Clinical characteristics and prognosis of serous body cavity effusions in patients with sepsis: a retrospective observational study.

BACKGROUND: Cavity effusion is common in patients with infectious diseases. However, the incidence rate and characteristics of serous cavity effusions (SCE) in septic patients are not clear to date. The objective of this study was to investigate the incidence and characteristics of SCE in septic patients and to explore the correlations between the bloody effusions and the illness severity/prognosis in septic patients. METHODS: From January 2010 to January 2015, a total of 214 patients with severe sepsis and septic shock were enrolled in this retrospective observational study. Thoracentesis or abdominal paracentesis was performed in 45 septic patients because of massive pleural effusions or ascites. The serum concentrations of VEGF, VEGFR, Ang, sICAM-1, sVCAM-1, E-selectin, Serpine1 and VE-cadherin in 45 septic patients underwent paracentesis were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Of the 214 septic patients, 155 (72.4%) had SCE according to imaging or ultrasound manifestations. 45 subjects with SCE underwent therapeutic thoracentesis or abdominal paracentesis. Effusion laboratory analysis showed that exudates were predominant when compared with transudates (95.6% vs. 4.4%), and 16 (35.6%) patients suffered bloody effusions. Compared with patients with non-bloody effusions, those with bloody effusions showed higher critical illness scores (13 vs. 17 for APACHE II; 7 vs. 9 for SOFA), and higher mortality (6.9% vs. 62.5%). Moreover, patients with bloody effusions had delayed TT and APTT, increased D-dimer concentration, and higher serum levels of CRP and PCT (P < 0.05). In addition, the serum levels of Ang2, sVCAM-1 and E-selectin were significantly higher in patients with bloody effusions than in those with non-bloody effusions (P < 0.05). However, the serum level of VEGFR2 was lower in patients with bloody fluids (P = 0.025). CONCLUSIONS: The incidence of serous cavity effusion is high in patients with sepsis. The septic patients with bloody effusions suffer a more inflammatory burden and a worse prognosis compared to septic patients with non-bloody effusions.

Artificial intelligence computed tomography helps evaluate the severity of COVID-19 patients: A retrospective study.

BACKGROUND: Computed tomography (CT) is a noninvasive imaging approach to assist the early diagnosis of pneumonia. However, coronavirus disease 2019 (COVID-19) shares similar imaging features with other types of pneumonia, which makes differential diagnosis problematic. Artificial intelligence (AI) has been proven successful in the medical imaging field, which has helped disease identification. However, whether AI can be used to identify the severity of COVID-19 is still underdetermined. METHODS: Data were extracted from 140 patients with confirmed COVID-19. The severity of COVID-19 patients (severe vs. non-severe) was defined at admission, according to American Thoracic Society (ATS) guidelines for community-acquired pneumonia (CAP). The AI-CT rating system constructed by Hangzhou YITU Healthcare Technology Co., Ltd. was used as the analysis tool to analyze chest CT images. RESULTS: A total of 117 diagnosed cases were enrolled, with 40 severe cases and 77 non-severe cases. Severe patients had more dyspnea symptoms on admission (12 vs. 3), higher acute physiology and chronic health evaluation (APACHE) II (9 vs. 4) and sequential organ failure assessment (SOFA) (3 vs. 1) scores, as well as higher CT semiquantitative rating scores (4 vs. 1) and AI-CT rating scores than non-severe patients (P<0.001). The AI-CT score was more predictive of the severity of COVID-19 (AUC=0.929), and ground-glass opacity (GGO) was more predictive of further intubation and mechanical ventilation (AUC=0.836). Furthermore, the CT semiquantitative score was linearly associated with the AI-CT rating system (Adj R 2=75.5%, P<0.001). CONCLUSIONS: AI technology could be used to evaluate disease severity in COVID-19 patients. Although it could not be considered an independent factor, there was no doubt that GGOs displayed more predictive value for further mechanical ventilation.

LPS pretreatment ameliorates multiple organ injuries and improves survival in a murine model of polymicrobial sepsis.

OBJECTIVE: The endotoxin tolerance phenotype is characterized with decreased inflammation and increased phagocytosis. We hypothesized that endotoxin tolerance would provide protective effects on experimental sepsis with multiple organ injuries induced by cecal ligation and puncture (CLP). METHODS: Endotoxin tolerance was induced in male Sprague-Dawley rats with daily intraperitoneal injection of either 0.6 mg/kg of lipopolysaccharide (LPS) or vehicle for four consecutive days before subsequent CLP. Biochemical parameters, histological changes, inflammatory cytokine production, and lung tissue nuclear factor-κB (NF-κB) activation were assessed post-CLP. In a separate experiment, survival rate was monitored for 7 days after CLP. RESULTS: In vehicle-treated animals, CLP caused multiple organ injuries confirmed by the biochemical variables and histological examination. This was accompanied by an early activation of NF-κB in the lung and a substantial increase in plasma levels of tumor necrosis factor-α, interleukin-6, and interleukin-10. In contrast, pretreatment with LPS not only alleviated the development of multiple organ injuries after CLP, but also decreased sepsis-induced activation of pulmonary NF-κB and reduced plasma cytokines production. In addition, LPS pretreatment improved the survival in rats subjected to CLP. CONCLUSIONS: The beneficial effects of endotoxin tolerance indicate the potential of immunomodulatory strategies in the management of severe sepsis.

MicroRNA-145 plays a role in mitochondrial dysfunction in alveolar epithelial cells in lipopolysaccharide-induced acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) causes substantial mortalities. Alveolar epithelium is one of the main sites of cell injuries in ARDS. As an important kind of microRNAs (miRNAs), microRNA-145 (miR-145) has been studied in various diseases, while its role in ARDS has not been investigated. METHODS: Lipopolysaccharide (LPS) was intratracheally instilled to establish a rat ARDS model. Cytokines from bronchoalveolar lavage fluid (BALF) were measured using rat tumor necrosis factor-α and interleukin-6 enzyme-linked immunosorbent assay kits (R&D Systems), and the pathological structures were evaluated using hematoxylin and eosin (H&E) staining and transmission electron microscope; the lung miR-145 messenger RNA (mRNA) was detected using quantitative polymerase chain reaction. Bioinformatics focused on the target genes and possible pathways of gene regulation. RESULTS: A rat model of LPS-induced ARDS was successfully established. The miR-145 was down-regulated in the LPS-induced ARDS lung, and mitochondrial dysfunction was observed in alveolar epithelial cells, most obviously at 72 hours after LPS. TargetScan and miRDB databases were used to predict the target genes of miR-145. A total of 428 overlapping genes were identified, seven genes were associated with mitochondrial function, and Ogt, Camk2d, Slc8a3, and Slc25a25 were verified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway, and Gene Ontology (GO) biological process was mainly enriched in signal transduction and transcription regulation. CONCLUSIONS: The miR-145 is down-regulated in LPS-induced ARDS, and affects its downstream genes targeting mitochondrial functions.

Prognosis-related classification and dynamic monitoring of immune status in patients with sepsis: A prospective observational study.

BACKGROUND: The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis. In this study, we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value. METHODS: A prospective observational study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between July 2016 and December 2018. Blood samples were collected at days 1 and 3. Serum cytokine levels (e.g., tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10]) and CD14+ monocyte human leukocyte antigen-D-related (HLA-DR) expression were measured to serve as immune markers. Classification of each immune status, namely systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS), and mixed antagonistic response syndrome (MARS), was defined based on levels of immune markers. Changes of immune status were classified into four groups which were stabilization (SB), deterioration (DT), remission (RM), and non-remission (NR). RESULTS: A total of 174 septic patients were enrolled including 50 non-survivors. Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors. Patients with MARS had the highest mortality rate. Immune status of 46.1% patients changed from day 1 to day 3. Among four groups of immune status changes, DT had the highest mortality rate, followed by NR, RM, and SB with mortality rates of 64.7%, 42.9%, and 11.2%, respectively. CONCLUSIONS: Severe immune disorder defined as MARS or deterioration of immune status defined as DT lead to the worst outcomes. The preliminary model of the classification and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.

[Predictors of peri-operative mortality in patients with aortic dissection].

OBJECTIVE: To analyze the peri-operative risk factors of mortality in patients with aortic dissection (AD). METHODS: Between January 2003 and June 2008, 361 AD patients at our hospital were enrolled. Their demographics, history, clinical characteristics and laboratory examinations were retrospectively analyzed. Twenty pre-operative variables were analyzed to identify the predictors of perioperative mortality of AD patients by the analyses of univariate and multivariate logistic regression. RESULTS: The analysis of univariate logistic regression showed that history of hypertension [odds ratio (OR) 0.465, 95% confidence interval (CI) 0.229 - 0.947, P = 0.035], Stanford type A (OR 2.758, 95%CI 1.054 - 7.213 P = 0.039), acute course (OR 7.897, 95%CI 1.874 - 33.275 P = 0.005), neurological symptoms (OR 0.275, 95%CI 0.140 - 0.541, P < 0.001) and operation or not (OR 8.206, 95%CI 4.205 - 16.012, P < 0.001) had a higher mortality in AD patients. The multivariate analysis revealed that acute course (OR 8.178, 95%CI 1.796 - 37.242, P = 0.007), Stanford type A (OR 3.236, 95%CI 1.104-9.487 P = 0.032), neurological symptoms (OR 0.350, 95%CI 0.159 - 0.770, P = 0.009) and operation or not (OR 9.429, 95%CI 4.456 - 19.952, P < 0.001) were significant independent predictors of perioperative mortality in AD patients. CONCLUSION: History of hypertension, acute course, Stanford A and positive neurological symptoms are the independent predictors of perioperative mortality in AD patients. Operation or not is a determinant of patient outcome.

Clinical characteristics and prognosis of community-acquired pneumonia in autoimmune disease-induced immunocompromised host: A retrospective observational study.

BACKGROUND: Community-acquired pneumonia (CAP) in autoimmune diseases (AID)-induced immunocompromised host (ICH) had a high incidence and poor prognosis. However, only a few studies had determined the clinical characteristics of these patients. Our study was to explore the characteristics and predictors of mortality in CAP patients accompanied with AID-induced ICH. METHODS: From 2013 to 2018, a total of 94 CAP patients accompanied with AID-induced ICH, admitted to Emergency Department of Zhongshan Hospital, Fudan University, were enrolled in this study. Clinical data and the risk regression estimates of repeated predictors were evaluated by generalized estimating equations (GEEs) analysis. An open-cohort approach was used to classify patient's outcomes into the survival or non-survival group. RESULTS: The hospital mortality of patients with CAP occurring in AID-induced ICH was 60.64%. No significant differences were found with respect to clinical symptoms and lung images between survival and non-survival groups, while renal insufficiency and dysfunction of coagulation had higher proportions in non-survival patients (P<0.05). Both noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) were performed more frequently in non-survival group (P< 0.05). By the multivariate GEEs analysis, the repeated measured longitudinal indices of neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR]=1.055, 95% confidence interval [95%CI] 1.025-1.086), lactate dehydrogenase (LDH) (OR=1.004, 95%CI 1.002-1.006) and serum creatinine (sCr) (OR=1.018, 95%CI 1.008-1.028), were associated with a higher risk of mortality. CONCLUSION: The CAP patients in AID-induced ICH had a high mortality. A significant relationship was demonstrated between the factors of NLR, LDH, sCr and mortality risk in these patients.

Effects of hypothermia on the liver in a swine model of cardiopulmonary resuscitation.

BACKGROUND: The study aimed to explore the effects of hypothermia state induced by 4 ºC normal saline (NS) on liver biochemistry, enzymology and morphology after restoration of spontaneous circulation (ROSC) by cardiopulmonary resuscitation (CPR) in swine. METHODS: After 4 minutes of ventricular fibrillation (VF), standard CPR was carried out. Then the survivors were divided into two groups: low temperature group and normal temperature group. The low temperature (LT) group (n=5) received continuously 4 ºC NS at the speed of 1.33 mL/kg per minute for 22 minutes, then at the speed lowering to 10 mL/kg per hour. The normal temperature (NT) group (n=5) received NS with normal room temperature at the same speed of the LT group. Hemodynamic status and oxygen metabolism were monitored and the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured in blood samples obtained at baseline and at 10 minutes, 2 hours and 4 hours after ROSC. At 24 hours after ROSC, the animals were killed and the liver was removed to determine the Na(+)-K(+)-ATPase and Ca(2+)-ATPase enzyme activities and histological changes under a light or electron microscope. RESULTS: Core temperature was decreased in the LT group (P<0.05), while HR, MAP and CPP were not significantly decreased (P>0.05) compared with the NT group (P>0.05). The oxygen extraction ratio was lower in the LT group than in the NT group (P<0.05). The serum levels of ALT, AST and LDH increased in both groups but not significantly in the LT group. The enzyme activity of liver ATP was much higher in the LT group (Na(+)-K(+)-ATP enzyme: 8.64±3.32 U vs. 3.28±0.71 U; Ca(2+)-ATP enzyme: 10.92±2.12 U vs. 2.75±0.78 U, P<0.05). The LT group showed less cellular edema, inflammation and few damaged mitochondria as compared with the NT group. CONCLUSION: These data suggested that infusing 4 ºC NS continuously after ROSC could quickly lower the core body temperature, while maintaining a stable hemodynamic state and balancing oxygen metabolism, which protect the liver in terms of biochemistry, enzymology and histology after CPR.

Association of genetic variants in the IRAK-4 gene with susceptibility to severe sepsis.

BACKGROUND: The association of genetic variation in the IRAK-1 gene with sepsis outcome has been proved. However, few studies have addressed the impact of the IRAK-4 gene variants on sepsis risk. This study aimed to determine whether the polymorphisms in the IRAK-4 gene are associated with susceptibility to and prognosis of severe sepsis in the Chinese Han ethnic population. METHODS: In this case-control study, 192 patients with severe sepsis hospitalized in the emergency department of Zhongshan Hospital from February 2006 to December 2009 and 192 healthy volunteers were enrolled. Exclusion criteria included metastatic tumors, autoimmune diseases, AIDS or treatment with immunosuppressive drugs. This study was approved by the ethical committee of Zhongshan Hospital, Fudan University. Sepsis patients were divided into a survival group (n=124) and a non-survival group (n=68) according to the 30-day mortality. Primer 3 software was used to design PCR and sequencing primers. Genomic DNA was extracted from peripheral blood mononuclear cells. Seven tagSNPs in IRAK-4 were selected according to the data of the Chinese Han population in Beijing from the Hapmap project and genotyped by direct sequencing. The chi-square test was used to evaluate the differences in genotype and allele frequencies between the two groups. RESULTS: The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium. The allele and genotype frequencies of rs4251545 (G/A) were significantly different between the severe sepsis and healthy control groups (P=0.015, P=0.035, respectively). Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G (OR=1.69, 95% CI: 1.10-2.58). The allele and genotype frequencies of all SNPs were not significantly different between the survival group and non-survival group. CONCLUSION: These findings indicate that the variants in IRAK-4 are significantly associated with susceptibility to severe sepsis in the Chinese Han ethnic population.

Ischemia-modified albumin measured with ultra-filtration assay in early diagnosis of acute coronary syndrome.

BACKGROUND: Patients with acute chest pain remain a great diagnostic challenge to emergency physicians. Ischemia-modified albumin (IMA) is a recently developed biomarker of transient myocardial ischemia. IMA has already been licensed by the US Food and Drug Administration for diagnosis of suspected myocardial ischemia. This study aimed to assess the diagnostic value of IMA in treatment of patients with acute coronary syndrome(ACS). METHODS: IMA level was detected by ultra-filtration assay combined with albumin-cobalt binding (ACB) test as well as tests of myoglobin (MYO), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) in 169 consecutive patients with acute chest pain onset within 24 hours. Receiver operating characteristic (ROC) curve for IMA in diagnosing ACS was established to determine the cut-off point. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of IMA and its combinations with other agents were analyzed. RESULTS: Area under the ROC curve (AUC) was 0.754. As the cut-off point for IMA in this study was 70.4 U/ml, the sensitivity, specificity, PPV and NPV of IMA were 79.8%, 65.2%±77.7%, and 69.7%, respectively. The sensitivity and NPV of IMA combined with the conventional cardiac marker panel for the diagnosis of ACS were 93.4% and 86.0%, respectively. CONCLUSION: IMA is a useful biochemical marker for the early diagnosis of ACS. IMA combined with the conventional cardiac marker panel can improve early diagnosis of ACS compared with the traditional combinations of myocardial biochemical markers.