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.

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.

May Measurement Month 2019: an analysis of blood pressure screening results from Argentina.

The Argentinean Society of Hypertension, in agreement with the May Measurement Month (MMM) initiative of the International Society of Hypertension, implemented for the third consecutive year a hypertension screening campaign. A volunteer cross-sectional survey was carried out in public spaces and health centres during the month of May 2019 across 33 cities in Argentina. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg and/or diastolic BP ≥90 mmHg based on the mean of the second and third BP measurements, or in those on treatment for high BP. A total of 94 523 individuals (53.9 ± 17.8 years old, 55 231women and 39 292 men), were evaluated. The age and sex standardized mean BP was 124.7/77.2 mmHg. Among participants, 34.7% were overweight (25-29.9 m/kg2) and 28.7% had obesity (≥30 m/kg2). Individuals identified as being overweight had BP 3/2 mmHg higher and individuals with obesity 6/4 mmHg higher than those with normal weight. The prevalence of hypertension was 52.5%. Although 81.1% were aware and 77.7% were on antihypertensive treatment, only 46.0% of all individuals with hypertension had their BP controlled. Moreover, 19.8% of those not on any antihypertensive medication were found with raised BP. The low level of control of hypertension generates the critical need for the development of community-based prevention strategies reinforcing strategies to increase the awareness and control of hypertension.

Classification of the Molecular Defects Associated with Pathogenic Variants of the SLC6A8 Creatine Transporter.

More than 80 loss-of-function (LOF) mutations in the SLC6A8 creatine transporter (hCRT1) are responsible for cerebral creatine deficiency syndrome (CCDS), which gives rise to a spectrum of neurological defects, including intellectual disability, epilepsy, and autism spectrum disorder. To gain insight into the nature of the molecular defects caused by these mutations, we quantitatively profiled the cellular processing, trafficking, expression, and function of eight pathogenic CCDS variants in relation to the wild type (WT) and one neutral isoform. All eight CCDS variants exhibit measurable proteostatic deficiencies that likely contribute to the observed LOF. However, the magnitudes of their specific effects on the expression and trafficking of hCRT1 vary considerably, and we find that the LOF associated with two of these variants primarily arises from the disruption of the substrate-binding pocket. In conjunction with an analysis of structural models of the transporter, we use these data to suggest mechanistic classifications for these variants. To evaluate potential avenues for therapeutic intervention, we assessed the sensitivity of these variants to temperature and measured their response to the proteostasis regulator 4-phenylbutyrate (4-PBA). Only one of the tested variants (G132V) is sensitive to temperature, though its response to 4-PBA is negligible. Nevertheless, 4-PBA significantly enhances the activity of WT hCRT1 in HEK293T cells, which suggests it may be worth evaluating as a therapeutic for female intellectual disability patients carrying a single CCDS mutation. Together, these findings reveal that pathogenic SLC6A8 mutations cause a spectrum of molecular defects that should be taken into consideration in future efforts to develop CCDS therapeutics.

Nicotinic Antagonist UFR2709 Inhibits Nicotine Reward and Decreases Anxiety in Zebrafish.

Zebrafish is becoming a popular animal model in neuropharmacology and drug discovery, mainly due to its ease of handling and low costs involved in maintenance and experimental work. This animal displays a series of complex behaviours that makes it useful for assessing the effects of psychoactive drugs. Here, adult zebrafish were used for assessment of the anxiolytic and anti-addictive properties of UFR2709, a nicotinic receptor (nAChR) antagonist, using two behavioural paradigms to test for addiction, the novel tank diving test to assess anxiety and the conditioned place preference (CPP). Furthermore, the expression of nAChR subunits α4 and α7 was measured in the zebrafish brain. The results show that UFR2709 exhibits an anxiolytic effect on zebrafish and blocks the effect evoked by nicotine on CPP. Moreover, UFR2709 significantly decreased the expression of α4 nicotinic receptor subunit. This indicates that UFR2709 might be a useful drug for the treatment of nicotine addiction.

Synthesis of Novel Nicotinic Ligands with Multimodal Action: Targeting Acetylcholine α4ß2, Dopamine and Serotonin Transporters.

Nicotinic acetylcholine receptors (nAChRs), serotonin transporters (SERT) and dopamine transporters (DAT) represent targets for the development of novel nicotinic derivatives acting as multiligands associated with different health conditions, such as depressive, anxiety and addiction disorders. In the present work, a series of functionalized esters structurally related to acetylcholine and nicotine were synthesized and pharmacologically assayed with respect to these targets. The synthesized compounds were studied in radioligand binding assays at α4ß2 nAChR, h-SERT and h-DAT. SERT experiments showed not radioligand [3H]-paroxetine displacement, but rather an increase in the radioligand binding percentage at the central binding site was observed. Compound 20 showed Ki values of 1.008 ± 0.230 µM for h-DAT and 0.031 ± 0.006 µM for α4ß2 nAChR, and [3H]-paroxetine binding of 191.50% in h-SERT displacement studies, being the only compound displaying triple affinity. Compound 21 displayed Ki values of 0.113 ± 0.037 µM for α4ß2 nAChR and 0.075 ± 0.009 µM for h-DAT acting as a dual ligand. Molecular docking studies on homology models of α4ß2 nAChR, h-DAT and h-SERT suggested potential interactions among the compounds and agonist binding site at the α4/ß2 subunit interfaces of α4ß2 nAChR, central binding site of h-DAT and allosteric modulator effect in h-SERT.

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies.

Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition.

Do differences in waist circumference modify the relationships among body mass index, insulin resistance, and related cardiometabolic risk factors in apparently healthy women?

OBJECTIVE: The aims of the study were to (1) compare the cardiometabolic risk profile between insulin-resistant and non-insulin-resistant women within similar body mass indexes (BMIs) and waist circumference (WC) groupings and (2) test the hypothesis that measurements of BMI are not inferior to WC in identifying insulin resistance. METHODS: The sample consisted of 899 women without known cardiovascular disease or diabetes. BMI was used to divide participants in normal (<25.0 kg/m(2)), overweight (≥25-29.9 kg/m(2)), and obese (≥30.0 kg/m(2)) subgroups, and waist circumference ≥88 cm was used to identify women with or without abdominal obesity. The 25% of the population with highest fasting insulin concentrations was classified as insulin resistant. BMI, WC, blood pressure, and fasting plasma glucose, insulin, triglyceride, and high-density lipoprotein cholesterol concentrations were compared using analysis of covariance (ANCOVA). The relationships between obesity and insulin resistance were analyzed using univariate, multivariate, and logistic regression. RESULTS: Triglyceride and glucose concentrations were higher and high-density lipoprotein cholesterol concentrations lower in the insulin-resistant group in each BMI category, as was the case when comparing by abdominal obesity. In the univariate analysis, correlations between obesity and the individual cardiometabolic risk factor were significant but weak. In multivariate analysis including both indices, only body mass independently predicted insulin resistance. CONCLUSION: Insulin-resistant women were at greater cardiometabolic risk, irrespective of adiposity category. Obesity contributed to a modest variability in insulin resistance, and abdominal obesity does not add to the ability of BMI to predict insulin resistance.

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.

Relationship between serum uric acid, nocturnal hypertension and risk for preeclampsia in high-risk pregnancies.

To analyze the possible association between serum uric acid (SUA) and nocturnal hypertension and to evaluate the ability of these variables (alone or in combination) to predict preeclampsia (PE) we conducted a historical cohort study in 532 high-risk pregnancies. Women were divided according to SUA values and nocturnal blood pressure (BP) into four groups: 1- normal SUA and nocturnal normotension; 2- high SUA and nocturnal normotension; 3- normal SUA and nocturnal hypertension and 4- high SUA and nocturnal hypertension. High SUA was defined by the top quartile values and nocturnal hypertension as BP ≥ 120/70 mmHg, using ambulatory blood pressure monitoring (ABPM), during nocturnal rest. Risks for PE were compared using logistic regression. SUA had a weak but significant correlation with daytime systolic ABPM (r = 0.11, p = 0.014), daytime diastolic ABPM (r = 0.13, p = 0.004), nighttime systolic ABPM (r = 0.16, p < 0.001) and nighttime diastolic ABPM (r = 0.18, p < 0.001). Also, all ABPM values were higher in women with high SUA. The absolute risk of PE increased through groups: 6.5%, 13.1%, 31.2%, and 47.9% for groups 1, 2, 3, and 4, respectively, p < 0.001. Compared with Group 1, Group 3 (OR 6.29 95%CI 3.41-11.60), but not Group 2 (OR 2.15 95%CI 0.88-5.24), had statistically significant higher risk for PE. Group 4 (women with both, high SUA and nocturnal hypertension) had the highest risk (OR 13.11 95%CI 6.69-25.70). Risks remained statistically significant after the adjustment for relevant variables. In conclusion, the combination of SUA > 4 mg/dL and nocturnal BP > 120/70 mmHg implies a very high risk to developed PE.

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.

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.

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.

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.

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 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.

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.

[Use of aspirin 100 mg / day to prevent Preeclampsia, in high risk pregnancies, in a cohort from Argentina]. / Utilización de aspirina 100 mg/día para prevenir Preeclampsia, en embarazos de alto riego, en una cohorte de Argentina.

Objectives: The objective of the present study was to analyse the use of 100 g aspirin dose as prevention method for preeclampsia in high risk pregnant patients. Methods: A retrospective cohort study was performed in high risk pregnant patients with a blood pressure protocol, and the use of 100 mg of aspirin vs. its non-use was evaluated in the incidence of PREEC. Estimations between the two groups were performed with and without variable adjustment by means of binary logistic regression models. Results: 633 high risk pregnant patients were evaluated. The average age was 30±7 years old, and 25±8 weeks of pregnancy. 281 women (44.3 %) within this group received aspirin. The total prevalence of PREEC in our sample was 151 pregnant women (23.8 %). Pregnant patients under the aspirin treatment developed less PREEC events (19.2% vs 27.5%, p=0.019); with OR not adjusted 0.62 (IC95% 0.43-0.91 p= 0.017). The risk was similar when it was adjusted by age, preeclampsia history, diabetes mellitus and chronic high blood pressure. (OR adjusted 0.63 IC95% 0.43-0.92 p= 0.017). Conclusions: The use of 100 mg of aspirin a day before the 20th week of pregnancy in high risk pregnant patients decreased the risk of developing PREEC, regardless the age and risk factors.

Objetivos: El objetivo de este estudio fue analizar la utilidad de la dosis de 100 mg de aspirina como medida de prevención para preeclampsia en pacientes embarazadas de alto riesgo. Métodos: Se realizó un estudio de cohorte retrospectivo de embarazadas de alto riesgo en seguimiento con un protocolo de tensión arterial y se evaluó la utilización de aspirina 100 mg vs la no utilización de la misma, en la incidencia de PREEC. Se realizó estimaciones de riesgos entre ambos grupos sin y con ajuste de variables con modelos de regresión logística binaria. Resultados: Fueron evaluadas 633 embarazadas de alto riesgo con promedio de 30±7 años y 25±8 semanas de gestación, de las cuales 281 mujeres (44,3%) recibieron aspirina. La prevalencia total de PREEC en nuestra muestra fue de 151 embarazadas (23,8%). Las embarazadas que estaban ingiriendo aspirina, desarrollaron menos eventos de PREEC (19.2% vs 27.5%, p=0.019); con OR no ajustado 0.62 (IC95% 0.43-0.91 p= 0.017). Siendo este riesgo similar cuando fue ajustado por edad, antecedentes de preeclampsia, diabetes mellitus e hipertensión arterial crónica. (OR ajustado 0.63 IC95% 0.43-0.92 p= 0.017). Conclusiones: La utilización de Aspirina 100 mg por día antes de las 20 semanas de gestación en embarazadas de alto riesgo disminuyó el riesgo de desarrollar PREEC, independientemente de la edad y factores de riesgo.