Safety and immunogenicity of NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Interim report of a phase I/II randomized controlled trial

BackgroundWe evaluated the safety and immunogenicity of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, in healthy Japanese participants.MethodsThis phase 1/2, randomized, observer-blind, placebo-controlled trial conducted in Japan (two sites), enrolled healthy Japanese adults aged ≥ 20 years with no history/risk of SARS-CoV-2 infection and no prior exposure to other approved/investigational SARS-CoV-2 vaccines or treatments. Participants were stratified by age (< 65 or ≥ 65 years) and randomized to receive two doses of either NVX-CoV2373 (5 μg SARS-CoV-2 rS; 50 μg Matrix-M1) or placebo, 21 days apart. Primary outcomes were safety and immunogenicity assessed by serum IgG antibody levels against SARS-CoV-2 rS protein on day 36. Herein, we report the primary data analysis at 4 weeks after the second dose, ahead of 12-month follow-up completion (data cut-off: 8 May 2021).ResultsBetween 12 February 2021 and 17 March 2021, 326 subjects were screened, and 200 participants enrolled and randomized: NVX-CoV2373, n = 150; placebo, n = 50. Solicited adverse events (AEs) through 7 days after each injection occurred in 121/150 (80.7%) and 11/50 (22.0%) participants in the NVX-CoV2373 and placebo arms, respectively. In the NVX-CoV2373 arm, tenderness and injection site pain were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with NVX-CoV2373 (n = 150) by day 36: IgG geometric mean fold rise (95% confidence interval) 259 (219, 306); seroconversion rate 100% (97.6, 100). No such response occurred with placebo (n = 49).ConclusionTwo doses of NVX-CoV2373 given with a 21-day interval demonstrated acceptable safety and induced robust anti-SARS-CoV-2 immune responses in healthy Japanese adults. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov identifier: NCT04712110.     

一测多评法在中药质量控制中的应用及研究进展＊

一测多评法（quantitative analysis of multi-components by single marker，QAMS）已成熟应用于中药材、中药提取物及中成药领域等中药复杂体系的质量评价研究中，有效解决了因对照品缺乏而导致的多指标质控技术推广难问题。本文查阅近五年的国内外研究文献，重点总结了高效液相色谱、气相色谱和质谱等技术在QAMS法中药质量控制中的应用。高效液相色谱联用紫外检测器（UV）技术应用最为广泛，最适合于中药QAMS法定量，结果稳定、准确；而高效液相色谱联用蒸发光检测器在中药QAMS法应用中，其测定准确性和适用性仍然需进一步探索和验证。液质联用技术虽然具有灵敏度高、线性范围宽等优点，但易受仪器参数、基质效应等的影响。进一步发展HPLC-UV技术在中成药制剂质量评价中的应用，是QAMS法多成分定量值得关注的方向；探索LC-MS和GC技术在中药QAMS质量评价中的稳定性和普适性是未来将面临的挑战。     

玻璃体腔内注射抗血管内皮生长因子治疗早产儿视网膜病复发的危险因素分析

目的 探讨玻璃体腔内注射抗血管内皮生长因子（vascular endothelial growth factor，VEGF）治疗早产儿视网膜病（retinopathy of prematurity，ROP）的效果及复发的危险因素。 方法 回顾性收集2016年1月—2021年12月在郑州大学第一附属医院出生行抗VEGF治疗的ROP患儿159例的临床资料，根据首次抗VEGF治疗后随访周期内ROP复发与否分为复发组（24例）和非复发组（135例），比较分析2组临床资料，采用多因素logistic回归分析探讨抗VEGF治疗ROP复发的危险因素。 结果 经单次抗VEGF治疗后，所有159例患儿均显示附加病变消退。24例（15.1%）抗VEGF治疗后复发，复发平均时间为治疗后（8.4±2.6）周。多因素logistic回归分析显示，术前眼底出血、总用氧时间较长是ROP复发的危险因素（P<0.05），而妊娠高血压是保护因素（P<0.05）。 结论 玻璃体腔内注射抗VEGF治疗ROP是有效的。术前眼底出血和氧疗时间较长可增加ROP复发的风险，而对于妊娠高血压对ROP复发的影响，还需进一步研究证实。     

Quantitative assessment of bony orbital volume symmetry: CT analysis in the uninjured caucasian population

There is a surprising lack of evidence documenting the volumetric symmetry of the bony orbit. This paper establishes reference values for orbital volume (OV) and symmetry in the 25 - 40 year old caucasian population. Secondarily, this paper sets a landmark for the tolerances in OV that can be expected when reconstructing the bony defects which may occur from trauma. A standardised method of quantitative OV measurement was developed using CT sinus examinations acquired for indications unrelated to orbital trauma. Sex, ethnicity, age, right and left OV were recorded. Data for 100 patients was obtained (50 male, 50 female). Mean left OV was 23.1cm³ and mean right OV was 23.3cm³. Left and right OV were strongly positively correlated (correlation coefficient: 0.96). Mean female OV was 21.6cm³ and mean male OV was 24.8cm³. On average, male OV is 3.2cm³ larger than female OV. The mean difference between left and right OV was 0.5cm³ in females and 0.6cm³ in males. The intra-class coefficient score between the two assessors was 0.973 (excellent). There is strong positive correlation between left and right OV in this study population. Previous work suggests that orbital volume loss less than 1cm³ would not lead to significant clinical symptoms of orbital fracture. When orbital reconstruction is undertaken, this study suggests that a volume symmetry difference of <0.5cm³ in females and <0.6cm³ in males would be consistent with the variation seen in the study population of uninjured caucasian 25-40 year olds and is therefore a reasonable goal of surgical management.     

Desarrollo y validación de la versión abreviada del Transsexual Voice Questionnaire for Male-to-Female Transsexuals en español

ObjectiveThe aim of this study was to create and validate an abbreviated version of the Spanish Transsexual Voice Questionnaire for Male-to-Female Transsexuals (SvTVQ^MtF).SettingThe study was conducted by two referral hospitals for voice feminization surgery and by a university department of psychology and speech therapy, all in Spain.Subjects and methodsWe prospectively studied 51 male-to-female transsexuals who underwent voice feminization surgery between January 2017 and December 2018. The SvTVQ^MtF was completed before and after surgery, and the 10 items with the greatest variation were selected by clinical consensus of an expert panel to develop the short version of the SvTVQ^MtF (SvTVQ^MtF-10). The correlation between the total score and the score for each item on the SvTVQ^MtF and the SvTVQMtF-10 was studied. The internal consistency of the SvTVQ^MtF-10 was analysed.ResultsGood correlation (Pearson coefficient above .90) was found between the two questionnaires. A significant correlation was found between the total SvTVQ^MtF-10 score and the score for each item. A significant negative correlation was found between the SvTVQ^MtF and fundamental frequency after voice feminization surgery. Cronbach's α was .79.ConclusionThe SvTVQ^MtF-10 is a valid short version of the SvTVQ^MtF and can be used to quantify voice-related quality of life in MtF transsexuals.     

出生免疫错误相关的肝脾问题

目前已用出生免疫错误（IEI）来替代原发性免疫缺陷病这一概念。IEI是一类由单基因突变引起免疫功能异常的遗传性疾病，肝脏和脾脏作为人类重要的免疫器官，与IEI疾病过程中伴发感染、淋巴增殖及自身免疫现象等有重要关联。文章就与IEI相关的肝脾问题进行概述。     

Contemporary Epidemiology of and Risk Factors Associated with Removal of a Pathologically Normal Appendix in Children with Suspected Appendicitis

BackgroundThe goal of this study was to characterize contemporary performance benchmarks and risk factors associated with negative appendectomy (NA) in children with suspected appendicitis.MethodsA multicenter retrospective cohort analysis of children undergoing appendectomy for suspected appendicitis was performed using data from the 2016–2021 NSQIP-Pediatric Appendectomy Targeted Public Use Files. Multivariable regression was used to evaluate the influence of year, age, sex, and WBC count on NA rate, and to generate rate estimates for NA based on different combinations of demographic characteristics and WBC profiles.Results100,322 patients were included from 140 hospitals. The overall NA rate was 2.4%, and rates decreased significantly during the study period (2016: 3.1% vs. 2021: 2.3%, p < 0.001). In adjusted analyses, the highest risk for NA was associated with a normal WBC (<9000/mm³; OR 5.31 [95% CI: 4.87–5.80]), followed by female sex (OR 1.55 [95% CI: 1.42–1.68]) and age <5 years (OR 1.64 [95% CI 1.39, 1.94]). Model-estimated risk for NA varied significantly across demographic and WBC strata, with a 14.4-fold range in rates between subgroups with the lowest and highest predicted risk (males 13–17 years with elevated WBC [1.1%] vs. females 3–4 years with normal WBC [15.8%]).ConclusionsContemporary NA rates have decreased over time, however NA risk remains high in children without a leukocytosis, particularly for girls and children <5 years of age. These data provide contemporary performance benchmarks for NA in children with suspected appendicitis and identify high-risk populations where further efforts to mitigate NA risk should be targeted.Level of EvidenceIII.     

Diagnosis of pituitary abscess and treatment via transsphenoidal surgery: experience from 15 cases

ObjectivePituitary abscess is an often misdiagnosed, rare clinical disorder. To improve diagnostic accuracy and the efficacy of surgical and antibiotic therapy for patients with pituitary abscess, herein, we retrospectively reviewed 15 patients who presented with pituitary abscesses from 2005 to 2022.DesignRetrospective study.PatientsFifteen patients underwent transsphenoidal surgery and received antibiotic treatment.MeasurementsComplete details regarding medical history, clinical manifestations, laboratory examinations, imaging studies, and treatment strategies were obtained for all patients.ResultsMost patients presented with hypopituitarism and headaches, while some presented with fever, visual disturbances, and diabetes insipidus (DI). Abscesses showed significant annular enhancement post gadolinium injection. In most patients, pituitary abscess can be cured via microscopic or endoscopic drainage of the abscess followed by antibiotic treatment. Complete cure of pituitary abscess was observed in nine patients, with six cases of prolonged hypopituitarism and only one case of recurrence. Long-term hormone replacement therapy was effective in the postoperative management of hypopituitarism.ConclusionsThe typical manifestations of pituitary abscess include hypopituitarism and headaches; the presence of an enhanced ring at the edge of the mass on contrast-enhanced magnetic resonance images (MRI) is highly suggestive of pituitary abscess. We recommend antibiotic treatment for 4–6 weeks postoperatively, based on the results of bacterial cultures or metagenomic next-generation sequencing (mNGS).     

Factors influencing the rating of sonographer students’ clinical performance

IntroductionLittle is known about the factors influencing clinical supervisor-assessors’ ratings of sonographer students’ performance. This study identifies these influential factors and relates them to professional competency standards, with the aim of raising awareness and improving assessment practice.MethodsThis study used archived written comments from 94 clinical assessors describing 174 sonographer students’ performance one month into their initial clinical practice (2015–6). Qualitative mixed method analysis revealed factors influencing assessor ratings of student performance and provided an estimate of the valency, association, and frequency of these factors.ResultsAssessors provided written comments for 93 % (n = 162/174) of students. Comments totaled 7190 words (mean of 44 words/student). One-third of comment paragraphs were wholly positive, two-thirds were equivocal. None were wholly negative. Thematic analysis revealed eleven factors, and eight sub-factors, influencing assessor impressions of five dimensions of performance. Of the factors mentioned, 84.6 % (n = 853/1008) related to professional competencies. While 15.4 % (n = 155/1008) were unrelated to competencies, instead reflecting humanistic factors such as student motivation, disposition, approach to learning, prospects and impact on supervisor and staff. Factors were prioritised and combined independently, although some associated.ConclusionClinical assessors formed impressions based on student performance, humanistic behaviours and personal qualities not necessarily outlined in educational outcomes or professional competency standards. Their presence, and interrelations, impact success in clinical practice, through their contribution to, and indication of, competence.Implications for practiceSonographer student curricula and assessor training should raise awareness of the factors influencing performance ratings and judgement of clinical competence, particularly the importance of humanistic factors. Inclusion of narrative comments, multiple assessors, and broad performance dimensions would enhance clinical assessment of sonographer student performance.