Clinical characteristics of pediatric patients with COVID-19 between Omicron era vs. pre-Omicron era

IntroductionDetailed data on clinical characteristics in children with the omicron strain of SARS-COV-2 are limited.MethodsWe conducted a retrospective observational study of children with COVID-19 at the National Center for Child Health and Development to evaluate the clinical manifestations during and before the emergence of the omicron variant. Only symptomatic patients without underlying diseases were included. Participants were divided into two temporal groups: the “omicron era” (1/2022–2/2022) and the “pre-omicron era,” where the delta variant predominated (7/2021–11/2021). The patients were subclassified into an older vaccine-eligible group (aged 12–17 years), a younger vaccine-eligible group (aged 5–11 years), and a vaccine-ineligible group (aged 0–4 years).ResultsWe compared 113 patients in the omicron era with 106 in the pre-omicron era. Most patients in both eras had non-severe disease, and no patients required mechanical ventilation or died. Among patients aged 0–4 years, sore throat and hoarseness were more common during the omicron era than the pre-omicron era (11.1% vs. 0.0% and 11.1% vs. 1.5%, respectively). Croup syndrome was diagnosed in all patients with hoarseness. Among patients aged 5–11 years, vomiting was more frequent during the omicron era (47.2%) than during the pre-omicron era (21.7%). Cough and rhinorrhea were less common during the omicron era in patients aged 0–4 and 5–11 years, respectively, than during the pre-omicron era.ConclusionsIn children with COVID-19, clinical manifestations differed between the omicron and pre-omicron eras. In the Omicron era, croup syndrome was more frequent in vaccine-ineligible children.     

RNA sequencing steps toward the first line

• DNA is the sequence that codes for proteins.
• Messenger RNA is transcribed from the DNA sequence of genes and translated into protein.
• It can be difficult to predict how a change in the DNA sequence will affect messenger RNA and protein quantity and quality.
• DNA translocation changes can cause the joining of sequences from two different genes or different parts of the same gene.
• DNA sequencing is often used clinically to predict how DNA changes might affect proteins.
• Alternatively, RNA sequencing can be used as a more direct measure of the effect of DNA changes on the protein products.
• This sequencing is important for identifying changes in cancer that may indicate response to targeted therapy, prognosis, or diagnosis.

     

Reflection of neuroblastoma intratumor heterogeneity in the new OHC-NB1 disease model

Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.     

Mutation status and burden can improve prognostic prediction of patients with lower‐risk myelodysplastic syndromes

Patients with lower‐risk myelodysplastic syndromes (LR‐MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter‐individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS‐relevant genes in 159 patients with LR‐MDS using next‐generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129‐4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144‐8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662‐14.230) and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848‐16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273‐4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR‐MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher‐risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS‐relevant genes may improve the prognostication of patients with LR‐MDS and could help identify those with worse‐than‐expected prognosis for more aggressive treatment.     

维生素D3治疗小儿变异性哮喘的效果

目的讨论思考丙酸氟替卡松、硫酸沙丁胺醇吸入联合维生素D3治疗小儿变异性哮喘的临床效果。方法抽选于2018年12月-2019年12月期间本院儿科门诊共收治的小儿变异性哮喘患儿72例入组,根据计算机随机分组法均分为两组。对照组(n=36)给予丙酸氟替卡松联合硫酸沙丁胺醇吸入治疗,研究组(n=36)给予丙酸氟替卡松、硫酸沙丁胺醇吸入联合维生素D3治疗。评价及对比两组的疗效、T淋巴细胞含量、血清生化指标。结果研究组的疗效高于对照组(P<0.05);研究组的血清生化指标均优于对照组(P<0.05);研究组的CD4^+、CD4^+/CD8^+含量低于对照组,且CD8^+含量高于对照组(P<0.05)。结论丙酸氟替卡松、硫酸沙丁胺醇吸入联合维生素D3治疗小儿变异性哮喘,疗效确切,可协同增效、相互补充,缓解症状,维持T淋巴细胞亚群平衡,减轻炎症反应,值得临床借鉴应用。     

Germline variant burden in multidrug resistance transporters is a therapy-specific predictor of survival in breast cancer patients

Multidrug resistance due to facilitated drug efflux mediated by ATP-binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease-specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug-specific for subgroups treated with the MRP1 substrates cyclophosphamide (log-rank p = 0.0011) and doxorubicin (log-rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log-rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine.     

滋阴清嗓汤对咳嗽变异性哮喘发作期患儿IgE、IL-4、IL-5水平的影响及安全性分析

目的:探究滋阴清嗓汤对咳嗽变异性哮喘(CVA)发作期患儿免疫球蛋白E(IgE)、白细胞介素-4(IL-4)、白细胞介素-5(IL-5)的影响及安全性。方法:选取2018年1月—2019年6月在河南省儿童医院东三街院区呼吸科一病区住院治疗的170例CVA患儿,随机分为中医联合组(85例)和西医常规组(85例)。所有患儿均给予西医常规治疗,中医联合组加用滋阴清嗓汤。两组均连续治疗14 d后,观察并比较两组的疗效、症状改善时间、临床主要症状积分、外周血单个核细胞(PBMC)内IL-4、IL-5、血清IgE水平、呼出气一氧化氮(FeNO)及肺功能指标水平。结果:中医联合组患儿痊愈率为80.00%(68/85),显著高于西医常规组痊愈率61.18%(52/85)(P<0.05)。中医联合组患儿症状改善时间(咳嗽减轻、咳嗽消退、夜咳停止的时间)均显著短于西医常规组(P<0.05)。治疗后,两组患儿咳嗽、咽痛、喉痒评分均显著下降,且中医联合组显著低于西医常规组(P<0.05)。治疗后,两组患儿PBMC内IL-4、IL-5及血清IgE水平均显著下降,且中医联合组均显著低于西医常规组(P<0.05)。治疗后,两组患者FeNO和1 s用力呼气容积(FEV1)均显著下降(P<0.05),呼气峰流速(PEF)均显著升高(P<0.05),组间比较,中医联合组均显著优于西医常规组(P<0.05)。两组患者在治疗期间均未发生明显不良反应和不良事件。结论:滋阴清嗓汤对CVA发作期患儿具有良好的疗效,可发挥较好的滋阴清热、止咳平喘、改善慢性炎症作用,有效改善其临床症状,安全性高,值得推广。     

Proteomic genotyping of fingermark donors with genetically variant peptides

Proteomic genotyping detects single amino acid polymorphisms to infer the genotype of corresponding non-synonymous SNPs. Like any DNA genotype, these inferences can be used to estimate random match probability. Fingermarks are a common source of biological evidence that is sample limited and a highly variable source of identifying DNA. Genetically variant peptides from fingermarks, that contain single amino acid polymorphisms, are an additional source of identifying genetic information. To discover these peptide biomarkers epidermal corneocytes from 9 subjects were isolated, processed, digested with trypsin and applied to mass spectrometry. The resulting proteomic and matching exome datasets were used to discover, characterize and validate 60 genetically variant peptides. An average of 28.8 ± 4.4 genetically variant peptides were detected from each subject resulting in a total of 264 SNP allele inferences with 260 true and 4 false positives, a false discovery rate of 1.5%. Random match probabilities were estimated using the genotype frequencies from the matching major populations in the 1000 Genomes Project. Estimates ranged up to a value of 1 in 1.7 × 10⁸, with a median probability of 1 in 2.4 × 10⁶. Furthermore, the proteomically-inferred genotypes are likely to be compatible with the STR-based random match probability estimates since the closest STR locus was 2.2 Mb from the nearest GVP-inferred SNP. This project represents a novel mode of genetic information that can be obtained from fingermarks and has the potential to complement other methods of human identification including analysis of ridge patterns or touch DNA.     

Comparison of the clinical characteristics and outcomes of COVID-19 in children before and after the emergence of Delta variant of concern in Japan

Delta variant of concern (VOC) is the current predominant severe acute respiratory coronavirus type 2 strain causing coronavirus disease 2019 (COVID-19); however, information regarding the impact of the Delta VOC on clinical features and outcomes in pediatric patients with COVID-19 is limited. We conducted a retrospective observational study using the data of patients <18 years of age in COVIREGI-JP, the COVID-19 registry in Japan. The patients were divided into two groups according to the timing of enrollment in the registry (pre-Delta VOC era, October 2020 to May 2021; and Delta VOC era, August to October 2021), and the clinical characteristics and outcomes were compared between the two groups. During the study period, 950 and 349 pediatric patients were registered in the pre-Delta VOC and Delta VOC eras, respectively. The median patient age was younger and the proportion of patients with underlying diseases was higher in the Delta VOC era than that in the pre-Delta VOC era (10.0 vs 7.0 years, P < 0.001, and 7.4% [n = 70] vs. 12.6% [n = 44], P = 0.004, respectively). Significantly more patients were admitted to the intensive care unit in the Delta VOC era than in the pre-Delta VOC era (1.4% [ n = 5] vs. 0.1% [n = 1], P = 0.006), but no patient in either group died or required mechanical ventilation or extracorporeal membrane oxygenation throughout the study period, suggesting that the overall outcomes in children with COVID-19 remained favorable even in the Delta VOC era in Japan.