Vitamin D levels in a population from Argentina with metabolic disorders.

Metabolic disorders are a public health problem worldwide. The vitamin D status in patients with metabolic diseases is not a routine procedure. The aim of this study was to determine the prevalence of vitamin D deficiency and examine the correlation between vitamin D status and cardiometabolic parameters in Latin American population with metabolic disorders. Methods: This observational study with a cross-sectional design included 151 patients with metabolic disorders (type 2 diabetes, hypothyroidism, type 2 diabetes with hypothyroidism, and excess weight). A fasting blood sample was collected and analyzed to determine the levels of 25-hydroxyvitamin D, calcium, glucose, hemoglobin A1c, thyroid-stimulating hormone, and free thyroxine. Anthropometric and blood pressure measurements were also performed. Results: According to vitamin D values established by the Institute of Medicine, subjects with metabolic disorders group showed: 23% risk to bone health (9.42 ±3.O4ng/mL), 45% risk of insufficiency/deficiency (17.05 ±2.12ng/mL), and 32% had sufficient levels (26.34±6.74ng/mL), whereas healthy subjects group showed significantly higher values than metabolic diseases group (37.25± 7.72). In addition, vitamin D levels were inversely correlated with elevated body mass index (29.13±5.15kg/m2), systolic blood pressure (126.50± 15.60 mm Hg), fast blood glucose (106.29±33.80 mg/dL), and hemoglobin A1c (6.40% ± 1.38%) values. Conclusion: Subjects with metabolic disorders and with adequate nutritional intake of vitamin D-rich foods and frequent exposure to sunlight have low serum vitamin D concentrations compared to the general population and vitamin D status should be assessed in these patients.

RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

BACKGROUND: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Marcadores bioquímicos en la detección y estadificación del riesgo de progresión de la enfermedad renal crónica / Biochemistry markers in detection and risk staging of chronic kidney disease progression / Marcadores bioquímicos na detecção e estadiamento do risco de progressão da doença renal crônica

Resumen La enfermedad renal crónica (ERC) se define como la pérdida progresiva de la estructura y función renal. Es asintomática en etapas iniciales, pero lleva a insuficiencia renal y mortalidad cardiovascular prematura. La investigación e marcadores de lesión y función renal permite su detección precoz y la evaluación del riesgo de progresión. Se estudiaron 73 voluntarios aparentemente sanos con factores de riesgo, de ambos sexos, asintomáticos y con edades entre 20 y 70 años, y se los comparó con una población control sin factores de riesgo. Fueron evaluadas las historias clínicas, los parámetros antropométricos y la presión arterial. Se analizó la creatinina sérica por métodos enzimático y cinético, se estimó la filtración glomerular con las ecuaciones CKD-EPI, MDRD-IDMS y MDRD-4 y la creatinina urinaria y la albuminuria por métodos cinético e inmunoturbidimétrico, respectivamente. La lipocalina asociada a gelatinasa de neutrófilos (NGAL) sérica y urinaria se determinó por ELISA. El 66% de la población estudiada presentaba sobrepeso, el 34% hipertensión arterial y el 31% tabaquismo. El riesgo de progresión de ERC se estadificó con el filtrado glomerular estimado y la albuminuria y se evidenció un 87% con bajo riesgo, 12% con riesgo moderado y 1% con riesgo alto. La NGAL sérica mostró diferencias significativas respecto al grupo control 11,65 vs. 5,4 ng/mL (p<0,05), e incrementos en las distintas categorías conforme aumentaba el riesgo de progresión. La detección de ERC temprana, en pacientes asintomáticos con factores de riesgo considerados modificables, permitirá la implementación de acciones que retrasen la progresión a estadios avanzados y las complicaciones cardiovasculares asociadas a la enfermedad.

Abstract Progressive loss of renal structure and function define chronic kidney disease (CKD). It is silent in early stages but leads to renal failure and premature cardiovascular mortality. Investigation of renal function and injury markers allows CKD early detection and progression risk evaluation. A total of 73 apparently healthy volunteers, both sexes, asymptomatic with risk factors, from 20 to 70 years old were studied compared to the control population without risk factors. Clinical histories, anthropometric parameters and blood pressure were evaluated. Serum creatinine was analyzed with enzymatic and kinetic methods. Estimated glomerular filtration was calculated with CKD-EPI, MDRD-IDMS and MDRD-4 equations, urinary creatinine by kinetics method and albuminuria by immunoturbidimetry. Serum and urinary neutrophil gelatinase-associated lipocalin (NGAL) were investigated by ELISA. Population risk factors analyzed showed 66% overweight, 34% hypertensive and 31% smoking patients. CKD risk progression was staged with estimated glomerular filtration and albuminuria, according to KDIGO 2012. Population showed 87% patients in low CKD risk, 12% with moderate risk, and only 1% with high risk progression. Serum NGAL showed significant differences with respect to the control group, 11.65 vs 5.4 ng/mL (p<0,05), and increases in different categories as progression risk increases. CKD detection of asymptomatic patients with modifiable risk factors, in reversible early stages, will allow implementing actions that delay associated cardiovascular complications and disease progression to advanced stages.

Resumo A doença renal crônica (DRC) é definida como a perda progressiva da estrutura e função dos rins. Assintomático nos estágios iniciais, leva à insuficiência renal e à mortalidade cardiovascular prematura. A pesquisa de marcadores de lesão e função renal permite sua detecção precoce e avaliação do risco de progressão. Foram estudados 73 voluntários aparentemente saudáveis com fatores de risco, de ambos os sexos, assintomáticos e idades entre 20 e 70 anos, comparados à população controle sem fatores de risco. Prontuários, parâmetros antropométricos e pressão arterial foram avaliados. A creatinina sérica foi analisada pelo método enzimático e cinético, estimando a filtração glomerular com as equações CKD-EPI, MDRD-IDMS e MDRD-4, e a creatinina urinária e albuminúria, pelos métodos cinético e imunoturbidimétrico, respectivamente. Lipocalina associada à gelatinase de neutrófílos (NGAL), sérica e urinária foi determinada pelo método ELISA. 66% da população estudada apresentavam sobrepeso, 34% pressão arterial alta e 31% tabagismo. O risco de progressão da DRC foi classificado com a filtração glomerular estimada e albuminúria, mostrando 87% com baixo risco, 12% com risco moderado e apenas 1% com alto risco. A NGAL sérica mostrou diferenças significativas em relação ao grupo controle 11,65 vs 5,4 ng/mL (p<0,05) e incrementos nas diferentes categorias à medida que o risco de progressão aumentava. A detecção da DRC precoce, em pacientes assintomáticos com fatores de risco considerados modificáveis, permitirá a implementação de ações que atrasem a progressão para estágios avançados e complicações cardiovasculares associadas à doença.

Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists

Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852–0·867])...