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.     

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.

A comparison of head injuries in male and female lacrosse participants seen in US emergency departments from 2005 to 2016

Introduction

In the United States there has been a large increase in participation in lacrosse for both males and females. The purpose of this study was to analyze the number of head injuries, injury rates (calculated using the reported number of participants) and types of head injuries that are seen in emergency departments in the United States.

Clinical outcomes of bypass-first versus endovascular-first strategy in patients with chronic limb-threatening ischemia due to infrageniculate arterial disease

Background

Chronic limb-threatening ischemia (CLTI), defined as ischemic rest pain or tissue loss secondary to arterial insufficiency, is caused by multilevel arterial disease with frequent, severe infrageniculate disease. The rise in CLTI is in part the result of increasing worldwide prevalence of diabetes, renal insufficiency, and advanced aging of the population. The aim of this study was to compare a bypass-first with an endovascular-first revascularization strategy in patients with CLTI due to infrageniculate arterial disease.

护理干预对急性心肌梗死患者负性情绪的影响

目的总结并归纳护理干预对急性心肌梗死患者负性情绪的影响。方法本文挑选100例医院急性心肌梗死患者(2017年2月—2018年2月)为对象。按建档时间分组,对照组50例患者(常规护理),分析组50例患者(加用人文性护理)。比较两组对疾病的了解程度及护理前后焦虑、抑郁等负性情绪的评分,随访1年,比较两组复发率。结果护理后分析组对疾病了解程度高于对照组(P<0.05);护理前分析组焦虑、抑郁评分同对照组无显著差异(P>0.05),提示可比;护理后,分析组焦虑、抑郁评分低于对照组(P<0.05);护理后分析组1年内复发率(8.00%)低于对照组(24.00%)(P<0.05)。结论在急性心肌梗死患者的护理中,人文性护理干预可显著改善患者负性情绪,改善患者预后,且可有效降低患者复发率。