Efficacy and Safety of Adintrevimab (ADG20) for the Treatment of High-Risk Ambulatory Patients With Mild or Moderate Coronavirus Disease 2019: Results From a Phase 2/3, Randomized, Placebo-Controlled Trial (STAMP) Conducted During Delta Predominance and Early Emergence of Omicron.

Background: Safe and effective treatments are needed to prevent severe outcomes in individuals with coronavirus disease 2019 (COVID-19). We report results from STAMP, a phase 2/3, multicenter, double-blind, randomized, placebo-controlled trial of adintrevimab, an extended half-life monoclonal antibody, for treatment of high-risk ambulatory patients with mild to moderate COVID-19. Methods: Nonhospitalized, unvaccinated participants aged ≥12 years with mild to moderate COVID-19 and ≥1 risk factor for disease progression were randomized to receive a single intramuscular injection of 300 mg adintrevimab or placebo. Enrollment was paused due to the global emergence of the Omicron BA.1/BA1.1 variants, against which adintrevimab showed reduced activity in vitro. The primary efficacy endpoint was COVID-19-related hospitalization or all-cause death through day 29 in participants with COVID-19 due to laboratory-confirmed or suspected non-Omicron severe acute respiratory syndrome coronavirus 2 variants. Results: Between 8 August 2021 and 11 January 2022, 399 participants were randomized to receive adintrevimab (n = 198) or placebo (n = 201), including 336 with COVID-19 due to non-Omicron variants. COVID-19-related hospitalization or all-cause death through day 29 occurred in 8 of 169 (4.7%) participants in the adintrevimab group and 23 of 167 (13.8%) participants in the placebo group, a 66% relative risk reduction in favor of adintrevimab (standardized risk difference, -8.7% [95% confidence interval, -14.71% to -2.67%]; P = .0047). Incidence of treatment-emergent adverse events (TEAEs) was similar between treatment groups (33.9% for adintrevimab and 39.5% for placebo). No adintrevimab-related serious TEAEs were reported. Conclusions: Treatment with a single intramuscular injection of adintrevimab provided protection against severe outcomes in high-risk ambulatory participants with COVID-19 due to susceptible variants, without safety concerns. Clinical Trial Registration. NCT04805671.

Serum Levels of Antibodies to Advanced Glycation End Products in Patients with Type 2 Diabetes Mellitus and Hypertension.

BACKGROUND AND AIMS: Proteins containing advanced glycation end products are highly immunogenic and anti-advanced glycation end products antibodies (anti-AGEs antibodies) are found in the sera of diabetics. MATERIALS AND METHODS: Enzyme-linked immunosorbent assay (ELISA) was used for measuring levels of anti-advanced glycation end products antibodies in sera of 93 patients with type 2 diabetes mellitus and arterial hypertension (mean age 61.4±11.3 years, diabetes duration 9.88±3.12 years; hypertension duration 9.28±4.98). These values were compared to serum anti-AGEs antibodies in 42 age and sex matched controls. Diabetics were divided in two groups according to presence or absence of microangiopathy, group 1 (n=67) and group 2 (n=26), respectively. RESULTS: Serum levels of anti-AGEs antibodies in patients with type 2 diabetes mellitus and arterial hypertension were statistically significantly higher than those in the control group (1.39±0.39 vs. 1.05±0.32), (p<0.05). Group 1 showed significantly higher levels of anti-AGEs antibodies than those of healthy controls (1.53±0.14 vs. 1.05±0.32), (p<0.01). Anti-AGEs antibodies levels were higher in patients with microvascular complications than these in patients without complications. Anti-AGEs antibodies correlate with diastolic blood pressure (r=0.26, p=0.05) and body mass index (r=0.37, p=0.03). We found significantly higher percentage of positive patients for anti-AGEs antibodies (mean+2SD) in group 1 than in group 2. CONCLUSION: Determining the levels of serum anti-AGEs antibodies can help physicians make early diagnosis and prognosis of the severity of late diabetic complications in hypertensive patients.

Plasma lipoprotein(a) concentration as an independent predictor of hemodynamic progression of aortic valve stenosis.

Calcific aortic valve disease (CAVD) is a common cardiovascular disorder of high social significance. This study aimed to identify independent predictors of hemodynamic progression of CAVD. The relationship between some risk factors, including the rs10455872 polymorphism in the intron 25 of the lipoprotein(a) [Lp(a)] coding region and the plasma Lp(a) concentration, and CAVD severity were prospectively examined in 114 patients. Age (p = 0.023), smoking (p = 0.038), lack of obesity (p = 0.005), triglyceride levels (p = 0.039), and plasma Lp(a) (p < 0.0001) levels were found to be significant determinants of stenosis progression. The rs10455872 polymorphism; however, was not found to be a significant factor for neither the stenosis severity (p = 0.773) nor for plasma Lp(a) levels (p = 0.617). We established a highly significant Lp(a) cut-off concentration (21.2 mg/dL) distinguishing the aortic valve calcification without stenosis from the significant stenosis. Plasma Lp(a) concentration was the only independent predictor of disease progression (p < 0.0001). Moreover, patients with plasma levels of Lp(a) ≥ 21.2 mg/dL were 55 times more likely to develop aortic valve stenosis. We conclude that Lp(a) concentration may prove valuable for more reliable identification of patients at risk of accelerated CAVD development. Future studies are desirable to determine whether plasma Lp(a) levels could be used as a potential biomarker for aortic stenosis progression.

Relationship between Lipid Indices, Type IV Collagen Turnover and the Development of Microvascular Complications in Diabetic Patients with Arterial Hypertension.

BACKGROUND AND AIMS: An important factor in the development of vascular wall lesions is the degradation of the major protein of connective tissue - type IV collagen. Type IV collagen peptides (CIVDP) derived from this degradation are present in the circulation and are a stimulus for production of anti-collagen type IV antibodies (ACIVAbs) IgM, IgG and IgA. The aim of this study was to find a possible association between ACIVAbs, lipid indices and the development of microvascular complications. MATERIALS AND METHODS: Sera of 93 patients (mean age 61.4±11.3 yrs, diabetes duration 9.88±3.12 yrs; hypertension duration 9.28±4.98) with type 2 diabetes mellitus (T2DM) and arterial hypertension (AH) were investigated. ACIVAbs was determined using ELISA and then compared to serum ACIVAbs in 42 age- and sex-matched controls. Diabetics were divided into two groups according to presence (group 1, n=67) or absence (group 2, n=26) of microangiopathy. Lipid profile and lipid indices (log TG/HDL, LDL/HDL, TC/HDL and TG/HDL) were examined too. RESULTS: Patients with T2DM and AH showed statistically significant higher levels of serum ACIVAbs IgG than healthy controls [0.298 (0.237÷0.381) vs 0.210 (0.149÷0.262), KW=14.01, p<0.0001]. Group 1 had statistically significant higher levels of ACIVAbs IgG than patients without microangiopathy [0.323 (0.243÷0.391) vs 0.241 (0.207÷0.291), KW=7.66, p=0.006] and healthy controls [0.210 (0.149÷0.262), KW=17.52, p<0.0001). ACIVAbs IgG showed correlation with duration of diabetes (r=0.49, p=0.01), retinopathy (r=-0.20, p=0.04) and BMI (r=-0.24, p=0.05), HbA1c (r=0.21, p=0.04), SBP (r=0.16, p=0.05). ACIVAbs IgG correlated with log TG/HDL (r=0.21, p=0.01), LDL/HDL (r=0.19, p=0.02) TC/HDL (r=0.16, p=0.05) and with TG/HDL (r=0.15, p=0.05). CONCLUSION: Our study shows relationship between elevation of ACIVAbs IgG, high lipid indices and development of microvascular complications in patients with type 2 diabetes mellitus and arterial hypertension.

Sociodemographic and lifestyle risk factors for incident dementia and cognitive decline in the HYVET.

INTRODUCTION: previous studies have suggested that smoking, living alone and having a high body mass index may increase risk of developing dementia whereas a normal body mass index, having received education and moderate alcohol consumption may decrease risk. Dementia risk also increases with age and is thought to be higher in hypertensives. METHOD: we used data collected in the Hypertension in the Very Elderly Trial (HYVET), and cognitive function was assessed using the Mini-Mental State Examination (MMSE) at baseline and annually. Participants with a fall in MMSE to <24 or with a fall of 3 points in any 1 year were investigated further. The association of baseline sociodemographic, medical and lifestyle factors with incident dementia or decline in MMSE scores was assessed by regression models. RESULTS: incident dementia occurred in 263 of 3,336 participants over a mean follow-up of 2 years. In multivariate analyses, being underweight, BMI < 18.5 (HR 1.90, 95% CI 1.06-3.39) or obese, BMI >30 (HR 1.84, 95% CI 1.24-2.72), increased risk of incident dementia as did piracetam use (HR 2.72, 95% CI 1.60-4.63). Receiving formal education was associated with a reduced risk (HR 0.59, 95% CI 0.45-0.78). There was no association with smoking, alcohol and gender. Similar results were found when examining mean annual change in the MMSE score. DISCUSSION: our results for BMI and education agree with those from other studies. The increased risk associated with piracetam may reflect awareness of memory problems before any diagnosis of dementia has been made. Trial participants may be healthier than the general population and further studies in the general population are required.