Pregnant outcomes of critically ill pregnant patients with pulmonary hypertension: A multicenter retrospective study.

Objective: To identify the pregnancy outcomes and risk factors of critically ill pulmonary hypertension (PH) patients with intensive care unit (ICU) admission. Methods: The multicenter, retrospective cohort study was performed on 60,306 parturients from January 2013 to December 2018 in China. Diagnosis of PH was based on the estimation of systolic pulmonary arterial pressure (sPAP) via echocardiography. Patients were stratified by sPAP into three groups, mild (30-50 mmHg), moderate (51-70 mmHg), and severe (>70 mmHg). The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of in-hospital death, heart failure, and sustained arrhythmias requiring treatment. The secondary outcome was fetal adverse clinical events (FACE), a composite of fetal/neonatal death, prematurity, small birth weight, and fetal distress. Results: A total of 181 pregnant patients were enrolled, including 101 patients with mild PH, 31 with moderate PH, and 49 with severe PH. The maternal median age was 32 (27, 35) years and 37% were nulliparous. The MACE occurred in 59 (59/181, 32.6%) women, including in-hospital death in 13 (13/181, 7.2%), heart failure in 53 (53/181, 29.3%), and sustained arrhythmias in 7 (7/181, 3.9%). The incidence of FACE was as high as 66.3% (120/181). Compared with mild and moderate PH patients, patients with severe PH had a significantly higher mortality rate (22.4 vs. 1.51%, P < 0.001) and MACE incidence (51.0 vs. 25.8%, P = 0.001). Although the incidence of FACE in severe PH was slightly higher than that in mild to moderate PH, there was no significant difference (69.4 vs. 65.1%, P = 0.724). PH complicated with left heart disease (OR = 4.365, CI: 1.306-14.591), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (OR = 1.051, CI:1.015-1.088), and sPAP level estimated by echocardiography (OR = 1.021; CI: 1.003-1.040) were independently associated with MACE in multivariable regression (P < 0.05). Increased risk of FACE was noted for PH patients combined with eclampsia/preeclampsia (OR = 6.713; CI: 1.806-24.959). Conclusion: The incidence of MACE and FACE remained high in critically ill pregnant patients with PH, particularly moderate and severe PH in China. Further studies are warranted to identify subsets of women with PH at lower pregnant risks and seek more effective therapy to improve pregnancy outcomes.

Corrigendum: Risk Factors for Maternal and Fetal Mortality in Acute Fatty Liver of Pregnancy and New Predictive Models.

[This corrects the article DOI: 10.3389/fmed.2021.719906.].

Risk Factors for Maternal and Fetal Mortality in Acute Fatty Liver of Pregnancy and New Predictive Models.

Acute fatty liver of pregnancy (AFLP) is a rare but potentially life-threatening hepatic disorder that leads to considerable maternal and fetal mortality. To explore the risk factors for maternal and fetal mortality in AFLP and develop new predictive models, through this retrospective study, we analyzed the demographic characteristics, clinical symptoms, and laboratory findings of 106 patients with AFLP who were admitted to Shandong Provincial Hospital. Risk factors for maternal and fetal mortality were analyzed by univariate and multivariate logistic regression analysis. The new models based on the multivariate logistic regression analysis and the model for end-stage liver disease (MELD) were tested in AFLP. The receiver operating characteristic curve (ROC) was applied to compare the predictive efficiency, sensitivity, and specificity of the two models. Prenatal nausea (p = 0.037), prolonged prothrombin time (p = 0.003), and elevated serum creatinine (p = 0.003) were independent risk factors for maternal mortality. The ROC curve showed that the area under the curve (AUC) of the MELD was 0.948, with a sensitivity of 100% and a specificity of 83.3%. The AUC of the new model for maternal mortality was 0.926, with a sensitivity of 90% and a specificity of 94.8%. Hepatic encephalopathy (p = 0.016) and thrombocytopenia (p = 0.001) were independent risk factors for fetal mortality. Using the ROC curve, the AUC of the MELD was 0.694, yielding a sensitivity of 68.8% and a specificity of 64.4%. The AUC of the new model for fetal mortality was 0.893, yielding a sensitivity of 100% and a specificity of 73.3%. Both the new predictive model for maternal mortality and the MELD showed good predictive efficacy for maternal mortality in patients with AFLP (AUC = 0.926 and 0.948, respectively), and the new predictive model for fetal mortality was superior to the MELD in predicting fetal mortality (AUC = 0.893 and 0.694, respectively). The two new predictive models were more readily available, less expensive, and easier to implement clinically, especially in low-income countries.

Sex Differences on Clinical Characteristics, Severity, and Mortality in Adult Patients With COVID-19: A Multicentre Retrospective Study.

Background: Coronavirus disease-2019 (COVID-19) epidemic is spreading globally. Sex differences in the severity and mortality of COVID-19 emerged. This study aims to describe the impact of sex on outcomes in COVOD-19 with a special focus on the effect of estrogen. Methods: We performed a retrospective cohort study which included 413 patients (230 males and 183 females) with COVID-19 from three designated hospitals in China with a follow up time from January 31, 2020, to April 17, 2020. Women over 55 were considered as postmenopausal patients according to the previous epidemiological data from China. The interaction between age and sex on in-hospital mortality was determined through Cox regression analysis. In addition, multivariate Cox regression models were performed to explore risk factors associated with in-hospital mortality of COVID-19. Results: Age and sex had significant interaction for the in-hospital mortality (P < 0.001). Multivariate Cox regression showed that age (HR 1.041, 95% CI 1.009-1.073, P = 0.012), male sex (HR 2.033, 95% CI 1.007-2.098, P = 0.010), the interaction between age and sex (HR 1.118, 95% CI 1.003-1.232, P = 0.018), and comorbidities (HR 9.845, 95% CI 2.280-42.520, P = 0.002) were independently associated with in-hospital mortality of COVID-19 patients. In this multicentre study, female experienced a lower fatality for COVID-19 than male (4.4 vs. 10.0%, P = 0.031). Interestingly, stratification by age group revealed no difference in-hospital mortality was noted in women under 55 compared with women over 55 (3.8 vs. 5.2%, P = 0.144), as well as in women under 55 compared with the same age men (3.8 vs. 4.0%, P = 0.918). However, there was significantly difference in women over 55 with men of the same age group (5.2 vs. 21.0%, P = 0.007). Compared with male patients, female patients had higher lymphocyte (P < 0.001) and high-density lipoprotein (P < 0.001), lower high sensitive c reaction protein level (P < 0.001), and lower incidence rate of acute cardiac injury (6.6 vs. 13.5%, P = 0.022). Conclusion: Male sex is an independent risk factor for COVID-19 in-hospital mortality. Although female mortality in COVID-19 is lower than male, it might not be directly related to the effect of estrogen. Further study is warranted to identify the sex difference in COVID-19 and mechanisms involved.

Risk factors for severe COVID-19 in middle-aged patients without comorbidities: a multicentre retrospective study.

BACKGROUND: Information regarding characteristics and risk factors of COVID-19 amongst middle-aged (40-59 years) patients without comorbidities is scarce. METHODS: We therefore conducted this multicentre retrospective study and collected data of middle-aged COVID-19 patients without comorbidities at admission from three designated hospitals in China. RESULTS: Among 119 middle-aged patients without comorbidities, 18 (15.1%) developed into severe illness and 5 (3.9%) died in hospital. ARDS (26, 21.8%) and elevated D-dimer (36, 31.3%) were the most common complications, while other organ complications were relatively rare. Multivariable regression showed increasing odds of severe illness associated with neutrophil to lymphocyte ratio (NLR, OR, 11.238; 95% CI 1.110-1.382; p < 0.001) and D-dimer greater than 1 µg/ml (OR, 16.079; 95% CI 3.162-81.775; p = 0.001) on admission. The AUCs for the NLR, D-dimer greater than 1 µg/ml and combined NLR and D-dimer index were 0.862 (95% CI, 0.751-0.973), 0.800 (95% CI 0.684-0.915) and 0.916 (95% CI, 0.855-0.977), respectively. SOFA yielded an AUC of 0.750 (95% CI 0.602-0.987). There was significant difference in the AUC between SOFA and combined index (z = 2.574, p = 0.010). CONCLUSIONS: More attention should be paid to the monitoring and early treatment of respiratory and coagulation abnormalities in middle-aged COVID-19 patients without comorbidities. In addition, the combined NLR and D-dimer higher than 1 µg/ml index might be a potential and reliable predictor for the incidence of severe illness in this specific patient with COVID-19, which could guide clinicians on early classification and management of patients, thereby relieving the shortage of medical resource. However, it is warranted to validate the reliability of the predictor in larger sample COVID-19 patients.

A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.

INTRODUCTION: Coronavirus disease 2019 (COVID­19) caused by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infection spread worldwide. OBJECTIVES: The aim of the study was to identify the clinical characteristics and risk factors associated with severe incidence of SARS ­CoV­2 infection. PATIENTS AND METHODS: All adult patients (median [IQR] age, 52 [37-58] years) consecutively admitted to the Dabieshan Medical Center from January 30, 2020 to February 11, 2020 were collected and reviewed. Only patients diagnosed with COVID­19  according to the World Health Organization interim guidance were included in this retrospective cohort study. RESULTS: A total of 108 patients with COVID­19 were retrospectively analyzed. Twenty­five patients (23.1%) developed severe disease, and of those 12 patients (48%) died. Advanced age, comorbidities (most commonly hypertension), higher blood leukocyte count, neutrophil count, higher C­reactive protein level, D­dimer level, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score were associated with greater risk of COVID­19, and so were lower lymphocyte count and albumin level. Multivariable regress ion showed increasing odds of severe COVID­19 associated with higher SOFA score (odds ratio [OR], 2.45; 95% CI, 1.302-4.608; P = 0.005), and lymphocyte count less than 0.8 × 109/l (OR, 9.017; 95% CI, 2.808-28.857; P <0.001) on admission. Higher SOFA score (OR, 2.402; 95% CI, 1.313-4.395; P = 0.004) on admission was identified as risk factor for in­hospital death. CONCLUSIONS: Lymphocytopenia and a higher SOFA score on admission could help clinicians to identify patients at high risk for developing severe COVID­19. More related studies are needed in the future.

[Incidence and mortality risk factors of acute kidney injury in critical ill pregnancies: a single center retrospective analysis].

OBJECTIVE: To evaluate the incidence and mortality risk factors of pregnancy-related acute kidney injury (PR-AKI) in intensive care unit (ICU). METHODS: A retrospective analysis was conducted. Critically ill pregnancies admitted to ICU of Shandong University Affiliated Provincial Hospital from January 1st, 2012 to December 31st, 2016 were enrolled. Based on the Kidney Disease: Improving Global Outcomes (KDIGO)-acute kidney injury (AKI) criteria, patients were divided into two groups: PR-AKI group and non-PR-AKI group. Clinical characteristics and laboratory data of two groups were compared. Risk factors of incidence and mortality of PR-AKI patients were analyzed, and the receiver operating characteristic (ROC) curve was drawn to evaluate the value of these risk factors in predicting mortality of PR-AKI patients in ICU. RESULTS: (1) A total of 219 pregnancies in ICU were included in the analysis, 85 cases (38.8%) were diagnosed with PR-AKI, with 29.4% in AKI stage 1, 27.1% in AKI stage 2 and 43.5% in AKI stage 3. (2) Nineteen of 219 critically ill pregnancies died in ICU, the total ICU mortality was 8.7%. The mortality of PR-AKI group was higher than non-PR-AKI group (16.5% vs. 3.7%, P = 0.003). The mortality was worsened with increasing severity of AKI (4.0% for AKI stage 1, 4.3% for AKI stage 2, 32.4% for AKI stage 3). (3) Acute fatty liver of pregnancy (AFLP) and lactate (Lac) were the independent risk factors for PR-AKI [AFLP: odds ratio (OR) = 6.081, 95% confidence interval (95%CI) was 1.587-23.308, P = 0.008; Lac: OR = 1.460, 95%CI was 1.078-1.977, P = 0.014]. (4) Age, Lac, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) were the independent risk factors associated with the mortality of PR-AKI patients in ICU (age: OR = 1.130, 95%CI was 1.022-1.249, P = 0.017; Lac: OR = 1.198, 95%CI was 1.009-2.421, P = 0.039; APACHE II: OR = 1.211, 95%CI was 1.102-1.330, P < 0.001; SOFA: OR = 1.411, 95%CI was 1.193-1.669, P < 0.001). (5) ROC curve analysis showed that age, Lac, APACHE II score and SOFA score all had good predictive values for in-hospital mortality among PR-AKI patients in ICU, the cut-off value was 29 years old, 3.8 mmol/L, 16 and 8, respectively, and the AUC was 0.751, 0.757, 0.892 and 0.919, respectively (all P < 0.01). CONCLUSIONS: The incidence and mortality of PR-AKI of critically ill pregnancies in ICU are high. Increased age, Lac, APACHE II score and SOFA score are independent risk factors associated with the mortality of PR-AKI patients in ICU, and have good predictive values for prognosis.

Expression of HMGB1/RAGE protein in renal carcinoma and its clinical significance.

OBJECTIVE: To investigate the expression of high mobility group protein B1 (HMGB1) and its receptor, receptor for advanced glycation end-product (RAGE), in renal cancer tissue and surrounding normal tissue and to analyze the relationship between the expression level of the protein and receptor as well as the clinical pathological characteristics and prognosis in renal cancer patients. METHODS: A total of 80 renal carcinoma patients who were surgically treated in our hospital from February 2004 to December 2012 were included in this study. Normal paratumoral tissues were collected as a control. All diagnoses were confirmed with a postoperative pathological examination. All patients had complete pathological data. The expression of HMGB1/RAGE proteins in renal cancer tissue and paratumoral tissue was examined using immunohistochemical methods. RESULTS: The positive expression rate of HMGB1 was 71% in renal cancer tissue, which was significantly higher than that in the paratumoral normal tissue (25%). The positive expression rate of RAGE was 72% in renal cancer tissue, which was significantly higher than that in the paratumoral normal tissue (27%). Further analysis did not indicate a correlation between the positive expression of HMGB1 and RAGE proteins and gender, age and tumor size (P > 0.05), whereas the expression patterns were shown to correlate with tumor differentiation, clinical stage and lymph node metastasis (P < 0.05). The expression of HMGB1 exhibited a significant positive correlation with RAGE level (P < 0.05), the expression of HMGB1/RAGE proteins exhibited a negative correlation with the prognosis of patients, and the five-year survival rate of patients with positive expression was significantly lower than that of patients with negative expression (P < 0.05). CONCLUSION: HMGB1/RAGE exhibited significantly elevated expression in renal cancer tissues that was closely related to the clinical prognosis of patients; thus, the expression levels may become a new target in the treatment of renal carcinoma.

[Study of the effects of high volume hemofiltration on extra vascular lung water and alveolar-arterial oxygen exchange in patients with septic shock].

OBJECTIVE: To explore the effects of high volume hemofiltration (HVHF) on inflammatory factors, extra vascular lung water and alveolar-arterial oxygen exchange in patients with septic shock. METHODS: The data of 87 patients with septic shock underwent fluid resuscitation admitted to intensive care unit (ICU) of Shandong Provincial Hospital Affiliated to Shandong University were retrospectively analyzed. According to whether HVHF was used or not, all the patients were divided into fluid resuscitation group (n=41) and HVHF group (n=46). The patients in HVHF group received bedside high volume continuous vein-vein hemofiltration for at least 3 days on the basis of fluid resuscitation. The inflammatory factors, indexes of heart function, hemodynamics monitored by pulse-indicated continuous cardiac output (PiCCO), oxygen exchange, the severity of the disease before and after treatment, and 28-day mortality were compared between the two groups. The relationship between extra-vascular lung water index (EVLWI) and alveolar-arterial oxygen pressure difference (P(A-a)DO2) was analyzed. RESULTS: (1) After treatment, the serum levels of interleukin-6 (IL-6), procalcitonin (PCT), and N-terminal pro-B-type natriuretic peptide (NT(-pro)BNP) in both group were gradually decreased. The IL-6, PCT, and NT(-pro)BNP on the 3rd day after treatment in HVHF group were significantly lower than those in fluid resuscitation group [IL-6 (µg/L): 34.8 ± 15.8 vs. 63.3 ± 21.2, PCT (µg/L): 7.5 ± 6.4 vs. 17.3 ± 11.2, NT(-pro)BNP (µg/L): 561.8 ± 23.7 vs. 584.3 ± 56.7, P<0.05 or P<0.01]. (2) The hemodynamics indexes were improved after treatment in both groups. The levels of intrathoracic blood volume index (ITBVI), EVLWI and pulmonary vascular permeability index (PVPI) on the 3rd day after treatment in HVHF group were significantly lower than those in fluid resuscitation group [ITBVI (mL/m²): 634.2 ± 125.8 vs. 963.8 ± 321.0, EVLWI (mL/kg): 7.5 ± 2.4 vs. 12.3 ± 4.2, PVPI: 2.2 ± 1.2 vs. 4.2 ± 2.0, all P<0.01]. (3) The levels of PA-aDO2and arterial blood lactic (Lac) were gradually decreased, and oxygenation index (PaO2/FiO2) was gradually increased in both groups. Compared with fluid resuscitation group, the P(A-a)DO2and Lac on the 3rd and the 7th day were significantly declined[P(A-a)DO2(mmHg, 1 mmHg=0.133 kPa) on the 3rd day: 252.37 ± 29.45 vs. 270.82 ± 38.07, on the 7th day: 181.08 ± 21.81 vs. 221.02 ± 29.13; Lac (mmol/L) on the 3rd day: 3.17 ± 2.03 vs. 4.07 ± 2.43, on the 7th day: 1.95 ± 0.97 vs. 2.45 ± 1.07, P<0.05 or P<0.01], and the PaO2/FiO2on the 7th day was significantly elevated (mmHg: 258 ± 41 vs. 178 ± 34, P<0.01). (4) A significant positive correlation was found between EVLWI and P(A-a)DO2(r=0.693, P=0.001), with the 95% confident interval (95% CI) 0.617-0.773. (5) The condition was improved after treatment in the two groups. The acute physiology and chronic health evaluationII (APACHEII) scores and sepsis-related organ failure assessment (SOFA) scores on the 7th day after treatment in HVHF group were significantly reduced compared with those in fluid resuscitation group (APACHEII score on the 3rd day: 18.2 ± 7.7 vs. 22.4 ± 8.6, on the 7th day: 8.2 ± 3.8 vs. 17.2 ± 6.8; SOFA score on the 3rd day: 13.6 ± 3.4 vs. 15.8 ± 5.0, on the 7th day: 7.6 ± 3.3 vs. 12.8 ± 3.9, P<0.05 or P<0.01). The 28-day mortality in HVHF group was significantly lower than that in fluid resuscitation group [15.22% (7/46) vs. 34.15% (14/41), χ² = 4.242, P=0.038]. CONCLUSIONS: HVHF could decrease blood inflammatory factors, and reduce the vaso-permeability and extra vascular lung water with a result of the improvement of the levels of alveolar- arterial oxygen exchange in patients with septic shock and the prognosis at the same time.

The roles of CD147 and/or cyclophilin A in kidney diseases.

CD147 is a widely expressed integral plasma membrane glycoprotein and has been involved in a variety of physiological and pathological activities in combination with different partners, including cyclophilins, caveolin-1, monocarboxylate transporters, and integrins. Recent data demonstrate that both CyPA and CD147 significantly contribute to renal inflammation, acute kidney injury, renal fibrosis, and renal cell carcinoma. Here we review the current understanding of cyclophilin A and CD147 expression and functions in kidney diseases and potential implications for treatment of kidney diseases.