Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol)

BackgroundA venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines.AimThe aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration.MethodsThrough a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports.     

Anatomic vs. reverse shoulder arthroplasty for glenohumeral osteoarthritis with intact rotator cuff: a retrospective comparison of patient-reported outcomes using the systems outcomes database with up to 5-year follow-up

BackgroundThe growing enthusiasm for the use of reverse shoulder arthroplasty (RSA) in the treatment of primary glenohumeral osteoarthritis (GHOA) with an intact rotator cuff is based on data derived from single-center studies with limited generalizability and follow-up. This study compared patient-reported outcomes (PROs) between RSA and total shoulder arthroplasty (TSA) for the treatment of primary GHOA with up to 5-year follow-up and examined temporal trends in the treatment of GHOA between 2012 and 2021.MethodsA retrospective review was performed on patients with primary GHOA undergoing primary arthroplasty surgery from the Surgical Outcomes System global registry between 2012 and 2021. PROs including the American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE) score, and visual analog scale (VAS) for pain were compared between RSA and TSA at 1, 2, and 5 years postoperatively.ResultsA total of 4451 patients were included, with 2693 (60.5%) undergoing TSA and 1758 (39.5%) undergoing RSA. Both RSA and TSA provided clinically excellent outcomes at 1 year postoperatively (ASES: 80.8 ± 17.9 vs. 85.9 ± 15.2, respectively; SANE: 74.8 ± 24.7 vs. 79.5 ± 22.9; VAS pain: 1.3 ± 2.0 vs. 1.1 ± 1.7; all P < .05) that were maintained at 2 years (ASES: 81.3 ± 19.3 vs. 87.3 ± 14.9; SANE: 74.8 ± 26.2 vs. 79.7 ± 24.7; VAS pain: 1.3 ± 2.1 vs. 1.0 ± 1.6; all P < .05) and 5 years (ASES: 81.7 ± 16.5 vs. 86.9 ± 15.3; SANE: 71.6 ± 28.5 vs. 78.2 ± 25.9; VAS pain: 1.0 ± 1.7 vs. 1.0 ± 1.7; all P < .05), with statistical significance favoring TSA. After controlling for age and sex, there was an adjusted difference of 4.5 units in the ASES score favoring TSA (P = .005) at 5 years postoperatively but no differences in adjusted SANE (P = .745) and VAS pain (P = .332) scores. The use of RSA for GHOA grew considerably over time, from representing only 17% of all replacements performed for GHOA in 2012 to nearly half (47%) in 2021 (P < .001).ConclusionRSA as a treatment for GHOA with an intact rotator cuff seems to yield PROs that are largely clinically equivalent to TSA extending to 5 years postoperatively. The observed statistical significance favoring TSA appears to be of marginal clinical benefit based on established minimal clinically important differences and may be a result of the large sample size. Further research using more granular clinical data and examining differences in range of motion and complications is warranted as it may change the value analysis.     

Genetic variation of 17 autosomal STR loci in the Lahu population from Yunnan and phylogenetic structure exploration among 28 populations

This study evaluated the genetic variation of 17 autosomal short tandem repeat (STR) loci included in the PowerPlex® 18D Kit. Samples of 562 unrelated healthy Lahu individuals living in Yunnan Province in southwestern China were investigated. The data were analyzed to provide information on allele frequencies and other statistical parameters relevant to the forensic population. Of the 17 loci, 16 reached the Hardy–Weinberg equilibrium after Bonferroni correction. A total of 176 alleles were identified in 17 STR loci, and allele frequencies ranged from 0.000 890 to 0.578 292. The combined discrimination power (CPD) and probability of excluding paternity (CPE) of the 17 STR loci were 0.999 999 999 999 999 999 489 and 0.999 998 301 753 122. The genetic relationships among 28 populations were also estimated.     

Ocular dysfunctions and toxicities induced by antiepileptic medications: Types,pathogenic mechanisms,and treatment strategies

Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.

Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.

Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk.     

A new aspect of in vitro antimicrobial leukocyte- and platelet-rich plasma activity based on flow cytometry assessment

The current literature suggests that the antibacterial effect of leukocyte- and platelet-rich plasma (L-PRP) is directly related to platelet and leukocyte concentrations. The aim of this study was twofold: first, to evaluate the antimicrobial effect of L-PRP against selected bacterial strains in vitro, and second, to correlate this effect with leukocyte and platelet content in the final concentration. Blood was collected from 20 healthy males, and L-PRP, acellular plasma (AP), and autologous thrombin were consecutively prepared. Flow cytometry analysis of the blood, L-PRP, and AP was performed. The L-PRP gel, liquid L-PRP, and thrombin samples were tested in vitro for their antibacterial properties against seven selected bacterial strains using the Kirby–Bauer disk-diffusion method. There was notable antimicrobial activity against selected bacterial strains. No statistically significant correlations between antimicrobial activities and the platelet concentration in L-PRP were observed. Statistically significant positive correlations between selected leukocyte subtypes and antimicrobial activity were noted. A negative correlation was found between elevated monocyte count and antimicrobial activity of L-PRP against one bacterial strain studied. L-PRP possesses antimicrobial activity and can be potentially useful in the fight against certain postoperative infections. The bactericidal effect of L-PRP is caused by leukocytes, and there exists a relationship among selected leukocyte subtypes and L-PRP antimicrobial activity.     

血流感染肺炎克雷伯菌中CRISPR-Cas系统的分布及其与毒力基因和耐药的关系

的 了解血流感染肺炎克雷伯菌中CRISPR-Cas系统的分布特征并分析其与毒力基因和耐药的关系。方法 收集非重复血流感染肺炎克雷伯菌248株，使用Vitek2-Compact全自动微生物分析系统进行菌株鉴定及药物敏感性分析，PCR检测CRISPR-Cas系统3个相关基因(CRISPR1、CRISPR2和cas1)、筛查6种常见高毒力荚膜血清型(K1、K2、K5、 K20、K54和K57)、12种毒力基因及检测13种耐药基因，用χ2检验比较携带有CRISPR-Cas系统菌株与不携带CRISPR-Cas系统菌株毒力及耐药差异。结果 CRISPR-Cas系统的检出率为29.8%(74/248)；K1型是携带CRISPR-Cas系统肺炎克雷伯菌的主要荚膜血清型，占 28.4%(21/74)；除kpn基因外，携带CRISPR-Cas系统菌株的毒力基因检出率均大于不携带CRISPR-Cas系统菌株，其中7种差异有统计学意义；除对氨苄西林耐药率达100%外，携带有CRISPR-Cas系统菌株的其他抗菌药物耐药率均小于不携带有CRISPR-Cas系统菌株，其中13种差异有统计学意义；携带CRISPR-Cas系统菌株的耐药基因阳性率小于不携带CRISPR-Cas系统的菌株，且blaKPC、blaSHV、qnrS基因差异有统计学意义。结论 高毒力荚膜血清型肺炎克雷伯菌中主要为K1型携带CRISPR-Cas系统，携带CRISPR-Cas系统的肺炎克雷伯菌相对于不携带CRISPR-Cas系统菌株的毒力基因阳性率高，耐药率低，耐药基因的阳性率低。CRISPR-Cas系统可能能降低耐药基因在肺炎克雷伯菌中的水平传播，尤其是在K1型肺炎克雷伯菌。     

基于代谢组学探讨艾灸关元穴对老年大鼠肾能量代谢的影响＊

目的 通过UHPLC-Q-TOF-MS代谢组学探讨艾灸关元穴对老年大鼠肾代谢物的影响，进而为艾灸关元穴的作用机制提供参考。方法 将8月龄SD雄性大鼠设为成年对照组（8只），21月龄SD雄性大鼠随机分为老年对照组（8只）、老年金匮肾气丸组（7只）、老年艾灸组（8只）。老年金匮肾气丸组每日按体重给药，老年艾灸组每日艾灸关元穴15 min，均每周5天。实验持续13周后检测大鼠肾组织线粒体呼吸耗氧速率、琥珀酸脱氢酶（SDH）活性以及血清肾功能指标，观察肾脏病理变化，结合UHPLC-Q-TOF-MS技术对大鼠的肾组织进行代谢轮廓分析，筛选代谢差异物并进行鉴定。结果 与老年对照组比较，老年艾灸组大鼠肾线粒体的呼吸耗氧速率和SDH酶的活力显著提高（P<0.01）。代谢组学结果显示，肾组织中筛选出13个共同差异化合物，分别是丁酸十二烷基酯、亚油酰胺、5-甲基四氢叶酸、PC（16∶0/22∶5（7Z，10Z，13Z，16Z，19Z））、6，8-二羟基嘌呤、1，2，3-丙烷三羧酸、3-（4-甲氧基苯基）-2-氧代丙酸、吲哚-3-乙酰甘氨酸、亚麻油酸、9，10-环氧十八烷酸、二十二碳五烯酸（22n-6）、牛磺胆酸、LysoPS （18∶0/0∶0）。结论 艾灸关元穴可通过调控老年大鼠的牛磺酸和亚牛磺酸代谢、α-亚麻酸代谢、亚油酸代谢、甘油磷脂代谢来调节肾的能量代谢。     

双环[1.1.1]戊烷衍生物的合成研究进展

双环[1.1.1]戊烷（BCP）是一种具有三维立体结构的桥环骨架，其作为苯环、叔丁基和炔烃的生物电子等排体，已经在药物化学领域得到广泛的应用。随着BCP应用范围的扩大，BCP及其衍生物的合成日益成为研究的热点。本文对BCP衍生物的主要合成策略和方法进行总结，旨在为新药研发人员提供参考。     

2例胰岛素自身免疫综合征临床病例分析

通过回顾分析我院2例确诊为胰岛素自身免疫综合征(IAS)患者的临床资料,并复习相关文献,总结发病机制及治疗方法,探讨IAS患者的临床特点,提高对低血糖症的诊治水平。