Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver.The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world.We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV.The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1.     

单纯 Ilizarov 环形外固定技术治疗合并骨筋膜室综合征的胫骨平台骨折

目的探讨单纯 Ilizarov 环形外固定技术治疗合并骨筋膜室综合征的胫骨平台骨折的疗效。方法2013 年 9 月—2017 年 3 月，收治 30 例合并骨筋膜室综合征的胫骨平台骨折患者，采用单纯 Ilizarov 环形外固定技术治疗。男 23 例，女 7 例；年龄 23～43 岁，平均 34.4 岁。致伤原因：交通事故伤 12 例，高处坠落伤 4 例，摔伤 8 例，重物砸伤 6 例。受伤至入院时间 1～12 h，平均 4.8 h。骨折 Schatzker 分型：Ⅱ型 1 例、Ⅲ型 3 例、Ⅳ型 10 例、Ⅴ型 7 例、Ⅵ型 9 例。30 例均因骨筋膜室综合征行切开减压；切开减压至手术时间为 10～15 d，平均 12.5 d。治疗后采用膝关节学会评分系统（KSS）及 Ilizarov 方法研究与应用协会（ASAMI）协议评价膝关节功能。结果手术时间 110～155 min，平均 123.1 min；术中出血量 100～500 mL，平均 245 mL；术后住院时间 3～5 d，平均 3.8 d。患者均获随访，随访时间 20～24 周，平均 22.7 周。除 2 例患者出现针道感染征象外，无其他并发症发生。X 线片复查显示骨折均愈合，愈合时间 10～20 周，平均 14.6 周。末次随访时，膝关节 KSS 临床评分总分为 70～95 分，平均 87.5 分；功能评分总分为 70～90 分，平均 79.0 分。参照 ASAMI 协议评价获优 24 例、良 3 例、可 2 例、差 1 例。结论对于合并骨筋膜室综合征的胫骨平台骨折，单纯 Ilizarov 环形外固定技术治疗后患者关节功能可以基本恢复且并发症少，是一项相对安全、有效的治疗方法。     

Screening for musculoskeletal problems in children using a questionnaire

Background

On April 1, 2016, the Ministerial ordinance was enforced, and musculoskeletal examination of the extremities was made mandatory. From 2008, the University of us started musculoskeletal direct examination. To expand the examination, from 2016, we started to use the marksheet-type questionnaire. This study aimed to report the results of a musculoskeletal examination and investigate the association between musculoskeletal examination and age/gender and reports the reliability of the collected questionnaire data.

Infective Endocarditis Due to Treponema pallidum: A Case Diagnosed Using Polymerase Chain Reaction Analysis of Aortic Valve

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Syphilitic aortitis might coexist in a dysfunctional aortic valve, but the etiology remains unclear, because microbiological diagnosis is difficult. A 62-year-old man with low-grade fever was diagnosed with aortitis and infective endocarditis, due to Treponema pallidum infection, using polymerase chain reaction analysis. This case suggests that syphilis might cause infective endocarditis.     

Recurrent respiratory papillomatosis in northern Sweden: Clinical characteristics and practical guidance

Conclusion: Recurrent respiratory papillomatosis (RRP) patients with high surgical treatment frequency (≥ 1/year, HF) were significantly younger and had a more widespread laryngeal disease compared to a low frequency treated group (< 1 treatment/year, LF). This study confirms the existence of a clinical RRP group, not primarily related to HPV sub-type, but more care-intensive and in need of more vigilant follow-up. Objectives: RRP is associated with high morbidity due to its influence on breathing and voice. The purpose of this study was to characterize RRP patients in northern Sweden and investigate possible predictor factors affecting therapeutic needs. Method: Patients from the regional referral area (northern Sweden) were categorized for age, disease duration, juvenile or adult onset, profile of disease development, number of surgical sessions in relation to disease duration, laryngeal deposition of papilloma, gender, and HPV sub-types, in order to identify patients with increased need for frequent surgical treatment. Results: The median age of the RRP patients (n = 48) was 44.5 years; 34 (71%) were males and 14 (29%) females, most were infected with HPV 6. Patients with high surgical treatment frequency/year were significantly younger and showed more widespread papillomatous vegetation in the larynx, compared to the low frequency treated group.     

Accuracy of prehospital triage systems for mass casualty incidents in trauma register studies - A systematic review and meta-analysis of diagnostic test accuracy studies

BackgroundPrioritising patients in mass casualty incidents (MCI) can be extremely difficult. Therefore, triage systems are important in every emergency medical service. This study reviews the accuracy of primary triage systems for MCI in trauma register studies.MethodsWe registered a protocol at PROSPERO ID: CRD42018115438. We searched MEDLINE, EMBASE, Central, Web of Science, Scopus, Clinical Trials, Google Scholar, and reference lists for eligible studies. We included studies that both examined a primary triage system for MCI in trauma registers and provided sensitivity and specificity for critically injured vs non-critically injured as results. We excluded studies that used paediatric, chemical, biological, radiological or nuclear MCIs populations or triage systems. Finally, we calculated intra-study relative sensitivity, specificity and diagnostic odds ratio for each triage system.ResultsTriage Sieve (TS) significantly underperformed in relative diagnostic odds ratio (DOR) when compared to START and CareFlight (CF) (START vs TS: 19.85 vs 13.23 (p<0.0001)│CF vs TS: 23.72 vs 12.83 (p<0.0001)). There was no significant difference in DOR between TS and Military Sieve (MS) (p<0.710). Compared to START, MS and CF TS had significantly higher relative specificity (START vs TS: 93.6% vs 96.1% (p=0.047)│CF vs TS: 96% vs 95.3% (p=0.0006)│MS vs TS: 94% vs 88.3% (p=0.0002)) and lower relative sensitivity (START vs TS: 57.8% vs 34.8% (p<0.0001)│CF vs TS: 53.9% vs 34.7% (p<0.0001)│MS vs TS: 51.9% vs 35.2% p<0.0001)).CF had significantly better relative DOR than START (CF vs START: 23.56 vs 27.79 (p=0.043)). MS had significantly better relative sensitivity than CF and START (MS vs CF: 49.5% vs 38.7% (p<0.0001)│MS vs START: 49.4% vs 43.9% (p=0.01)). In contrast, CF had significantly better relative specificity than MS (MS vs CF: 91.3% vs 93.3% (p<0.0001)). The remaining comparisons did not yield any significant differences.ConclusionAs the included studies were at risk of bias and had heterogenic characteristics, our results should be interpreted with caution. Nonetheless, our results point towards inferior accuracy of Triage Sieve compared to START and CareFlight, and less firmly point towards superior accuracy of Military Sieve compared to START, CareFlight and Triage Sieve     

Switch From Twice-daily Tacrolimus to Once-daily,Prolonged-release Tacrolimus in Kidney Transplantation: Long-term Outcome

Background

One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety.

Vaccination against HPV: boosting coverage and tackling misinformation

The availability of human papillomavirus (HPV) vaccines and screening tests has raised the possibility of globally eliminating cervical cancer, which is caused by HPV. Cervical cancer is a very common malignancy worldwide, especially among deprived women. High vaccination coverage is key to the containment and eventual elimination of the infection. Public HPV vaccination programmes in Italy and Denmark were swiftly established and are among the most successful worldwide. Still, in both countries, it has been challenging to achieve and maintain the recommended coverage of > 80% in girls. In a well‐studied Italian region, vaccination coverage in girls at age 15 years (World Health Organization''s gold standard) reached 76% in 2015 but decreased to 69% in 2018, likely due to work overload in public immunization centres. In Denmark, doubts about safety and efficacy of the HPV vaccine generated a decline in coverage among girls age 12–17, from 80% in 2013 down to 37% in 2015, when remedial actions made it rise again. Insights from these two countries are shared to illustrate the importance of monitoring coverage in a digital vaccine registry and promptly reacting to misinformation about vaccination.

Abbreviations

CC

cervical cancer

FVG

Friuli Venezia Giulia

HICs

high‐income countries

HPV

human papillomavirus

LMICs

middle‐income countries

WHO

World Health Organization