Crack propagation modeling in functionally graded materials using Moving Mesh technique and interaction integral approach

This paper presents a novel FE modeling approach based on Moving Mesh technique to reproduce crack propagation mechanisms in Functionally Graded Materials. The moving mesh is consistent with the Arbitrary Lagrangian-Eulerian formulation, which is suited to handle growing random cracks, avoiding extensive remeshing processes. This approach is based on the Interaction Integral Method to extract the mixed-mode Stress Intensity Factors, which are necessary to establish crack onset conditions and propagation direction. Among the different available options for FGM, the incompatibility formulation is adopted. The proposed scheme reproduces the propagation mechanisms by moving the computational nodes around the crack tip, according to standard fracture criteria. Mesh regularization technique based on proper rezoning equations ensures the consistency of the motion, reducing mesh distortion. The reliability of the proposed method is evaluated through comparisons with experimental data and existing numerical approaches. The computational efficiency is checked through parametric analyses on mesh discretization and accuracy in the prediction of the crack path and fracture variables. The results show how the proposed method could represent a valid tool to simulate the propagation mechanisms in FGM, in which heterogeneous macro-properties involve complex crack paths

A Multidisciplinary Perspective on the Subcutaneous Administration of Trastuzumab in HER2-Positive Breast Cancer

Trastuzumab is the standard treatment in Canada for patients with breast cancer positive for HER2 (human epidermal growth factor receptor 2), dramatically improving outcomes in that patient group. However, its current intravenous (IV) administration is associated with long infusion times that place a significant burden on health care resources and patient quality of life. In an effort to provide a faster and easier administration method, a subcutaneous (SC) formulation of trastuzumab has been developed. Data from comparative trials demonstrate that the two formulations are comparable with respect to pharmacokinetics and efficacy. They also have similar safety profiles, with the exception of mild local and administration reactions with the SC formulation. Furthermore, the SC formulation is preferred by patients and health care professionals, and greatly reduces administration and chair time. Additional advantages include easier preparation and dosing, reduced drug wastage, and reduced discomfort at the injection site. By using well-thought-out administration procedures, the SC formulation can be given safely and effectively, potentially reducing the burden on health care resources and improving quality of life for patients

Prevalence and predictive role of hypertriglyceridemia in statin-treated patients at very high risk: Insights from the START study

Background and aim: Elevated triglyceride (TG) levels seem to identify subjects at increased cardiovascular risk, independent of LDL-C levels. We sought to evaluate the predictive role of hypertriglyceridemia, defined as TG levels ≥150 mg/dl, in very high risk (VHR) patients with chronic coronary syndromes (CCS) treated with statins. Methods and results: Using the data from the STable Coronary Artery Diseases RegisTry (START) study, an Italian nationwide registry, we assessed the association between the TG levels and baseline clinical characteristics, pharmacological treatment and major adverse cardio-cerebrovascular events (MACCE) at 1 year in a large cohort of statin-treated patients at VHR. Of the 4751 consecutive patients with CCS enrolled in the registry and classified as VHR, 2652 (55.8%) had TG values available (mean 120.6 ± 54.9) and were treated with at least a statin at baseline: 2019 (76.1%) with TG < 150 and 633 (23.9%) with TG ≥ 150 mg/dl. At 1 year from enrolment, MACCE occurred in 168 (6.3%) patients, without differences between the two groups of TG (5.9 vs 7.6%; p = 0.14). At multivariable analysis, hypertriglyceridemia did not result as independent predictor of the MACCE (hazard ratio: 1.16; 95% confidence intervals: 0.82–1.64; p = 0.42). Conclusions: In the present large, nationwide cohort of consecutive CCS patients at VHR with statin-controlled LDL-C levels, hypertriglyceridemia was present in around 24% of cases and did not result as predictor of MACCE at 1 year. Further studies with a longer follow-up and larger sample size are needed to better define the prognostic role of TG levels when intensive LDL lowering therapies are used

Cohort profile. the ESC-EORP chronic ischemic cardiovascular disease long-term (CICD LT) registry

The European Society of cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischemic Cardiovascular Disease registry Long Term (CICD) aims to study the clinical profile, treatment modalities and outcomes of patients diagnosed with CICD in a contemporary environment in order to assess whether these patients at high cardiovascular risk are treated according to ESC guidelines on prevention or on stable coronary disease and to determine mid and long term outcomes and their determinants in this population

COMPASS criteria applied to a contemporary cohort of unselected patients with stable coronary artery diseases: insights from the START registry

Aims Recently, the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial demonstrated that dual therapy reduced cardiovascular outcomes compared with aspirin alone in patients with stable atherosclerotic disease. Methods and We sought to assess the proportion of patients eligible for the COMPASS trial and to compare the epidemiology results and outcome of these patients with those without COMPASS inclusion or with any exclusion criteria in a contemporary, nationwide cohort of patients with stable coronary artery disease. Among the 4068 patients with detailed information allowing evaluation of eligibility, 1416 (34.8%) did not fulfil the inclusion criteria (COMPASS-Not-Included), 841 (20.7%) had exclusion criteria (COMPASS-Excluded), and the remaining 1811 (44.5%) were classified as COMPASS-Like. At 1 year, the incidence of major adverse cardiovascular event (MACE), a composite of cardiovascular death, myocardial infarction, and stroke, was 0.9% in the COMPASS-Not-Included and 2.0% in the COMPASS-Like (P = 0.01), and 5.0% in the COMPASS-Excluded group (P < 0.0001 for all comparisons). Among the COMPASS-Like population, patients with multiple COMPASS enrichment criteria presented a significant increase in the risk of MACE (from 1.0% to 3.3% in those with 1 and >_3 criteria, respectively; P = 0.012), and a modest absolute increase in major bleeding risk (from 0.2% to 0.4%, respectively; P = 0.46). Conclusion In a contemporary real-world cohort registry of stable coronary artery disease, most patients resulted as eligible for the COMPASS. These patients presented a considerable annual risk of MACE that consistently increases in the presence of multiple risk factors

Clinical outcomes, pharmacological treatment, and quality of life of patients with stable coronary artery diseases managed by cardiologists: 1-year results of the START study

Aims: We evaluated the 1-year clinical events, pharmacological management, and quality of life in a contemporary cohort of stable coronary artery disease (CAD) patients managed by cardiologists. Methods and results: START (STable Coronary Artery Diseases RegisTry) was a prospective, observational, nationwide study that enrolled 5070 stable CAD patients over 3 months in 183 cardiology centres in Italy. At 1 year, 4790 (94.5%) patients had data on vital status. Death occurred in 107 (2.2%) patients and the cause of death was cardiovascular in 41 (38.3%) of cases. Among the 4775 patients with follow-up data on clinical events available, a hospitalization due to cardiovascular and non-cardiovascular causes occurred in 523 (11.0%) and in 231 (4.8%) of cases, respectively. Over 60% of patients reported as 'no problems' in all domains (61.4-84.5%) of the EuroQoL quality of life 5D-5L questionnaire. Among the 3239 patients with clinical visit/telephone interview at follow-up, in whom optimal medical therapy (OMT; aspirin or thienopyridine, β-blocker, and statin) was prescribed at enrolment, 2971 (91.7%) were still receiving OMT at follow-up. At multivariable analysis, only increasing age (odds ratio 0.98; 95% confidence interval 0.97-0.99; P = 0.04) resulted as independent negative predictor of OMT persistence at 1 year from enrolment. Conclusion: In this large, contemporary registry, stable CAD patients managed by cardiologists presented a high rate of clinical events at 1 year. Nevertheless, the persistence to OMT and quality of life appeared reasonable