Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

扶正化痰固本方对早期非小细胞肺癌术后患者免疫功能的影响

目的:观察扶正化痰固本方运用于早期非小细胞肺癌术后的临床疗效及其对患者免疫功能的影响。方法:将70例早期非小细胞肺癌患者按照随机数字表法分为对照组和观察组,每组各35例。两组患者均接受肺癌切除术治疗,对照组术后3周开始接受MVP方案化疗,观察组在对照组的基础上加用扶正化痰固本方治疗。比较两组患者的临床疗效及治疗前后中医证候积分、卡氏评分(karnofsky performance status,KPS)及生活质量评分变化情况。检测两组患者治疗前后免疫功能指标、血清肿瘤标志物[癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原153(carbohydrate antigen 153,CA153)]水平。结果:观察组有效率为91.43%,对照组有效率为71.43%,两组患者有效率比较,差异具有统计学意义(P<0.05)。两组患者治疗后中医证候积分低于本组治疗前,且观察组治疗后低于对照组治疗后,差异具有统计学意义(P<0.05)。两组患者治疗后免疫功能指标检测结果低于本组治疗前,且观察组治疗后低于对照组治疗后,差异具有统计学意义(P<0.05)。两组患者治疗后血清CEA、CA153水平低于治疗前,KPS评分、QLQ-C30评分均高于治疗前,且观察组治疗后血清CEA、CA153水平低于对照组,KPS评分、QLQ-C30评分均高于对照组,差异具有统计学意义(P<0.05)。观察组胃肠道反应及骨髓抑制发生率均低于对照组,差异具有统计学意义(P<0.05)。结论:扶正化痰固本方运用于早期肺癌术后,能够有效改善患者免疫功能,减轻毒副反应,提高患者生活质量。     

The role of geriatric palliative care in hospitalized older adults

ABSTRACT

Take-Away Points:

1. Geriatric palliative care requires integrating the disciplines of hospital medicine and palliative care in pursuit of delivering comprehensive, whole-person care to aging patients with serious illnesses.

2. Older adults have unique palliative care needs compared to the general population, different prevalence and intensity of symptoms, more frequent neuropsychiatric challenges, increased social needs, distinct spiritual, religious, and cultural considerations, and complex medicolegal and ethical issues.

3. Hospital-based palliative care interdisciplinary teams can take many forms and provide high-quality, goal-concordant care to older adults and their families.