A genome wide association study identifies new genes potentially associated with eyelid sagging

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10^‐10) and rs4746957 (P = 1.06 × 10^‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.     

Phase 1 Study of Erlotinib and Metformin in Metastatic Triple-Negative Breast Cancer

BackgroundEpidermal growth factor receptor (EGFR) is frequently overexpressed in metastatic triple-negative breast cancer (mTNBC). One strategy for overcoming resistance to EGFR inhibition is concomitant inhibition of downstream signaling. The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling. We evaluated the combination of erlotinib and metformin in a phase 1 study of patients with mTNBC.Patients and MethodsPatients with mTNBC who had received at least one prior line of therapy for metastatic disease were eligible. Erlotinib dose was fixed at 150 mg daily. Metformin dose escalation was planned according to a 3 + 3 design. Dose-limiting toxicities (DLT) were assessed during the first 5 weeks of therapy. The primary objective was to determine the maximum tolerated dose of metformin with fixed-dose erlotinib. Secondary endpoints were response rate, stable disease rate, and progression-free survival.ResultsEight patients were enrolled. The median number of prior therapies for metastatic disease was 2.5 (range, 1-6). No DLT events were reported during the DLT assessment period. Most adverse events were grade 1/2. Grade 3 diarrhea despite maximum supportive care required dose reduction of metformin in one patient. Grade 3 rash led to study withdrawal in one patient. No grade 4 adverse events were reported. The best observed response was stable disease in 2 patients (25%). Median progression-free survival was 60 days (range, 36-61 days).ConclusionErlotinib and metformin were well tolerated in a population of pretreated mTNBC patients but did not demonstrate efficacy in this population.     

缓解视疲劳功能中药复方保健产品配方规律及特点分析

目的通过检索特殊食品信息查询平台公布的具有缓解视疲劳功能的保健食品信息资料,以及药智数据网的中成药处方数据库中眼科中成药中有保健功能的产品信息资料,为具有缓解视疲劳功能的保健产品的组方与产品开发提供依据与参考。方法运用Microsoft Excel2016软件及中医传承辅助平台对检得的产品信息进行统计,分析其配方特点。结果共收集到141个具有缓解视疲劳功能的保健食品,其中64个(45.4%)保健食品配方中含有中药类原料。使用频次≥5的中药原料有6味,累计使用145次(72%),由高到低分别是菊花、枸杞子、决明子、桑椹、熟地黄、茯苓。通过无监督的熵层次聚类得到3个新处方。非中药原料在缓解视疲劳功能的保健食品中应用较为普遍,含有外来天然植物资源的60个产品,含叶黄素及维生素类的17个。统计眼科中成药中有保健功能的产品可知,使用频次≥4的中药原料有7味,累计使用32次(29%),由高到低分别是枸杞子、决明子、菟丝子、熟地黄、菊花、五味子、车前子。通过无监督的熵层次聚类得到1个新处方。结论保健食品在中药原料的选择上与中医药理论治疗视疲劳的原则基本契合,即滋补肝肾、平肝明目。但二者在中药原料选择范围、原料配伍、剂型种类等方面有所不同。此外,还在辨证保健理论指导下,尝试探讨应用文献数据处理统计方法筛选新配方、开发新产品,为中药复方保健产品的研发开辟了新思路、新方法。     

The comparative effects of metabolic surgery,SGLT2i,or GLP-1RA in patients with obesity and type 2 diabetes: a retrospective cohort study

BackgroundNew antidiabetic agents (sodium-glucose cotransporter-2 inhibitor [SGLT2i] and glucagon-like peptide-1 receptor agonist [GLP-1RA]) and metabolic surgery have protective effects on metabolic syndromes.ObjectivesTo compare the changes of metabolic parameters and costs among patients with obesity and type 2 diabetes undergoing metabolic surgery and initiating new antidiabetic agents over 12 months.SettingHong Kong Hospital Authority database from 2006–2017.MethodsThis is a population-wide retrospective cohort study consisting of 2616 patients (1810 SGLT2i, 528 GLP-1RA, 278 metabolic surgery). Inverse probability treatment weighting of propensity score was applied to balance baseline covariates of patients with obesity and type 2 diabetes who underwent metabolic surgery, or initiated SGLT2i or GLP-1RA. Metabolic parameters and direct medical costs were measured and compared from baseline to 12 months in metabolic surgery, SGLT2i, and GLP-1RA groups.ResultsPatients in all 3 groups had improved metabolic parameters over a 12-month period. Patients with metabolic surgery achieved significantly better outcomes in BMI (?5.39, ?.56, ?.40 kg/m², P < .001), % total weight loss (15.16%, 1.34%, 1.63%, P < .001), systolic (?2.21, ?.59, 1.28 mm Hg, P < .001) and diastolic (?1.16, .50, ?.13 mm Hg, P < .001) blood pressure, HbA1c (?1.80%, ?.77%, ?.80%, P < .001), triglycerides (?.64, ?.11, ?.09 mmol/L, P < .001), and estimated glomerular filtration rate (3.08, ?1.37, ?.41 mL/min/1.73m², P < .001) after 12 months compared with patients with SGLT2i and GLP1-RA. Although the metabolic surgery group incurred the greatest direct medical costs (US$33,551, US$10,945, US$10,627, P < .001), largely due to the surgery itself and related hospitalization, the total monthly direct medical expenditure of metabolic surgery group became lower than that of SGLT2i and GLP-1RA groups at 7 months.ConclusionBeneficial weight loss and metabolic outcomes at 12 months were observed in all 3 groups, among which the metabolic surgery group showed the most remarkable effects but incurred the greatest medical costs. However, studies with a longer follow-up period are warranted to show long-term outcomes.     

Ceftaroline fosamil for the treatment of Gram-positive endocarditis: CAPTURE study experience

Background

The clinical experience of ceftaroline fosamil (CPT-F) therapy for Gram-positive infective endocarditis is reported from CAPTURE, a retrospective study conducted in the USA.