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.

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Registration of NP36 and NP37, Two Random-Mating Grain Sorghum Populations Selected for Reduced Dhurrin Content

NP36 and NP37 grain sorghum [Sorghum bicolor (L.) Moench] (Reg. no. GP-244 and GP-245; PI 535780 and PI 535781), two random-mating populations of grain sorghum, were developed cooperatively by the USDA-ARS and the Nebraska Agricultural Research Division and were released in April 1989. Both populations were selected for reduced dhurrin content, and they have potential value as sources of A- and B-lines of grain sorghum for use in producing low-dhurrin sorghum-sudangrass hybrids. NP37 also contains the bmr-6 gene for brown midribs and, therefore, may be useful in producing sorghum-sudangrass or forage sorghum hybrids with brown midribs

Registrationo f NP22 Sudangrass Germplasm

\u27NP22\u27 Sudangrass [Sorghum bicolor (L.) Moench] [formerly S. sudanense (Piper) Staph] (Reg. No. GPI38), a random-mating population carrying the mS3 gene and selected primarily for low dhurrin content, is generally similar in appearance to \u27Piper\u27 sudangrass with mostly dry stalks (white midrib) and purple plant color. Seed color is heterogeneous and includes straw, sienna, mahogany, and black glumes. NP22 was developed cooperatively by USDA-ARS and the Nebraska Agricultural Experiment Station and released in May 1982

Breeding and Agronomic Studies with Sorghum in Puerto Rico

Sorghum (Sorghum bicolor [L.] Moench.) research activities at the Tropical Agriculture Research Station (TARS), Mayaguez, Puerto Rico, are described. In cooperation with the Texas Agricultural Experiment Station, 423 daylength insensitive lines from the Sorghum Conversion Program were developed. Numerous new collections were evaluated and classified. Other activities include the evaluation of new cytoplasms and their reactions when crossed to converted lines, the evaluation of grain and forage hybrids, the comparison of daylength sensitive versus daylength insensitive forage hybrids and the development of single and three-way hybrids. Newly developed single and three-way forage hybrids yield over 25 tons ha-1 of dry forage in 180 days. Sorghum populations developed, or in process of development, at TARS in cooperation with other scientists include: 1. populations with reduced hydrocyanic acid (HCN) potential; 2. populations of high yield potential; and 3. populations with increased resistance to common tropical diseases of sorghum

Registration of NP25 Low-dhurrin Sudangrass Germplasm

NP25 sudangrass [Sorghum bicolor (L.) Moench] (Reg. no. GP-180), a low-dhurrin, random-mating population that carries the ms3 gene for genetic male sterility, was developed cooperatively by USDA-ARS and the Nebraska Agricultural Research Division and released in April 1984. Plants of NP25 are leafy and fine-stemmed, 160 to 170 cm in height with dry stalks (white midrib), tan plant color, sienna glumes, and brown pericarp. NP25 restores fertility to hybrids when crossed to male steriles with A1 cytoplasm