Preventive Strategies Against Cytomegalovirus and Incidence of α‐Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella‐zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person‐years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5–5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7–14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2–4] versus 9.8% [95% CI 8.4–11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus‐positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.     

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation

The availability of direct‐acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end‐stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV‐viremic patients into non–HCV‐viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C–infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.     

血液制品病毒灭活／去除技术平台的建立与应用

目的：建立血液制品病毒灭活／去除技术并应用于血液制品的病毒灭活／去除工艺验证。方法建立指示病毒库以及S／D处理法、低pH孵放法、干热法、巴氏消毒法、纳米膜过滤法等血液制品病毒灭活／去除技术,采用细胞病变法测定病毒滴度,Spearman和Karber法计算病毒滴度,病毒滴度降低量（ LRV）≥4判为有效,对企业的血液制品样品进行病毒灭活／去除验证。结果 S／D处理法和低pH孵放法可有效灭活有包膜指示病毒,干热法和巴氏消毒法可有效灭活有、无包膜指示病毒,纳米膜过滤法可在一定过滤量范围内去除PPV指示病毒。结论所建立的血液制品病毒灭活／去除技术可用于血液制品的病毒灭活／去除工艺验证,以提高血液制品的病毒安全性。     

Combination Drug Products for HIV—A Word of Caution for the Transplant Clinician

Modern‐day treatment regimens for human immunodeficiency virus (HIV) are not only highly effective, but are now more often available as convenient fixed‐dose combination products. Furthermore, as medication adherence is of utmost importance in this setting, national guidelines endorse the use of such products. Transplant providers of HIV‐infected patients will undoubtedly encounter these products, some of which contain medications known to drastically alter the metabolism of certain immunosuppressants. Herein, we describe an instance of drug interaction–induced calcineurin inhibitor (CNI) nephrotoxicity in a renal transplant recipient being started on a cobicistat‐containing combination product for HIV. CNI toxicity, in turn, was resolved with the aid of phenytoin as an inducer of drug metabolism. This case underscores the importance of familiarity with newer combination products on the market and constant communication with HIV‐positive transplant recipients and their providers.     

妊娠合并重症肝炎剖宫产术的麻醉处理

目的分析晚期妊娠合并重症肝炎行剖宫产术围麻醉期的麻醉处理。方法我院1990～2004年合并重症肝炎产妇行剖宫产术12例,ASAⅢ～Ⅳ级,按麻醉方式分为两组:全身麻醉组(G组,6例),硬膜外麻醉组(E组,6例)。收集资料包括两组产妇术前一般情况;术中出血量、尿量、输液量、手术时间、胎儿娩出时间;新生儿Apgar评分;两组手术前后肝功能指标的变化;两组凝血物质使用及凝血功能的比较。术后母婴恢复情况。结果两组产妇术前的凝血功能比较,G组Plt值明显小于E组(P<0.05),PT、APTT则大于E组(P<0.05)。两组凝血物质使用无显著性差异。术中出血量、尿量、输液量、手术时间、胎儿娩出时间无显著性差异。两组新生儿Apgar评分无显著性差异。两组术前、术后肝功能指标无显著性差异。结论应根据患者的凝血功能选择麻醉方式。麻醉处理的要点在于维持呼吸循环的稳定,改善凝血功能及尽量应用对肝功能损害少的药物。     

干扰素α1b改善慢性乙型肝炎患者肝纤维化的疗效观察

目的：探讨应用干扰素α1b治疗慢性乙型肝炎（乙肝）患者改善其肝纤维化情况的疗效观察。方法：2005年3月-2008年2月期间门诊经病理确诊的慢性乙肝致肝纤维化患者96例,随机分为干扰素治疗组（46例）和对照组（50例）,两组均给予常规中药保肝降酶治疗,干扰素治疗组加用干扰素α1b（商品名运德素）50μg肌肉注射,隔日1次,疗程均为24周。观察两组患者症状、体征,肝功能指标如丙氨酸转氨酶（ALT）、胆红素（BIL）、白蛋白（A）和白蛋白/球蛋白比例（A/G）,以及肝纤维化指标血清透明质酸（HA）、层黏连蛋白（LN）、Ⅲ前型胶原（PCⅢ）和Ⅳ型胶原（CⅣ）的变化。结果：与对照组比较,干扰素治疗组治疗后腹胀、肝区疼痛、脾肿大、肝肿大等临床症状和体征明显改善（P〈0.05）,ALT[（55.7±20.2）U/Lvs.（133.4±56.3）U/L,P〈0.01]、BIL[（32.9±21.5）μmol/Lvs.（46.7±26.8）μmol/L,P〈0.01]水平下降明显,血清A[（41.8±7.5）g/Lvs.（37.9±7.8）g/L,P〈0.01]和A/G（1.8±0.6vs.1.7±0.3,P〈0.01）显著升高,HA[（101.8±50.2）ng/mlvs.（149.9±54.3）ng/ml,P〈0.01]、LN[（93.3±23.7）ng/mlvs.（122.1±37.4）ng/ml,P〈0.01]、CⅣ[（104.6±23.1）ng/mlvs.（107.3±34.7）ng/ml,P〈0.01]和PCⅢ[（190.7±59.0）ng/mlvs.（260.1±83.5）ng/ml,P〈0.01]等肝纤维化指标也明显下降,干扰素治疗组与对照组比较各检查指标差异均有显著性。结论：应用干扰素α1b治疗慢性乙肝致肝纤维化患者对改善患者临床症状、体征,促进肝功能恢复,改善其肝纤维化有显著疗效。     

孟鲁司特治疗呼吸道合胞病毒毛细支气管炎症状及反复喘息疗效研究

背景　呼吸道合胞病毒（RSV）毛细支气管炎易出现反复喘息,且下呼吸道分泌物中半胱氨酸白三烯（CysLTs）水平升高。而孟鲁司特是一种白三烯受体拮抗剂,关于其治疗RSV毛细支气管炎症状的研究相对较少。目的　探讨孟鲁司特改善婴幼儿RSV毛细支气管炎后症状及减轻反复喘息发作的有效性和安全性。方法　2015年6月-2017年6月连续纳入在潍坊市妇幼保健院出院的RSV毛细支气管炎患儿,随机分为治疗组、对照组。Ⅰ期,治疗组：口服孟鲁司特颗粒（4 mg）12周,1次/d;对照组：口服安慰剂12周,1次/d。对两组无症状天数、个人日记评分进行评估。随访9个月（Ⅱ期）,观察Ⅰ+Ⅱ期反复喘息人数和医疗资源应用情况等。依据意向性分析（ITT）原则,应用全分析集（FAS）分析数据。结果　共纳入研究对象186例,治疗组92例,对照组94例。治疗组完成Ⅰ期研究的患儿为89例,对照组为90例;治疗组完成Ⅰ+Ⅱ期的患儿为84例,对照组为86例。治疗组平均依从性为97.8%（7 560/7 728）,对照组平均依从性为97.4%（7 690/7 896）,两组患儿平均依从性比较,差异无统计学意义（χ2=3.16,P=0.07）。在Ⅰ期研究期间,两组无症状天数、日间无症状天数、夜间无症状天数、个人日记评分比较,差异均无统计学意义（P>0.05）。在整个研究过程中（Ⅰ+Ⅱ期）,治疗组RSV毛细支气管炎喘息复发人数少于对照组（P<0.05）,治疗组喘息患儿出现2次及以上喘息比例低于对照组（χ2=5.14,P=0.02）。Ⅰ+Ⅱ期研究期间治疗组医疗资源应用人数、β-受体激动剂应用人数、糖皮质激素应用人数、住院人数低于对照组（P<0.05）。在事后亚组分析中,治疗组有湿疹史与父母哮喘史的患儿中无症状天数〔（49.7±20.2）、（51.3±20.9）d〕多于对照组〔（36.3±20.4）、（37.8±19.3）d〕（t=2.19,P=0.03;t=2.24,P=0.03）。整个研究过程中没有患儿因不良反应退出研究,两组间胃肠道紊乱、皮疹、转氨酶升高发生率比较,差异均无统计学意义（χ2=0.23,P=0.63;χ2=0.03,P=0.86;χ2=0.15,P=0.69）。结论　口服孟鲁司特（4 mg）12周不能改善RSV毛细支气管炎患儿呼吸道症状,但能降低患儿反复喘息发作次数。口服孟鲁司特（4 mg）有一定效果且安全。     

Treatment with convalescent plasma in solid organ transplant recipients with COVID-19: Experience at large transplant center in New York City

Solid organ transplant (SOT) recipients may be at higher risk for poor outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Convalescent plasma is an investigational therapy that may benefit immunosuppressed patients by providing passive immunity. Convalescent plasma was administered to hospitalized patients with coronavirus disease-2019 (COVID-19) at an academic transplant center in New York City. Eligible patients were hospitalized and required to have positive nasopharyngeal polymerase chain reaction (PCR) diagnosis of SARS-CoV-2 infection, be at least 18 years old, and have either dyspnea, blood oxygen saturation ≤ 93% on ambient air, respiratory frequency ≥ 30 breaths/min, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, or lung infiltrates > 50%. Thirteen SOT recipients received convalescent plasma from April 9, 2020, to May 17, 2020. The median time from symptom onset to plasma infusion was 8 days. Eight of 13 patients (62%) had de-escalating oxygenation support by day 7 post-convalescent plasma. Nine (69%) patients were discharged, 1 (7%) patients remain hospitalized, and 3 (23%) patients died. This series supports the need for additional studies on convalescent plasma use in SOT recipients with COVID-19 to better determine efficacy and identify patients who are likely to benefit.     

The PB2 and M genes are critical for the superiority of genotype S H9N2 virus to genotype H in optimizing viral fitness of H5Nx and H7N9 avian influenza viruses in mice

Genotype S H9N2 avian influenza virus, which has been predominant in China since 2010, contributed its entire internal gene cassette to the genesis of novel reassortant influenza viruses, including H5Nx, H7N9 and H10N8 viruses that pose great threat to poultry and humans. A key feature of the genotype S H9N2 virus is the substitution of G1‐like M and PB2 genes for the earlier F/98‐like M and PB2 of genotype H virus. However, how this gene substitution has influenced viral adaptability of emerging influenza viruses in mammals remains unclear. We report here that reassortant H5Nx and H7N9 viruses with the genotype S internal gene cassette displayed enhanced replication and virulence over those with genotype H internal gene cassette in cell cultures as well as in the mouse models. We showed that the G1‐like PB2 gene was associated with increased polymerase activity and improved nuclear accumulation compared with the F/98‐like counterpart, while the G1‐like M gene facilitated effective translocation of RNP to cytoplasm. Our findings suggest that the genotype S H9N2 internal gene cassette, which possesses G1‐like M and PB2 genes, is superior to that of genotype H, in optimizing viral fitness, and thus have implications for assessing the potential risk of these gene introductions to generate emerging influenza viruses.     

病毒性心肌炎患儿血清IMA、h-FABP 水平变化及与心肌损害的相关性

目的 探讨病毒性心肌炎患儿血清缺血修饰白蛋白（IMA）、心型脂肪酸结合蛋白（h-FABP） 水平变化,并分析血清IMA、h-FABP 水平与心肌损害的相关性。方法 选取2016 年10 月—2019 年10 月 在绵阳市中心医院确诊的病毒性心肌炎患儿96 例作为观察组,根据临床表现和相关检查,将观察组分为轻症 组（54 例）和重症组（42 例）。选取同期该院健康体检儿童50 例作为对照组。采用白蛋白钴结合试验检测 血清IMA 浓度,酶联免疫吸附试验检测血清h-FABP 水平,化学发光免疫分析法测定血清心肌肌钙蛋白I 水 平。采用Pearson 法分析血清IMA、h-FABP 水平与心肌损害的相关性。结果 观察组血清IMA、h-FABP 水平较对照组高（P <0.05）。重症组血清IMA、h-FABP 水平较轻症组高（P <0.05）。病毒性心肌炎患儿血 清心肌肌钙蛋白I 水平为（0.26±0.12）ng/ml。病毒性心肌炎患儿血清IMA、h-FABP 水平与心肌肌钙蛋白I 水平呈正相关（r =0.803 和0.851,P <0.05）。结论 病毒性心肌炎患儿存在血清IMA、h-FABP 的高表达, 血清IMA、h-FABP 水平随病情严重程度的增加而升高,且与心肌损伤程度呈正相关,具有良好的临床早期 诊断及病情评估价值。