Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Future directions in managing aniridia-associated keratopathy

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.     

儿童1型糖尿病骨密度变化及影响因素分析

目的 测定儿童1型糖尿病(T1DM)患者骨密度(BMD),分析探讨骨密度变化的影响因素。方法 选取于2018年1月—2021年6月于我院收治的儿童1型糖尿病患者76例,收集性别、年龄、发病年龄、身高、体重、BMI、病程等基本资料,检测空腹血糖、空腹C肽、糖化血红蛋白(HbA1c)、血碳酸氢根(HCO3-)、血清碱性磷酸酶(ALP),应用双能X线吸收测定法测定骨密度,获取Z值。结果 76例儿童1型糖尿病患者骨密度Z值为-0.93±2.14。HbA1c、病程与骨密度Z值呈负相关,差异具有统计学意义(分别B=-0.334,P<0.001;B=-0.191,P=0.017)。结论 儿童1型糖尿病患者骨密度低于健康儿童,血糖控制不良、病程长是1型糖尿病儿童骨密度减低的危险因素。     

SAA、hs-CRP、IL-6联合检测在儿童感染性疾病中的诊断价值

目的:分析SAA、hs-CRP、IL-6联合检测在儿童感染性疾病中的诊断价值。方法:选择2019年1月~2020年10月某院收治的72例感染性疾病患儿开展研究,根据患儿的病原体检测结果划分为病毒感染组和细菌感染组各36例,另选择同期体检的36名健康儿童作为研究的参照组,分别比较3组的SAA、hs-CRP、IL-6等指标水平的差异。结果:细菌感染组的SAA、hs-CRP、IL-6等指标水平及阳性率均高于病毒感染组、参照组,同时病毒感染组的SAA、hs-CRP、IL-6等指标水平及阳性率高于参照组(P<0.05);SAA、hs-CRP、IL-6联合诊断的敏感度、准确度、阳性预测值、阴性预测值均高于SAA、hs-CRP、IL-6三个指标单独检测的敏感度、准确度、阳性预测值、阴性预测值,差异有统计学意义(P<0.05);联合检测的特异度与单独检测特异度对比无统计学意义(P>0.05)。结论:SAA、hs-CRP、IL-6联合诊断在儿童感染性疾病中具备较高的诊断价值,临床可将SAA、hs-CRP、IL-6作为该病的诊断辅助指标,有效提高疾病的诊断准确性。     

适量运动对心房颤动患者预后的影响:系统综述与Meta分析

目的 分析适量运动对于心房颤动(房颤)患者的运动能力以及远期临床预后的影响。方法 通过检索中国知网,万方,维普,Pubmed,OVID,Cochrane Central Register of Controlled Trials (CENTRAL),web of science数据库,纳入对房颤患者进行适量体育活动干预的临床试验。本研究的主要终点为静息心率,最大心率,6 min步行试验,最大运动功率,全因死亡率以及卒中发生率,用以评估适量运动对房颤患者活动耐力以及预后的影响。结果 本研究共纳入7项试验,2 452例患者,试验组为适量运动干预组,对照组为不活跃组。适量运动并不会显著增加患者的静息心率(MD=-1.68,P=0.70)以及最大心率(RD=9.72,P=0.11)。运动训练可显著提高房颤患者的运动能力,明显增加6 min步行距离(MD=59.07,95%CI=11.70-106.44,P<0.05),并且在一定程度上提高运动功率(MD=17.96,95%CI=-6.30-42.22,P=0.15)。适量运动对房颤患者的远期预后不会造成不良影响,适量运动组对比不活跃组,全因死亡率为15.7% vs 14.2%(RD=0.03,95%CI=-0.18-0.25,P=0.75);卒中发生率5.0% vs 2.9%(RD=0.02,95%CI=-0.06-0.09,P=0.69),两组差异无统计学意义。结论 适量运动可在一定程度上提高房颤患的活动耐力,且不增加卒中以及全因死亡率。     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Overview of CF lung pathophysiology

Defects of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein affect the homeostasis of chloride, bicarbonate, sodium, and water in the airway surface liquid, influencing the mucus composition and viscosity, which induces a severe condition of infection and inflammation along the whole life of CF patients. The introduction of CFTR modulators, novel drugs directly intervening to rescue the function of CFTR protein, opens a new era of experimental research. The review summarizes the most recent advancements to understand the characteristics of the infective and inflammatory pathology of CF lungs.     

The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events

Objective To explore associations between lipoprotein-associated phospholipase A2(Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up.Methods A random sample of 2,031 participants(73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study(APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay(ELISA). The composite endpoint was a combination of first-eve...     

儿童社区获得性肺炎血清维生素A的变化及与免疫功能相关性

目的 研究社区获得性肺炎(community acquired pneumonia,CAP)患儿血清维生素A(vitamin A,VA)水平及与免疫功能的相关性,为肺炎病情评估提供一定参考。方法 以入住新乡医学院第一附属医院PICU的63例重度社区获得性肺炎(severe community acquired pneumonia, SCAP)患儿(SCAP组)、普通儿科病区的30例轻度社区获得性肺炎(mild community acquired pneumonia, MCAP)患儿(MCAP组),以及同期体检的30名健康儿童(对照组)为研究对象,检测其血清中VA和免疫球蛋白(immunoglobulin,Ig)G、IgA、IgM水平,及SCAP组体内T淋巴细胞亚群(总T淋巴细胞、CD4、CD8、CD4/CD8),并对SCAP组体内VA水平及以上指标的相关性进行分析。结果 3组性别和年龄差异无统计学意义;血清中VA的平均含量分别为0.36、0.25和0.19 mg/L,CAP组VA的含量较对照组明显降低,且SCAP组明显低于MCAP组(P<0.05)。根据WHO推荐的VA诊断标准,3组VA临床缺乏/亚临床缺乏率分别为10.00%、36.67%和61.90%,差异有统计学意义(P<0.05)。CAP组血清中Ig水平较对照组明显降低,且SCAP组明显低于MCAP组(P<0.05)。SCAP组血中总T淋巴细胞、CD4、CD8和CD4/CD8的平均水平分别为53.28%、30.26%、20.24%和1.59;分析VA水平与免疫相关指标关系发现VA水平与Ig(IgG、IgA、IgM)水平、总T淋巴细胞、CD4呈正相关,与CD8水平不相关。结论 肺炎患儿血清VA水平与病情严重程度及机体免疫功能相关。