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.

Stroke prevention in patients from Latin American countries with non-valvular atrial fibrillation: Insights from the GARFIELD-AF registry.

BACKGROUND: Atrial fibrillation (AF) is an important preventable cause of stroke. Anticoagulation (AC) therapy can reduce this risk. However, prescribing patterns and outcomes in patients with non-valvular AF (NVAF) from Latin American countries are poorly described. METHODS: Using data from the Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF), we examined the stroke prevention strategies and the 1-year outcomes in patients from four Latin American countries: Argentina, Brazil, Chile, and Mexico. RESULTS: A total of 4162 patients (2010-2014) were included in this analysis. At the time of AF diagnosis, 39.9% of patients were prescribed vitamin K antagonists (VKA) ± antiplatelet (AP) therapy, 21.8% non-VKA oral anticoagulant (NOAC) ± AP, 24.1% AP only and 14.1% no antithrombotic treatment. The proportion of moderate-high risk patients receiving no AC therapy at participating centers was highest in Mexico (46.4%) and lowest in Chile (14.3%). During 1-year follow-up, the rates of all-cause mortality, stroke/SE and major bleeding were: 5.77 (95% CI) (5.06-6.56), 1.58 (1.23-2.02), and 0.99 (0.72-1.36) and per 100 person-years, respectively, which are higher than the global rates across all countries in GARFIELD-AF. Unadjusted rates of all-cause mortality were highest in Argentina, 6.95 (5.43-8.90), and lowest in Chile, 4.01 (2.92-5.52). CONCLUSIONS: GARFIELD-AF results describes the marked variation in the baseline characteristics and patterns of antithrombotic treatments in patients with NVAF in four Latin American countries. Over one-third of patients with a moderate-to-high risk of stroke received no AC therapy, highlighting the need for improved management of patients according to national guideline. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

[Prevalence of thyroid dysfunction in patients with type 2 diabetes mellitus]. / Prevalencia de disfunción tiroidea en pacientes con diabetes mellitus tipo 2.

Diabetes mellitus (DM) and thyroid dysfunction (TD) are two common endocrine disorders. The unrecognized subclinical TD may adversely affect metabolic control and increase cardiovascular risk. Our aim was to investigate the prevalence of TD in patients with type 2 diabetes mellitus in an observational cross-sectional study. Clinical and laboratory evaluation was performed to 205 consecutive outpatients at Endocrinology Diabetes and Nutrition Center in Concepcion City, Tucuman, Argentina. Thyroid dysfunction was classified as clinical hypothyroidism with TSH > 4.20 mUI / ml and FT4 < 0.93 ng / dl, subclinical hypothyroidism with TSH > 4.20 mUI / ml and free T4 0.93 to 1.70 ng / dl. Subclinical hyperthyroidism was considered with TSH < 0.27 mUI / ml and free T4 was in normal range (0.93 to 1.70 ng / dl); and clinical hyperthyroidism with TSH < 0.27 mUI / ml and free T4 > 1.70 mUI / ml. Autoimmunity was diagnosed with anti-TPO > 34 IU / ml. TD prevalence in type 2 diabetic patients was 48% (n = 92). In subjects who denied prior TD, the prevalence was 40% (n = 37), 15 with subclinical hypothyroidism (45%). In the whole study population prevalence of subclinical hypothyroidism was 8%. Globally, subclinical DT prevalence was 9% (n = 17) and anti-TPO 13% (n = 25). Early detection of thyroid dysfunction in patients with type 2 diabetes mellitus should be performed routinely, given the high rate of newly diagnosed cases, and increased cardiovascular risk associated with undiagnosed thyroid dysfunction.

Prevalencia de disfunción tiroidea en pacientes con diabetes mellitus tipo 2 / Prevalence of thyroid dysfunction in patients with type 2 diabetes mellitus

La diabetes mellitus (DM) y la disfunción tiroidea (DT) son dos frecuentes desórdenes endocrinos. La DT subclínica no reconocida puede afectar adversamente el control metabólico y aumentar el riesgo cardiovascular. Nuestro objetivo fue determinar la prevalencia de DT en pacientes con diabetes mellitus tipo 2, en un estudio observacional de corte transversal con evaluación clínica y de laboratorio a 205 pacientes consecutivos atendidos en consulta externa del Centro de Endocrinología, Diabetes y Nutrición de la ciudad de Concepción, Tucumán, Argentina. La disfunción tiroidea se clasificó como hipotiroidismo clínico con TSH > 4.20 μUI/ml y T4L < 0.93 ng/dl; hipotiroidismo subclínico con TSH > 4.20 μUI/ml y T4 libre 0.93 a 1.70 ng/dl. hipertiroidismo subclínico con TSH < 0.27 μUI/ml y T4 libre en rango normal (0.93-1.70 ng/dl). Se consideró hipertiroidismo clínico con TSH < 0.27 μUI/ml y T4 libre > 1.70 μUI/ml. Se diagnosticó autoinmunidad con anti-TPO > 34 UI/ml. La prevalencia de DT en los diabéticos tipo 2 fue 48% (n = 92). En aquellos que negaron DT previa, la prevalencia fue 40% (n = 37), 15 presentaron hipotiroidismo subclínico (45%). En el total de la población estudiada la prevalencia de hipotiroidismo subclínico fue 8%. En forma global la prevalencia de DT subclínica fue 9% (n = 17) y la de anticuerpos anti-TPO 13% (n = 25). La detección temprana de disfunción tiroidea en diabetes mellitus tipo 2 debería realizarse rutinariamente, dada la elevada tasa de nuevos casos diagnosticados y el aumento del riesgo cardiovascular asociado a la disfunción tiroidea no diagnosticada oportunamente.

Diabetes mellitus (DM) and thyroid dysfunction (TD) are two common endocrine disorders. The unrecognized subclinical TD may adversely affect metabolic control and increase cardiovascular risk. Our aim was to investigate the prevalence of TD in patients with type 2 diabetes mellitus in an observational cross-sectional study. Clinical and laboratory evaluation was performed to 205 consecutive outpatients at Endocrinology Diabetes and Nutrition Center in Concepcion City, Tucuman, Argentina. Thyroid dysfunction was classified as clinical hypothyroidism with TSH > 4.20 mUI / ml and FT4 < 0.93 ng / dl, subclinical hypothyroidism with TSH > 4.20 mUI / ml and free T4 0.93 to 1.70 ng / dl. Subclinical hyperthyroidism was considered with TSH < 0.27 mUI / ml and free T4 was in normal range (0.93 to 1.70 ng / dl); and clinical hyperthyroidism with TSH < 0.27 mUI / ml and free T4 >1.70 mUI / ml. Autoimmunity was diagnosed with anti-TPO > 34 IU / ml. TD prevalence in type 2 diabetic patients was 48% (n = 92). In subjects who denied prior TD, the prevalence was 40% (n = 37), 15 with subclinical hypothyroidism (45%). In the whole study population prevalence of subclinical hypothyroidism was 8%. Globally, subclinical DT prevalence was 9% (n = 17) and anti-TPO 13% (n = 25). Early detection of thyroid dysfunction in patients with type 2 diabetes mellitus should be performed routinely, given the high rate of newly diagnosed cases, and increased cardiovascular risk associated with undiagnosed thyroid dysfunction.

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]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably.

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])...

[Determination of blood markers and inflammation in subjects with impaired glucose tolerance]. / Determinación de marcadores séricos de trombosis e inflamación en sujetos con intolerancia a la glucosa: evidencia de un estado protrombótico.

OBJECTIVE: This study was designed to explore the presence of a prothrombotic state, fibrinolytic dysfunction and inflammation in impaired glucose tolerance subjects, by evaluating serum markers of thrombosis, fibrinolysis and inflammation. METHODS: In 48 consecutive adults, 25 patients with impaired glucose tolerance (nine men and 16 women, 50.0 ± 9.2 years) were compared with 23 control subjects (six men and 17 women, 48.0 ± 11 years). The markers of thrombotic activation used were D-dimer and fibrinogen. Fibrinolysis dysfunction was evaluated with plasminogen activator inhibitor 1 (PAI-1) and the inflammatory marker studied was hs-C reactive protein (hs-CRP). RESULTS: The markers of thrombotic state were significantly higher in patients with impaired glucose tolerance (IGT) than in controls: D dimer (489.6 ± 277.3 vs. 345.8 ± 158.9 ng/mL) (p< 0.01) and fibrinogen (317.7 ± 32.1 vs. 266.7 ± 25.4 mg/dL) (p < 0.0001). Fibrinolytic marker PAI-1 also differed significantly between the two study groups (66.4 ± 30.7 vs. 35.5 ± 31.0 ng/mL) (p < 0.006). However, hs-CRP, as inflammation marker, (0.45 ± 0.62 mg/dL vs. 0.38 ± 0.47) did not differ significantly between the two study groups (<0.28). CONCLUSION: This result suggests the presence of a prothrombotic state with fibrinolytic dysfunction in subjects with impaired glucose tolerance.

Determinación de marcadores séricos de trombosis e inflamación en sujetos con intolerancia a la glucosa: evidencia de un estado protrombótico / Determination of blood markers and inflammation in subjects with impaired glucose tolerance

Objetivo: Este estudio fue diseñado para explorar la presencia de un estado protrombótico, disfunción fibrinolítica e inflamación en sujetos con intolerancia a la glucosa, mediante la evaluación de los marcadores séricos de trombosis, fibrinólisis e inflamación. Métodos: Se estudiaron 48 individuos consecutivos, 25 intolerantes a la glucosa: (nueve hombres y 16 mujeres, 50.0 ±9.2 años) y 23 sujetos control (seis hombres y 17 mujeres, 48.0 ±11 años). Se compararon entre ambos grupos los niveles de dímero-D y fibrinógeno como marcadores de trombosis, el PAI-1 como marcador de fibrinólisis y la proteína C reactiva ultrasensible (PCR-us) como marcador de inflamación. Resultados: En los sujetos intolerantes a la glucosa respecto al grupo control, se observaron diferencias significativas en los marcadores de trombosis: fibrinógeno 317.7 ± 32.1 vs. 266.7 ± 25.4 mg/dL (p<0.0001), dímero-D 489.6 ± 277.3 vs. 345.8 ± 158.9 ng/mL (p<0.01) y en el marcador de fibrinólisis PAI-1 66.4 ± 30.7 vs. 35.5 ± 31.0 ng/mL (p<0.006). En el marcador de inflamación, PCR-us no se observó diferencia significativa, respecto al grupo control 0.45 ± 0.6 vs. 0.38 ± 0.4 mg/dL (p<0.28). Conclusiones: Estos resultados sugieren la presencia de un estado protrombótico con disfunción del sistema fibrinolítico, en sujetos intolerantes a la glucosa.

Objective: This study was designed to explore the presence of a prothrombotic state, fibrinolytic dysfunction and infammation in impaired glucose tolerance subjects, by evaluating serum markers of thrombosis, fibrinolysis and infammation. Methods: In 48 consecutive adults, 25 patients with impaired glucose tolerance (nine men and 16 women, 50.0 ±9.2 years) were compared with 23 control subjects (six men and 17 women, 48.0 ±11 years). The markers of thrombotic activation used were D-dimer and fibrinogen. Fibrinolysis dysfuntion was evaluated with plasminogen activator inhibitor 1 (PAI-1) and the infammatory marker studied was hs-C reactive protein (hs-CRP). Results: The markers of thrombotic state were significantly higher in patients with impaired glucose tolerance (IGT) than in controls: D dimer (489.6 ± 277.3 vs. 345.8 ± 158.9 ng/mL) (p < 0.01) and fibrinogen (317.7 ±32.1 vs. 266.7 ±25.4 mg/dL) (p < 0.0001). Fibrinolytic marker PAI-1 also differed significantly between the two study groups (66.4 ± 30.7 vs. 35.5 ± 31.0 ng/ mL) (p < 0.006). However, hs-CRP, as infammation marker, (0.45 ± 0.62 mg/dL vs. 0.38 ± 0.47) did not differ significantly between the two study groups (<0.28). Conclusion: This result suggests the presence of a prothrombotic state with fibrinolytic dysfunction in subjects with impaired glucose tolerance.