携带同源重组修复相关基因突变的消化道肿瘤的临床特点

目的:探讨消化道肿瘤中同源重组修复相关基因(homologous recombination repair related gene，HRR)突变的发生情况及临床意义。方法:共92例消化道肿瘤患者，79例患者进行了血液标本HRR检测，53例患者进行了组织标本HRR检测，40例患者同时行血液和组织的HRR基因检测，收集患者基因检测结果及临床相关资料。结果:在79例患者血液标本检测中发现10例（12.6%）有临床意义HRR突变，在53例患者组织标本检测中发现9例（17.0%）有临床意义HRR突变。40例同时行血液和组织的HRR基因检测患者中常见的有临床意义HRR突变为CDK12突变4例（10.0%）、ATM突变3例（7.5%）、BRCA1突变2例（5.0%）。13例有临床意义HRR突变患者中常见共存突变为TP53突变10例（76.9%）、APC突变5例（38.5%）、PIK3CA突变4例（30.8%）。40例患者中13例患者血液和/或组织中有临床意义HRR突变，27例患者血液和组织中均无任何临床意义HRR突变且两组相比，有临床意义HRR突变组肿瘤突变负荷（tumor mutational burden，TMB）为6.17(2.24～11.52)，而未携带HRR突变组TMB为0.4(0～3.75)，差异有统计学意义（P＜0.05）。40例患者组织检测中7例HRR有临床意义的突变，33例无HRR突变，血液检测中10例HRR有临床意义的突变，30例无HRR突变，一致性检验的Kappa值为0.333（P=0.031）。结论:携带有临床意义HRR突变的消化道肿瘤患者TMB更高，血液和组织检测HRR突变有较好的一致性。     

Silver Diamine Fluoride Protocol for Reducing Preventable Dental Hospitalisations in Victorian Children

IntroductionThis study was designed to assess whether a dental caries management protocol combining a single application of 38% silver diamine fluoride (SDF) with comprehensive oral health education will successfully divert high-risk children from dental treatment under dental general anaesthesia (DGA), arrest active caries in primary teeth, and improve parent-reported child oral health–related quality of life (OHRQoL).MethodsChildren aged 2 to 10 years, who attended two public dental agencies in Victoria, Australia, and were unable to tolerate restorative treatments in the clinic setting, elected to participate in either a 38% SDF intervention protocol or, alternatively, referral for DGA. Follow-up examinations were completed at 6 months to assess caries progression, decayed missing filled tooth index, PUFA index (pulpal involvement, ulceration, fistula, abscess), DGA referral rates, and OHRQoL (Early Childhood Oral Health Impact Scale [ECOHIS]).ResultsOf the total sample, 89.5% of children (n = 102) [mean (SD) age, 4.1 (1.0) years] with 401 active carious lesions elected to participate in the 38% SDF protocol; 10.5% (n = 12) of parents opted for referral for treatment under DGA. The proportion of active caries subsequently arrested at follow-up (number of arrested lesions/number of lesions treated) was 0.78 (95% CI, 0.69 to 0.87). There was an 88% reduction in referrals for DGA in eligible children over the 6-month period. The 38% SDF intervention group showed a significant improvement in ECOHIS scores at follow-up (P < .001).DiscussionAdoption of the 38% SDF intervention protocol resulted in a significant reduction in the rate of preventable dental hospitalisations. Most parents opted against referral for DGA. Parent-reported OHRQoL for children improved significantly.     

肿瘤坏死因子-α-308基因对导管相关性脓毒症患者病情的影响

目的探究肿瘤坏死因子-α(Tumornecrosis factor-α,TNF-α)-308基因对导管相关性脓毒症(Catheter related sepsis,CRS)患者病情的影响,旨在为临床治疗CRS提供科学依据。方法选取2017年7月-2018年10月于浙江大学医学院附属杭州市第一人民医院接受治疗的86例CRS患者为研究对象,按照是否并发多器官功能障碍综合征将患者分为试验组和对照组,对照组共48例,未并发多器官功能障碍综合征,试验组共38例,并发多器官功能障碍综合征,分析两组患者TNF-α-308基因多态性差异,使用多因素Logistic回归分析CRS患者并发多器官功能障碍综合征的危险因素。结果试验组GA基因型频率34.21%、AA基因型频率50.00%、高G等位基因频率18.42%均高于对照组,GG基因型频率52.63%、A等位基因频率28.95%均低于对照组,差异均具有统计学意义(P<0.05);多因素Logistic回归分析结果显示,低GG基因型频率、低G等位基因频率、高GA基因型频率、高AA基因型频率、高A等位基因频率是CRS患者并发多器官功能障碍综合征的危险因素(P<0.05)。结论TNF-α-308基因与CRS患者病情密切相关,GG基因型频率和G等位基因频率降低,GA基因型频率、AA基因型频率、A等位基因频率升高会加重患者的病情,增加多器官功能障碍综合征的发生风险,临床上应该加以重视。     

Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies

The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC₆₀) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity.     

Daily coping moderates the relations between stress and actigraphic sleep: a daily intensive longitudinal study with ecological momentary assessments

BackgroundTheoretical models argue that coping reduces stress responses, yet no studies have tested whether coping moderates the prospective stress effects on sleep in daily life.PurposeThis study tested if coping moderates the stress-sleep association using a daily, intensive longitudinal design across 7–12 days.Methods326 young adults (M_age = 23.24 ± 5.46) reported perceived stress and coping (problem-focused, emotional-approach, and avoidance) every evening between 20:00–02:00, providing over 2400 nights of sleep data and 3000 stress surveys from all participants. Actigraphy and sleep diaries measured total-sleep-time and sleep efficiency. Multilevel models tested the interaction effects of within- and between-person stress and coping on sleep.ResultsWithin-person problem-focused and emotional-approach coping moderated the within-person stress effects on actigraphic total-sleep-time (both p = 0.02); higher stress predicted shorter total-sleep-time only during high use of problem-focused or emotional-approach coping (both p = 0.01). Between-person avoidance moderated the between-person stress effect on actigraphic total-sleep-time (p = 0.04); higher stress predicted shorter total-sleep-time for high avoidance coping (p = 0.02). Within-person emotional-approach coping buffered the between-person stress effect on actigraphic sleep efficiency (p = 0.02); higher stress predicted higher sleep efficiency for high emotional-approach coping (p = 0.04).ConclusionsThis study showed that daily coping moderates the effects of evening stress on sleep that night. More efforts to cope with stress before bedtime had a short-term cost of shorter sleep that night. However, high use of emotional-approach coping buffered the impact of stress to promote sleep efficiency.     

Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.     

2型糖尿病患者不同脂质参数与糖尿病肾病的关系

目的:探讨2型糖尿病(T2DM)患者不同脂质参数与糖尿病肾病(DKD)发生的相关性。方法:检测226例T2DM患者血清TC、TG、LDL-C、HDL-C水平及相关生化指标,计算血浆致动脉硬化指数(AIP)以及脂质三角相关指标(TC/HDL-C、TG/HDL-C、LDL-C/HDL-C)。根据DKD临床诊断标准和Mogensen分期标准分为:Ⅰ~Ⅱ期组136例,Ⅲ期组55例,Ⅳ~Ⅴ期组35例。应用多因素logistic回归分析不同脂质参数与DKD发生的关系。结果:与Ⅰ~Ⅱ期组相比,随着DKD分期加重,TC、TG、LDL-C、LDL-C/HDL-C、AIP水平明显增高(P<0.01)。LDL-C/HDL-C和AIP与24 h尿蛋白水平呈正相关(r=0.724;r=0.769,均P<0.05)。LDL-C/HDL-C和AIP是T2DM合并DKD患者的独立预测因子(P=0.002;P=0.004)。结论:LDL-C/HDL-C和AIP对T2DM合并DKD病情进展有较高的预测价值,可为临床诊治提供参考。