Tissue oxygen saturation is predictive of lactate clearance in patients with circulatory shock.

BACKGROUND: Tissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2 and lactate clearance was unknown. METHODS: This was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2 on 6-hour lactate clearance > 10% since StO2 initially monitored was assessed. RESULTS: A total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac < 10% group (11 ± 3 vs. 15 ± 4, p = 0.007). Other baseline characteristics were comparable between groups. Compared to non-clearance group, StO2 in deltoid, thenar and knee were significantly higher in clearance group. The area under the receiver operating curves (AUROC) of BSA-weighted StO2 for prediction of lactate clearance (0.92, 95% CI [Confidence Interval] 0.82-1.00) was significantly higher than StO2 of masseter (0.65, 95% CI 0.45-0.84; p < 0.01), deltoid (0.77, 95% CI 0.60-0.94; p = 0.04), thenar (0.72, 95% CI 0.55-0.90; p = 0.01), and similar to knee (0.87, 0.73-1.00; p = 0.40), mean StO2 (0.85, 0.73-0.98; p = 0.09). Additionally, BSA-weighted StO2 model had continuous net reclassification improvement (NRI) over the knee StO2 and mean StO2 model (continuous NRI 48.1% and 90.2%, respectively). The AUROC of BSA-weighted StO2 was 0.91(95% CI 0.75-1.0) adjusted by mean arterial pressure and norepinephrine dose. CONCLUSIONS: Our results suggested that BSA-weighted StO2 was a strong predictor of 6-hour lactate clearance in patients with shock.

Cross-sectional study for the clinical application of extracorporeal membrane oxygenation in Mainland China, 2018.

BACKGROUND: To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018. METHODS: Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database. RESULTS: The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31-63), and 1346 were male. The average hospital stay was 17 days (IQR 7-30), and the average costs per case was $36,334 (IQR 22,547-56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality. CONCLUSIONS: Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.

Lung ultrasound can be used to predict the potential of prone positioning and assess prognosis in patients with acute respiratory distress syndrome.

BACKGROUND: It is very important to assess the effectiveness of prone positioning (PP) in patients with severe acute respiratory distress syndrome (ARDS). However, it is difficult to identify patients who may benefit from PP. The purpose of this study was to investigate whether prone positioning potential (PPP) can be predicted by lung ultrasound in patients with ARDS. METHODS: In this prospective study, 45 patients with ARDS were included for the assessment of PPP. A PP lung ultrasound examination (PLUE) protocol was performed in the dorsal regions of the lung in 16 areas at H0, H3, and H6 (0, 3, and 6 h after PP). The ultrasonography videos were blindly evaluated by two expert clinicians to classify the lung regions as normal pattern (N), moderate loss of lung aeration (B1), severe loss of lung aeration (B2), and consolidation (C). The aeration scores were collected at H0, H3, and H6. According to the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (P/F ratio) at 7 days, patients were classified into PPP-positive (P/F ratio >300) and PPP-negative groups; also, the patients were classified into survival and nonsurvival groups according to 28-day mortality. RESULTS: Aeration scores was compared at H0, H3, and H6. The scores were significantly reduced between H3 and H0, but there was no difference between H3 and H6. The aeration score variation (ASV) of the PPP-positive group between H3 and H0 was significantly higher than that in the PPP-negative group, and the sensitivity and specificity of ASV ≥5.5 for the PPP-positive group were 73.9% and 86.4%, respectively. The area under the receiver operating characteristic curve (AUROC) was 0.852 for the ASV. The ASV between H3 and H0 in the survival group was significantly higher than in the nonsurvival group. The sensitivity and specificity of ASV ≥7 for survival were 51.5% and 75%, respectively. The AUROC was 0.702 for the ASV. CONCLUSIONS: The PLUE protocol can be used to predict PPP and assess prognosis in patients with ARDS.

Prognostic value of procalcitonin in pneumonia: A systematic review and meta-analysis.

This meta-analysis was performed to determine the accuracy of procalcitonin (PCT) in predicting mortality in pneumonia patients with different pathogenic features and disease severities. A systematic search of English-language articles was performed using PubMed, Embase, Web of Knowledge and the Cochrane Library to identify studies. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. The Q-test and I(2) index were used to test heterogeneity. A total of 21 studies comprising 6007 patients were included. An elevated PCT level was a risk factor for death from community-acquired pneumonia (CAP) (risk ratio (RR) 4.38, 95% confidence interval (CI) 2.98-6.43), particularly in patients with a low CURB-65 score. The commonly used cut-off, 0.5 ng/mL, had low sensitivity (SEN) and was not able to identify patients at high risk of dying. Furthermore, the PCT assay with functional SEN <0.1 ng/mL was necessary to predict mortality in CAP in the clinic. For critically ill patients, an elevated PCT level was associated with an increased risk of mortality (RR 4.18, 95% CI: 3.19-5.48). The prognostic performance was nearly equal between patients with ventilator-associated pneumonia (VAP) and patients with CAP.

Effects of vitamin b6 therapy for sepsis patients with linezolid-associated cytopenias: a retrospective study.

BACKGROUND: The common adverse effects of linezolid for treating septic patients with gram-positive cocci is anemia and thrombocytopenia, which limit its clinical application. OBJECTIVES: We determined the effects of vitamin B6 adjunctive therapy on linezolid-associated cytopenias, and retrospectively studied 75 septic patients who received at least 7 days of linezolid treatment. METHODS: Patients were divided into a linezolid treatment group (LTG; n = 41) that received linezolid only and a combination treatment group (CTG; n = 34) that received both linezolid and vitamin B6. Each group was further subdivided into those with sepsis and those with severe sepsis. Each patient had red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), and platelet (PLT) measurements at baseline (day 0) and every other day for 2 weeks during treatment; these parameters were compared between the groups and assessed for time-dependent trends. RESULTS: For patients in the LTG, RBC, Hb, and Hct values showed statistically significant reductions over time, and these values were lower compared with the values in the CTG. The CTG also showed downward trends, except on the first day of treatment. The PLT count also decreased in both groups. Patients with severe sepsis had lower PLT counts in both treatment groups compared with the septic patients. CONCLUSIONS: Septic patients who received a combination treatment of linezolid and vitamin B6 might show positive effects for linezolid-associated reductions in some hematologic parameters (RBC, Hb, and Hct). This combined treatment might also slow PLT reduction, which was more evident in patients with severe sepsis. ClinicalTrials.gov identifier: NCT01295801.

[Assessment of prognostic and influencing factors in elderly patients with multiple organ dysfunction syndrome].

OBJECTIVE: To preliminarily assess the prognosis of patients with multiple organ dysfunction syndrome (MODSE) and analyze their influencing factors. METHODS: The clinical data of 365 MODSE patients admitted into Chinese PLA General Hospital during January 2009 to June 2012 were analyzed retrospectively. According to 28-day outcomes, they were divided into 2 groups (28-day survival and non-survival) while 4 groups according to age. Then these prognosis were evaluated with the current scoring systems ((acute physiology and chronic health evaluation II (APACHEII and III), sample acute physiological score (SAPSII) and multiple organ dysfunction score (MODS)). The predictive powers were compared by receiver operating characteristic (ROC) curve. Finally a binary Logistic regression analysis was performed to evaluate the relevant influencing prognostic factors of MODSE. RESULTS: The mean age was (77.8 ± 9.1) years, mean number of failed organs (3.6 ± 1.2) and a 28-day mortality 45.8%. The ages of non-survival group were older than those of survival group ((78.1 ± 9.1) vs (76.7 ± 11.0) years). The number of organ failures ((4.3 ± 1.1) vs (3.1 ± 1.0)) and scores (APACHEII: (28 ± 7) vs (20 ± 8), APACHE III: (106 ± 27) vs (75 ± 31), SAPSII: (64 ± 16) vs (46 ± 18), MODS: (9 ± 3) vs (6 ± 3)) of non-survivals were significantly higher than that of survivals. The area under ROC curve of these four score systems were 0.790, 0.781, 0.780 and 0.780 respectively. Compared to the above systems, SAPSII had the best performance in sensitivity while APACHEII was more valuable in specificity. All clinical data underwent binary Logistic regression and the results showed that plasma concentration of albumin and mean arterial pressure (MAP) offered beneficial outcomes while age and number of organ failures had unfavorable prognosis. The greater patient age, the higher their mortality. CONCLUSIONS: All four scoring systems have accurate prognostic predictions of MODSE patients. And the predictive power of APACHEII is the best. Plasma concentration of albumin, MAP, age and organ failure number are independent prognostic factors in MODSE patients.

[Protective effects of hepatocyte growth factor on hypoxic human pulmonary microvascular endothelial cells].

OBJECTIVE: To investigate the protective effects of hepatocyte growth factor (HGF) on hypoxic human pulmonary microvascular endothelial cells (HPMECs). METHODS: HPMECs were cultured in vitro, and the hypoxic model was established by the physical method. Cells were divided into 4 groups: the control group, the hypoxic group, HGF group, and phytohemagglutinin (PHA) group. The 7(th) generation of HPMECs was evaluated by the method of immunocytochemistry. The persistence rate of HPMECs was measured by MTT assay and the adhesive cells were counted by the microscopy. The expression of intercellular adhesion molecule-1 (ICAM-1) protein was determined by immunofluorescence staining. RESULTS: The adherence percentage of cells significantly decreased after hypoxia, whereas the expression of the ICAM-1 protein was significantly higher in the hypoxia group than in control group (P<0.01). Compared with the hypoxia group, the persistence and adherence percentage of cells in the HGF group significantly increased (P<0.01), whereas the expression of the ICAM-1 protein significantly dropped (P<0.01). In the PHA group, the persistence and adhesion rate were significantly different from those in the hypoxia group and HGF group (P<0.01), and the expression of the ICAM-1 protein increased significantly (P<0.01). CONCLUSION: HGF could inhibit the hypoxic damage of HPMECs by decreasing the persistence and the adhesive capacity of these cells and inducing the expression of ICAM-1.

Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study.

INTRODUCTION: We explored the diagnostic value of a urine soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for early sepsis identification, severity and prognosis assessment, and for secondary acute kidney injury (AKI). We compared this with white blood cell (WBC) counts, serum C-reactive protein (CRP), serum procalcitonin (PCT), urine output, creatinine clearance (CCr), serum creatinine (SCr), and blood urea nitrogen (BUN). METHODS: We enrolled 104 subjects admitted to the ICU: 16 cases with systemic inflammatory response syndrome (SIRS); 35 with sepsis and 53 with severe sepsis. Results for urine sTREM-1, WBC, serum CRP and serum PCT were recorded on days 1, 3, 5, 7, 10, and 14. For 17 sepsis cases diagnosed with secondary AKI, comparisons between their urine sTREM-1, urine output, CCr, SCr and BUN at diagnosis and 48 h before diagnosis were made. RESULTS: On the day of admission to the ICU, and compared with the SIRS group, the sepsis group exhibited higher levels of urine sTREM-1 and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) scores (P < 0.05). Areas under the curve (AUC) shaped by the scores were 0.797 (95% CI 0.711 to 0.884) and 0.722 (95% CI 0.586 to 0.858), respectively. On days 1, 3, 5, 7, 10, and 14, urine sTREM-1, serum PCT and WBC levels registered higher in the severe sepsis group in contrast to the sepsis group (P < 0.05). Urine sTREM-1 and serum PCT levels continuously increased among non-survivors, while WBC and serum CRP levels in both groups declined. For 17 patients with AKI, urine sTREM-1, SCr and BUN levels at 48 h before AKI diagnosis were higher, and CCr level was lower than those for non-AKI subjects (P < 0.05). AUC for urine sTREM-1 was 0.922 (95% CI 0.850 to 0.995), the sensitivity was 0.941, and the specificity was 0.76 (based on a cut-off point of 69.04 pg/ml). Logistic regression analysis showed that urine sTREM-1 and severity were risk factors related to AKI occurrence. CONCLUSIONS: Besides being non-invasive, urine sTREM-1 testing is more sensitive than testing WBC, serum CRP, and serum PCT for the early diagnosis of sepsis, as well as for dynamic assessments of severity and prognosis. It can also provide an early warning of possible secondary AKI in sepsis patients. TRIAL REGISTRATION: ClinicalTrial.gov identifier NCT01333657.

Acute respiratory distress syndrome: focusing on secondary injury.

ABSTRACT: Acute respiratory distress syndrome (ARDS) is one of the most common severe diseases seen in the clinical setting. With the continuous exploration of ARDS in recent decades, the understanding of ARDS has improved. ARDS is not a simple lung disease but a clinical syndrome with various etiologies and pathophysiological changes. However, in the intensive care unit, ARDS often occurs a few days after primary lung injury or after a few days of treatment for other severe extrapulmonary diseases. Under such conditions, ARDS often progresses rapidly to severe ARDS and is difficult to treat. The occurrence and development of ARDS in these circumstances are thus not related to primary lung injury; the real cause of ARDS may be the "second hit" caused by inappropriate treatment. In view of the limited effective treatments for ARDS, the strategic focus has shifted to identifying potential or high-risk ARDS patients during the early stages of the disease and implementing treatment strategies aimed at reducing ARDS and related organ failure. Future research should focus on the prevention of ARDS.

The effects of UCP2 on autophagy through the AMPK signaling pathway in septic cardiomyopathy and the underlying mechanism.

BACKGROUND: Mitochondrial dysfunction plays an important role in the development of septic cardiomyopathy. This study aimed to reveal the protective role of uncoupling protein 2 (UCP2) in mitochondria through AMP-activated protein kinase (AMPK) on autophagy during septic cardiomyopathy. METHODS: UCP2 knockout mice via a cecal ligation and puncture (CLP) model and the H9C2 cardiomyocyte cell line in response to lipopolysaccharide (LPS) in vitro were used to study the effect. The myocardial morphological alterations, indicators of mitochondrial injury and levels of autophagy-associated proteins (pAMPK, pmTOR, pULK1, pTSC2, Beclin-1, and LC3-I/II) were assessed. In addition, the mechanism of the interaction between UCP2 and AMPK was further studied through gain- and loss-of-function studies. RESULTS: Compared with the wild-type mice, the UCP2 knockout mice exhibited more severe cardiomyocyte injury after CLP, and the AMPK agonist AICAR protected against such injury. Consistent with this result, silencing UCP2 augmented the LPS-induced pathological damage and mitochondrial injury in the H9C2 cells, limited the upregulation of autophagy proteins and reduced AMPK phosphorylation. AICAR protected the cells from morphological changes and mitochondrial membrane potential loss and promoted autophagy. The silencing and overexpression of UCP2 led to correlated changes in the AMPK upstream kinases pLKB1 and CAMKK2. CONCLUSIONS: UCP2 exerts cardioprotective effects on mitochondrial dysfunction during sepsis via the action of AMPK on autophagy.

Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Induction and deduction in sepsis-induced cardiomyopathy: five typical categories.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The heart is one of the most important oxygen delivery organs, and dysfunction significantly increases the mortality of the body. Hence, the heart has been studied in sepsis for over half a century. However, the definition of sepsis-induced cardiomyopathy is not unified yet, and the conventional conception seems outdated: left ventricular systolic dysfunction (LVSD) along with enlargement of the left ventricle, recovering in 7 to 10 days. With the application of echocardiography in intensive care units, not only LVSD but also left ventricular diastolic dysfunction, right ventricular dysfunction, and even diffuse ventricular dysfunction have been seen. The recognition of sepsis-induced cardiomyopathy is gradually becoming complete, although our understanding of it is not deep, which has made the diagnosis and treatment stagnate. In this review, we summarize the research on sepsis-induced cardiomyopathy. Women and young people with septic cardiomyopathy are more likely to have LVSD, which may have the same mechanism as stress cardiomyopathy. Elderly people with ischemic cardiomyopathy and hypertension tend to have left ventricular diastolic dysfunction. Patients with mechanical ventilation, acute respiratory distress syndrome or other complications of increased right ventricular afterload mostly have right ventricular dysfunction. Diffuse cardiac dysfunction has also been shown in some studies; patients with mixed or co-existing cardiac dysfunction are more common, theoretically. Thus, understanding the pathophysiology of sepsis-induced cardiomyopathy from the perspective of critical care echocardiography is essential.

Rules of anti-infection therapy for sepsis and septic shock.

OBJECTIVE: Sepsis is a deadly infection that causes injury to tissues and organs. Infection and anti-infective treatment are the eternal themes of sepsis. The successful control of infection is a key factor of resuscitation for sepsis and septic shock. This review examines evidence for the treatment of sepsis. This evidence is combined with clinical experiments to reveal the rules and a standard flowchart of anti-infection therapy for sepsis. DATA SOURCES: We retrieved information from the PubMed database up to October 2018 using various search terms and their combinations, including sepsis, septic shock, infection, antibiotics, and anti-infection. STUDY SELECTION: We included data from peer-reviewed journals printed in English on the relationships between infections and antibiotics. RESULTS: By combining the literature review and clinical experience, we propose a 6Rs rule for sepsis and septic shock management: right patients, right time, right target, right antibiotics, right dose, and right source control. This rule encompasses rational decisions regarding the timing of treatment, the identification of the correct pathogen, the selection of appropriate antibiotics, the formulation of a scientifically based antibiotic dosage regimen, and the adequate control of infectious foci. CONCLUSIONS: This review highlights how to recognize and treat sepsis and septic shock and provides rules and a standard flowchart for anti-infection therapy for sepsis and septic shock for use in the clinical setting.

Critical hemodynamic therapy oriented resuscitation helping reduce lung water production and improve survival.

BACKGROUND: Increased extravascular lung water (EVLW) in shock is common in the critically ill patients. This study aimed to explore the effect of cardiac output (CO) on EVLW and its relevant influence on prognosis. METHODS: The hemodynamic data of 428 patients with pulse-indicated continuous CO catheterization from Department of Critical Care Medicine, Peking Union Medical College Hospital were retrospectively collected and analyzed. The patients were assigned to acute respiratory distress syndrome group, cardiogenic shock group, septic shock group, and combined shock (cardiogenic and septic) group according to their symptoms. Information on 28-day mortality and renal function was also collected. RESULTS: The CO and EVLW index (EVLWI) in the cardiogenic and combined shock groups were lower than those in the other groups (acute respiratory distress syndrome group vs. cardiogenic shock group vs. septic shock group vs. combined shock group: CO, 5.1 [4.0, 6.2] vs. 4.7 [4.0, 5.7] vs. 5.5 [4.3, 6.7] vs. 4.6 [3.5, 5.7] at 0 to 24 h, P = 0.009; 4.6 [3.8, 5.6] vs. 4.8 [4.1, 5.7] vs. 5.3 [4.4, 6.5] vs. 4.5 [3.8, 5.3] at 24 to 48 h, P = 0.048; 4.5 [4.1, 5.4] vs. 4.8 [3.8, 5.5] vs. 5.3 [4.0, 6.4] vs. 4.0 [3.2, 5.4] at 48 to 72 h, P = 0.006; EVLWI, 11.4 [8.7, 19.1] vs. 7.9 [6.6, 10.0] vs. 8.8 [7.4, 11.0] vs. 8.2 [6.7, 11.3] at 0 to 24 h, P < 0.001; 11.8 [7.7, 17.2] vs. 7.8 [6.3, 10.2] vs. 8.7 [6.6, 12.2] vs. 8.0 [6.6, 11.1] at 24 to 48 h, P < 0.001; and 11.3 [7.7, 18.7] vs. 7.5 [6.3, 10.0] vs. 8.8 [6.3, 12.2] vs. 8.4 [6.4, 11.2] at 48 to 72 h, P < 0.001. The trend of the EVLWI in the septic shock group was higher than that in the cardiogenic shock group (P < 0.05). Moreover, there existed some difference in the pulmonary vascular permeability index among the cardiogenic shock group, the septic shock group, and the combined shock group, without statistical significance (P > 0.05). In addition, there was no significant difference in tissue perfusion or renal function among the four groups during the observation period (P > 0.05). However, the cardiogenic shock group had a higher 28-day survival rate than the other three groups [log rank (Mantel-Cox) = 31.169, P < 0.001]. CONCLUSION: Tissue-aimed lower CO could reduce the EVLWI and achieve a better prognosis.

Vimentin modulates apoptosis and inflammatory cytokine release by a human monocytic cell line (THP-1) in response to lipopolysaccharides in vitro.

BACKGROUND: It has recently been recognized that serum vimentin is elevated in infectious diseases, and that vimentin plays a role in regulating neutrophils and macrophages associated inflammation. However, the mechanisms are unclear. This study was designed to explore the role of vimentin in regulating monocyte survival or apoptosis as well as inflammatory cytokine secretion in response to lipopolysaccharides (LPSs). METHODS: A human monocytic leukemia cell line (THP-1) was transfected with vimentin-specific small interfering RNA (siRNA) or vimentin over-expressing plasmid. Apoptosis was assessed by TdT-mediated dUTP Nick-End Labeling (TUNEL) and DNA content assay. Immunoblotting was performed to detect apoptosis-associated proteins. Cytokines (interleukin [IL]-6, IL-10, and tumor necrosis factor α [TNF-α]) were measured by enzyme-linked immuno sorbent assay. Two-way analysis of variance followed by Student's t test was used to compare means between different groups. RESULTS: Suppression of vimentin in THP-1 cells resulted in increased apoptotic response in the presence of LPS, while over-expression of vimentin could prevent the cells from apoptosis in response to LPS. LPS alone or suppression of vimentin resulted in significant up-regulation of caspase-3 (1.42 ±â€Š0.20 of LPS alone and 1.68 ±â€Š0.10 of vimentin suppression vs. control, t = 5.21 and 10.28, respectively, P < 0.05). In addition, pro-inflammatory cytokines (IL-6 and TNF-α) was significantly increased (IL-6: 577.90 ±â€Š159.90 pg/day/10 cells vs. 283.80 ±â€Š124.60 pg/day/10 cells of control, t = 14.76, P < 0.05; TNF-α: 54.10 ±â€Š5.80 vs. 17.10 ±â€Š0.10 pg/day/10 cells of control, t = 6.71, P < 0.05), while anti-inflammatory cytokine (IL-10) was significantly up-regulated in the THP-1 cells that over-expressed vimentin (140.9 ±â€Š17.2 pg/day/10 cells vs. undetectable in control cells). CONCLUSIONS: In summary, the vimentin may regulate innate immunity through modulating monocytes viability as well as inflammatory response in sepsis through shifting the balance of pro-inflammatory and anti-inflammatory cytokines.

Early initiation renal replacement therapy for fluid management to reduce central venous pressure is more conducive to renal function recovery in patients with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a serious complication in critically ill patients with septic shock treated in the intensive care unit. Renal replacement therapy (RRT) is a treatment for severe AKI; however, the time of initiation of RRT and factors that affect the recovery of kidney function remains unclear. This study was to explore whether early initiation of RRT treatment for fluid management to reduce central venous pressure (CVP) can help to improve patients' kidney function recovery. METHODS: A retrospective analysis of septic patients who had received RRT treatment was conducted. Patients received RRT either within 12 h after they met the diagnostic criteria of renal failure (early initiation) or after a delay of 48 h if renal recovery had not occurred (delayed initiation). Parameters such as patients' renal function recovery at discharge, fluid balance, and levels of CVP were assessed. RESULTS: A total of 141 patients were eligible for enrolment: 40.4% of the patients were in the early initiation group (57 of 141 patients), and 59.6% were in the delayed initiation group (84 of 141 patients). There were no significant differences in the characteristics at baseline between the two groups, and there were no differences in 28-day mortality between the two groups (χ = 2.142, P = 0.143); however, there was a significant difference in the recovery rate of renal function between the two groups at discharge (χ = 4.730, P < 0.001). More importantly, early initiation of RRT treatment and dehydration to reduce CVP are more conducive to the recovery of renal function in patients with AKI. CONCLUSION: Compared with those who received delayed initiation RRT, patients who received early-initiation RRT for dehydration to reduce CVP have enhanced kidney function recovery.

A cross-sectional study of acute cor pulmonale in acute respiratory distress syndrome patients in China.

BACKGROUND: Increased right ventricle afterload during acute respiratory distress syndrome (ARDS) may induce acute cor pulmonale (ACP), which is associated with a poor clinical outcome. Echocardiography is now considered as a rapid and non-invasive tool for diagnosis of ACP. The aims of this study were to investigate the morbidity and mortality rates of ACP in ARDS patients in intensive care units (ICUs) across the mainland of China and to determine the severity and prognosis of ACP in ARDS patients through an ultrasound protocol (TRIP). And the association between ACP related factors and the ICU mortality will be revealed. METHODS: This study is a multicenter and cross-sectional study in China which will include ICU participants when diagnosed as ARDS. The ultrasound protocol, known as the TRIP, is proposed as severity assessment for ACP, which includes tricuspid regurgitation velocity (T), right ventricular size (R), inferior vena cava diameter fluctuation (I), and pulmonary regurgitation velocity (P). The 28-day mortality, ICU/hospital mortality, the length of stay in ICU, mechanical ventilation days, hemodynamic parameters and lab parameters of liver function and kidney function are all recorded. DISCUSSION: This large-scale study would give a sufficient epidemic investigation of ACP in ARDS patients in China. In addition, with the TRIP protocol, we expect that we could stratify ACP with more echocardiography parameters. TRIAL REGISTRATION: NCT03827863, https://clinicaltrials.gov/ct2/show/NCT03827863.

Role of Combining Peripheral with Sublingual Perfusion on Evaluating Microcirculation and Predicting Prognosis in Patients with Septic Shock.

BACKGROUND: Measurement of general microcirculation remains difficult in septic shock patients. The peripheral perfusion index (PI) and sublingual microcirculation monitoring are thought to be possible methods. This study was performed to determine whether assessing microcirculation by PI and a new parameter, proportion of perfusion vessel change rate (△PPV) from sublingual microcirculation monitoring, can be associated with patients' outcome. METHODS: A prospective observational study was carried out, including 74 patients with septic shock in a mixed intensive care unit. Systemic hemodynamic variables were obtained at T0 and 6 h after (T6). PI and sublingual microcirculation indicators were obtained using a bedside monitor and a sidestream dark-field device, respectively. The t-test, analysis of variance, Mann-Whitney U-test, Kruskal-Wallis test, receiver operating characteristic curve analysis with the Hanley-McNeil test, survival curves using the Kaplan-Meier method, and the log-rank (Mantel-Cox) test were used to statistical analysis. RESULTS: Systemic hemodynamics and microcirculation data were obtained and analyzed. Patients were divided into two groups based on whether the first 6 h lactate clearance (LC) was ≥20%; PI and △PPV were lower at T6 in the LC <20% group compared with LC ≥20% (PI: 1.52 [0.89, 1.98] vs. 0.79 [0.44, 1,81], Z = -2.514, P = 0.012; △PPV: 5.9 ± 15.2 vs. 17.9 ± 20.0, t = -2.914, P = 0.005). The cutoff values of PI and △PPV were 1.41% and 12.1%, respectively. The cutoff value of the combined indicators was 1.379 according to logistic regression. Area under the curve demonstrated 0.709 (P < 0.05), and the sensitivity and specificity of using combined indicators were 0.622 and 0.757, respectively. Based on the PI and △PPV cutoff, all the participants were divided into the following groups: (1) high PI and high △PPV group, (2) high PI and low △PPV group, (3) low PI and high △PPV group, and (4) low PI and low △PPV group. The highest Sequential Organ Failure Assessment score (14.5 ± 2.9) was in the low PI and low △PPV group (F = 13.7, P < 0.001). Post hoc tests showed significant differences in 28-day survival rates among these four groups (log rank [Mantel-Cox], 20.931; P < 0.05). CONCLUSION: PI and △PPV in septic shock patients are related to 6 h LC, and combining these two parameters to assess microcirculation can predict organ dysfunction and 28-day mortality in patients with septic shock.

Accelerated Autophagy of Cecal Ligation and Puncture-Induced Myocardial Dysfunction and Its Correlation with Mammalian Target of Rapamycin Pathway in Rats.

BACKGROUND: Recent studies have indicated that autophagy is involved in sepsis-induced myocardial dysfunction. This study aimed to investigate the change of autophagy in cecal ligation and puncture (CLP)-induced myocardium dysfunction and its relationship with mammalian target of rapamycin (mTOR) pathway. METHODS: Totally, 12 rats were randomly divided into CLP group or sham-operated (SHAM) group. Cardiac tissues were harvested 18 h after CLP or sham operation. Pathology was detected by hematoxylin and eosin staining, cardiac functions by echocardiography, distribution of microtubule-associated protein light chain 3 type II (LC3II) by immunohistochemical staining, and autophagic vacuoles by transmission electron microscopy. Moreover, phosphorylation of mTOR (p-mTOR), phosphorylation of S6 kinase-1 (PS6K1), and LC3II and p62 expression were measured by western blotting. Pearson's correlation coefficient was used to analyze the correlation of two parameters. RESULTS: The results by pathology and echocardiography revealed that there was obvious myocardial injury in CLP rats (left ventricle ejection fraction: SHAM 0.76 ± 0.06 vs. CLP 0.59 ± 0.11, P < 0.01; fractional shortening: SHAM 0.51 ± 0.09 vs. CLP 0.37 ± 0.06, P < 0.05). We also found that the autophagy process was elevated by CLP, the ratio of LC3II/LC3I was increased (P < 0.05) while the expression of p62 was decreased (P < 0.05) in the CLP rats, and there were also more autophagosomes and autolysosomes in the CLP rats. Furthermore, the mTOR pathway in CLP myocardium was inhibited when compared with the sham-operated rats; p-mTOR (P < 0.01) and PS6K1 (P < 0.05) were both significantly suppressed following CLP challenge. Interestingly, we found that the mTOR pathway was closely correlated with the autophagy processes. In our study, while p-mTOR in the myocardium was significantly correlated with p62 (r = 0.66, P = 0.02), PS6K1 was significantly positively correlated with p62 (r = 0.70, P = 0.01) and negatively correlated with LC3II (r = -0.71, P = 0.01). CONCLUSIONS: The autophagy process in the myocardium was accelerated in CLP rats, which was closely correlated with the inhibition of the mTOR pathway.