Circulating angiotensin-(1-7) is decreased in patients with isolated nocturnal hypertension.

Isolated nocturnal hypertension (INHT), defined as nighttime elevated blood pressure (BP) with normal daytime BP assessed by ambulatory BP monitoring, is associated with higher cardiovascular morbidity and mortality. We hypothesized that an alteration in the circulating renin-angiotensin system (RAS) contributes to INHT development. We examined circulating levels of angiotensin (Ang) (1-7) and Ang II and ACE2 activity in 26 patients that met the INHT criteria, out of 50 that were referred for BP evaluation (62% women, 45 ±â€Š16 years old). Those with INHT were older, had a higher BMI, lower circulating Ang-(1-7) (P = 0.002) and Ang II levels (P = 0.02) and no change in ACE2 activity compared to those normotensives. Nighttime DBP was significantly correlated with Ang-(1-7) and Ang II levels. Logistic regression showed significant association in Ang-(1-7) and Ang II levels with INHT. Our study reveals differences in circulating RAS in individuals with INHT.

Desarrollo de un modelo por inteligencia artificial con hemodinamia no invasiva para predecir preeclampsia en embarazos de alto riesgo / Artificial Intelligence Modeling with Non-Invasive Hemodynamics to Predict Preeclampsia in High-Risk Pregnancy

RESUMEN Introducción: la preeclampsia (PE) es la principal causa de morbimortalidad materno-fetal en nuestro país. Alteraciones hemodinámicas precoces durante el embarazo podrían predecir la evolución a PE. El machine learning (ML) permite el hallazgo de patrones ocultos que podrían detectar precozmente el desarrollo de PE. Objetivos: desarrollar un árbol de clasificación con variables de hemodinamia no invasiva para predecir precozmente desarrollo de PE. Material y métodos: estudio observacional prospectivo con embarazadas de alto riesgo (n=1155) derivadas del servicio de Obstetricia desde enero 2016 a octubre 2022 para el muestreo de entrenamiento por ML con árbol de clasificación j48. Se seleccionaron 112 embarazadas entre semanas 10 a 16, sin tratamiento farmacológico y que completaron el seguimiento con el término de su embarazo con evento final combinado (PE): preeclampsia, eclampsia y síndrome HELLP. Se evaluaron simultáneamente con cardiografía de impedancia y velocidad de onda del pulso y con monitoreo ambulatorio de presión arterial de 24 hs (MAPA). Resultados: presentaron PE 17 pacientes (15,18%). Se generó un árbol de clasificación predictivo con las siguientes variables: índice de complacencia arterial (ICA), índice cardíaco (IC), índice de trabajo sistólico (ITS), cociente de tiempos eyectivos (CTE), índice de Heather (IH). Se clasificaron correctamente el 93,75%; coeficiente Kappa 0,70, valor predictivo positivo (VPP) 0,94 y negativo (VPN) 0,35. Precisión 0,94, área bajo la curva ROC 0,93. Conclusión: las variables ICA, IC, ITS, CTE e IH predijeron en nuestra muestra el desarrollo de PE con excelente discriminación y precisión, de forma precoz, no invasiva, segura y con bajo costo.

ABSTRACT Background: Preeclampsia (PE) is the main cause of maternal-fetal morbidity and mortality in our country. Early hemodynamic changes during pregnancy could predict progression to PE. Machine learning (ML) enables the discovery of hidden patterns that could early detect PE development. Objectives: The aim of this study was to build a classification tree with non-invasive hemodynamic variables for the early prediction of PE occurrence. Results: Seventeen patients (15.18%) presented PE. A predictive classification tree was generated with arterial compliance index (ACI), cardiac index (CI), cardiac work index (CWI), ejective time ratio (ETR), and Heather index (HI). A total of 93.75% patients were correctly classified (Kappa 0.70, positive predictive value 0.94 and negative predictive value 0.35; accuracy 0.94, and area under the ROC curve 0.93). Conclusion: ACI, CI, CWI, ETR and HI variables predicted the early development of PE in our sample with excellent discrimination and accuracy, non-invasively, safely and at low cost.

Uncontrolled and masked uncontrolled blood pressure in treated pregnant women with chronic hypertension and risk for preeclampsia/eclampsia.

To analyze the relationship between the level of BP achieved with treatment and the risk for development of preeclampsia/eclampsia (PE), we conducted a historical cohort study on 149 consecutive pregnant women with treated chronic hypertension, evaluated between January 1, 2016, and November 31, 2022. According to office BP readings and ambulatory blood pressure monitoring (ABPM) performed after 20 weeks of gestation, the cohort was classified in controlled hypertension, white-coat uncontrolled hypertension, masked uncontrolled hypertension and sustained hypertension. Risks for the development of PE were estimated using logistic regression. One hundred and twenty-four pregnant women with a control BP evaluation were included in this analysis. The rates of PE were 19.4%, 27.3%, 44.8% and 47.1% for controlled, white-coat uncontrolled, masked uncontrolled and sustained uncontrolled hypertension, respectively. Compared with women with controlled hypertension, the relative risk for PE increased markedly in women with sustained uncontrolled (OR 3.69, 95% CI, 1.19-11.45) and masked uncontrolled (OR 3.38, 95% CI, 1.30-11.45) hypertension, but not in those with white-coat uncontrolled (OR 1.56 95% CI, 0.36-6.70); adjustment for covariates did not modify the results. Each mmHg higher of systolic and diastolic daytime ABPM increased the relative risk for PE ~4% and ~5%, respectively. Each mmHg higher of systolic and diastolic nocturnal BP increased the risk ~5% and ~6%, respectively. When these risks were adjusted for ABPM values in opposite periods of the day, only nocturnal ABPM remained as a significant predictor. In conclusion, masked uncontrolled hypertension implies a substantial risk for the development of PE, comparable to those of sustained uncontrolled. The presence of nocturnal hypertension seems important.

Protection of homologous and heterologous boosters after primary schemes of rAd26-rAd5, ChAdOx1 nCoV-19 and BBIBP-CorV during the omicron outbreak in adults of 50 years and older in Argentina: a test-negative case-control study.

Background: After primary vaccination schemes with rAd26-rAd5 (Sputnik V), ChAdOx1 nCoV-19, BBIBP-CorV or heterologous combinations, the effectiveness of homologous or heterologous boosters (Sputnik V, ChAdOx, Pfizer-BioNTech, Moderna) against SARS-CoV-2 infections, hospitalisations and deaths has been scarcely studied. Methods: Test-negative, case-control study, conducted in Argentina during omicron BA.1 predominance, in adults ≥50 years old tested for SARS-CoV-2 who had received two or three doses of COVID-19 vaccines. Outcomes were COVID-associated infections, hospitalisations and deaths after administering mRNA and vectored boosters, < or ≥60 days from the last dose. Findings: Of 422,124 individuals tested for SARS-CoV-2, 221,993 (52.5%) tested positive; 190,884 (45.2%) and 231,260 (54.8%) had received 2-dose and 3-dose vaccination schemes, respectively. The 3-dose scheme reduced infections, hospitalisations and death (OR 0.81 [0.80-0.83]; 0.28 [0.25-0.32] and 0.25 [0.22-0.28] respectively), but protection dropped after 60 days to 1.04 [1.01-1.06]; 0.52 [0.44-0.61] and 0.38 [0.33-0.45]). Compared with 2-dose-schemes, homologous boosters after primary schemes with vectored-vaccines provided lower protection against infections < and ≥60 days (0.94 [0.92-0.97] and 1.05 [1.01-1.09], respectively) but protected against hospitalisations (0.30 [0.26-0.35]) and deaths (0.29 [0.25-0.33]), decreasing after 60 days (0.59 [0.47-0.74] and 0.51 [0.41-0.64], respectively). Heterologous boosters protected against infections (0.70 [0.68-0.71]) but decreased after 60 days (1.01 [0.98-1.04]) and against hospitalisations and deaths (0.26 [0.22-0.31] and 0.22 [0.18-0.25], respectively), which also decreased after 60 days (0.43 [0.35-0.53] and 0.33 [0.26-0.41], respectively). Heterologous boosters protected against infections when applied <60 days (0.70 [0.68-0.71], p < 0.001), against hospitalisations when applied ≥60 days (0.43 [0.35-0.53], p < 0.01), and against deaths < and ≥60 days (0.22 [0.18-0.25], p < 0.01 and 0.33 [0.26-0.41], p < 0.001). Interpretation: During omicron predominance, heterologous boosters such as viral vectored and mRNA vaccines, following Sputnik V, ChAdOx1, Sinopharm or heterologous primary schemes might provide better protection against death; this effect might last longer in individuals aged ≥50 than homologous boosters. Funding: None.

Single-Cell RNA Sequencing Reveals That Adaptation of Human Aortic Endothelial Cells to Antiproliferative Therapies Is Modulated by Flow-Induced Shear Stress.

BACKGROUND: Endothelial cells (ECs) are capable of quickly responding in a coordinated manner to a wide array of stresses to maintain vascular homeostasis. Loss of EC cellular adaptation may be a potential marker for cardiovascular disease and a predictor of poor response to endovascular pharmacological interventions such as drug-eluting stents. Here, we report single-cell transcriptional profiling of ECs exposed to multiple stimulus classes to evaluate EC adaptation. METHODS: Human aortic ECs were costimulated with both pathophysiological flows mimicking shear stress levels found in the human aorta (laminar and turbulent, ranging from 2.5 to 30 dynes/cm2) and clinically relevant antiproliferative drugs, namely paclitaxel and rapamycin. EC state in response to these stimuli was defined using single-cell RNA sequencing. RESULTS: We identified differentially expressed genes and inferred the TF (transcription factor) landscape modulated by flow shear stress using single-cell RNA sequencing. These flow-sensitive markers differentiated previously identified spatially distinct subpopulations of ECs in the murine aorta. Moreover, distinct transcriptional modules defined flow- and drug-responsive EC adaptation singly and in combination. Flow shear stress was the dominant driver of EC state, altering their response to pharmacological therapies. CONCLUSIONS: We showed that flow shear stress modulates the cellular capacity of ECs to respond to paclitaxel and rapamycin administration, suggesting that while responding to different flow patterns, ECs experience an impairment in their transcriptional adaptation to other stimuli.

Efectividad de refuerzos homólogos y heterólogos luego de esquemas primarios con Sputnik V, Astra-Zeneca y Sinopharm durante el período omicron en adultos mayores de 50 años en la provincia de Buenos Aires / Effectiveness of homologous and heterologous boosters after primary regimens with Sputnik V, AstraZeneca, and Sinopharm during the omicron variant period in adults over 50 years old in the province of Buenos Aires

Objetivo: Evaluar la efectividad de esquemas primarios de Sputnik V, Astra-Zeneca, Sinopharm o combinaciones heterólogas seguidos de refuerzos a vector viral (Sputnik V, Astra-Zeneca) o ARNm (Pfizer-BioNTech, Moderna) frente a infecciones, hospitalizaciones y muertes por SARS-CoV-2. Material y métodos: Estudio de casos y controles con test negativo realizado en la provincia de Buenos Aires, durante el predominio de ómicron BA.1, que incluyó individuos ≥ 50 años con test positivo para SARS-CoV-2 que habían recibido 2 o 3 dosis de vacunas. Se registraron infecciones, hospitalizaciones y muertes después de administrar refuerzos con Sputnik V, Astra-Zeneca o ARNm. Resultados: De 422 124 personas analizadas para SARS-Cov-2, 221 993 (52.5%) presentaron test positivos; 190 884 (45.2%) y 231.260 (54.8%) recibieron esquemas de vacunación de 2 y 3 dosis, respectivamente. Los esquemas primarios con Astra-Zeneca, Sputnik V o vector viral, combinados con un refuerzo a vector viral, mostraron protección contra infecciones (OR: 0.94 [0.92 a 0.97]), hospitalizaciones (OR: 0.30 [0.26 a 0.35]) y muertes (OR: 0.29 [0.25 a 0.33]. Los esquemas primarios con Astra-Zeneca y Sputnik V más refuerzo de ARNm, o con Sinopharm más refuerzo de ARNm o vector viral otorgaron protección adicional contra infecciones (OR: 0.70 [0.68 a 0.71]). Hubo un efecto protector frente a hospitalizaciones y muertes (OR: 0.26 [0.22 a 0.31] y 0.22 [0.18 a 0.25]) en todos los casos. Conclusiones: Durante el predominio de ómicron, los refuerzos heterólogos con vacunas a vector viral y de ARNm, posteriores a los esquemas primarios de Sputnik V, Astra-Zeneca, Sinopharm o heterólogos, podrían proporcionar mejor protección y mayor duración del efecto contra la muerte en personas mayores de 50 años, en comparación con refuerzos homólogos

Objective: To evaluate the effectiveness of primary vaccination regimens involving Sputnik V, Astra-Zeneca, Sinopharm, or heterologous combinations followed by viral vector boosters (Sputnik V, As-traZeneca) or mRNA boosters (Pfizer-BioNTech, Moderna) against infections, hospitalizations and deaths caused by SARS-CoV-2. Material and methods: Case-control studies with negative tests conducted in the Buenos Aires province during the Omicron BA.1 predominance. The study included patients ≥ 50 years of age, who tested positive for SARS-CoV-2 and had received two or three doses of vaccines. Infections, hospitalizations, and deaths were registered following the administration of Sputnik V, AstraZeneca, or mRNA boosters. Findings: Out of 422 124 people tested for SARS-Cov-2, 221 993 (52.5%) had positive test results; 190,884 (45.2%) and 231 260 (54.8%) received two-dose and three-dose vaccination schemes, respectively. Primary regimens with AstraZeneca, Sputnik V, or viral vector, combined with a viral vector booster demonstrated protection against infections (OR 0.94 [0.92 to 0.97]), hospitalizations (OR 0.30 [0.26 to 0.35]) and deaths (OR 0.29 [0.25 to 0.33]. Primary regimens with AstraZeneca and Sputnik V combined with mRNA boosters, as well as pri-mary schemes with Sinopharm combined with mRNA or viral vectored boosters showed additional protection against infections (OR 0.70 [0.68 to 0.71]). There was a protective effect against hospi-talizations and deaths (OR 0.26 [0.22-0.31] and 0.22 [0.18 -0.25]) in all cases. Conclusions: During Omicron predominance, heterologous boosters with viral-vector and mRNA vaccines, administered after Sputnik V, AstraZeneca, Sinopharm, or heterologous primary regimens, could provide enhanced protection and prolonged effectiveness against mortality in individuals aged ≥ 50, compared to ho-mologous boosters

Do antihypertensive drugs combinations in single-pill combination improve cardiovascular outcomes?

Recommendations and guidelines propose to combine antihypertensive drugs to improve BP control, highlighting the advantages of single-pill combinations (SPCs) to improve treatment adherence. It is speculated that, compared with free-dose combinations (Free-DCs), SPC should achieve a reduction in cardiovascular (CV) events and mortality through better adherence and BP control. However, there is little information in this regard. For this reason, the objective of this review was to provide a descriptive analysis the differences in CV outcomes between SPCs antihypertensive drugs treatments vs. Free-DCs treatments. Ten studies were found and none had a randomized controlled design. Medication adherence was higher with SPCs, but outcomes were not adjusted for the adherence / persistence. When groups were compared according to similar adherence degrees, the statistical significance in favor of SPCs disappeared. Thus, randomized controlled studies are necessary to evaluate if SPCs have any effect beyond the improvement of the adherence to hypertensive treatment.

Las recomendaciones y las guías proponen combinar fármacos antihipertensivos para mejorar el control de la presión arterial, destacando las ventajas de las combinaciones en un solo comprimido para mejorar la adherencia al tratamiento. Se especula que, en comparación con las combinaciones en varios comprimidos, deberían lograr una reducción de los eventos cardiovasculares y de la mortalidad a través de una mejor adherencia y control de la presión. Sin embargo, hay poca información al respecto. Por esta razón, el objetivo de esta revisión fue proporcionar un análisis descriptivo de las diferencias en los resultados cardiovasculares y la mortalidad entre los tratamientos con combinaciones de antihipertensivos en un solo comprimido vs. combinaciones de los mismos grupos de fármacos en varios comprimidos. Se encontraron diez estudios, pero ninguno tenía un diseño controlado aleatorio. La adherencia a la medicación fue mayor con las combinaciones en un comprimido, pero los resultados no se ajustaron por la adherencia / persistencia. Cuando se compararon los grupos según grados de adherencia similares, la significación estadística a favor de las combinaciones en un comprimido se perdió. Por lo tanto, son necesarios estudios controlados aleatorios para evaluar si las combinaciones de antihipertensivos en un comprimido tienen algún efecto más allá de la mejora de la adherencia al tratamiento.

Do antihypertensive drugs combinations in single-pill combination improve cardiovascular outcomes? / ¿Las combinaciones de medicamentos antihipertensivos en un solo comprimido mejoran los resultados cardiovasculares?

Abstract Recommendations and guidelines propose to com bine antihypertensive drugs to improve BP control, highlighting the advantages of single-pill combinations (SPCs) to improve treatment adherence. It is speculated that, compared with free-dose combinations (Free-DCs), SPC should achieve a reduction in cardiovascular (CV) events and mortality through better adherence and BP control. However, there is little information in this regard. For this reason, the objective of this review was to provide a descriptive analysis the differences in CV outcomes between SPCs antihypertensive drugs treat ments vs. Free-DCs treatments. Ten studies were found and none had a randomized controlled design. Medi cation adherence was higher with SPCs, but outcomes were not adjusted for the adherence/persistence. When groups were compared according to similar adherence degrees, the statistical significance in favor of SPCs disappeared. Thus, randomized controlled studies are necessary to evaluate if SPCs have any effect beyond the improvement of the adherence to hypertensive treatment.

Resumen Las recomendaciones y las guías proponen combinar fármacos antihipertensivos para mejorar el control de la presión arterial, destacando las ventajas de las combi naciones en un solo comprimido para mejorar la adhe rencia al tratamiento. Se especula que, en comparación con las combinaciones en varios comprimidos, deberían lograr una reducción de los eventos cardiovasculares y de la mortalidad a través de una mejor adherencia y con trol de la presión. Sin embargo, hay poca información al respecto. Por esta razón, el objetivo de esta revisión fue proporcionar un análisis descriptivo de las diferencias en los resultados cardiovasculares y la mortalidad entre los tratamientos con combinaciones de antihipertensi vos en un solo comprimido vs. combinaciones de los mismos grupos de fármacos en varios comprimidos. Se encontraron diez estudios, pero ninguno tenía un dise ño controlado aleatorio. La adherencia a la medicación fue mayor con las combinaciones en un comprimido, pero los resultados no se ajustaron por la adherencia/ persistencia. Cuando se compararon los grupos según grados de adherencia similares, la significación estadís tica a favor de las combinaciones en un comprimido se perdió. Por lo tanto, son necesarios estudios controlados aleatorios para evaluar si las combinaciones de antihi pertensivos en un comprimido tienen algún efecto más allá de la mejora de la adherencia al tratamiento.

Behavioral Study of 3- and 5-Halocytisine Derivatives in Zebrafish Using the Novel Tank Diving Test (NTT).

Anxiety is a serious mental disorder, and recent statistics have determined that 35.12% of the global population had an anxiety disorder during the COVID-19 pandemic. A mechanism associated with anxiolytic effects is related to nicotinic acetylcholine receptor (nAChR) agonists, principally acting on the α4ß2 nAChR subtype. nAChRs are present in different animal models, including murine and teleosteos ones. Zebrafish has become an ideal animal model due to its high human genetic similarities (70%), giving it high versatility in different areas of study, among them in behavioral studies related to anxiety. The novel tank diving test (NTT) is one of the many paradigms used for studies on new drugs related to their anxiolytic effect. In this work, an adult zebrafish was used to determine the behavioral effects of 3- and 5-halocytisine derivatives, using the NTT at different doses. Our results show that substitution at position 3 by chlorine or bromine decreases the time spent by the fish at the bottom compared to the control. However, the 3-chloro derivative at higher doses increases the bottom dwelling time. In contrast, substitution at the 5 position increases bottom dwelling at all concentrations showing no anxiolytic effects in this model. Unexpected results were observed with the 5-chlorocytisine derivative, which at a concentration of 10 mg/L produced a significant decrease in bottom dwelling and showed high times of freezing. In conclusion, the 3-chloro and 3-bromo derivatives show an anxiolytic effect, the 3-chlorocytisine derivative being more potent than the 3-bromo derivative, with the lowest time at the bottom of the tank at 1mg/L. On the other hand, chlorine, and bromine at position 5 produce an opposite effect.

Utilización precoz de tocilizumab en pacientes internados con COVID-19 grave y crítica: un estudio multicéntrico en la Provincia de Buenos Aires / Early use of tocilizumab in hospitalized patients with severe and critical COVID-19 in the Province of Buenos Aires: a multicentric study

Resumen Introducción: El objetivo principal del estudio fue evaluar la mortalidad en los pacientes con COVID-19 graves y críticos, que recibieron tocilizumab (TCZ) -un antagonista monoclonal del receptor de IL-6- de forma temprana vs. tardía. Métodos: Cohorte retrospectiva multicéntrica de pacientes >18 años internados con COVID-19 desde el 1/7/2021-1/8/2022, con 5-7 puntos de gravedad inicial (GI) según Escala de la OMS. Se consideró adminis tración temprana o tardía a la infusión de TCZ ≤ ó > a 48 h del ingreso. Las variables de resultado fueron mortalidad a 28 días y cambio de la GI. Los factores relacionados con la mortalidad fueron evaluados con regresión de Cox. Resultados: Se incluyeron 266 pacientes, 159(60%) varones; edad 58(± 15); con hipertensión arterial (43%), obesidad (37%) y diabetes (27%);70 presentaban GI = 5 (oxígeno suplementario), 143 GI = 6 (ventilación no inva siva o cánula nasal de alto flujo) y 53 GI = 7 (ventilación mecánica invasiva). La mortalidad a 28 días fue 42%, asociada independientemente a: edad, obesidad, GI, días entre la internación y administración del TCZ, y días entre la fecha de inicio de síntomas y el TCZ. La mortalidad para GI 5, 6 y 7 fue 26%, 39% y 72%, respectivamente; 76% y 62% de los pacientes permanecieron estables o mejoraron la GI a los días 3 y 7 de la infusión de TCZ. La mortalidad a 28 días fue 39% (TCZ temprano) vs. 57% (TCZ tardío); p = 0.02; HR = 0.63[0.41-0.99, p = 0.05]). Discusión: Estos resultados apoyan la administración temprana de TCZ en pacientes con COVID-19 grave y crítica.

Abstract Introduction: Tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody is warranted in severe and critically-ill COVID-19 patients. The objective was to evaluate 28-day mortality of patients with severe or critical COVID-19 treated with early vs delayed TCZ. Methods: Multicenter, retrospective cohort study in cluding patients>18 years hospitalized between 7/1/2021- 8/1/2022 with confirmed COVID-19, with 5, 6 and 7 points of WHO Ordinal Initial Severity Scale [SS]. Early or late administration was considered if TCZ was administered before or after 48 hours from admission. Outcomes were28-day mortality and change of SS. Factors related to 28-day mortality were evaluated with Cox regression. Results: 266 patients were included, 159(60%) male; aged 58(± 15); frequent comorbidities were hypertension (42%), obesity (37%) and diabetes (27%). Seventy patients had a SS = 5 (Supplemental O2), 143 had SS = 6 (NIV/ HFNC), and 53 had SS = 7 (IMV). 28-day mortality was 42%(112/266); predictors were age, obesity, higher SS, days between hospitalization and TCZ administration, and fewer days between symptoms onset and TCZ. Mortality of SS 5, 6 and 7 was 26%, 39% and 72% respectively. Com pared with baseline SS points, 76% and 62% of patients remained stable or improved on days 3 and 7 since TCZ administration. 28-day mortality was lower when TCZ was administered before 48 hours (39% vs 57%; p = 0.02; HR = 0.63;[0.41-0.99, p = 0.05]). Discussion: This study supports the early use of TCZ in patients with severe or critical COVID-19.

Ambulatory Blood Pressure Monitoring for Diagnosis and Management of Hypertension in Pregnant Women.

Hypertension disorders during pregnancy has a wide range of severities, from a mild clinical condition to a life-threatening one. Currently, office BP is still the main method for the diagnosis of hypertension during pregnancy. Despite of the limitation these measurements, in clinical practice office BP of 140/90 mmHg cut point is used to simplify diagnosis and treatment decisions. The out-of-office BP evaluations are it comes to discarding white-coat hypertension with little utility in practice to rule out masked hypertension and nocturnal hypertension. In this revision, we analyzed the current evidence of the role of ABPM in diagnosing and managing pregnant women. ABPM has a defined role in the evaluation of BP levels in pregnant women, being appropriate performing an ABPM to classification of HDP before 20 weeks of gestation and second ABMP performed between 20-30 weeks of gestation to detected of women with a high risk of development of PE. Furthermore, we propose to, discarding white-coat hypertension and detecting masked chronic hypertension in pregnant women with office BP > 125/75 mmHg. Finally, in women who had PE, a third ABPM in the post-partum period could identify those with higher long-term cardiovascular risk related with masked hypertension.

[Early use of tocilizumab in hospitalized patients with severe and critical COVID-19 in the Province of Buenos Aires: a multicentric study]. / Utilización precoz de tocilizumab en pacientes internados con COVID-19 grave y crítica: un estudio multicéntrico en la Provincia de Buenos Aires.

INTRODUCTION: Tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody is warranted in severe and critically-ill COVID-19 patients. The objective was to evaluate 28-day mortality of patients with severe or critical COVID-19 treated with early vs delayed TCZ. METHODS: Multicenter, retrospective cohort study including patients >18 years hospitalized between 7/1/2021-8/1/2022 with confirmed COVID-19, with 5, 6 and 7 points of WHO Ordinal Initial Severity Scale [SS]. Early or late administration was considered if TCZ was administered before or after 48 hours from admission. Outcomes were 28-day mortality and change of SS. Factors related to 28-day mortality were evaluated with Cox regression. RESULTS: 266 patients were included, 159(60%) male; aged 58(± 15); frequent comorbidities were hypertension (42%), obesity (37%) and diabetes (27%). Seventy patients had a SS = 5 (Supplemental O2), 143 had SS = 6 (NIV/ HFNC), and 53 had SS = 7 (IMV). 28-day mortality was 42%(112/266); predictors were age, obesity, higher SS, days between hospitalization and TCZ administration, and fewer days between symptoms onset and TCZ. Mortality of SS 5, 6 and 7 was 26%, 39% and 72% respectively. Compared with baseline SS points, 76% and 62% of patients remained stable or improved on days 3 and 7 since TCZ administration. 28-day mortality was lower when TCZ was administered before 48 hours (39% vs 57%; p = 0.02; HR = 0.63;[0.41-0.99, p = 0.05]). DISCUSSION: This study supports the early use of TCZ in patients with severe or critical COVID-19.

Introducción: El objetivo principal del estudio fue evaluar la mortalidad en los pacientes con COVID-19 graves y críticos, que recibieron tocilizumab (TCZ) -un antagonista monoclonal del receptor de IL-6- de forma temprana vs. tardía. Métodos: Cohorte retrospectiva multicéntrica de pacientes > 18 años internados con COVID-19 desde el 1/7/2021-1/8/2022, con 5-7 puntos de gravedad inicial (GI) según Escala de la OMS. Se consideró administración temprana o tardía a la infusión de TCZ = ó > a 48 h del ingreso. Las variables de resultado fueron mortalidad a 28 días y cambio de la GI. Los factores relacionados con la mortalidad fueron evaluados con regresión de Cox. Resultados: Se incluyeron 266 pacientes, 159(60%) varones; edad 58(± 15); con hipertensión arterial (43%), obesidad (37%) y diabetes (27%);70 presentaban GI = 5 (oxígeno suplementario), 143 GI = 6 (ventilación no invasiva o cánula nasal de alto flujo) y 53 GI = 7 (ventilación mecánica invasiva). La mortalidad a 28 días fue 42%, asociada independientemente a: edad, obesidad, GI, días entre la internación y administración del TCZ, y días entre la fecha de inicio de síntomas y el TCZ. La mortalidad para GI 5, 6 y 7 fue 26%, 39% y 72%, respectivamente; 76% y 62% de los pacientes permanecieron estables o mejoraron la GI a los días 3 y 7 de la infusión de TCZ. La mortalidad a 28 días fue 39% (TCZ temprano) vs. 57% (TCZ tardío); p = 0.02; HR = 0.63[0.41-0.99, p = 0.05]). Discusión: Estos resultados apoyan la administración temprana de TCZ en pacientes con COVID-19 grave y crítica.

Masked hypertension and neonatal outcome in high-risk pregnancies.

We previously showed that masked hypertension is a frequent finding in high-risk pregnancies and a strong predictor of preeclampsia/eclampsia. However, neonatal consequences of masked hypertension have not been deeply analyzed. Consequently, the aim of this study was to determine if masked hypertension is a risk factor for poor neonatal outcome. We evaluated a cohort of 588 high-risk pregnant women (29 ± 7 years old with 27 ± 6 weeks of gestation at blood pressure evaluation); 22.1%, 8.5%, 2.9%, and 2.6% had history of hypertension, diabetes, collagen diseases and chronic renal disease, respectively. According to the data of office and ambulatory blood pressures monitoring, women was classified as normotension (61.7%), white-coat hypertension (5.4%), masked hypertension (21.6%) and sustained hypertension (11.2%) respectively. Compared to normotension, all neonatal outcomes were worst in women with masked hypertension; neonates had lower mean birth weight (2577 (842) vs. 3079 (688) g, P < 0.001), higher prevalence of very low (12.1% vs 2.0%, P = .002) and extremely low birth weight (4.3% vs 0%, P < 0.001), and low one-minute APGAR score (7.8% vs 1.8%, P < 0.001). Furthermore, 14.2% needed admission to neonatal intensive care unit (NICE) (P = 0.001). Compared with normotension the risk for poor the combined neonatal outcome (admission to NICE plus still born) was significantly higher in masked hypertension (adjusted OR 2.58 95% CI 1.23-5.40) but not in white-coat hypertension (adjusted OR 0.41 95% CI 0.05-3.12). In conclusion, in high-risk pregnancies, masked hypertension was a strong and independent predictor for poor neonatal outcomes.

Hypertension, a linchpin between environmental noise exposure and the development of cardiovascular disease?

Environmental noise exposure has been considered one of the most common hazards worldwide, especially in the workplace environment, and could produce a variety of health issues. Some epidemiological evidence supports the association between occupational noise exposition and a high risk for hypertension and cardiovascular diseases. Wang et al. has conducted an observational cross-sectional study using occupational data of 4746 workers, 32.4% were exposed to high occupational noise. These exposed individuals had a moderate increase in the risk for hypertension (adjusted odds ratio [OR], 1.30; 95% confidence interval [CI], 1.05-1.62). The subgroup analyses showed that the relationship between noise and hypertension prevalence was stronger in young participants (OR, 1.70; 95% CI, 1.21-2.40). Noise exposure activates the sympathetic and endocrine systems producing an increase in blood pressure and the changes in other biological risk factors. Moreover, a recently published study showed that oxidative stress and DNA damage were significantly higher in subjects exposed to noise. Emotional stress reactions and unconscious physiological stress could also be potential mechanisms for hypertension. Finally, physiological stress caused by noise exposure may also increase indulgence in unhealthy behaviors, such as smoking and alcohol consumption, and indirectly result in an increased risk of hypertension and cardiovascular diseases. Previously published studies showed relationships between environmental noise exposure (including road traffic, railway, and aircraft noises) and the development of hypertension and cardiovascular diseases. Thus, the study by Wang et al. emphasizes the importance of environmental control in the prevention of cardiovascular diseases, not only in the workplace but also outside it.

Hypertension arising after 20 weeks of gestation: gestational hypertension or masked chronic hypertension?

The objectives of this study were 1-to evaluate the prevalence of masked chronic hypertension in pregnant women classified as gestational hypertension 2-to compare the risks of developing preeclampsia in true gestational hypertension vs those women classified as having gestational hypertension but who had had masked hypertension in the first half of pregnancy. We conducted a cohort study in consecutive high-risk pregnancies who were evaluated before 20 weeks of gestation. Women who developed gestational hypertension (normotension in the office before 20 weeks of gestation and office BP ≥ 140/90 mmHg and/or antihypertensive treatment in the second half of gestation) were divided, according to an ABPM performed before 20 weeks of pregnancy, in two subgroups: subgroup 1-if their ABPM was normal, and subgroup 2-if they had masked chronic hypertension. Risks for preeclampsia (PE) were estimated and compared with normotensive women. Before 20 weeks of gestation, 227 women were evaluated (age 32 ± 6 years, median gestation age 15 weeks); 67 had chronic hypertension (29.5%). Of the remaining 160, 39 developed gestational hypertension (16 in subgroup 1 and 23 insubgroup 2. Compared with normotensive pregnant women, subgroup 1 of women with gestational hypertension did not increase the risk of developing PE (OR = 0.76, 95% CI = 0.16-6.65). Conversely, subgroup 2 of gestational hypertension increased the risk of PE more than 4 times (0R = 4.47 CI = 1.16-12.63). Risk estimation did not change substantially after the adjustment for multiple possible confounders. In conclusion, the59% of women initially diagnosed as gestational hypertensive according to current recommendations had masked chronic hypertension and a very high risk of developing PE.

Effectiveness of BBIBP-CorV, BNT162b2 and mRNA-1273 vaccines against hospitalisations among children and adolescents during the Omicron outbreak in Argentina: A retrospective cohort study.

Background: Although paediatric clinical presentations of COVID-19 are usually less severe than in adults, serious illness and death have occurred. Many countries started the vaccination rollout of children in 2021; still, information about effectiveness in the real-world setting is scarce. The aim of our study was to evaluate vaccine effectiveness (VE) against COVID-19-associated-hospitalisations in the 3-17-year population during the Omicron outbreak. Methods: We conducted a retrospective cohort study including individuals aged 3-17 registered in the online vaccination system of the Buenos Aires Province, Argentina. mRNA-1273 and BNT162b2 were administered to 12-17-year subjects; and BBIBP-CorV to 3-11-year subjects. Vaccinated group had received a two-dose scheme by 12/1/2021. Unvaccinated group did not receive any COVID-19 vaccine between 12/14/2021 and 3/9/2022, which was the entire monitoring period. Vaccine effectiveness (VE) against COVID-19-associated hospitalisations was calculated as (1-OR)x100. Findings: By 12/1/2021, 1,536,435 individuals aged 3-17 who had received zero or two doses of SARS-CoV-2 vaccines were included in this study. Of the latter, 1,440,389 were vaccinated and 96,046 not vaccinated. VE were 78.0%[68.7-84.2], 76.4%[62.9-84.5] and 80.0%[64.3-88.0] for the entire cohort, 3-11-year (BBIBP-CorV) subgroup and 12-17 (mRNA vaccines) subgroup, respectively. VE for the entire population was 82.7% during the period of Delta and Omicron overlapping circulation and decreased to 67.7% when Omicron was the only variant present. Interpretation: This report provides evidence of high vaccine protection against associated hospitalisations in the paediatric population during the Omicron outbreak but suggests a decrease of protection when Omicron became predominant. Application of a booster dose in children aged 3-11-year warrants further consideration. Funding: None.

UFR2709, an Antagonist of Nicotinic Acetylcholine Receptors, Delays the Acquisition and Reduces Long-Term Ethanol Intake in Alcohol-Preferring UChB Bibulous Rats.

Alcoholism is a worldwide public health problem with high economic cost and which affects health and social behavior. It is estimated that alcoholism kills 3 million people globally, while in Chile it is responsible for around 9 thousand deaths per year. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels expressed in the central nervous system, and they were suggested to modulate the ethanol mechanism involved in abuse and dependence. Previous work demonstrated a short-term treatment with UFR2709, a nAChRs antagonist, which reduced ethanol intake using a two-bottle free-choice paradigm in University of Chile bibulous (UChB) rats. Here, we present evidence of the UFR2709 efficacy in reducing the acquisition and long-term ethanol consumption. Our results show that UFR2709 (2.5 mg/kg i.p.) reduces the seek behavior and ethanol intake, even when the drug administration was stopped, and induced a reduction in the overall ethanol intake by around 55%. Using naïve UChB bibulous rats, we demonstrate that UFR2709 could delay and reduce the genetically adaptive impulse to seek and drink ethanol and prevent its excessive intake.

Plasmatic renin-angiotensin system in normotensive and hypertensive patients hospitalized with COVID-19.

BACKGROUND: Besides its counterbalancing role of the renin-angiotensin system (RAS), angiotensin-converting enzyme (ACE) 2 is the receptor for the type 2 coronavirus that causes severe acute respiratory syndrome, the etiological agent of COVID-19. COVID-19 is associated with increased plasmatic ACE2 levels, although conflicting results have been reported regarding angiotensin (Ang) II and Ang-(1-7) levels. We investigated plasmatic ACE2 protein levels and enzymatic activity and Ang II and Ang-(1-7) levels in normotensive and hypertensive patients hospitalized with COVID-19 compared to healthy subjects. METHODS: Ang II and Ang-(1-7), and ACE2 activity and protein levels were measured in 93 adults (58 % (n = 54) normotensive and 42 % (n = 39) hypertensive) hospitalized with COVID-19. Healthy, normotensive (n = 33) and hypertensive (n = 7) outpatient adults comprised the control group. RESULTS: COVID-19 patients displayed higher ACE2 enzymatic activity and protein levels than healthy subjects. Within the COVID-19 group, ACE2 activity and protein levels were not different between normotensive and hypertensive-treated patients, not even between COVID-19 hypertensive patients under RAS blockade treatment and those treated with other antihypertensive medications. Ang II and Ang-(1-7) levels significantly decreased in COVID-19 patients. When COVID-19 patients under RAS blockade treatment were excluded from the analysis, ACE2 activity and protein levels remained higher and Ang II and Ang-(1-7) levels lower in COVID-19 patients compared to healthy people. CONCLUSIONS: Our results support the involvement of RAS in COVID-19, even when patients under RAS blockade treatment were excluded. The increased circulating ACE2 suggest higher ACE2 expression and shedding.