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A shortage of beds in ICUs and conventional wards during the COVID-19 pandemic led to a collapse of health care resources.Can admission data and minor criteria by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) help identify patients with low-risk SARS-CoV-2 pneumonia?This multicenter cohort study included 1,274 patients in a derivation cohort and 830 (first wave) and 754 (second wave) patients in two validation cohorts. A multinomial regression analysis was performed on the derivation cohort to compare the following patients: those admitted to the ward (assessed as low risk); those admitted to the ICU directly; those transferred to the ICU after general ward admission; and those who died. A regression analysis identified independent factors for low-risk pneumonia. The model was subsequently validated.In the derivation cohort, similarities existed among those either directly admitted or transferred to the ICU and those who died. These patients could, therefore, be merged into one group. Five independently associated factors were identified as being predictors of low risk (not dying and/or requiring ICU admission) (ORs, with 95% CIs): peripheral blood oxygen saturation/FioInitial biochemical findings and the application of 3 IDSA/ATS minor criteria make early identification of low-risk SARS-CoV-2 pneumonia (approximately 80% of hospitalized patients) feasible. This scenario could facilitate and streamline health care resource allocation for patients with COVID-19.

Preeclampsia (PE) remains a major cause of maternal/fetal morbidity-mortality worldwide. The first stage of PE is characterized by placental hypoxia due to a relative reduction in uteroplacental blood flow, resulting from restricted trophoblast invasion. However, hypoxia is also an essential element for the success of invasion. Under hypoxic conditions, 2-methoxyestradiol (2-ME) could induce the differentiation of cytotrophoblast cells into an invasive phenotype in culture. 2-Methoxyestradiol is generated by catechol-O-methyltransferase, an enzyme involved in the metabolic pathway of estrogens. During pregnancy, circulating 2-ME levels increase significantly when compared to the menstrual cycle. Interestingly, plasma levels of 2-ME are lower in women with PE than in controls, and these differences are apparent weeks or even months before the clinical manifestations of the disease. This article reviews the metabolic pathways involved in 2-ME synthesis and discusses the roles of these pathways in normal and abnormal pregnancies, with particular emphasis on PE.

Background Among patients hospitalized for community-acquired pneumonia (CAP), the risk factors for short-term hospital readmission after discharge are unknown. Methods We conducted a prospective observational study of 1,117 patients who had been discharged alive after hospitalization for CAP. We collected variables associated with CAP severity at hospital admission, in-hospital clinical evolution, clinical instability factors on hospital discharge, therapy employed during hospitalization, and diagnostic bacteriology. We assessed hospital readmission within 30 days after discharge for the index hospitalization. Risk factors independently associated with 30-day hospital readmission were identified using Cox regression models. Results Of the 81 patients (7.3%) who were readmitted to the hospital within 30 days, 29 (35.8%) were rehospitalized for pneumonia-related causes. Variables associated with pneumonia-related hospital readmission were treatment failure (hazard ratio [HR], 2.9; 95% CI, 1.2 to 6.8), and one or more instability factors on hospital discharge (HR, 2.8; 95% CI, 1.3 to 6.2). The predictive performance of these variables measured by the area under the curve (AUC) of the receiver operating characteristic was 0.65. Variables associated with pneumonia-unrelated hospital readmission were age ≥ 65 years (HR, 4.5; 95% CI, 1.4 to 14.7), Charlson comorbidity index ≥ 2 (HR, 1.9; 95% CI, 1.0 to 3.4), and decompensated comorbidities during in-hospital evolution (HR, 3.5; 95% CI, 2.0 to 6.3); the AUC for this model was 0.77. Patients with at least two risk factors were at significantly increased risk of 30-day hospital readmission (pneumonia-related CAP: HR, 9.0; 95% CI, 3.2 to 25.3; pneumonia-unrelated CAP: HR, 5.3; 95% CI, 1.6 to 18.1). Conclusions Among patients hospitalized for CAP, different risk factors are associated with hospital readmission related to pneumonia or to other causes. The identification of two different groups of patients who were at high risk of hospital readmission raises the possibility that different management strategies could decrease the rate of hospital readmissions.

The comparative accuracy and discriminatory power of three validated rules for predicting clinically relevant outcomes other than mortality in patients hospitalized with community-acquired pneumonia (CAP) are unknown.We prospectively compared the newly developed severe community-acquired pneumonia (SCAP) score, pneumonia severity index (PSI), and the British Thoracic Society confusion, urea7 mmol/L, respiratory rateor = 30 breaths/min, BP90 mm Hg systolic or60 mm Hg diastolic, ageor = 65 years (CURB-65) rule in an internal validation cohort of 1,189 consecutive adult inpatients with CAP from one hospital and an external validation cohort of 671 consecutive adult inpatients from three other hospitals. Major adverse outcomes were admission to ICU, need for mechanical ventilation, progression to severe sepsis, or treatment failure. Mean hospital length of stay (LOS) was also evaluated. The rules were compared based on sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic.The rate of all adverse outcomes and hospital LOS increased directly with increasing SCAP, PSI, or CURB-65 scores (p0.001) in both cohorts. Patients classified as high risk by the SCAP score showed higher rates of adverse outcomes (ICU admission, 35.8%; mechanical ventilation, 16.4%; severe sepsis, 98.5%; treatment failure, 22.4%) than PSI and CURB-65 high-risk classes. The discriminatory power of SCAP, as measured by AUC, was 0.75 for ICU admission, 0.76 for mechanical ventilation, 0.79 for severe sepsis, and 0.61 for treatment failure in the external validation cohort. AUC differences with PSI or CURB-65 were found.The SCAP score is as accurate or better than other current scoring systems in predicting adverse outcomes in patients hospitalized with CAP while helping classify patients into different categories of increasing risk for potentially closer monitoring.

Urinary pneumococcal antigen detection provides good results in the diagnosis of pneumococcal pneumonia but has rarely been used in bacteraemic pneumococcal pneumonia and it is not known whether it is associated with outcome in this type of pneumonia. Our objectives were to assess the usefulness of an immunochromatographic technique for detecting the pneumococcal antigen in urine in a large prospective study of patients with bacteraemic pneumococcal pneumonia and explore any potential association with outcomes.This study, carried out over 8 years, included all adult immunocompetent patients admitted for bacteraemic pneumococcal pneumonia. An immunochromatographic test for the Streptococcus pneumoniae antigen in urine was performed in the first 24 h. The sensitivity of test was assessed and patients were divided into two groups according to test results to explore differences on admission and during the course of the illness using logistic regression models.Of the 350 patients with bacteraemic pneumococcal pneumonia included, 261 (74.6%) were positive for the antigen. Patient characteristics were very similar on admission and differences in severity (Pneumonia Severity Index) were not statistically significant. In the adjusted analysis, antigen-positive patients had a higher risk of intensive care unit admission, treatment failure and adverse outcome.The sensitivity of the immunochromatographic urinary antigen test was 74.6% and positive results were associated with poorer clinical outcome. We therefore recommend systematic use of this test when pneumonia is diagnosed in the emergency department.

Objective. To evaluate the role of key enzymes in the methionine-homocysteine metabolism (MHM) in the physiopathology of preeclampsia (PE).Methods. Plasma and placenta from pregnant women (32 controls and 16 PE patients) were analyzed after informed consent. Protein was quantified by western blot. RNA was obtained with RNA purification kit and was quantified by reverse transcritase followed by real-time PCR (RT-qPCR). Identification of the C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) and A2756G methionine synthase (MTR) SNP was performed using PCR followed by a high-resolution melting (HRM) analysis. S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH) were measured in plasma using high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). The SNP association analysis was carried out using Fisher’s exact test. Statistical analysis was performed using a Mann-Whitney test.Results. RNA expression of MTHFR and MTR was significantly higher in patients with PE as compared with controls. Protein, SAM, and SAH levels showed no significant difference between preeclamptic patients and controls. No statistical differences between controls and PE patients were observed with the different SNPs studied.Conclusion. The RNA expression of MTHFR and MTR is elevated in placentas of PE patients, highlighting a potential compensation mechanism of the methionine-homocysteine metabolism in the physiopathology of this disease.

A study was undertaken to identify and weigh at the time of hospital discharge simple clinical variables that could predict short-term outcomes in patients with pneumonia.In a prospective observational cohort study of 870 patients discharged alive after hospitalization for pneumonia, we collected oxygenation and vital signs on discharge and assessed mortality and readmission within 30 days. From the beta-parameter obtained in a multivariate Cox proportional hazard regression model, a score was assigned to each predictive variable. The effects of instability at discharge on outcomes within 30 days thereafter were examined by adjusted models with use of the pneumonia severity index at hospital admission, the length of stay, the Charlson comorbidity index, or the preillness functional status.Four variables related to a 30-day mortality rate from all causes were identified in the multivariate model; these included one major criterion (temperature37.5 degrees C) and three minor criteria (systolic BP90 mm Hg or diastolic BP60 mm Hg, respiratory rate24 breaths/min, and oxygen saturation90%). The developed score remained significantly associated with a higher risk-adjusted rate of death. Patients with a scoreor = 2 (one major criterion or two minor criteria) had a sixfold-greater risk-adjusted hazard ratio (HR) of death (HR, 5.8; 95% confidence interval, 2.5 to 13.1).Four criteria of instability on discharge seem to be related to the mortality rate after discharge, but each of the factors must be weighed differently. The resulting score is a simple alternative that can be used by clinicians in the discharge process.

Introduction Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE. Methods Serum samples were collected at 32–36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16) and pregnant controls (n = 32). The effect of oxygen tension on placental cells was assessed by incubation JEG–3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6) were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels). Aromatase content and estrogens and androgens concentrations were measured. Results The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG–3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic placental ischemia and hypoxia later in gestation. Conclusions Placental aromatase expression and functionality are diminished in pregnancies complicated by preeclampsia in comparison with healthy pregnant controls.