Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Assessment of socio-relational self-efficacy in breast cancer patients: Italian validation of the social relationship coping efficacy scale (SRCE-I)

Background: Social relationship coping efficacy (SRCE) represents the ability to maintain or enhance social relationships in the context of serious illness. The purpose of the current study was to confirm the factor structure, psychometric properties, and utility of the Italian version of the SRCE scale. Methods: 181 breast cancer patients completed the SRCE-Italian (SRCE-I), the Cancer Behavior Inventory–Brief/Italian (CBI–B/I), quality of life (QOL) measures (EORTC QLQ-C30; EORTC QLQ-BR23), and the Hospital Anxiety and Depression Scale (HADS). Results: The SRCE-I was internally consistent (Cronbach alpha =.95) and factor analysis confirmed that the SRCE-I was a unidimensional construct. In terms of validity, the SRCE-I was correlated with QOL (EORTC QLQ-30, Social Functioning, r =.33, Emotional Functioning, r =.57, and Global Health/Quality of Life; r =.54) and scales of the EORTC QLQ-BR23 (e.g., Future Perspective, r =.38; Breast Symptoms, −.31). SRCE-I was also correlated negatively with the HADS (r = −.72) and positively with the CBI–B/I (r =.79), a measure of coping efficacy (all ps <.001). Mediation analyses confirmed the utility of the SRCE-I scale as a mediating mechanism in enhancing social functioning and QOL. Conclusions: The SRCE-I is a structurally sound, reliable, and valid measure that assesses the ability to maintain or enhance social support and mitigate the loss of social support. The SRCE-I can be used as a screening measure to assess low efficacy for maintaining social support or as a measure to detect the change in efficacy for enhancing social support in interventions to improve the QOL of patients

Gemcitabine plus Epirubicin in patients with advanced urothelial carcinoma who are not eligible for platinum-based regimens.

The objective of this study was to evaluate the efficacy and toxicity of gemcitabine plus epirubicin in previously untreated patients with advanced urothelial carcinoma who were not eligible for cisplatin-based regimens. METHODS: Patients with advanced urothelial carcinoma and at least one of the following characteristics were eligible: impaired renal function (creatinine clearance or= 2, and age >or= 75 years. The treatment included epirubicin 70 mg/m(2) as an intravenous bolus on Day 1 and gemcitabine 1000 mg/m(2) over 30 minutes on Days 1 and 8 of a 21-day cycle. RESULTS: Thirty-eight patients entered the study, and a total of 152 cycles were administered, with a median of 4 cycles per patient (range, 1-6 cycles per patient). The following Grade 3-4 hematologic toxicities were reported (percent of cycles): neutropenia, 22.4%; anemia, 11.2%; and thrombocytopenia, 6.5%. No cardiac, renal, or hepatic toxicities were observed. Dose intensities of epirubicin and gemcitabine were 19.6 mg/m(2) per week (84%) and 532.2 mg/m(2) per week (80%), respectively. There were 2 complete responses (5.3%), 13 partial responses (34.2%), 11 patients with stable disease (28.9%), and 12 patients with progressive disease (31.6%), for an overall response rate of 39.5% (95% confidence interval, 25.1-55.1). The median progression free survival (PFS) and overall survival (OS) rates were 4.8 months and 8.0 months, respectively. The 1-year survival rate was 38%, and the median PFS and OS were 6.4 months and 16.4 months, respectively, in patients with PS 0-1. Thirty patients were symptomatic: Seventeen patients (56.7%) achieved a complete response, and 5 patients (16.7%) achieved a partial symptomatic response. CONCLUSIONS: At the doses given in this study, gemcitabine and epirubicin had a good tolerability profile with interesting activity in patients with advanced urothelial carcinoma who were not fit for cisplatin-based regimens. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.1086

Assessment of self-efficacy for caregiving in oncology: Italian validation of the caregiver inventory (CGI-I)

Background: The Caregiver Inventory (CGI), a measure of self-efficacy for caregiving that takes into account aspects of caregiving that are neglected by current measures of caregiving, was translated into Italian and validated. Methods: Ninety-one caregivers from a variety of locations in Italy completed the CGI-Italian (CGI-I) as well as the Hospital Anxiety and Depression Scale (HADS) and the Family Strain Questionnaire - Short Form (FSQ-SF). Results: A confirmatory factor analysis based on the original CGI factor structure resulted in an adequate fit of the CGI-I using standard fit indices. Thus, the original factor structure was validated in the CGI-I: Managing Medical Information (α = 0.87), Caring for Care Recipient (α = 0.68), Caring for Oneself (α = 0.78), and Managing Difficult Interactions/Emotions (α = 0.55). The CGI-I total score was inversely related to anxiety (HADS, r = − 0.35, p = <.05), and depression (HADS, r = − 0.45, p = <.05). In addition, the CGI-I was inversely related to caregiver stress (FSQ-SF, r = − 0.39, p = <.05). Care of Oneself and Managing Difficult Interactions/Emotions emerged as the strongest and most robust negative relationships with anxiety, depression, and caregiver stress, which replicated, with similar constructs, findings from the original CGI. Conclusions: The results of this study established the CGI-I as a reliable and valid measure of self-efficacy for caregiving. This study also confirms the importance of self-care and managing difficult communication in the process of successfully navigating the demands of caregiving and in constructing interventions for caregivers who need support

Hyperglycemia, inflammatory response and infarct size in obstructive acute myocardial infarction and MINOCA

Background: Hyperglycemia has been associated with increased inflammatory indexes and larger infarct sizes in patients with obstructive acute myocardial infarction (obs-AMI). In contrast, no studies have explored these correlations in non-obstructive acute myocardial infarction (MINOCA). We investigated the relationship between hyperglycemia, inflammation and infarct size in a cohort of AMI patients that included MINOCA. Methods: Patients with AMI undergoing coronary angiography between 2016 and 2020 were enrolled. The following inflammatory markers were evaluated: C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR). Myocardial infarct size was measured by peak high sensitivity troponin I (Hs-TnI) levels, left-ventricular-end-diastolic-volume (LVEDV) and left ventricular ejection fraction (LVEF). Results: The final study population consisted of 2450 patients with obs-AMI and 239 with MINOCA. Hyperglycemia was more prevalent among obs-AMI cases. In all hyperglycemic patients\u2014obs-AMI and MINOCA\u2014NLR, NPR, and LPR were markedly altered. Hyperglycemic obs-AMI subjects exhibited a higher Hs-TnI (p &lt; 0.001), a larger LVEDV (p = 0.003) and a lower LVEF (p &lt; 0.001) compared to normoglycemic ones. Conversely, MINOCA patients showed a trivial myocardial damage, irrespective of admission glucose levels. Conclusions: Our data confirm the association of hyperglycemic obs-AMI with elevated inflammatory markers and larger infarct sizes. MINOCA patients exhibited modest myocardial damage, regardless of admission glucose levels