Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.     

电针复合TCI靶控输注在单肺通气食管癌开胸手术麻醉中的应用与安全性＊

目的 探讨电针复合靶控输注（Target Controlled Infusion， TCI）在单肺通气食管癌开胸手术麻醉中的应用价值。方法 选取于我院拟行单肺通气食管癌开胸切除手术患者60例作为研究对象。随机将其分为试验组与对照组，对照组30例采取气管插管全麻及TCI靶控输注维持麻醉深度，试验组30例则在对照组方案基础上辅助电针麻醉，记录两组患者手术麻醉时间、药物用量、苏醒时间、并发症；以及术前（T_Ⅰ）、插管前即刻（T_Ⅱ）、插管后1 min（T_Ⅲ）、切皮即刻（T_Ⅳ）、去骨时（T_Ⅴ）、拔管即刻（T_Ⅵ）时平均动脉压（MAP）、平均心率（HR）、BIS值；术前、术后1天、术后3天简易智能精神状态检查量表（MMSE）；并于麻醉诱导前（T₀）、手术开始2 h（T₁）、术后1天（T₂）、术后3天（T₃）时抽取患者外周静脉血检测IL-1β、IL-6、IL-10、TNF-α浓度。结果 试验组手术用时、麻醉时间略低于对照组，但差异无统计学意义（P>0.05），试验组异丙酚、舒芬太尼用量以及苏醒时间均明显低于对照组（P<0.05）；T_Ⅱ时两组平均动脉压（Mean Arterial Pressure， MAP）、心率（Heartrate， HR）较术前明显降低，且试验组MAP明显低于对照组（P<0.05），但两组T_Ⅱ时HR比较无显著差异（P>0.05）；T_Ⅲ、T_Ⅵ时对照组MAP、HR明显高于T_Ⅰ时，而试验组MAP、HR与T_Ⅰ比较无显著差异（P>0.05）。术后1天、3天试验组简易智能精神状态检查量表（Mini-Mental State Examination， MMSE）评分低于对照组，有显著性差异（P<0.05）。T₁、T₂、T₃时试验组白介素-1β（IL-1β）、白介素-6（IL-6）、肿瘤坏死因子（Tumor Necrosis Factor-α， TNF-α）水平明显低于对照组（P<0.05），白介素-10（IL-10）水平明显高于对照组（P<0.05）。结论 采用电针复合TCI靶控输注麻醉方案可有效提升单肺通气食管癌开胸手术麻醉效果，能够降低患者术后认知功能障碍发生风险。     

加速康复外科在肾移植术后静脉补液中的应用

目的探讨加速康复外科(ERAS)在肾移植术后静脉补液中的应用。 方法回顾性分析陆军军医大学第一附属医院124例肾移植受者临床资料。根据肾移植术后多尿期每24小时静脉补液量分为3组，A组每24小时静脉补液量2 500～<4 000 mL，术后6 h进食流质；B组每24小时补液量4 000～6 000 mL，肛门排气后进食；C组每24小时补液量>6 000 mL，肛门排气后进食。采用单因素方差分析比较3组受者术后1周中心静脉压(CVP)、心率、血压、尿量和血糖以及平均特护时间、平均住院日和术后1个月血清肌酐。采用χ²检验比较3组受者性别、供肾类型以及术后高血糖、伤口延迟愈合和移植肾功能延迟恢复(DGF)发生率。P<0.05为差异有统计学意义。 结果A、B和C组受者术后1个月血清肌酐分别为(110±23)、(114±22)和(118±22)μmol/L，差异无统计学意义(F＝1.19，P>0.05)。A组受者术后1周CVP、收缩压、尿量和血糖均低于B、C组(P均<0.05)，平均特护时间和平均住院日均短于B、C组(P均<0.05)。3组受者术后高血糖和DGF发生率差异均无统计学意义(χ²＝4.581和0.404，P均>0.05)，A组受者伤口愈合延迟发生率低于C组(χ²＝7.303，P<0.017)。仅C组1例受者因心力衰竭和肺水肿死亡。 结论ERAS适用于肾移植受者术后静脉补液策略，鼓励受者尽早饮水进食，在保证血压正常或偏高的情况下，适当减少静脉补液量，有利于减少并发症，促进受者恢复。     

Time course of arsenic species in red blood cells of acute promyelocytic leukemia (APL) patients treated with single agent arsenic trioxide

Background:Arsenic trioxide (ATO) is widely applied to treat acute promyelocytic leukemia (APL). To elucidate metabolism and toxicity of arsenic, we analyzed time course of arsenic species in red blood cells (RBCs) of APL patients.

Methods:Nine APL patients received ATO (0.16 mg/kg/day) through 18-h infusion. Blood was collected before daily administration (days 2 to 9), and at different time points on day 8. Inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were detected by HPLC-ICP-MS.

Results:Arsenic species reached C_max at 18 h on day 8. Arsenicals gradually accumulated during days 2 to 9, whereas their percentages remained almost constant. The general trend in red blood cells (RBCs) was iAs > MMA > DMA. MMA was consistently the predominant methylated arsenic metabolite in RBCs. iAs, MMA, and tAs (tAs = iAs + DMA + MMA) concentrations (P < 0.0001), MMA/DMA ratios (P = 0.0016) and iAs% (P = 0.0013) were higher in RBCs than in plasma.

Conclusions:Time course of arsenic species reveal kinetic characteristic of ATO metabolites in RBCs. Arsenic species accumulated with administration frequency. Arsenic species in RBCs were remarkably different from those in plasma. Time course of arsenic species in RBCs is important in ATO clinical application.     

Surgical delay may extend the indications for nipple-sparing mastectomy: A multicentric study

IntroductionNipple-sparing mastectomy (NSM) is considered an oncologically sound procedure but necrosis of the nipple-areola complex (NAC) or skin flaps is a concern, particularly in the presence of risk factors. To increase the indications for NSM and decrease such complications, different procedures of “surgical delay” (SD) have been described.Materials and methodsA retrospective analysis of patients who underwent SD for NSM at four Italian Breast Centers from 2014 to 2017 was performed. SD generally consisted of a periareolar or “hemi-batwing” incision, dissecting the skin and the NAC from the underlying breast tissue. NSM was scheduled after 2–3 weeks.ResultsEighty-eight procedures were analyzed. Mild complications of SD were registered in 7.9% of cases. NSM was performed in 85 cases, whereas in three cases (3.4%) a “skin-sparing” mastectomy was necessary due to positivity of the retroareolar biopsy for cancer at SD.A direct-to- implant (DTI) reconstruction was performed in 42 cases (49.4%), while in 43 (50.6%) a tissue-expander (TE) was inserted. After NSM, eight complications (9.4%) were recorded: one total necrosis (1.2%), one partial necrosis (1.2%) and four minimal ischemia (4.7%) of NAC, one skin flap necrosis (1.2%), one haematoma (1.2%). In only two cases (2.3%) prosthesis removal was needed. Aesthetic outcome was evaluated excellent or good in 92.9% of cases.At a median follow-up of 24 months no local recurrences were seen.ConclusionThis is the largest series of SD with NSM presented so far in the literature. In our experience, SD extends indications for NSM in high-risk women.     

Perioperative management of diabetes

Diabetes is a complex, chronic metabolic disorder affecting approximately 9.3% of the adult population with the estimated number of adults with diabetes worldwide having more than tripled since 2000. This increase has largely been attributed to global urbanization and lifestyle changes. Diabetes affects 10–15% of the surgical population. These patients are frequently elderly, have complex medical co-morbidities and present for both high-risk elective and emergency surgery. This multisystem disease poses a significant challenge to both anaesthesia and surgery with patients with diabetes demonstrating higher morbidity and mortality rates compared to their non-diabetic counterparts. It is crucial that good glycaemic control is maintained throughout the perioperative period as this has been shown to correlate with positive patient outcomes. It is well-recognized that a co-ordinated, multidisciplinary approach aimed at optimizing every point in the patient pathway from GP referral to post-discharge care is required to obtain the best outcomes for the surgical patient with diabetes. The anaesthetist has a key role in the perioperative diabetes multidisciplinary team. Patients themselves are well experienced in manging their own diabetes and should be involved in doing so whenever possible.     

重症烧伤患者急救期输液及营养的路径护理

目的讨论研究对重症烧伤患者实行急救期输液及营养的路径护理的临床疗效与意义。方法选择医院烧伤科重症烧伤患者100例随机分组委观察组与对照组各50例。对照组给予急救期输液及营养常规护理。观察组提供急救期营养及输液路径护理。比较两组患者不同护理方式后营养状况、不良反应人数及护理满意度。结果治疗后观察组各项营养指标均显著优于对照组(P<0.05);观察组不良反应发生人数较少,护理服务满意程度较高。结论为重症烧伤患者提供急救期输液与营养路径护理可降低不良反应发生率并为患者加强营养支持,增强免疫力,有助于帮助其有效度过危险期,可促进患者后期治疗与恢复,更有助于拉近护患距离,提升医疗护理服务满意度。     

63例儿童流行性感冒合并塑型性支气管炎的临床特征分析

目的 研究儿童流行性感冒（简称流感）合并塑型性支气管炎的临床特征。方法 回顾性分析63例流感合并塑型性支气管炎患儿的临床表现、实验室检查、影像学、治疗及转归特点。结果 63例患儿中，男52例（83%），女11例（17%），其中甲型流感42例，乙型流感21例。3~6岁儿童38例（60％）。15例（24%）有基础性疾病。主要的临床表现包括高热（90%）、咳嗽（95%）和气促（73%）。影像学检查显示肺不张24例（38%）。16例（25%）听诊无肺部啰音。入住重症监护室41例，呼吸机辅助通气32例。63例患儿均行纤维支气管镜检查及肺泡灌洗。好转60例，死亡3例。结论 儿童流感合并塑型性支气管炎以男性及学龄前儿童多见。对于有气促的流感患儿，即使胸部X线未提示肺不张或听诊无肺部啰音，也需要警惕合并塑型性支气管炎的可能。     

自然杀伤细胞治疗急性髓系白血病的研究进展

自然杀伤细胞(natural killer cell,NK)为一种存在于天然免疫系统中的淋巴细胞,具有杀伤肿瘤细胞和抗病毒感染的能力,在天然免疫和过继免疫治疗中发挥重要作用。随着NK细胞的特征和功能越来越被熟知,其已被广泛应用于临床抗肿瘤治疗,特别是血液系统恶性肿瘤如急性髓系白血病(acute myeloid leukemia,AML)、淋巴瘤等治疗。目前,基于NK细胞的免疫治疗主要包括自体NK细胞输注、异体NK细胞输注、嵌合抗原修饰NK(chimeric antigen receptor,CAR)细胞输注以及基于NK细胞的其他免疫治疗等。以NK细胞为基础的免疫治疗旨在增强NK细胞的抗肿瘤能力以及克服肿瘤免疫逃逸。随着研究进展,NK细胞将成为治疗AML的有效方法。