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.     

Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

银杏叶制剂联合地塞米松在老年突聋治疗中对血清炎症指标的影响

目的: 探讨银杏叶制剂联合地塞米松在老年突聋治疗中对血清炎症指标的影响。方法: 按随机数字表法将我院2016年7月-2021年7月收治的102例老年突聋患者分入两组（各51例）。对照组用地塞米松治疗，治疗组加用银杏叶制剂治疗。观察两组治疗前后纯音听阈和血管内皮功能指标[超氧化物歧化酶（SOD）、脂质过氧化物（LPO）、一氧化氮（NO）]、血清炎症指标[肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）、白细胞介素-6（IL-6）]，分析其疗效与不良反应。结果: 与对照组比较，治疗组总有效率更高（96.08％vs 82.35％）（χ2=4.993，P=0.025）；两组治疗后各频率点阈值均下降，且相比对照组，治疗组治疗后各频率点阈值更低（P<0.05）；治疗后两组SOD、NO水平均升高，LPO水平降低（P<0.05），且相比对照组，治疗组治疗后SOD、NO水平更高，LPO水平更低（P<0.05）；治疗后两组血清TNF-α、CRP、IL-6水平降低，且相比对照组，治疗组TNF-α、CRP、IL-6水平更低（P<0.05）；治疗组不良反应发生率5.88％，对照组为9.80％，两组比较差异无统计学意义（P=0.543，χ2=0.461）。结论: 银杏叶制剂联合地塞米松治疗老年突聋患者疗效理想，能恢复各频率点听力，安全可靠，推测改善患者血管内皮功能和炎症因子水平是其重要作用机制。     

Cytokine and LL-37 gene expression levels in Bartonella spp. seropositive and seronegative patients of a rheumatology clinic

PurposeThe variation in the immune response to Bartonella spp. infection in humans remains unclear. The present study compares the expression of selected interleukins, cytokines and cathelicidin (LL-37) in rheumatology clinic patients suffering from musculoskeletal symptoms with healthy blood donors. The patients had previously been tested for the presence of Bartonella henselae antibodies.MethodsGene expression of LL-37, interleukin (IL)-2, IL-4, IL-6, IL-12, interferon-(IFN)-γ, and tumor necrosis factor (TNF-α)-α was determined in blood samples using quantitative Polymerase Chain Reaction (qPCR). Statistical analysis was prepared with STATISTICA.ResultsStatistically significant differences in the mRNA levels of the tested cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-12; p<0.0001) were observed between the healthy controls and patients; however, no difference was observed for LL37 mRNA (p ?= ?0.1974). No significant differences in mRNA expression were observed between IgG in anti-Bartonella seropositive and seronegative individuals (p>0.05). The only significant differences between the Bartonella spp. DNA positive and negative patients, indicated by PCR, were observed for TNF-α and IL-12 mRNA (p ?= ?0.0045 and p ?= ?0.0255, respectively).ConclusionA broadly similar immune response to the tested cytokines was observed among the participants irrespective of anti-Bartonella spp. IgG seropositivity. However, the Bartonella DNA-positive participants demonstrated significantly lower expression of IL-12 and TNF-α mRNA; this may indicate that these bacteria have a suppressive influence on the immune system.     

ArgD of Mycobacterium tuberculosis is a functional N-acetylornithine aminotransferase with moonlighting function as an effective immune modulator

Mycobacterium tuberculosis (M. tuberculosis) encodes an essential enzyme acetyl ornithine aminotransferase ArgD (Rv1655) of arginine biosynthetic pathway which plays crucial role in M. tuberculosis growth and survival. ArgD catalyzes the reversible conversion of N-acetylornithine and 2 oxoglutarate into glutamate-5-semialdehyde and L-glutamate. It also possesses succinyl diaminopimelate aminotransferase activity and can thus carry out the corresponding step in lysine biosynthesis. These essential roles played by ArgD in amino acid biosynthetic pathways highlight it as an important metabolic chokepoint thus an important drug target. We showed that M. tuberculosis ArgD rescues the growth of ΔargD E. coli grown in minimal media validating its functional importance. Phylogenetic analysis of M. tuberculosis ArgD showed homology with proteins in gram positive bacteria, pathogenic and non-pathogenic mycobacteria suggesting the essentiality of this protein. ArgD is a secretory protein that could be utilized by M. tuberculosis to modulate host innate immunity as its moonlighting function. In-silico analysis predicted it to be a highly antigenic protein. The recombinant ArgD protein when exposed to macrophage cells induced enhanced production of pro-inflammatory cytokines TNF, IL6 and IL12 in a dose dependent manner. ArgD also induced the increased production of innate immune effector molecule NOS2 and NO in macrophages. We also demonstrated ArgD mediated activation of the canonical NFkB pathway. Notably, we also show that ArgD is a specific TLR4 agonist involved in the activation of pro-inflammatory signaling for sustained production of effector cytokines. Intriguingly, ArgD protein treatment activated macrophages to acquire the M1 phenotype through the increased surface expression of MHCII and costimulatory molecules CD80 and CD86. ArgD induced robust B-cell response in immunized mice, validating its antigenicity potential as predicted by the in-silico analysis. These properties of M. tuberculosis ArgD signify its functional plasticity that could be exploited as a possible drug target to combat tuberculosis.     

翁舌汤灌肠治疗大肠湿热型溃疡性结肠炎临床研究

目的:观察翁舌汤灌肠治疗大肠湿热型溃疡性结肠炎的疗效及其对患者血清炎症因子水平的影响。方法:将80例大肠湿热型溃疡性结肠炎患者按随机数字表法分为观察组和对照组各40例。观察组给予翁舌汤灌肠治疗,对照组给予美沙拉嗪栓肛门塞入治疗,两组均连续治疗8周。比较两组患者的临床疗效、肠黏膜征象积分和血清炎症因子水平。结果:治疗后,观察组和对照组总有效率分别为95.00%、70.00%,两组疗效比较,差异有统计学意义(P<0.05)。治疗后,观察组患者炎症增生、黏膜溃疡、黏膜糜烂、黏膜水肿、黏膜充血积分均下降,与治疗前比较,差异有统计学意义(P<0.05);且观察组各项积分均低于对照组,差异有统计学意义(P<0.05)。治疗后,两组血清白细胞介素-8(IL-8)、肿瘤坏死因子-β(TNF-β)水平均降低,血清白细胞介素-10(IL-10)水平均升高,与治疗前比较,差异均有统计学意义(P<0.05);且观察组血清IL-8、TNF-β水平明显低于对照组,血清IL-10水平明显高于对照组,差异有统计学意义(P<0.05)。结论:翁舌汤灌肠治疗大肠湿热型溃疡性结肠炎疗效较好,可改善患者肠黏膜征象积分,调节血清炎症因子水平。     

阿奇霉素序贯给药辅助治疗小儿大叶性肺炎的效果及对患儿血清炎症因子水平的影响

目的探讨阿奇霉素序贯给药辅助治疗小儿大叶性肺炎的效果及对患儿血清炎症因子水平的影响。方法回顾性分析我院2014年10月至2019年10月收治的120例大叶性肺炎患儿的临床资料,根据治疗方式的不同将其分为对照组(60例,阿奇霉素静脉滴注治疗)和观察组(60例,阿奇霉素序贯给药治疗)。比较两组的治疗效果、不良反应情况、血清炎症因子及肺功能指标水平。结果观察组的治疗总有效率显著高于对照组,不良反应总发生率显著低于对照组(P<0.05)。治疗后,两组的TNF-α、PCT、IFN-γ、TM水平均降低,FVC、TLC、Cdyn水平均升高,且观察组显著优于对照组(P<0.05)。结论阿奇霉素序贯给药辅助治疗小儿大叶性肺炎的效果显著,可有效改善患儿血清炎症因子水平和肺功能指标水平,降低不良反应发生率,值得临床推广应用。     

膳食炎症指数与炎症的相关性及研究进展

膳食炎症指数(DII)来源于将饮食和炎症联系起来的文献,被开发用来量化饮食的整体炎症潜能。饮食在调节慢性炎症中起着核心作用,是重要的调节因子,如果饮食的炎症潜能很高,则能够激发免疫调节作用,引起慢性炎症。DII可用于评估和指导个人饮食计划。本研究收集国外相关文献,就DII与炎症之间的相关性予以综述,以期通过减少饮食中的炎性成分而对慢性炎症引起的相关疾病进行一级预防。