Over-expression of programmed death-ligand 1 and programmed death-1 on antigen-presenting cells as a predictor of organ dysfunction and mortality during early sepsis: a prospective cohort study.

BACKGROUND: This study aimed to explore the changes of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) expression on antigen-presenting cells (APCs) and evaluate their association with organ failure and mortality during early sepsis. METHODS: In total, 40 healthy controls and 198 patients with sepsis were included in this study. Peripheral blood was collected within the first 24 h after the diagnosis of sepsis. The expression of PD-L1 and PD-1 was determined on APCs, such as B cells, monocytes, and dendritic cells (DCs), by flow cytometry. Cytokines in plasma, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, and IL-17A were determined by Luminex assay. RESULTS: PD-1 expression decreased significantly on B cells, monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) as the severity of sepsis increased. PD-1 expression was also markedly decreased in non-survivors compared with survivors. In contrast, PD-L1 expression was markedly higher on mDCs, pDCs, and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors. The PD-L1 expression on APCs (monocytes and DCs) was weakly related to organ dysfunction and inflammation. The area under the receiver operating characteristic curve (AUC) of the PD-1 percentage of monocytes (monocyte PD-1%)+APACHE II model (0.823) and monocyte PD-1%+SOFA model (0.816) had higher prognostic value than other parameters alone. Monocyte PD-1% was an independent risk factor for 28-day mortality. CONCLUSION: The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs. PD-L1 in monocytes and DCs was weakly correlated with inflammation and organ dysfunction during early sepsis. The combination of SOFA or APACHE II scores with monocyte PD-1% could improve the prediction ability for mortality.

Predictive value of presepsin and acylcarnitines for severity and biliary drainage in acute cholangitis.

BACKGROUND: Bacteremia, which is a major cause of mortality in patients with acute cholangitis, induces hyperactive immune response and mitochondrial dysfunction. Presepsin is responsible for pathogen recognition by innate immunity. Acylcarnitines are established mitochondrial biomarkers. AIM: To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage. METHODS: Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018. Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry, respectively. RESULTS: The concentrations of presepsin, procalcitonin, short- and medium-chain acylcarnitines increased, while long-chain acylcarnitines decreased with the severity of acute cholangitis. The areas under the receiver operating characteristic curves (AUC) of presepsin for diagnosing moderate/severe and severe cholangitis (0.823 and 0.801, respectively) were greater than those of conventional markers. The combination of presepsin, direct bilirubin, alanine aminotransferase, temperature, and butyryl-L-carnitine showed good predictive ability for biliary drainage (AUC: 0.723). Presepsin, procalcitonin, acetyl-L-carnitine, hydroxydodecenoyl-L-carnitine, and temperature were independent predictors of bloodstream infection. After adjusting for severity classification, acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality (hazard ratio 14.396; P < 0.001) (AUC: 0.880). Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine. CONCLUSION: Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage. Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis. Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.

Dynamic blood presepsin levels are associated with severity and outcome of acute pancreatitis: A prospective cohort study.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of the pancreas with an unpredictable course of illness. A major challenge of AP is the early identification of patients at high-risk for organ failure and death. However, scoring systems are complicated and time consuming, and the predictive values for the clinical course are vague. AIM: To determine whether the dynamic changes in presepsin levels can be used to evaluate the severity of disease and outcome of AP. METHODS: In this multicentric cohort study, 133 patients with AP were included. Clinical severity was dynamically evaluated using the 2012 revised Atlanta Classification. Blood presepsin levels were measured at days 1, 3, 5 and 7 after admission by chemiluminescent enzyme immunoassay. RESULTS: The median concentration of presepsin increased and the clearance rate of presepsin decreased with disease severity and organ failure in AP patients. The presepsin levels on days 3, 5 and 7 were independent predictors of moderately severe and severe AP with time-specific area under the curve (AUC) values of 0.827, 0.848 and 0.867, respectively. The presepsin levels positively correlated with bedside index of severity in AP, Ranson, acute physiology and chronic health evaluation II, computed tomography severity index and Marshall scores. Presepsin levels on days 3, 5 and 7 were independent predictors of 28-d mortality of AP patients with AUC values of 0.781, 0.846 and 0.843, respectively. CONCLUSION: Blood presepsin levels within 7 d of admission were associated with and may be useful to dynamically predict the severity of disease course and 28-d mortality in AP patients.

Increasing angiotensin-converting enzyme (ACE) 2/ACE axes ratio alleviates early pulmonary vascular remodeling in a porcine model of acute pulmonary embolism with cardiac arrest.

BACKGROUND: Acute pulmonary embolism (APE) with cardiac arrest (CA) is characterized by high mortality in emergency due to pulmonary arterial hypertension (PAH). This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme (ACE) 2-angiotensin (Ang) (1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor (AT1) axis (ACE2/ACE axes) ratio on pulmonary artery lesion after return of spontaneous circulation (ROSC). METHODS: To establish a porcine massive APE with CA model, autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg (1 mmHg=0.133 kPa). Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation. Pigs were divided into four groups of five pigs each: control group, APE-CA group, ROSC-saline group, and ROSC-captopril group, to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril. RESULTS: Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells. Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor (VEGF) in the APE-CA group compared with the control group. Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC. Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X (Bax) ratio and decreasing cleaved caspase-3 expression. CONCLUSION: Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.

Presepsin as a biomarker for risk stratification for acute cholangitis in emergency department: A single-center study.

BACKGROUND: Acute cholangitis is caused by bacterial infection and has high morbidity and mortality risk. The grade of cholangitis can guide clinical treatment from single antibiotic treatment to biliary drainage. With the introduction of white blood cell (WBC) count, C-reactive protein (CRP), and total bilirubin (T-Bil) into the diagnostic criteria and severity grading for acute cholangitis, the diagnosis rate and grading have significantly improved. However, early risk stratification assessments are challenging in the emergency department. Therefore, we hope to find an ideal predictive biomarker for cholangitis grade. Presepsin is a promising biomarker for the early diagnosis, severity, and prognosis of acute bacterial infections. AIM: To assess the grading value of presepsin in patients with acute cholangitis. METHODS: This clinical study was conducted at the Beijing Friendship Hospital, a 2000-bed teaching hospital with approximately 200000 emergency admissions per year. In this prospective observational study, 336 patients with acute cholangitis meeting the Tokyo Guidelines 2018 diagnostic criteria in the emergency department from May 2019 to December 2020 were analyzed. WBC count, CRP, procalcitonin (PCT), presepsin, T-Bil, and blood culture results were collected. The values were compared using the Pearson χ 2 test, Fisher's exact test, or Mann-Whitney U test. The area under the receiver operating characteristic curve (AUC) of the value was examined using the Delong test. The correlations among the key research indicators were determined using Pearson correlation. RESULTS: In total, 336 patients were examined, which included 107, 106, and 123 patients classified as having mild, moderate, and severe cholangitis, respectively. WBC count, CRP, PCT, presepsin, T-Bil, direct bilirubin, and sequential organ failure assessment scores of moderate and severe cholangitis patients were higher than those of mild cholangitis patients (P = 0.000). The AUC of presepsin in predicting moderate acute cholangitis was 0.728, which was higher than that of CRP (0.631, P = 0.043) and PCT (0.585, P = 0.002), and same as that of WBC count (0.746, P = 0.713) and T-Bil (0.686, P = 0.361). The AUC of presepsin in predicting severe acute cholangitis was 0.715, which was higher than that of WBC count (0.571, P = 0.008), CRP (0.590, P = 0.009), PCT (0.618, P = 0.024), and T-Bil (0.559, P = 0.006). The presepsin levels in the positive blood culture group were higher (2830.8pg/mLvs1987.8pg/mL, P = 0.000), and the AUC of presepsin (0.688) proved that it was a good biomarker for predicting positive bacterial culture. CONCLUSION: Presepsin can predict positive blood culture in patients with acute cholangitis. It is superior to WBC count, CRP, PCT, and T-Bil for the risk stratification of acute cholangitis.

Case Report: Disseminated Cysticercosis due to Intentional Ingestion of Parasitic Worm Eggs for Weight Loss.

A 20-year-old female resident of Beijing intended to consume the eggs of the parasitic worm, Taenia saginata, for weight loss; however, she apparently inadvertently ingested Taenia solium (pork tapeworm) eggs, which resulted in disseminated cysticercosis. Cysticerci developed in the brain, tongue, muscles, liver, peritoneum, and subcutaneous tissues. She was administered oral albendazole and praziquantel. After four 10-day courses of treatment, most of the cysts disappeared and she recovered. After 3 years, the patient remains in good health.

Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model.

Acute pulmonary embolism (APE) with cardiac arrest (CA) is associated with a high mortality rate. Even upon return of the spontaneous circulation (ROSC), APE­CA survivors are prone to myocardial cell apoptosis, a key cellular mechanism that induces heart failure. A recent study by our group discovered a post­resuscitation imbalance in the serum angiotensin­converting enzyme (ACE)2/ACE axis of the renin­angiotensin system (RAS), as well as regressive cardiac function in a porcine model of APE­CA. However, it has remained elusive how this imbalance in the ACE2/ACE axis affects myocardial cell apoptosis. In the present study, western blot and immunohistochemical analyses demonstrated that the RAS was only activated in the left myocardium, as evidenced by a decreased ACE2/ACE ratio following APE­CA and ROSC, but not the right myocardium. Ultrastructural analysis confirmed myocardial apoptosis in the left and right myocardium. Furthermore, B­cell lymphoma 2 (Bcl­2)­associated X protein (Bax) and caspase­3 levels were elevated and Bcl­2 levels were decreased in the left myocardium following APE­CA and ROSC. Treatment with the ACE inhibitor captopril for 30 min after initiation of ROSC prevented the increase in Bax and the decrease in Bcl­2 in the left myocardium compared with that in saline­treated pigs. Captopril also inhibited the activation of extracellular signal­regulated kinase (ERK)1/2 in the left myocardium. The results of the present study suggest that an imbalance in the ACE2/ACE axis has an important role in myocardial apoptosis following APE­CA, which may be attributed to decreased ERK1/2 activation. In addition, it was indicated that captopril prevents apoptosis in the left myocardium after ROSC.

Association between ACE2/ACE balance and pneumocyte apoptosis in a porcine model of acute pulmonary thromboembolism with cardiac arrest.

Acute pulmonary embolism (APE) is frequently reported in patients with cardiac arrest (CA) in emergency care. Pneumocyte apoptosis is commonly observed in the lungs following an APE. An important pathological mechanism evoking apoptosis during a lipopolysaccharide­induced acute lung injury is the angiotensin­converting enzyme 2 (ACE2)/ACE imbalance. The present study uses a porcine model to examine the anti­apoptotic effects of captopril on APE­CA and the return of spontaneous circulation (ROSC). Pigs were randomly assigned into four groups: Control, APE­CA, ROSC­saline, and ROSC­captopril. Surviving pigs were euthanized at 6 h and lungs were isolated for analysis using several biochemical assays. Compared with the control group, the ACE2/ACE ratio was lower in the APE­CA and ROSC pigs. In addition, APE­CA pigs had higher Bcl­2­associated X protein (Bax) and cleaved caspase­3 levels, and lower B­cell lymphoma­2 (Bcl­2) level compared to control pigs. Captopril treatment reduced lung apoptosis, as demonstrated by lower TUNEL­positive cells, higher Bcl­2, and lower cleaved caspase­3 protein levels in the lung. Notably, the ACE2/ACE ratio was positively correlated with Bcl­2 protein levels and Bcl­2/Bax ratio. In conclusion, captopril has a protective effect against lung apoptosis following ROSC and that maintaining the balance of the ACE2/ACE axis is important for inhibiting pulmonary apoptosis during APE.

[A survey on knowledge of recommended heart failure guidelines among Chinese physicians].

OBJECTIVE: To obtain the knowledge status on recommended heart failure (HF) guidelines among Chinese physicians. METHODS: Questionnaire on heart failure including 20 multiple choice questions and 10 fill in the blank questions was designed based on the Chinese guidelines for the diagnosis and treatment of chronic heart failure in 2007 and the Chinese guidelines for the diagnosis and treatment of acute heart failure in 2010. The rate of correct answer for each item was calculated and compared among physicians specialized for cardiovascular diseases and not. RESULTS: The Questionnaire was completed in 400 physicians, including 208 physician specialized for cardiovascular disease and 192 physicians not specialized in cardiovascular disease. The rate of correct answer for 20 multiple choice questions was lower than 60% in 8 questions, 60%-80% in 8 questions, higher than 80% in 4 questions. The rate of correct answers for 10 fill in the blank questions focusing on the aimed dosage of 10 ACEI/ARB/ß-blockers was 49%. The 8 multiple choice questions with correct answer rate <60% are detailed items of myocardial remodeling, symptoms suggestive of HF, diagnosis tools for patients with suspected HF, the AHA stages of heart failure, the Forrester's hemodynamic classes of acute heart failure, the goals of ACEI/ARBs treatment in patients with HF, names of heart diseases which might benefit from ACEI/ARBs treatment defined by evidenced based medicine, and detailed application methods of ACEI/ARBs and ß-blockers for HF patients. In general, the rate of correct answer was significantly higher in physicians specialized for cardiovascular disease compared physicians not specialized for cardiovascular disease. CONCLUSION: There is a considerable knowledge gap on the Chinese guidelines for the diagnosis and treatment of chronic heart failure and the Chinese guidelines for the diagnosis and treatment of acute heart failure among Chinese physicians. Efforts must be made to educate physicians to improve their knowledge and improve HF patient care.

[Mild hypothermia therapy for brain recovery after cardiopulmonary resuscitation and analysis of prognostic factors].

OBJECTIVE: To explore the prognostic factors of mild hypothermia therapy in patients after cardiopulmonary resuscitation (CPR) and the prognostic value of the active electroencephalogram (AEEG). METHODS: Mild hypothermia therapy was applied in 42 patients after CRP whose circulation was stable on the basis of systemic treatment. Body temperature (jugular bulb temperature) was controlled at 31-34 centigrade for 3-6 days before rewarming. During treatment, routine examinations were made, and electroencephalogram was monitored and Hockday grade was estimated. Glasgow outcome scale (GOS) was use to evaluate the nervous system function of patients who survived for 3 months. RESULTS: There were varying degrees of difference between the good prognosis group (good recovery, moderate disability, n=19) and the poor outcome group (severe disability, vegetative state, death, n=23) in the time of CPR after cardiac arrest (minutes: 4.11±1.80 vs. 13.08±11.37), Glasgow coma scale (GCS) after the recovery (5.48±1.32 vs. 4.13±1.61), blood base excess (mmol/L: -10.27±6.23 vs. -13.18±7.29) and lactate concentration (mmol/L: 6.82±3.12 vs. 8.47±4.14, P<0.05 or P<0.01). There were significant differences between Hockday stage II and III in the rates of good prognosis in 37 patients who underwent the AEEG monitoring [85.7% (12/14) vs. 37.5% (3/8), P<0.05]. CONCLUSION: The duration between CPR and cardiac arrest, GCS after resuscitation, blood base excess and lactate concentration can help determine the prognosis of patients after mild hypothermia therapy; electroencephalogram monitor is a helpful measure to determine the neurological outcome of patients after mild hypothermia therapy.

[Use of acute physiology and chronic health evaluation III in evaluating prognosis of chronic obstructive pulmonary disease in elderly patients on mechanical ventilation].

OBJECTIVE: To investigate the feasibility of estimating risk of prognosis and hospital mortality in elderly patients (> or =60 years old) with chronic obstructive pulmonary disease (COPD) under the treatment of mechanical ventilation by using acute physiology and chronic health evaluation III (APACHE III). METHODS: Fifty elderly patients with COPD treated with mechanical ventilation were analyzed retrospectively. A risk estimation equation for hospital mortality was first developed by using APACHE III in evaluating 40 randomly-selected patients before mechanical ventilation. Changes in APACHE III on the 1 st, 3 rd and 7 th day for each patient after intubation were recorded and analyzed. RESULTS: The risk estimate equation for hospital mortality was developed as p=Apa(gamma)/(D(gamma)(50)+Apa(gamma)), D(50)=73.4, gamma=8 with 80% prediction accuracy. A statistical significant cutoff was developed by dynamically recording acute physiology scores after intubation, and a decrease of 32.8% or more (compared with APACHE III before intubation) of APACHE III on the 3 rd day predicted survival of the patient. CONCLUSION: APACHE III score and its dynamic change could be an ideal tool to predict risk for hospital mortality in elderly patients with COPD on mechanical ventilation.

[Protective effects of dexamethasone on myocardium in rats with sepsis].

OBJECTIVE: To investigate the changes in heart function and myocardial mechanics in murine sepsis model, and the mechanism of the protective effect of dexamethasone on heart. METHODS: Wistar rats were randomly divided into control group, lipopolysaccharide (LPS) group (4 mg/kg LPS intravenously), LPS+dexamethasone group (4 mg/kg LPS+2 mg/kg dexamethasone intravenously), with 32 rats in each group. A catheter was passed through right common carotid artery to the left cardiac ventricle. Function of the left ventricle was monitored, and blood was drawn at 0, 2, 4, 6 hours to detect concentrations of tumor necrosis factor-alpha (TNF-alpha), troponin T (TnT), with 8 rats for each time point. RESULTS: In sepsis rats, TnT increased significantly and could be lowered by dexamethasone [at 6 hours after the treatment (1.76+/-0.57) microg/L vs. (0.70+/-0.36) microg/L, P<0.01]. There were changes in left ventricular peak systolic pressure (LVPP) and maximum rate of intraventricular pressure rise/down (+/-dp/dt max) to certain extent, and increase in left ventricular end-diastolic pressure (LVEDP), but these changes could be ameliorated by using dexamethasone. TNF-alpha increased significantly in sepsis rats, but dexamethasone could lower its level [at 2 hours after the treatment (11.22+/-2.38) pmol/L vs. (7.62+/-3.21) pmol/L, P<0.01]. CONCLUSION: Myocardium is remarkably damaged in rats with sepsis. TNF-alpha could be regarded as one of the factors which could produce injury to myocardium. Dexamethasone could alleviate cardiac damage produced by endotoxin in sepsis model.