Efferocytosis in dendritic cells: an overlooked immunoregulatory process.

Efferocytosis, the process of engulfing and removing apoptotic cells, plays an essential role in preserving tissue health and averting undue inflammation. While macrophages are primarily known for this task, dendritic cells (DCs) also play a significant role. This review delves into the unique contributions of various DC subsets to efferocytosis, highlighting the distinctions in how DCs and macrophages recognize and handle apoptotic cells. It further explores how efferocytosis influences DC maturation, thereby affecting immune tolerance. This underscores the pivotal role of DCs in orchestrating immune responses and sustaining immune equilibrium, providing new insights into their function in immune regulation.

COMPARISON AMONG PRESEPSIN, PROCALCITONIN, AND C-REACTIVE PROTEIN IN PREDICTING BLOOD CULTURE POSITIVITY AND PATHOGEN IN SEPSIS PATIENTS.

ABSTRACT: Background: Sepsis is caused by the invasion of the bloodstream by microorganisms from local sites of infection, leading to high mortality. This study aimed to compare the predictive ability of the biomarkers presepsin, procalcitonin (PCT), and C-reactive protein for bacteraemia. Methods: In this retrospective, multicentre study, a dataset of patients with sepsis who were prospectively enrolled between November 2017 and June 2021 was analyzed. The performances of the biomarkers for predicting positive blood cultures and infection with specific pathogens were assessed by the areas under the receiver operating characteristic curves (AUCs). The independent effects of the pathogen and foci of infection on presepsin and PCT levels were assessed by linear logistic regression models. Results: A total of 577 patients with 170 positive blood cultures (29.5%) were enrolled. The AUC achieved using PCT levels (0.856) was significantly higher than that achieved using presepsin (0.786, P = 0.0200) and C-reactive protein (0.550, P < 0.0001) levels in predicting bacteraemia. The combined analysis of PCT and presepsin levels led to a significantly higher AUC than the analysis of PCT levels alone for predicting blood culture positivity (0.877 vs. 0.856, P = 0.0344) and gram-negative bacteraemia (0.900 vs. 0.875, P = 0.0216). In a linear regression model, the elevated concentrations of presepsin and PCT were both independently related to Escherichia coli , Klebsiella species, Pseudomonas species, and Streptococcus species infections and Sequential Organ Failure Assessment score. Presepsin levels were also associated with Acinetobacter species and abdominal infection, and PCT levels were positively associated with other Enterobacteriaceae and negatively associated with respiratory infection. Combined analysis of presepsin and PCT levels provided a high sensitivity and specificity in identifying E. coli or Klebsiella species infection. Conclusions: Presepsin and PCT were promising markers for predicting bacteraemia and common pathogens at the time of sepsis onset with a synergistic effect.

CLINICAL CHARACTERISTICS AND PREDICTORS OF MORTALITY DIFFER BETWEEN PULMONARY AND ABDOMINAL SEPSIS.

ABSTRACT: Background: Pulmonary sepsis and abdominal sepsis have pathophysiologically distinct phenotypes. This study aimed to compare their clinical characteristics and predictors of mortality. Methods: In this multicenter retrospective trial, 1,359 adult patients who fulfilled the Sepsis-3 criteria were enrolled and classified into the pulmonary sepsis or abdominal sepsis groups. Plasma presepsin was measured, and the scores of Acute Physiology and Chronic Health Evaluation (APACHE) II, Mortality in Emergency Department Sepsis (MEDS), and Simplified Acute Physiology Score (SAPS) II were calculated at enrollment. Data on 28-day mortality were collected for all patients. Results: Compared with patients with abdominal sepsis (n = 464), patients with pulmonary sepsis (n = 895) had higher 28-day mortality rate, illness severity scores, incidence of shock and acute kidney injury, and hospitalization costs. Lactate level and APACHE II and MEDS scores were independently associated with 28-day mortality in both sepsis types. Independent predictors of 28-day mortality included Pa o2 /F io2 ratio (hazard ratio [HR], 0.998; P < 0.001) and acute kidney injury (HR, 1.312; P = 0.039) in pulmonary sepsis, and SAPS II (HR, 1.037; P = 0.017) in abdominal sepsis. A model that combined APACHE II score, lactate, and MEDS score or SAPS II score had the best area under the receiver operating characteristic curve in predicting mortality in patients with pulmonary sepsis or abdominal sepsis, respectively. Interaction term analysis confirmed the association between 28-day mortality and lactate, APACHE II score, MEDS score, SAPS II score, and shock according to the sepsis subgroups. The mortality of patients with pulmonary sepsis was higher than that of patients with abdominal sepsis among patients without shock (32.9% vs. 8.8%; P < 0.001) but not among patients with shock (63.7 vs. 48.4%; P = 0.118). Conclusions: Patients with pulmonary sepsis had higher 28-day mortality than patients with abdominal sepsis. The study identified sepsis subgroup-specific mortality predictors. Shock had a larger effect on mortality in patients with abdominal sepsis than in those with pulmonary sepsis.

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.

Management strategy of a carotid-esophageal fistula with a right common carotid artery pseudoaneurysm due to chicken bone ingestion: A case report and literature review.

Common carotid artery (CCA) pseudoaneurysm is a rare clinical disorder. CCA pseudoaneurysm that occurs with a carotid-esophageal fistula and causes massive upper gastrointestinal bleeding is especially uncommon but can be life-threatening. Accurate diagnosis and prompt managements are essential to save lives. Here, we report a case of a 58-year-old female who presented with dysphagia and throat pain after accidental ingestion of a chicken bone. The patient presented with active upper gastrointestinal bleeding which quickly developed into hemorrhage shock. Imaging studies confirmed a diagnosis of right CCA pseudoaneurysm and carotid-esophageal fistula. The patient had a satisfactory recovery after a right CCA balloon occlusion, right CCA pseudoaneurysm excision, and right CCA and esophageal repairs. We present and discuss this case here to remind physicians to rule out rare causes of upper gastrointestinal bleeding. A multidisciplinary approach is commonly required to achieve satisfactory outcomes in these cases.

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.

In vitro Antimicrobial Activity and the Mechanism of Berberine Against Methicillin-Resistant Staphylococcus aureus Isolated from Bloodstream Infection Patients.

Purpose: To investigate the antimicrobial activity of berberine and the mechanism by which it combats methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from patients with bloodstream infections. Methods: Fifteen clinical MRSA isolates were collected, and their Multi-locus Sequence Types (MLST) were examined. The minimum inhibitory concentration (MIC) and combined antibacterial activity of berberine alone, and when combined with clindamycin and rifampicin separately, were determined. Additionally, two MRSA strains (ST239 and ST5) were selected to perform the time-killing assay and biofilm formation test. Cell wall alterations and cell membrane integrity were measured by confocal laser scanning microscopy (CLSM) and electron microscopy to assess the influence on cell morphology. Results: Our data showed berberine was effective against MRSA at MIC values varying from 256 to 64 mg*L-1 for different MLST types. Berberine alone, and when combined with clindamycin and rifampicin separately, displayed excellent antibacterial activity which reduced the bacterial counts by 2lgCFU*mL within 24h and significantly weakened biofilm formation compared with control strain. Additionally, bacterial cytological profiling indicates that berberine destroyed the structure of the cell walls, membrane integrity and further changed the cell morphology with concentration increased. Conclusion: In our study, berberine has excellent anti-MRSA activities and has synergistic antibacterial property when combined with clindamycin and rifamycin separately, and the mechanism of activities involves the destruction of cell wall and membrane.

Potential Value of Presepsin Guidance in Shortening Antibiotic Therapy in Septic Patients: a Multicenter, Prospective Cohort Trial.

INTRODUCTION: Long-term use of antibiotics for septic patients leads to bacterial resistance, increased mortality, and hospital stay. In this study, we investigated an emerging biomarker presepsin-guided strategy, which can be used to evaluate the shortening of antibiotic treatment in patients with sepsis without risking a worse outcome. METHODS: In this multicenter prospective cohort trial, patients were assigned to the presepsin or control groups. In the presepsin group, antibiotics were ceased based on predefined cut-off ranges of presepsin concentrations. The control group stopped antibiotics according to international guidelines. The primary endpoints were the number of days without antibiotics within 28 days and mortality at 28 and 90 days. Secondary endpoints were the percentage of patients with a recurrent infection, length of stay in ICU and hospital, hospitalization costs, days of first episode of antibiotic treatment, percentage of antibiotic administration and multidrug-resistant bacteria, and SOFA score. RESULTS: Overall, 656 out of an initial 708 patients were eligible and assigned to the presepsin group (n = 327) or the control group (n = 329). Patients in the presepsin group had significantly more days without antibiotics than those in the control group (14.54 days [SD 9.01] vs. 11.01 days [SD 7.73]; P < 0.001). Mortality in the presepsin group showed no difference to that in the control group at days 28 (17.7% vs. 18.2%; P = 0.868) and 90 (19.9% vs. 19.5%; P = 0.891). Patients in the presepsin group had a significantly shorter mean length of stay in the hospital and lower hospitalization costs than control subjects. There were no differences in the rate of recurrent infection and multidrug-resistant bacteria and the SOFA score tendency between the two groups. CONCLUSIONS: Presepsin guidance has potential to shorten the duration of antibiotic treatment in patients with sepsis without risking worse outcomes of death, recurrent infection, and aggravation of organ failure. TRIAL REGISTRATION: ChiCTR, ChiCTR1900024391. Registered 9 July 2019-Retrospectively registered, http://www.chictr.org.cn.

Glucocorticoid receptor expression in patients with cardiac arrest in the early period after the return of spontaneous circulation: a prospective observational single-centre study.

OBJECTIVES: Rapid changes in glucocorticoid (GC) levels and adrenal insufficiency are related to the development of post-cardiac arrest (CA) syndrome. However, GC receptor (GR) expression changes have not been studied. Hence, this study aimed to investigate the association of early changes in GR expression and prognosis and immune response in patients who experienced CA. DESIGN: Prospective observational study. SETTING: Emergency department. PARTICIPANTS: Patients (85) in the early period of return of spontaneous circulation (ROSC) after CA were admitted between October 2018 and October 2019. After a physical examination, age-matched and sex-matched healthy individuals (40) were recruited for the control group. PRIMARY AND SECONDARY OUTCOME MEASURES: GR expression and cell counts of circulatory T and B lymphocytes, natural killer cells and regulatory T (Treg) cells were assessed. Plasma total cortisol and adrenocorticotrophic hormone (ACTH) levels were also tested. RESULTS: All cell counts were lower, and plasma total cortisol levels were higher (p<0.001) in patients who experienced CA than in the healthy control group. GR expression in Treg cells and CD3+CD4+ T lymphocytes were not significantly different, but the mean fluorescence intensity and GR expression in other cells were lower in patients who experienced CA (p<0.05) than in the healthy control group. ACTH levels were not different. There were no significant differences between survivors and non-survivors. CONCLUSIONS: This study revealed that GR expression and cell counts rapidly decreased, whereas plasma total cortisol levels increased in the early period after ROSC among patients who experienced CA. Our findings provide important information about GR level and function, and immunosuppressive status in these patients. Assessing GR expression in patients who experienced CA may help screening for those who are more sensitive to GC therapy.

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.

Leukocyte glucocorticoid receptor expression and related transcriptomic gene signatures during early sepsis.

PURPOSE: The study aimed to understand the molecular mechanisms that might lead to differences in the glucocorticoid response during sepsis. METHODS: Patients diagnosed with sepsis (n = 198) and 40 healthy controls were enrolled. Glucocorticoid receptor (GR) expression in circulating leukocytes and plasma levels of adrenocorticotropic hormone and cortisol on days 1 and 7 were measured in all participants. Expression profiling of 16 genes associated with GR expression in peripheral blood mononuclear cells (PBMCs) in 12 healthy controls and 26 patients with sepsis was performed by PCR. RESULTS: Cortisol levels were higher in patients with sepsis than in healthy controls on day 1 after admission and recovered to normal levels by day 7. GR expression was gradually downregulated in leukocyte subsets. Non-survivors showed lower GR and higher cortisol levels than survivors. GRα expression was lower in patients with sepsis than in controls, whereas GRß showed the opposite trend. MicroRNAs related to GR resistance and suppression were altered in PBMCs during sepsis. CONCLUSION: Patients with sepsis showed upregulated plasma cortisol levels along with downregulated GR expression on various leukocyte subtypes, portending poor cortisol response and outcome. Changes in GR-regulatory miRNAs may be responsible for GR low expression.

[Great role and position of emergency department in the prevention and control of infectious diseases].

The emergency department is not only the place of treating emergency and critically ill patients, but also the frontline of identification and treatment of infectious disease. To ensure the treatment of the acute and critical diseases and the safety of the hospital, the emergency department should be included in the prevention and control system of infectious diseases. Therefore, we should attach great importance to the role of emergency department in the prevention and control system of infectious diseases, by establishing standardized protocols of ward layout, treatment procedure, management and training. We suggest that it is essential to strengthen the integrated management with the infectious diseases department, and jointly build a new emergency medical service system to deal with infectious diseases.

Association between elevation of plasma biomarkers and monocyte dysfunction and their combination in predicting sepsis: An observational single-centre cohort study.

This study aimed to investigate the possible relationship between the two biomarkers presepsin and procalcitonin (PCT) and monocyte immune function, and to explore their combination in mortality prediction in the early stage of sepsis. A total of 198 patients with bacterial infection and diagnosed with sepsis and 40 healthy control subjects were included. Blood samples were collected on admission within 24 h. Plasma concentrations of presepsin and PCT were measured. Expression of monocyte surface CD14, programmed cell death receptor ligand-1 (PD-L1) and human leucocyte Ag (HLA)-DR were determined using flow cytometry. Levels of plasma presepsin and PCT were significantly higher under septic conditions, and increased with the progression of sepsis. Monocyte CD14 and HLA-DR expression were decreased, while PD-L1 was overexpressed in sepsis compared to control. Presepsin and PCT concentrations were positively correlated with Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation System II score and PD-L1, while they were negatively correlated with CD14 and HLA-DR. Presepsin plus monocyte HLA-DR mean fluorescence intensity had the highest prognostic value over other parameters alone or in combination. Presepsin and PCT had a weak correlation with monocyte dysfunction during early sepsis. The combination of presepsin and monocyte HLA-DR could help improve prognostic value.

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.