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.     

个体化糖尿病教育对初次使用胰岛素的2型糖尿病患者的疗效评价

目的探讨针对初次应用胰岛素治疗的2型糖尿病患者开展个体化糖尿病教育的临床价值。方法对照组患者开展常规的糖尿病健康教育,观察组则在该基础上开展个体化糖尿病教育。结果两组健康教育前SDSCA-6依从性量表各维度评分较低;健康教育后观察组SDSCA-6依从性量表各维度评分均高于对照组(P<0.05);两组健康教育FPG、2 hPG、HbAlc前较高(P>0.05);健康教育后观察组FPG、2 hPG、HbAlc低于对照组(P<0.05)。结论对于首次应用胰岛素治疗的2型糖尿病患者进行个体化的糖尿病教育可以有效提升其依从性,并更好的控制血糖水平。     

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.     

Subdental synchondrosis and anatomy of the axis in aging: a histomorphometric study on 30 autopsy cases

During skeletal development the two ossification centers of the odontoid process are separated from the corpus of the axis by a subdental synchondrosis. This synchondrosis is thought to close and disappear spontaneously in adolescence although this has never been studied in detail. The basis of the dens is of clinical relevance as type II dens fractures are located here. To characterize the morphological architecture of the axis with particular attention to the subdental synchondrosis, the complete axis was harvested from thirty age-matched and gender-matched patients of the three different age groups at autopsy. The subdental synchondrosis and the bone structure of the dens, the basis of the dens and the body of C2 were analyzed by radiography, histology and quantitative histomorphometry. At the macroscopic level the persistency of the subdental synchondrosis in the adult cervical spine was detected in 87% (26 of 30) of the specimens. Histomorphometry revealed a residual disc blastema with an average size of 25.8% of the sagittal depth of the basis of the dens at this level. Bony integration of the synchondrosis was poor throughout all ages. Histologically a cartilaginous matrix composition of the subdental synchondrosis persisted throughout all groups. The trabecular microarchitecture demonstrated a significant reduction of bone volume and trabecular number as well as an increased trabecular separation within the basis of the dens as compared to the corpus or the dens of C2. This histomorphometric data regarding a poor integration of the synchondrosis into the trabecular network and the reduced bone mass within the basis of the dens might offer a previously underestimated explanation for the occurrence of type II dens fractures and their association with pseudoarthrosis, respectively.Matthias Gebauer and Christian Lohse contributed equally to this study and therefore share first authorship.     

中国优秀马拉松运动员ACE基因I/D多态性频率分布特征

通过分析中国马拉松运动员ACE基因I/D多态频率分布特征,探讨其作为杰出耐力基因标记的可行性。选择我国马拉松健将、国际健将级运动员26名作为马拉松运动员组,汉族学生216名作为对照组。对两组受试者进行ACE基因I/D多态性测定。结果显示:我国马拉松运动员组的等位基因频率和基因型频率与对照组比较无显著差异,其中15名国际健将中无一DD型纯合子,提示我国优秀马拉松运动员的纯合子DD型频率低下是其ACE基因多态频率分布的主要特征。     

诺和锐胰岛素治疗儿童1型糖尿病的临床观察

目的:观察诺和锐胰岛素治疗儿童1型糖尿病的疗效。方法:对10例应用诺和灵短效胰岛素联合诺和灵中效胰岛素治疗的1型糖尿病患儿以超短效胰岛素诺和锐等量替代短效胰岛素联合诺和灵中效胰岛素治疗1个月,观察HbA1c等代谢指标变化。结果:用诺和锐治疗后患儿餐后2 h血糖、HbA1c显著下降,P<0．01,平均下降值分别为3．51±1．10 mmol／L与0．64％±0．19％。胰岛素用量与血脂无明显变化,P>0．05。治疗期间未发现明显低血糖。结论:超短效胰岛素诺和锐替代短效胰岛素可进一步控制餐后血糖．并显著降低HbA1c,有利于血糖控制。     

Application of an augmented reality tool for maxillary positioning in orthognathic surgery – A feasibility study

BACKGROUND: An augmented reality tool for computer assisted surgery named X-Scope allows visual tracking of real anatomical structures in superposition with volume rendered CT or MRI scans and thus can be used for navigated translocation of bony segments. METHODS: In a feasibility study X-Scope was used in orthognathic surgery to control the translocation of the maxilla after Le Fort I osteotomy within a bimaxillary procedure. The situation achieved was compared with the pre-operative situation by means of cephalometric analysis on lateral and frontal cephalograms. RESULTS: The technique was successfully utilized in 5 patients. Maxillary positioning using X-Scope was accomplished accurately within a range of 1mm. The tool was used in all cases in addition to the usual intra-operative splints. A stand-alone application without conventional control does not yet seem reasonable. CONCLUSION: Augmented reality tools like X-Scope may be helpful for controlling maxillary translocation in orthognathic surgery. The application to other interventions in cranio-maxillofacial surgery such as Le Fort III osteotomy, fronto-orbital advancement, and cranial vault reshaping or repair may also be considered.     

4110例肝炎分型分析

[目的]探讨各型肝炎的感染率。[方法]研究对象为我院住院及门诊患者，共计4110例。采用微粒子酶免分析法（MEIA）及酶联免疫吸附法（ELISA）进行肝炎分型（甲、乙、丙、丁、戊、庚肝）检测。[结果]4110例受检者中，单纯乙肝感染者133例，占3．24％；单纯丙肝感染者134例，占3．26％；单纯戊肝感染者2例，占0．05％；乙肝合并丙肝感染者3例，占0．07％；丙肝合并戊肝感染者1例，占0．02％；HAV、HDV、HGV无一例感染，感染率为0。另外，男性受检者2088人，乙肝感染者88人，占4．21％；丙肝感染者48人，占2．30％；女性受检者2022人，乙肝感染45人，占2．23％；丙肝感染86人，占4．25％。[结论]除丙肝外，各型感染率均低于全国平均感染率，与相关资料报道相差甚远。乙肝及丙肝仍以单纯感染多见。另，本组资料还显示，男性较女性更易感染乙肝病毒，而女性感染丙肝者远远高于男性，对于丙肝感染的性别差异，尚无报道，需进一步探讨。     

Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis

Introduction Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α, and interleukin-6. Methods We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1β and BMD at all sites. Results In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. Conclusions These findings may have therapeutic implications for enhancing bone density in these patients.