Compliance to Advisory Committee on Immunization Practices recommendations for pneumococcal vaccination

We evaluated compliance to the ACIP pneumococcal vaccination recommendations issued in 2014 for adults aged ≥ 65 years and in 2012 for adults with high-risk (HR) conditions. The MarketScan® Commercial and Medicare Supplemental databases (January 2007-June 2019) were used to identify the cohorts of interest. Analyses for adults aged ≥ 65 years were adjusted to account for missing vaccination history. Two HR cohorts were identified. The HR1 cohort included patients with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leak, or cochlear implant. The HR2 cohort included patients with chronic heart, lung, or liver disease; diabetes mellitus; alcoholism; cirrhosis; or cigarette smoking. Full compliance for those aged ≥ 65 years or in the HR1 cohort was defined as receipt of PCV13 and PPSV23, and partial compliance was defined as receipt of PCV13 or PPSV23. For those in the HR2 cohort, full compliance was defined as receipt of PPSV23. Annual compliance rates were estimated using the Kaplan–Meier method.Among those aged ≥ 65 years, partial compliance at 4 years post index was 53% and full compliance was 17% in adjusted analyses. In subjects ≥ 65 years receiving the first vaccination, 42% received the second vaccination by year 4. For the HR1 cohort, partial compliance was 19% and full compliance was 5% at 6 years post index date. For the HR2 cohort, full compliance was 20% at 6 years, with the highest rate in patients with diabetes (27%) and the lowest rate in patients with alcoholism (8%).Additional efforts are needed to maximize compliance to the ACIP pneumococcal vaccine recommendations among adults ≥ 65 years of age and adults with HR conditions including streamlined recommendations and single-dose vaccines. These efforts may subsequently reduce the incidence and burden of pneumococcal disease.     

外伤性晶状体脱位合并周边隐匿性视网膜病变的临床特征及预后分析

目的观察分析眼球钝挫伤合并外伤性晶状体脱位患者周边隐匿性视网膜病变的临床特点及预后。 方法本研究纳入2013年1月至2020年1月在柳州市人民医院眼科住院诊断为眼球钝挫伤合并外伤性晶状体脱位，并行23G微创玻璃体切割联合白内障摘除手术的72例（72眼）患者。根据裂隙灯和超声生物显微镜（UBM）检查，将患者分为晶状体不全脱位组和全脱位组，详细记录2组患者的术中周边视网膜病变情况，并分析其临床特征及疗效。 结果眼球钝挫伤合并外伤性晶状体脱位患者中有周边隐匿性视网膜病变的占72.22%，其中晶状体不全脱位组发生率高达80.95%，显著大于晶状体全脱位组的60.00%（P＜0.05）。2组患者的周边隐匿性视网膜病变均以隐匿性视网膜裂孔、变性和出血为最常见。所有患者术后视网膜情况稳定，视力预后较好。 结论眼球钝挫伤合并外伤性晶状体脱位患者常出现周边隐匿性视网膜病变，最常见的是视网膜裂孔、出血、变性。23G微创玻璃体切割联合白内障摘除手术是有效治疗手段，具有创伤小、并发症少的优势。     

一测多评法同时测定艾纳香油中5种成分

目的建立一测多评法同时测定艾纳香Blumea balsamifera(L.)DC.油中β⁃蒎烯、β⁃石竹烯、樟脑、α⁃石竹烯和龙脑5种成分的含有量。方法艾纳香油乙酸乙酯提取物的分析采用PEG⁃20 M柱(30 m×0.32 mm,1.0μm);程序升温;载气为高纯氮气(99.999%);FID检测器温度240℃,进样口温度240℃。以龙脑为内标,计算其他4种成分的相对校正因子,再测定其含有量。结果蒎烯、β⁃石竹烯、樟脑、α⁃石竹烯和龙脑分别在1.49~59.5μg/mL(r=0.9996)、2.22~88.8μg/mL(r=0.9996)、6.48~259μg/mL(r=0.9997)、3.64~146μg/mL(r=0.9991)和16.4~656μg/mL(r=0.9998)范围内线性关系良好,平均加样回收率(RSD)分别为97.4%(0.9%)、99.0%(1.3%)、98.9%(0.9%)、97.6%(0.9%)和99.7%(1.0%)。一测多评法所得结果接近于外标法。结论该方法准确稳定,重复性好,可用于艾纳香油的质量控制。     

IL‐17A synergistically enhances TLR3‐mediated IL‐36γ production by keratinocytes: A potential role in injury‐amplified psoriatic inflammation

Skin injury can trigger formation of new lesions in psoriasis (Koebner phenomenon). The mechanisms through which injury exacerbates psoriasis are unclear. During wound repair, epidermal keratinocytes are activated and produce abundant IL‐36γ, further promoting the skin inflammation. IL‐17A is the cornerstone cytokine in the pathogenesis of psoriasis. We sought to investigate the effects of IL‐17A on injury‐induced keratinocyte activation and IL‐36γ production. Here, we demonstrated that dsRNA released from necrotic keratinocytes induced the expression of IL‐36γ. Silencing of TLR3 by siRNA decreased the IL‐36γ induction by necrotic keratinocyte supernatant. Co‐stimulation with dsRNA and IL‐17A synergistically increased the expression of IL‐36γ and other proinflammatory mediators (CCL20, CXCL8, DEFB4 and LCN2) in keratinocytes. The synergistic effects were not dependent on TLR3 upregulation, TNF receptor signalling and mRNA stabilization. Co‐stimulation with dsRNA and IL‐17A resulted in an accumulation of IκBζ. The synergistic upregulation of IL‐36γ and proinflammatory mediators were inhibited by IκBζ siRNA. Co‐stimulation with IL‐17A and poly(I:C) markedly activated the p38 MAPK and NF‐κB pathway, compared with poly(I:C). Blockade of p38 MAPK and NF‐κB suppressed dsRNA/IL‐17A–mediated IκBζ and IL‐36γ induction. These findings demonstrated that IL‐17A synergistically enhanced the dsRNA‐mediated IL‐36γ production through a p38 MAPK‐, NF‐κB–, and IκBζ‐dependent mechanism.     

Impaired function of fibroblast growth factor 23 / Klotho protein axis in prediabetes and diabetes mellitus: Promising predictor of cardiovascular risk

The discovery of clear molecular mechanisms of early cardiac and vascular complications in patients with prediabetes and known diabetes mellitus are core element of stratification at risk with predictive model creation further. Previous clinical studies have shown a pivotal role of impaired signaling axis of fibroblast growth factor 23 (FGF23), FGF23 receptor isoforms and its co-factor Klotho protein in cardiovascular (CV) complications in prediabetes and diabetes. Although there were data received in clinical studies, which confirmed a causative role of altered function of FGF-23/Klotho protein axis in manifestation of CV disease in prediabetes and type 2 diabetes mellitus (T2DM), the target therapy of these diseases directing on improvement of metabolic profiles, systemic and adipokine-relating inflammation by beneficial restoring of dysregulation in FGF-23/Klotho protein axis remain to be not fully clear. The aim of the review was to summarize findings regarding the role of impaired FGF-23/Klotho protein axis in developing CV complications in patients with prediabetes and type 2 diabetes mellitus. It has been elucidated that elevated levels of FGF-23 and deficiency of Klotho protein in peripheral blood are predictors of CV disease and CV outcomes in patients with (pre) diabetes, while predictive values of dynamic changes of the concentrations of these biomarkers require to be elucidated in detail in the future.     

Impact of various culture conditions on ex vivo expansion of polyclonal T cells for adoptive immunotherapy

Currently, adoptive immunotherapy is considered as one of the leading treatments in cancer. Successful adoptive immunotherapy depends on producing large numbers of desired T cells ex vivo for infusion. This requires an effective protocol for maximum functional T‐cell expansion while keeping the time and costs to a minimum. Current T‐cell expansion protocols are diverse in their methodology, and a universal protocol of expansion is wanting. Also, new findings regarding T‐cell biology, signaling, and activation have reshaped the strategies of T‐cell propagation over the years, introducing new ways to expand T cells. Here, we reviewed different conditions for blood‐derived polyclonal T‐cell expansion so as to elucidate the influential factors of T‐cell expansion and their efficacy.     

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.     

Total neoadjuvant therapy: Fact,fantasy, or fallacy?

Colorectal cancer is the second leading cause of cancer death in the United States for men and women, with an estimated 146,000 new cases per year - a staggering 53,000 patients die each year. Rectal cancer comprises a third of these patients, with a 5-year survival rate of 67%. Management of locally advanced rectal cancer in the U.S. had remained stagnant for more than a decade, with most of these patients being treated with long-course chemoradiotherapy, surgery, followed by adjuvant chemotherapy; adjuvant chemotherapy being administered despite lacking a high level of evidence. Over the past few years, with rectal cancer death rates exceeding 30% from metastatic disease, growing interest focused on the attributes of induction chemotherapy to eradicate minimal residual disease and purportedly increase survival. This led to the development of total neoadjuvant therapy (TNT). We now have high-quality data from randomized prospective trials to review the facts, fantasies, and fallacies of TNT.     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.