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.

High Gain Circularly Polarized Pentagonal Microstrip for Massive MIMO Base Station

In this paper we propose a circularly polarized pentagonal microstrip antenna on a suspended substrate with coaxial probe feed and five loaded slits for Massive MIMO BS Antenna applications. Massive Multiple-Input Multiple-Output (MIMO) is one of the key component to be incorporated in the 5G cellular systems. The proposed antenna is successfully simulated using HFSS 13.0, fabricated on a FR-4 substrate and measured. The proposed antenna exhibits a much higher gain of 6.17dB, improved impedance bandwidth of 171.9 MHz (Return loss, S11= -10dB) , axial ratio bandwidth (< 3dB) of 135 MHz , patch area of 1775 mm2  , and also yields return loss better than -15 dB around the center frequency of 2.45 GHz (ISM Band). Measured characteristics of the antenna are in good agreement with the simulated results

Microalbuminuria: A biomarker of sepsis and efficacy of treatment in patients admitted to a medical intensive care unit of a tertiary referral center

Background: The outcome of sepsis is significantly affected by early institution of goal-directed therapies and hence, the search for an early marker of sepsis continues. Aims and Objectives: To observe microalbuminuria levels between patients with sepsis and those without sepsis s admitted to the medical intensive care unit (MICU) of a tertiary referral centre (primary) as also to assess the change in microalbuminuria levels in the first 24 hours as a predictor of mortality and morbidity relative to the APACHE II and SOFA scores. Materials and Methods: This was a prospective observational study where 125 patients with sepsis and 38 without were assessed. Trend of microalbuminuria was assessed from the change of ACR value within 6 hours of admission (ACR1) to the ACR value at 24 hours (ACR2) in both groups of patients. Results and Conclusion: Significantly higher levels of microalbuminuria were found among patients with sepsis as compared to those without sepsis. The levels decreased in survivors with sepsis after 24 hours, whereas they continued to remain almost at the same levels among those without sepsis. The change in microalbuminuria levels over 24 hours can be used to measure the effectiveness of therapy. Persistence of high levels or increasing trend of microalbuminuria levels over 24 hours was found to be a predictor of a poor outcome. A high level of microalbuminuria at 24 hours and increasing trend of microalbuminuria also predicted mortality better than APACHE II and SOFA scores

Acute kidney injury of infectious etiology in monsoon season: A prospective study using acute kidney injury network criteria

The epidemiological pattern of acute kidney injury (AKI) in tropical countries during monsoon reflects infectious disease as the most important cause. AKI is a confounding factor and may be overlooked by primary health-care providers and underreported in health statistics. The present study prospectively helps estimate the burden of disease and analyze etiology, clinical profile, and outcome in a tertiary care hospital of a metropolitan city in a tropical country. The study period included monsoon season of 2012 and 2013, a total of 8 months. AKI staging was done as per the AKI Network (AKIN) criteria. Patients were treated for primary disease. Renal replacement therapy (RRT) was given as required. Patients were followed up during hospitalization till recovery/death. Out of a total of 9930 admissions during this period, 1740 (17.52%) were for infections and 230 (2.31%) had AKI secondary to infectious diseases during monsoon. The incidence of AKI (230/1740) in infectious diseases during monsoon was 13.21%. The study population (n = 230) comprised 79.5% of males and the mean age was 40.95 ± 16.55 years. Severe AKI: AKIN Stage III was seen in 48.26% of patients and AKIN Stage I in 41.74%. The most common etiology of AKI was malaria (28.3%) followed by acute gastroenteritis (23%), dengue (16.5%), leptospirosis (13%), undifferentiated fever (10.4%), more than one etiology (5.4%), and enteric fever (3.5%). RRT was required in 44.78% of patients. Requirement for RRT was maximum in patients with more than one etiology followed by leptospirosis, malaria, dengue, and least in typhoid. The overall mortality was 12.17%. In multivariate analysis, vasopressor support and assisted ventilation were risk factors for mortality

Apixaban versus Enoxaparin for Thromboprophylaxis in Medically Ill Patients

BACKGROUND: The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin. METHODS: In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated. RESULTS: A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome--2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62 to 1.23; P=0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P=0.04). CONCLUSIONS: In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparin. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00457002.)