaten food security in sub-Saharan Africa (SSA), and one (tomato yellow leaf curl) doing so globally. A further example describes a virus disease pandemic threatening a major plantation crop producing a vital food export for West Africa (cacao swollen shoot). Also described are two examples of major virus disease epidemics that threaten SSA’s food security (rice yellow mottle, groundnut rosette). In addition, brief accounts are provided of two major maize virus disease epidemics (maize streak in SSA, maize rough dwarf in Mediterranean and Middle Eastern regions), a major rice disease epidemic (rice hoja blanca in the Americas), and damaging tomato tospovirus and begomovirus disease epidemics of tomato that impair food security in different world regions. For each pandemic or major epidemic, the factors involved in driving its initial emergence, and its subsequent increase in importance and geographical distribution, are explained. Finally, clarification is provided over what needs to be done globally to achieve effective management of severe virus disease pandemics and epidemics initiated by spillover events.     

陕西省新型结核病防治管理模式实施前后能力建设与诊治效果分析

目的 分析陕西省新型结核病防治管理模式实施前后结核病防治能力建设及诊治效果,为进一步完善我省结核病防控政策和措施提供参考。方法 本研究采用描述性研究,对全省10个地级市、108个县(区)结核病防治能力建设情况,以及患者发现、治疗管理等指标变化情况进行对比分析。能力建设情况以2014年和2017年数据作对比,分别来源于《陕西省“十二五”结核病防治规划》评估和2017年全省结核病防治工作联合大检查。患者发现、治疗管理指标来源于《结核病信息管理系统》,以实施前3年(2012—2014年)与实施后3年(2015—2017年)的数据作对比。运用SPSS 19.0处理数据,率和构成比的比较采用χ ²检验,以P<0.05为差异有统计学意义。 结果 2014年和2017年全省设有结核病定点医院的数量分别为20家和107家,2017年较2014年增加了87家。2014年全省共有结核病防治人员923名,其中疾病预防控制中心(CDC)656名,定点医院267名。2017年全省共有结核病防治人员1200名,其中CDC 403名,定点医院797名;与2014年相比,CDC人员减少了38.57%,定点医院人员增加了198.50%。2014年全省有3个地级市开展了分子生物学耐药检测,5.56%(6/108)的县(区)开展了分子生物学检测,12.04%(13/108)的县(区)开展了痰培养。2017年全省有8个地级市开展了分子生物学耐药检测,49.07%(53/108)的县(区)开展了分子生物学检测,55.56%(60/108)的县(区)开展了痰培养。新型防治模式实施前3年全省初诊查痰率为98.50%(329981/335014),发现肺结核患者63892例(其中结核性胸膜炎患者4089例),发现病原学阳性患者14087例,病原学阳性率为23.56%(14087/59803)。实施后3年全省初诊查痰率为95.00%(312503/328948),发现肺结核患者61583例(其中结核性胸膜炎5295例),病原学阳性患者10588例,病原学阳性率为18.81%(10588/56288)。新型防治模式实施前后初诊查痰率降低(χ ²=6484.178,P=0.000),病原学阳性率降低(χ ²=390.104,P=0.000)。实施前3年因症就诊发现肺结核患者占29.43%(18805/63892),转诊发现患者占43.90%(28047/63892)。实施后3年因症就诊发现肺结核患者占25.38%(15628/61583),转诊发现患者占57.79%(35586/61583)。转型后因症就诊发现患者的构成比下降(χ ²=259.002,P=0.000),转诊发现患者的构成比上升(χ ²=2419.762,P=0.000)。新模式实施前后3年非结核病防治机构报告患者总体到位率分别为93.18%(62177/66726)和89.96%(61323/68169),实施后总体到位率下降(χ ²=453.550,P=0.000)。新模式实施前后患者治疗成功率分别为95.04%(60464/63619)和94.97%(57872/60939),实施前后比较差异无统计学意义(χ ²=0.356,P=0.551)。 结论 我省新型结核病防治管理模式推进顺利,防治能力加强,但部分患者诊治及管理指标有所下滑,实施质量仍需提升。     

Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases Pub Med(June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications(required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar(discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.     

dsRNA-Dependent Protein Kinase PKR and its Role in Stress,Signaling and HCV Infection

The double-stranded RNA-dependent protein kinase PKR plays multiple roles in cells, in response to different stress situations. As a member of the interferon (IFN)‑Stimulated Genes, PKR was initially recognized as an actor in the antiviral action of IFN, due to its ability to control translation, through phosphorylation, of the alpha subunit of eukaryotic initiation factor 2 (eIF2α). As such, PKR participates in the generation of stress granules, or autophagy and a number of viruses have designed strategies to inhibit its action. However, PKR deficient mice resist most viral infections, indicating that PKR may play other roles in the cell other than just acting as an antiviral agent. Indeed, PKR regulates several signaling pathways, either as an adapter protein and/or using its kinase activity. Here we review the role of PKR as an eIF2α kinase, its participation in the regulation of the NF-κB, p38MAPK and insulin pathways, and we focus on its role during infection with the hepatitis C virus (HCV). PKR binds the HCV IRES RNA, cooperates with some functions of the HCV core protein and may represent a target for NS5A or E2. Novel data points out for a role of PKR as a pro-HCV agent, both as an adapter protein and as an eIF2α-kinase, and in cooperation with the di-ubiquitin-like protein ISG15. Developing pharmaceutical inhibitors of PKR may help in resolving some viral infections as well as stress-related damages.     

A comparison of stapled and handsewn anastomoses in patients undergoing resection for Dukes' B and C colorectal cancer

This study was to assess the effect of stapled colorectal anastomoses on local recurrence, disease-free survival, and survival following curative resection for Dukes' B and C adenocarcinoma. Data were derived from two randomized prospective trials of the National Surgical Adjuvant Breast and Bowel Project designed to evaluate the efficacy of adjuvant therapy in colorectal cancer. Of 1111 patients with colonic anastomoses, 255 were stapled mechanically. There were no significant differences in disease-free survival, survival, or local tumor recurrence among patients subjected to stapled or handsewn anastomoses. Of the 181 patients undergoing anterior resection for rectal cancer, 82 anastomoses were fashioned with staples. No significant disadvantage in disease-free survival, survival, or local recurrence could be attributed to use of the mechanical stapling devices. Twelve percent of patients undergoing stapled rectal anastomoses developed a local recurrence as a first sign of treatment failure compared with 19 percent for the handsewn group. No significant differences in the length of distal margins were detectable. The average time on study was 41 months. The use of stapled anastomoses for carcinoma of the colon or rectum is not associated with an adverse effect on long-term outcome. Read at the meeting of the American Society of Colon and Rectal Surgeons, San Diego, California, May 5 to 10, 1985. Supported by USPHS NIH-U10-34212 and an American Cancer Society Grant RC-13.     

Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.     

Advances in the Diagnosis and Management of Inflammatory Bowel Disease: Challenges and Uncertainties

Over the past two decades, several advances have been made in the management of patients with inflammatory bowel disease (IBD) from both evaluative and therapeutic perspectives. This review discusses the medical advancements that have recently been made as the standard of care for managing patients with ulcerative colitis (UC) and Crohn''s Disease (CD) and to identify the challenges associated with implementing their use in clinical practice. A comprehensive literature search of the major databases (PubMed and Embase) was conducted for all recent scientific papers (1990–2013) giving the recent updates on the management of IBD and the data were extracted. The reported advancements in managing IBD range from diagnostic and evaluative tools, such as genetic tests, biochemical surrogate markers of activity, endoscopic techniques, and radiological modalities, to therapeutic advances, which encompass medical, endoscopic, and surgical interventions. There are limited studies addressing the cost-effectiveness and the impact that these advances have had on medical practice. The majority of the advances developed for managing IBD, while considered instrumental by some IBD experts in improving patient care, have questionable applications due to constraints of cost, lack of availability, and most importantly, insufficient evidence that supports their role in improving important long-term health-related outcomes.     

Crohn's disease and growth deficiency in children and adolescents

Nutritional concerns, linear growth deficiency, and delayed puberty are currently detected in up to 85% of patients with Crohn’s disease (CD) diagnosed at childhood. To provide advice on how to assess and manage nutritional concerns in these patients, a Medline search was conducted using “pediatric inflammatory bowel disease”, “pediatric Crohn’s disease”, “linear growth”, “pubertal growth”, “bone health”, and “vitamin D” as key words. Clinical trials, systematic reviews, and meta-analyses published between 2008 and 2013 were selected to produce this narrative review. Studies referring to earlier periods were also considered if the data was relevant to our review. Although current treatment strategies for CD that include anti-tumor necrosis factor-α therapy have been shown to improve patients’ growth rate, linear growth deficiencies are still common. In pediatric CD patients, prolonged diagnostic delay, high initial activity index, and stricturing/penetrating type of behavior may cause growth deficiencies (in weight and height) and delayed puberty, with several studies reporting that these patients may not reach an optimal bone mass. Glucocorticoids and inflammation inhibit bone formation, though their impact on skeletal modeling remains unclear. Long-term control of active inflammation and an adequate intake of nutrients are both fundamental in promoting normal puberty. Recent evidence suggests that recombinant growth factor therapy is effective in improving short-term linear growth in selected patients, but is of limited benefit for ameliorating mucosal disease and reducing clinical disease activity. The authors conclude that an intense initial treatment (taking a “top-down” approach, with the early introduction of immunomodulatory treatment) may be justified to induce and maintain remission so that the growth of children with CD can catch up, ideally before puberty. Exclusive enteral nutrition has a key role in inducing remission and improving patients’ nutritional status.