Skeletal muscle α-actin diseases (actinopathies): pathology and mechanisms

Mutations in the skeletal muscle α-actin gene (ACTA1) cause a range of congenital myopathies characterised by muscle weakness and specific skeletal muscle structural lesions. Actin accumulations, nemaline and intranuclear bodies, fibre-type disproportion, cores, caps, dystrophic features and zebra bodies have all been seen in biopsies from patients with ACTA1 disease, with patients frequently presenting with multiple pathologies. Therefore increasingly it is considered that these entities may represent a continuum of structural abnormalities arising due to ACTA1 mutations. Recently an ACTA1 mutation has also been associated with a hypertonic clinical presentation with nemaline bodies. Whilst multiple genes are known to cause many of the pathologies associated with ACTA1 mutations, to date actin aggregates, intranuclear rods and zebra bodies have solely been attributed to ACTA1 mutations. Approximately 200 different ACTA1 mutations have been identified, with 90 % resulting in dominant disease and 10 % resulting in recessive disease. Despite extensive research into normal actin function and the functional consequences of ACTA1 mutations in cell culture, animal models and patient tissue, the mechanisms underlying muscle weakness and the formation of structural lesions remains largely unknown. Whilst precise mechanisms are being grappled with, headway is being made in terms of developing therapeutics for ACTA1 disease, with gene therapy (specifically reducing the proportion of mutant skeletal muscle α-actin protein) and pharmacological agents showing promising results in animal models and patient muscle. The use of small molecules to sensitise the contractile apparatus to Ca²⁺ is a promising therapeutic for patients with various neuromuscular disorders, including ACTA1 disease.     

Parental smoking impairs vaccine responses in children with atopic genotypes

BACKGROUND: Gene-environment interactions play central roles in controlling postnatal maturation of immune function, but their effects on infant vaccine responses are unknown. Genetic variants associated with atopy and the environmental factor of exposure to parental smoking (PS) of tobacco independently alter immune responses. OBJECTIVE: We sought to investigate the hypothesis that genetic variants associated with atopy and their interaction with PS influence infant vaccine responsiveness. METHODS: In 200 infants with parental atopic history, relationships were sought between polymorphisms in the IL-4, IL-4 receptor alpha (IL-4Ralpha), and IL-13 genes; PS; and immune responses to diphtheria/tetanus vaccination. RESULTS: Analyses stratified by PS unmasked negative associations between atopic alleles of these genes and vaccine outcomes. The most consistent involved the IL-4Ralpha 551 QR/QQ genotypes, which were associated with reduced IgG levels (P = .02) and T-cell responses (IFN-gamma, P = .002; IL-10, P = .01; 1L-13, P = .01; IL-5, P = .06) to tetanus toxoid and parallel reductions in polyclonal T-cell responses and innate immune responses in PS-exposed infants. CONCLUSION: PS potentiates suppressive effects of variants in immune response genes in children. These effects are not observed in the absence of this exposure. Ultimately, this finding might have implications for infant vaccination in countries with high smoking rates. It might also have broader implications in relation to environmental toxicology because it demonstrates specific mechanisms through which the developing immune system might be differentially sensitive to low-level toxicant exposures. CLINICAL IMPLICATIONS: PS interacts with genes associated with atopy to impair vaccine responses. These interactions might have vaccine design and public health implications.     

The Combined SIRS + qSOFA (qSIRS) Score is More Accurate Than qSOFA Alone in Predicting Mortality in Patients with Surgical Sepsis in an LMIC Emergency Department

Background

qSOFA has been proposed as a prognostic tool in patients with sepsis. This study set out to assess the sensitivity of several scores, namely: the pre-ICU qSOFA, the qSOFA with lactate (qSOFA L), SIRS score, qSOFA + SIRS score (qSIRS) and qSIRS with lactate (qSIRS L) in predicting in-hospital mortality in patients with surgical sepsis as well as the sensitivity of these scores in predicting high-grade sepsis. The secondary aim was to determine which of these scores is best suited to predict high-grade surgical sepsis.

Methods

This was a retrospective cohort study that was conducted between December 2012 and August 2017 in a public metropolitan surgical service. Data from patients aged > 13 years, who were admitted to the hospital and who had an emergency surgical procedure for source control were retrieved from a prospectively maintained hybrid electronic database. The qSOFA, qSOFA plus lactate (qSOFA L), SIRS and qSOFA + SIRS (qSIRS), as well as the qSIRS plus lactate (qSIRS L), were calculated for each patient. A lactate level that was greater than 2mmol/L was deemed to be a positive finding. Any score ≥2 was deemed to be a positive score. The outcome measure was in-hospital mortality. The prognostic value of qSOFA, qSOFA L, SIRS, qSIRS and qSIRS L was studied. Receiver operating characteristic analyses were performed to determine the area under the curve (AUC), sensitivity, specificity and positive and negative likelihood ratios for positive qSOFA, qSOFA L, SIRS, qSIRS, and qSIRS L. Contingency tables were used to calculate the sensitivity, specificity, PPV and NPV for predicting severe or high-grade surgical sepsis.

Results

There were a total number of 1884 patients in the sample group of whom 855 were female (45.4%). The median patient age was 36 years (IQR 23–56). A total of 1489 patients (79%) were deemed to have high-grade sepsis based on an advanced EGS AAST grading, whilst 395 patients (21%) had low-grade sepsis. A total of 71 patients died (3.8%). Of these patients who died, 67 (94.4%) had high-grade sepsis and 4 (5.6%) had low-grade sepsis. The mortality rate in the high-grade sepsis group was 4.5%, whilst the mortality rate in the low-grade sepsis group was 1%. The scores with the greatest accuracy in predicting mortality were qSIRS (AUROC 0.731, 95% CI 0.68–0.78), followed by SIRS (AUROC 0.70, 95% CI 0.65–0.75). The qSOFA and qSOFA L were the least accurate in predicting mortality (AUROC 0.684, 95% CI 0.63–0.74 for both). The addition of lactate had no significant effect on the accuracy of the five scores in predicting mortality. Patients with a qSOFA ≥ 2 have an increased risk of dying (OR 5.8), as do patients with a SIRS score ≥2 (OR 2.7). qSIRS L had the highest sensitivity (69%) in predicting the presence of high-grade surgical sepsis, followed by qSIRS (65.5% sensitivity). qSOFA showed a very low sensitivity of only 4.5% and a high specificity of 99.2%. The addition of lactate to the score marginally improved the sensitivity. Lactate of 2mmol/L or more was also an independent predictor of high-grade sepsis.

Conclusion

The qSIRS score is most accurate in predicting mortality in surgical sepsis. The qSOFA score is inferior to both the SIRS and the qSIRS scores in predicting mortality. The qSIRS score with the addition of lactate to the qSIRS score made it the most sensitive score in predicting high-grade surgical sepsis.

     

急性胰腺炎患者的护理

目的探讨急性胰腺炎的护理方法。方法1999年7月-2005年5月对52例急性胰腺炎患者实施胃肠减压等相应的护理措施。结果52例患者，手术6例，保守治疗46例，其中治愈51例，死亡1例。结论密切观察病情变化，根据病情变化及时制订护理措施，预防各种并发症，降低手术风险，是提高治愈率的关键。     

湛江地区缺血性脑卒中相关危险因素的分析

目的了解湛江地区缺血性脑卒中的相关危险因素,为指导干预措施提供科学依据。方法回顾性分析本院门诊、住院部就诊并确诊为缺血性脑卒中患者1000例的临床资料,评价缺血性脑卒中的相关危险因素。结果男性患者、年龄≥50岁、高血压、糖尿病、吸烟、颈动脉斑块、高血脂患者缺血性脑卒中发生率较高,是缺血性脑卒中的高危因素,差异有统计学意义（P〈0.05）。结论分析湛江地区缺血性脑卒中的危险因素,从而通过控制其危险因素、改变不良生活方式等方法来进行预防干预,进而降低缺血性脑卒中的发生率。     

不同手术方法治疗骨质疏松性脊柱压缩性骨折的临床效果

目的：探讨并比较微创手术和传统开放手术治疗骨质疏松性脊柱压缩性骨折的临床效果。方法选取本院2012年1月～2014年1月收治的骨质疏松性脊柱压缩性骨折患者60例,随机分为观察组和对照组各30例,对照组行传统开放手术治疗,观察组行经皮椎体后凸成形术（PKP）治疗,比较两组的治疗效果。结果观察组手术时间、术后下床活动时间及住院时间短于对照组,术中出血量少于对照组,差异有统计学意义（P＜0.05）;观察组术后椎体高度、椎体压缩率及Cobb角的改善情况均明显优于对照组,差异有统计学意义（P＜0.05）;观察组无一例患者出现严重并发症,对照组并发症发生率为13.33%,两组并发症发生率差异有统计学意义（P＜0.05）;观察组日常活动能力评分明显高于对照组,差异有统计学意义（P＜0.05）。结论与传统开放手术比较,微创PKP治疗骨质疏松性脊柱压缩性骨折具有创伤小、恢复快、并发症少等优势,并可显著改善患者的日常活动能力,提高预后。     

大学生预防艾滋病相关知识、行为、态度调查分析

目的了解大学生预防艾滋病的相关知识、行为和态度,探索健康教育的新模式。方法采用随机抽样方法对长春科技学院869名一、二年级在校生进行问卷调查。结果预防艾滋病相关知识知晓率为60.49%,知道性接触传播、血液传播、母婴传播的学生分别为74.22%、82.39%和70.31%,对蚊虫叮咬、握手或共用厕所是否传播艾滋病的回答正确率分别是31.65%、24.17%。70.20%的学生不想与艾滋病感染者或患者接触,92.06%的学生认为艾滋病预防知识宣传还不够,应扩大宣传覆盖面,以多种形式开展艾滋病宣传活动。结论被调查的大学生对于如何有效预防艾滋病的知识掌握不全面,部分学生对艾滋病患者或感染者表现出不宽容或歧视态度。建议学校采取积极措施,加大宣传力度,普及健康教育。     

肱骨外科颈骨折克氏针内固定和锁定钢板内固定的临床疗效分析

目的：探讨克氏针内固定和锁定钢板内固定治疗肱骨外科颈骨折的临床效果。方法选取本院2011年12月~2013年12月诊治的肱骨外科颈骨折患者66例,将患者根据随机数字表法分为两组,每组33例。对照组给予克氏针内固定治疗,观察组给予锁定钢板内固定治疗,比较两组的临床疗效。结果观察组的手术时间、住院时间、骨折愈合时间均明显长于对照组,Neer功能评分(疼痛、功能、运动限制、解剖复位、总分)、优良率均明显高于对照组,并发症发生率明显低于对照组,差异均有统计学意义(P<0.05)。结论与克氏针内固定相比,锁定钢板内固定治疗肱骨外科颈骨折的操作时间和术后恢复时间较长,但固定效果好,且安全性高,值得临床推广应用。     

食管癌术前半量放疗的疗效观察

目的：探讨食管癌术前半量放疗的临床效果。方法选取本院肿瘤科2012年4月~2013年4月收治的80例食管癌患者作为研究对象,其中可采取直接手术的40例设为对照组,40例需术前半量放疗再行手术的设为观察组。比较两组的临床总切除术率、根除术切除率、区域淋巴结转移率、断端残癌阳性率及随访1年生存率,观察相关并发症发生的情况。结果观察组的临床总切除术率、根除术切除率和随访1年生存率明显高于对照组,区域淋巴结转移率和断端残癌阳性率明显低于对照组,差异有统计学意义(P<0.05);观察组的总并发症发生率为10.0%,明显低于对照组的15.0%,差异有统计学意义(P<0.05)。结论食管癌术前行半量放疗,可改善患者的生活质量,延长生存期,减少转移和复发,延长远期生存率,对保障患者预后有非常重要的意义。