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.

Clinicopathological, therapeutic and prognostic features of the triple-negative tumors in moroccan breast cancer patients (experience of Hassan II university hospital in Fez)

<p>Abstract</p> <p>Introduction</p> <p>Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors (ER, PR) and Her2, we can distinguish between two groups: basal-like (ER-, PR-, Her2-, cytokeratin (CK) 5/6+ and/or Her1+) and unclassified subtype (ER-, PR-, Her2-, Her1- and CK5/6-).</p> <p>The aim of this study is to determine the clinicopathological, histological, therapeutic and prognostic features associated with this type of breast cancer.</p> <p>Methods</p> <p>This is a retrospective study of 366 female breast cancer patients, diagnosed between January 2007 and June 2010 at the Department of Pathology. Epidemiological, clinical, histological, therapeutic and evolutive data were analyzed. OS and DFS rates were estimated by Kaplan-Meier analysis and a log-rank test to estimate outcome.</p> <p>Results</p> <p>A total of 64 women were identified as having TNBC (17.5% of all female breast cancer patients), 12.6% were basal-like, 4.9% were unclassified subtype, with a median age of 45 years. The median histological tumor diameter was 4.3 cm. TNBC were most often associated with a high grade, 49.2% grade III (53% for unclassified subtype, 47.6% for basal-like). Vascular invasion was found in 26.6% of cases (22% for unclassified subtype and 28.3% for basal-like). For the lymph node involvement: 51% had positive lymph nodes, and 22.4% had distant metastases. Neoadjuvant chemotherapy was administered to 18% patients with 26% of complete pathologic response; therefore adjuvant chemotherapy was given to 82%. 98% received anthracycline based regimen and only 30% received taxanes.</p> <p>The Kaplan-Meier curves based showed the lowest survival probability at 3-years (49% of OS, and 39% of DFS).</p> <p>Conclusion</p> <p>TNBC is associated with young age, high grade tumors, advanced stage at diagnosis, difference chemo response compared to other subtypes, and shortest survival. Critical to optimal future management is accurate identification of truly triple negative disease, and adequately powered prospective TNBC trials to establish treatment efficacy and define predictive biomarkers.</p

Designing DNA nanodevices for compatibility with the immune system of higher organisms

DNA is proving to be a powerful scaffold to construct molecularly precise designer DNA devices. Recent trends reveal their ever-increasing deployment within living systems as delivery devices that not only probe but also program and reprogram a cell, or even whole organisms. Given that DNA is highly immunogenic, we outline the molecular, cellular and organismal response pathways that designer nucleic acid nanodevices are likely to elicit in living systems. We address safety issues applicable when such designer DNA nanodevices interact with the immune system. In light of this, we discuss possible molecular programming strategies that could be integrated with such designer nucleic acid scaffolds to either evade or stimulate the host response with a view to optimizing and widening their applications in higher organisms

Abstract WP451: “Development, Feasibility and Validation of “Stroke Home Care” Application in a Resource Limited Setting: A Proof of Concept Study”

Introduction: Stroke rehabilitation and caregivers training is central to improve post stroke care and reduce caregivers’ burden. Mobile applications(app) may provide a patient and caregiver centric modality to improve stroke care Aim: To develop and evaluate feasibility of a medical application for delivering post stroke care. Methods: A mobile app was developed on an android operating system following a preliminary assessment of post stroke complications to train caregivers. App consists of videos of home based care strategies for bedsore prevention, feeding, mouth care, ROM exercises, catheter care, psychological support to patients etc. App includes awareness videos on stroke, problems faced after stroke, follow up schedule, feedback option. App feasibility was assessed among 25 bedridden stroke survivors and their caregivers selected purposely. App validation was done by 16 stroke experts including neurologists, nurses, psychologists, physiotherapists using semi-structured-questionnaire for data collection. Following this, final "Stroke Home Care" app was developed. Results Feasibility: Mean age of patients and caregivers was 52.6±14.8 and 32.4±8.9years, respectively. 64% patients females, 75% caregivers males. 56% lived in rural. Median NIHSS 14 (IQR: 12-17). Complications were 56% Ryle’s tube, 72% Foley’s catheter, 12% bedsore. 64% caregivers were graduates. 52% sons. All caregivers responded that app contents, videos and language was understandable and appropriate. 92% preferred ‘Hindi’ language. All agreed to App enhancing their stroke knowledge. All were satisfied. Validation: Mean age of experts was 33.2±4years. 75% females. 56% nursing experts and postgraduates,19% MDs. 50% Nursing teachers, 19% Neurology fellows. None faced any app installation problem. 81.3% experts highly satisfied with app functions, its contents, voice clarity, video clarity and duration, contents’ sequence, understandability. Discussion/Conclusion: “Stroke Home Care” App is feasible, pragmatic and user-friendly for use by caregivers of stroke survivors in a resource limited setting/developing country. It should be tested by an RCT to evaluate its efficacy in reducing post stroke complications and reducing caregivers’ burden. </jats:p

Abstract P839: ‘Stroke Home Care’- A Mobile Application: Home Based Innovative Nursing Care Intervention Developed by Stroke Nurse: A Need of the Time in Covid-19 Pandemic Like Situation

Introduction: Stroke nurse is functioning as a vital member of the stroke team. She/he provides care to the stroke patients in acute as well as post-acute periods. She/he coordinates among other team members to facilitate the stroke care continuum. Post-stroke care is always a challenge for health care professional as well as caregivers. During current pandemic conditions, it is essential to provide quality care at their home. Purpose: To develop a mobile application to provide home based care for prevention and management of post stroke complications among survivors. Methods: Survey was carried out among 170 bedridden stroke survivors and their caregivers to assess problems faced like aspiration pneumonia, bedsore, urinary tract infection, deep vein thrombosis, frozen shoulder, contractures, and caregiver burden. On the basis of findings ‘Stroke home care’ a bilingual (in Hindi and English) mobile application was developed which contains step by step nursing-care-procedural videos to prevent bedsore, bedsore dressing, positioning change, Ryle’s tube feeding, Foley’s catheter care, active and passive range of motion exercises, hand washing with soap-water as well with sanitizer, psychological support to patients. Results: Through this intervention, caregivers of bedridden stroke patients get trained for care procedures so that they can provide best possible nursing care to their patients at home and can prevent post stroke complications and ultimately enhances quality of life of survivors and reduce caregivers’ burden. Conclusion: ‘Stroke Home Care’ is a novel intervention developed by a stroke nurse which has been developed and tested not just for its feasibility and acceptability but also proven for its clinical applicability through PROBE designed study. This web based intervention can provide rehabilitation services to bedridden stroke survivors at their home in this pandemic. </jats:p