Long-term effect of perindopril on coronary atherosclerosis progression (from the perindopril's prospective effect on coronary atherosclerosis by angiography and intravascular ultrasound evaluation [PERSPECTIVE] study)

The multicenter EUROPA trial of 12,218 patients showed that perindopril decreased adverse clinical events in patients with established coronary heart disease. The PERSPECTIVE study, a substudy of the EUROPA trial, evaluated the effect of perindopril on coronary plaque progression as assessed by quantitative coronary angiography and intravascular ultrasound (IVUS). In total 244 patients (mean age 57 years, 81% men) were included. Evaluable paired quantitative coronary angiograms were obtained from 96 patients randomized to perindopril and from 98 patients to placebo. Concomitant treatment at baseline consisted of aspirin (90%), lipid-lowering agents (70%), and beta blockers (60%). The primary and secondary end point was the difference of minimum and mean lumen diameters (quantitative coronary angiography) or mean plaque cross-sectional area (IVUS) measured at baseline and 3-year follow-up between the perindopril and placebo groups. After a median follow-up of 3.0 years (range 1.9 to 4.1), no differences in change in quantitative coronary angiographic or IVUS measurements were detected between the perindopril and placebo groups (minimum and mean luminal diameters -0.07 +/- 0.4 vs -0.02 +/- 0.4 mm, p = 0.34; mean luminal diameter -0.05 +/- 0.2 vs -0.05 +/- 0.3 mm, p = 0.89; mean plaque cross-sectional area -0.18 +/- 1.2 vs -0.02 +/- 1.2 mm(2), p = 0.48). In conclusion, we found no progression in coronary artery disease by quantitative coronary angiography and IVUS with long-term administration of perindopril or placebo, possibly because most patients were on concomitant treatment with a statin.     

Exposure–Response Analysis of Osimertinib in EGFR Mutation Positive Non-Small Cell Lung Cancer Patients in a Real-Life Setting

Pharmaceutical Research - Osimertinib, an irreversible inhibitor of the epidermal growth factor receptor (EGFR) is an important drug in the treatment of EGFR-mutation positive non-small cell lung...     

Circulating cell death products predict clinical outcome of colorectal cancer patients

Background  

Tumor cell death generates products that can be measured in the circulation of cancer patients. CK18-Asp396 (M30 antigen) is a caspase-degraded product of cytokeratin 18 (CK18), produced by apoptotic epithelial cells, and is elevated in breast and lung cancer patients.     

Sarcopenia measured with handgrip strength and skeletal muscle mass to assess frailty in older patients with head and neck cancer

ObjectivesPatients with head and neck cancer (HNC) have a risk of sarcopenia which is associated with adverse health outcomes. Frailty is also associated with adverse outcomes and is diagnosed by a comprehensive geriatric assessment (CGA). Because a CGA is time-consuming and not all patients benefit from it, frailty screening questionnaires are used to select patients for CGA. Sarcopenia measurement may be a biomarker for frailty. Our objective was to examine the association between sarcopenia and a frailty screening questionnaire.Materials and MethodsIn this single-center retrospective study, 150 patients (≥ 60-years old) with HNC were reviewed. Sarcopenia was defined as the combination of reduced handgrip strength and loss of skeletal muscle mass, calculated as skeletal muscle index (SMI), according to the EWGSOP-criteria. Frailty screening was performed using the Geriatrics 8 (G8) questionnaire.ResultsThe 150 patients included 101 men and 49 women. Frail patients were more likely to be sarcopenic at diagnosis. G8 frailty score showed a significant though weak correlation with SMI. Univariate regression analysis with frailty as a dependent variable distinguished comorbidity score, handgrip strength, SMI, and sarcopenia as significant. These variables were subjected to a multivariate analysis in which comorbidity score and SMI remained significant.ConclusionThere is an association between sarcopenia and the G8 frailty screening questionnaire. Therefore, sarcopenia measurement could be interchangeable with the G8 frailty screening questionnaire. Further research should compare the gold standard for frailty, i.e. CGA, with sarcopenia.     

Predictors of left ventricular remodeling after ST-elevation myocardial infarction

Adverse left ventricular (LV) remodeling after acute ST-elevation myocardial infarction (STEMI) is associated with morbidity and mortality. We studied clinical, biochemical and angiographic determinants of LV end diastolic volume index (LVEDVi), end systolic volume index (LVESVi) and mass index (LVMi) as global LV remodeling parameters 4 months after STEMI, as well as end diastolic wall thickness (EDWT) and end systolic wall thickness (ESWT) of the non-infarcted myocardium, as compensatory remote LV remodeling parameters. Data was collected in 271 patients participating in the GIPS-III trial, presenting with a first STEMI. Laboratory measures were collected at baseline, 2 weeks, and 6–8 weeks. Cardiovascular magnetic resonance imaging (CMR) was performed 4 months after STEMI. Linear regression analyses were performed to determine predictors. At baseline, patients were 21% female, median age was 58 years. At 4 months, mean LV ejection fraction (LVEF) was 54?±?9%, mean infarct size was 9.0?±?7.9% of LVM. Strongest univariate predictors (all p?<?0.001) were peak Troponin T for LVEDVi (R²?=?0.26), peak CK-MB for LVESVi (R²?=?0.41), NT-proBNP at 2 weeks for LVMi (R²?=?0.24), body surface area for EDWT (R²?=?0.32), and weight for ESWT (R²?=?0.29). After multivariable analysis, cardiac biomarkers remained the strongest predictors of LVMi, LVEDVi and LVESVi. NT-proBNP but none of the acute cardiac injury biomarkers were associated with remote LV wall thickness. Our analyses illustrate the value of cardiac specific biochemical biomarkers in predicting global LV remodeling after STEMI. We found no evidence for a hypertrophic response of the non-infarcted myocardium.     

Noninvasive assessment of coronary plaque burden using multislice computed tomography

We performed coronary plaque imaging with 16-row multislice computed tomography in 85 patients who had stable angina pectoris and a high pretest likelihood of having coronary plaque to evaluate plaque burden, i.e., extent (number of diseased coronary segments) and size (small vs large) of plaque. We also assessed type of plaque (calcified, noncalcified, or mixed) and its anatomic distribution. Of 85 patients included, 78 (92%) had fully evaluable multislice computed tomograms that allowed assessment of coronary plaque burden, including major and side branches (>or=2 mm), yielding a total of 855 segments. These 78 patients (92% men; mean age +/- SD 58 +/- 11.5 years) were in sinus rhythm, with heart rates of <70 beats/min (spontaneous or induced by beta blocker). Plaque was detected in 57% of all segments (487 of 855). The mean number of segments with plaque per patient +/- SD was 6.2 +/- 3.9. Plaque was classified as large in 33% of segments and small in 67%. Overall, 65% of plaques were calcified, 24% were noncalcified, and 11% were mixed. Plaques were predominantly located in the proximal and middle segments of the main coronary vessels.     

Small-molecule XIAP antagonist restores caspase-9 mediated apoptosis in XIAP-positive diffuse large B-cell lymphoma cells

Clinical outcome in patients with primary nodal diffuse large B-cell lymphomas (DLBCLs) is correlated with expression of inhibitors of the intrinsic apoptosis pathway, including X-linked inhibitor of apoptosis protein (XIAP). XIAP suppresses apoptosis through inhibiting active caspase-3, caspase-7, and caspase-9. In this study, we investigated to see if the small-molecule XIAP antagonist 1396-12 induces cell death in cultured lymphoma cells of patients with DLBCL. Treatment with this XIAP antagonist resulted in relief of caspase-3 inhibition and in induction of apoptosis in 16 of 20 tested DLBCL samples. Sensitivity to the XIAP antagonist was observed in both chemotherapy-refractory and -responsive DLBCL, but did not affect peripheral blood mononuclear cells and tonsil germinal-center B cells from healthy donors. XIAP antagonist-sensitive samples were characterized by high expression levels of XIAP, relatively low expression levels of Bcl-2, and by constitutive caspase-9 activation. These data indicate that the small-molecule XIAP antagonist can induce apoptosis in cultured DLBCL cells and therefore should be considered for possible development as a therapy for these patients. In vitro sensitivity to the XIAP antagonist can be predicted based on biological markers, suggesting the possibility of predefining patients most likely to benefit from XIAP antagonist therapy.     

The unrestricted use of paclitaxel- versus sirolimus-eluting stents for coronary artery disease in an unselected population: one-year results of the Taxus-Stent Evaluated at Rotterdam Cardiology Hospital (T-SEARCH) registry

OBJECTIVES: We investigated the efficacy of paclitaxel-eluting stents (PES) compared to sirolimus-eluting stents (SES) when used without restriction in unselected patients. BACKGROUND: Both SES and PES have been separately shown to be efficacious when compared to bare stents. In unselected patients, no direct comparison between the two devices has been performed. METHODS: Paclitaxel-eluting stents have been used as the stent of choice for all percutaneous coronary interventions in the prospective Taxus-Stent Evaluated At Rotterdam Cardiology Hospital (T-SEARCH) registry. A total of 576 consecutive patients with de novo coronary artery disease exclusively treated with PES were compared with 508 patients treated with SES from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. RESULTS: The PES patients were more frequently male, more frequently treated for acute myocardial infarction, had longer total stent lengths, and more frequently received glycoprotein IIb/IIIa inhibitors. At one year, the raw cumulative incidence of major adverse cardiac events was 13.9% in the PES group and 10.5% in the SES group (unadjusted hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.95 to 1.88, p = 0.1). Correction for differences in the two groups resulted in an adjusted HR of 1.16 (95% CI 0.81 to 1.64, p = 0.4, using significant univariate variables) and an adjusted HR of 1.20 (95% CI 0.85 to 1.70, p = 0.3, using independent predictors). The one-year cumulative incidence of clinically driven target vessel revascularization was 5.4% versus 3.7%, respectively (HR 1.38, 95% CI 0.79 to 2.43, p = 0.3). CONCLUSIONS: The universal use of PES in an unrestricted setting is safe and is associated with a similar adjusted outcome compared to SES. The inferior trend in crude outcome seen in PES was due to its higher-risk population. A larger, randomized study enrolling an unselected population may assist in determining the relative superiority of either device.