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Background: Hypoxia is associated with the onset of cardiovascular diseases including cardiac hypertrophy and pulmonary hypertension. HIF2 (hypoxia-inducible factor 2) signaling in the endothelium mediates pulmonary arterial remodeling and subsequent elevation of the right ventricular systolic pressure during chronic hypoxia. Thus, novel therapeutic opportunities for pulmonary hypertension based on specific HIF2 inhibitors have been proposed. Nevertheless, HIF2 relevance beyond the pulmonary endothelium or in the cardiac adaptation to hypoxia remains elusive. Wt1 (Wilms tumor 1) lineage contributes to the heart and lung vascular compartments, including pericytes, endothelial cells, and smooth muscle cells., Methods: Here, we describe the response to chronic hypoxia of a novel HIF2 mutant mouse model in the Wt1 lineage ( Hif2/Wt1 cKO), characterizing structural and functional aspects of the heart and lungs by means of classical histology, immunohistochemistry, flow cytometry, echocardiography, and lung ultrasound analysis., Results: Hif2/Wt1 cKO is protected against pulmonary remodeling and increased right ventricular systolic pressure induced by hypoxia but displays alveolar congestion, inflammation, and hemorrhages associated with microvascular instability. Furthermore, lack of HIF2 in the Wt1 lineage leads to cardiomegaly, capillary remodeling, right and left ventricular hypertrophy, systolic dysfunction, and left ventricular dilation, suggesting pulmonary-independent cardiac direct roles of HIF2 in hypoxia. These structural defects are partially restored upon reoxygenation, while cardiac functional parameters remain altered., Conclusions: Our results indicate that cardiopulmonary HIF2 signaling prevents excessive vascular proliferation during chronic hypoxia and define novel protective roles of HIF2 to warrant stable microvasculature and organ function.

Objective: The aim of the present study was to identify the risk factors for severe maternal outcomes (SMO) of women with suspected or confirmed infections using the data from the WHO global maternal sepsis study (GLOSS)., Methods: We conducted a secondary analysis of the GLOSS cohort study, which involved pregnant or recently pregnant women with suspected or confirmed infection around 713 health facilities in 52 low- and middle-income countries, and high-income countries. A nested case-control study was conducted within the GLOSS cohort. Cases included infection-related maternal deaths or near misses, while controls represented non-SMO. Logistic mixed models, adjusting for country variations, were employed. Using univariate analysis, we calculated crude odds ratios (crude OR) and their 95% confidence interval (95% CI). Variables were identified with less than 16% missing data, and P values less than 0.20 were used to perform the multivariate logistic model multilevel., Results: A total of 2558 women were included in the analysis. As for the cases, 134 patients were found in the pregnant in labor or not in labor group and 246 patients in the postpartum or postabortion group. Pregnant women with prior childbirths faced a 64% increased risk of SMO. Ante- or intrapartum hemorrhage increased risk by 4.45 times, while trauma during pregnancy increased it by 4.81 times. Pre-existing medical conditions elevated risk five-fold, while hospital-acquired infections increased it by 53%. Secondary infections raised risk six-fold. Postpartum/postabortion women with prior childbirths had a 45% elevated risk, and pre-existing medical conditions raised it by 2.84 times. Hospital-acquired infections increased risk by 93%. Postpartum hemorrhage increased risk approximately five-fold, while abortion-related bleeding doubled it. Previous cesarean, abortion, and stillbirth also elevated risk., Conclusions: Key risk factors for SMO include prior childbirths, hemorrhage, trauma, pre-existing conditions, and hospital-acquired or secondary infections. Implementing effective alert systems and targeted interventions is essential to mitigate these risks and improve maternal health outcomes, especially in resource-limited settings., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: There has been debate over whether the existing World Health Organization (WHO) criteria accurately represent the severity of maternal near misses., Objective: This study assessed the diagnostic accuracy of two WHO clinical and laboratory organ dysfunction markers for determining the best cutoff values in a Latin American setting., Methods: A prospective multicenter cohort study was conducted in five Latin American countries. Patients with severe maternal complications were followed up from admission to discharge. Organ dysfunction was determined using clinical and laboratory data, and participants were classified according to severe maternal outcomes. This study compares the diagnostic criteria of Latin American Centre for Perinatology, Network for Adverse Maternal Outcomes (CLAP/NAMO) to WHO standards., Results: Of the 698 women studied, 15.2% had severe maternal outcomes. Most measured variables showed significant differences between individuals with and without severe outcomes (all P-values <0.05). Alternative cutoff values suggested by CLAP/NAMOs include pH ≤7.40, lactate ≥2.3 mmol/L, respiratory rate ≥ 24 bpm, oxygen saturation ≤ 96%, PaO 2 /FiO 2  ≤ 342 mmHg, platelet count ≤189 × 10 9  × mm 3 , serum creatinine ≥0.8 mg/dL, and total bilirubin ≥0.67 mg/dL. No significant differences were found when comparing the diagnostic performance of the CLAP/NAMO criteria to that of the WHO standards., Conclusion: The CLAP/NAMO values were comparable to the WHO maternal near-miss criteria, indicating that the WHO standards might not be superior in this population. These findings suggest that maternal near-miss thresholds can be adapted regionally, improving the identification and management of severe maternal complications in Latin America., (© 2024 International Federation of Gynecology and Obstetrics.)