RESUMO
The primary intervention for pre-eclampsia (PE) remains iatrogenic delivery, which can be very preterm and not optimal for the fetus. Although many efforts have been made to prevent and manage PE, there is still a dearth of drugs to treat its pathophysiological progression. Pravastatin (PRA), a hydrophilic statin, has gained interest for the prevention and treatment of PE. The aim of the present study was to evaluate the ability of PRA to modulate factors involved in placentation, such as Epidermal Growth Factor-Like Domain 7 (EGFL7), in human chorionic villous culture from healthy controls and women with PE. A total of 18 women were enrolled: 10 controls and 8 cases. Chorionic villous explants were maintained in culture for 24 h with or without 10 µM Pravastatin, and the expression of EGFL7 and NOTCH1 pathway members was evaluated by qRT-PCR and Western blot analysis. The rationale of the present study was to establish an ex vivo model to identify potential different responses to PRA treatment of chorionic villous explants in order to clarify the molecular mechanism of PRA in the prevention and treatment of PE and to predict whether there are specific clinical conditions that modulate the response to the drug treatment. Within PE patients, two different groups were identified: the high responders, whose villous cultures exhibit significantly increased expressions of the EGFL7 and Notch pathways after PRA incubation; and the low responders, who are high-risk PE patients in which prophylaxis failed to prevent PE and PRA was not able to modulate EGFL7 expression. In conclusion, we identified EGFL7 as a new factor regulated by PRA, placing interest in early discrimination between low- and high- risk women, in which the well-known pharmacological prophylaxis seems to be ineffective, and to explore new potential prevention strategies.
RESUMO
BACKGROUND: Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values. OBJECTIVE: This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings. STUDY DESIGN: This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm2]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm2]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy. RESULTS: A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02). CONCLUSION: In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile.
Assuntos
Anti-Hipertensivos , Hemodinâmica , Labetalol , Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/administração & dosagem , Estudos Prospectivos , Adulto , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/diagnóstico , Labetalol/administração & dosagem , Labetalol/farmacologia , Débito Cardíaco/efeitos dos fármacos , Débito Cardíaco/fisiologia , Nifedipino/farmacologia , Nifedipino/administração & dosagem , Nifedipino/uso terapêutico , Resistência Vascular/efeitos dos fármacos , Metildopa/administração & dosagem , Metildopa/farmacologia , Metildopa/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Hipertensão Induzida pela Gravidez/fisiopatologia , Hipertensão Induzida pela Gravidez/diagnóstico , Resultado do Tratamento , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Vasodilatadores/administração & dosagem , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêuticoRESUMO
OBJECTIVE: To systematically review and meta-analyze the predictive value of the Fournier gangrene severity index (FGSI), the simplified FGSI (SFGSI), and the Uludag FGSI (UFGSI) on mortality in patients affected by Fournier's Gangrene (FG). METHODS: A search was performed in PubMed, Web of Science, Embase, and the Cochrane Library, from January 2000 to May 2023, to identify original cohorts comparing data between surviving and non-surviving FG patients. The statistical analysis consisted of two parts. First, the mean and standard deviation (SD) of the FGSI, SFGSI, and UFGSI at admission were extrapolated from each study, and the pooled mean difference (MD) with 95% confidence interval (95% CI) was obtained using the Der Simonian-Laird random-effect model. Second, to evaluate the accuracy of the FGSI, SFGSI, and UFSGI in predicting mortality, true positive (TP), false positive (FP), true negative (TN), and false negative (FN) values were extracted where possible and reported in 2 × 2 contingency tables. The sensitivity, specificity, and AUC values were pooled, and summary receiver operating characteristic (SROC) curves were constructed. RESULTS: Overall, forty studies comprising 2257 patients were included. The pooled analysis revealed that the FGSI, SFGSI, and UFGSI values at admission were higher in non-survivors than survivors (MD: 5.53 (95% CI: 4.68-6.37); MD: 2.41 (95% CI: 1.06-3.77); and MD: 5.47 (95% CI: 3.68-7.26), respectively). Moreover, the AUC values of the FGSI, SFGSI, and UFGSI were 0.90 (95% CI: 0.87-0.92), 0.84 (95% CI: 0.80-0.87), and 0.94 (95% CI: 0.92-0.96), respectively. CONCLUSIONS: The higher scores of the FGSI, SFGSI, and UFGSI on admission were associated with mortality. Moreover, when comparing accuracy rates, the UFGSI exhibited the highest AUC value.
RESUMO
Introduction: The current COVID-19 pandemic has been associated with high rates of mortality and significant morbidity. Both the risk of infection for pregnant women and the risk of vertical transmission have been evaluated, and the presence of the SARS-CoV-2 virus has been demonstrated both in the placenta and in the amniochorionic membranes. However, the actual effects of this pathogen on pregnancy and on placental morphology are still unclear. Objective: To describe histopathologic findings in the placentas of women with SARS-CoV-2 infection during pregnancy and their correlation with clinical signs and perinatal outcome. Methods: Placental tissues from pregnant women with SARS-CoV-2 infection delivering between March 2020 and February 2021 were analyzed. Results: One hundred six placentas from women with SARS-CoV-2 infection during pregnancy who delivered in Fondazione Policlinico A. Gemelli were examined. Most of them were asymptomatic. All neonates had available test results for SARS-CoV-2 and only one resulted positive. Placental tissues mainly showed signs of maternal vascular malperfusion and of placenta injury in terms of syncytial node increase (96.2%), villar agglutination (77.3%), neointimal hyperplasia (76.4%), excessive fibrin deposition (43.3%), and chorangiosis (35.8%). No significant differences in the frequency of the histopathological lesions were observed according to maternal symptoms. Conclusion: Looking to placental tissues from SARS-CoV-2 positive women at the screening performed close to delivery, placental injuries could be detected without any correlation with fetal and neonatal outcomes. We hypothesize that short latency between SARS-CoV-2 infection and delivery is the main reason for these observations.