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。     

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.     

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.     

沉默TRIM23基因抑制骨肉瘤细胞的增殖

目的 探讨TRIM23基因对骨肉瘤细胞增殖能力的影响.方法 应用Western blot实验检测TRIM23基因在骨肉瘤细胞中的表达;应用shRNA质粒转染骨肉瘤细胞系U2OS,通过MTT与平板克隆形成实验评估细胞增殖能力;应用Westernblot实验检测U2OS细胞Akt/P53/P21通路的表达改变.结果 TRIM23蛋白在骨肉瘤细胞中的表达高于成骨细胞;沉默TRIM23基因可以抑制骨肉瘤细胞的增殖能力;沉默TRIM23基因下调P-Akt表达,但总Akt的表达无明显改变,上调P53与P21的表达.结论 TRIM23在骨肉瘤细胞中表达升高,TRIM23能通过调节Akt/P53/P21通路影响骨肉瘤细胞的增殖.     

Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infants

BackgroundPapua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity. This study investigated PCV13 impact on serotype-specific pneumococcal carriage prevalence, density, and serotype diversity in PNG infants, who have some of the highest reported rates of pneumococcal carriage and disease in the world.MethodsNasopharyngeal swabs were collected at 1, 4 and 9 months of age from PCV13-vaccinated infants (n = 57) and age-/season-matched, unvaccinated infants (at approximately 1 month, n = 53; 4 months, n = 57; 9 months, n = 52). Serotype-specific pneumococcal carriage density and antimicrobial resistance genes were identified by qPCR and microarray.ResultsPneumococci were present in 89% of swabs, with 60 different serotypes and four non-encapsulated variants detected. Multiple serotype carriage was common (47% of swabs). Vaccine type carriage prevalence was similar between PCV13-vaccinated and unvaccinated infants at 4 and 9 months of age. The prevalence of non-vaccine type carriage was also similar between cohorts, with non-vaccine types present in three-quarters of samples (from both vaccinated and unvaccinated infants) by 4 months of age. The median pneumococcal carriage density was high and similar at each age group (~7.0 log₁₀ genome equivalents/mL). PCV13 had no effect on overall pneumococcal carriage density, vaccine type density, non-vaccine type density, or the prevalence of antimicrobial resistance genes.ConclusionPNG infants experience dense and diverse pneumococcal colonisation with concurrent serotypes from 1 month of age. PCV13 had no impact on pneumococcal carriage density, even for vaccine serotypes. The low prevalence of vaccine serotypes, high pneumococcal carriage density and abundance of non-vaccine serotypes likely contribute to the lack of PCV13 impact on carriage in PNG infants. Indirect effects of the infant PCV programs are likely to be limited in PNG. Alternative vaccines with broader coverage should be considered.     

Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion

Background

Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.

A novel splice-site variant in CDH23 in a patient with Usher syndrome type 1

ABSTRACT

Background: Gene editing has shown huge potential in correcting aberrant splicing and Cas13 has been identified as being particularly suitable for targeting RNA. It has therefore become increasingly important to highlight new splice site mutations that may be correctable, particularly in genes that are too large to be encoded by AAV vectors. About 20% of Usher Type 1 cases are caused by mutations in CDH23.

Purpose: To report a novel splice site mutation of CDH23 associated with Usher Type 1D.

Materials and Methods: Case report.

Results: A 35-year-old Caucasian female who is congenitally deaf with vestibular dysfunction presented with visual acuity of 6/12 in both eyes. Fundus examination revealed findings typical of retinitis pigmentosa with foveal preservation of photoreceptor layer. Next generation sequencing analysis revealed a novel homozygous variant, c.9319 + 1G>T in CDH23 consistent with the diagnosis of Usher Syndrome Type 1D. The c.9319 + 1G>T variant is predicted to affect splicing at the exon 65/intron 65 boundary, which highly likely leads to complete skipping of exon 65.

Conclusions: We describe a case of a typical Usher Syndrome Type 1D caused by a novel splice site variant in CDH23. Currently there are no treatments for CDH23 related retinal degeneration, partly because the cDNA size of 10kb is too large for AAV vector gene augmentation therapy. Alternative strategies include CRISPR-Cas9 adenine base editors and RNA editing with CRISPR-Cas13. Single-nucleotide editing represents a promising approach for targeting this variant in CDH23 to restore the wildtype splice donor site at this position.