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The clinical research in the field of extracorporeal life support (ECLS) in 2023 has focused on the efficacy of veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with infarct-related cardiogenic shock. Additionally, the research also explored the efficacy of prone positioning during veno-venous ECMO, transfusion strategies, and the impact of obesity on outcomes. Awake veno-venous ECMO has shown novel therapeutic potential, but its optimal practice methods and management strategies remain to be determined. In in-hospital cardiac arrest patients, extracorporeal cardiopulmonary resuscitation has demonstrated higher survival rates and better neurological recovery compared to conventional cardiopulmonary resuscitation. The effectiveness of extracorporeal carbon dioxide removal varies among patients with different types of respiratory failure. Future research should focus on optimizing the application strategies and process management of ECLS technologies, investigating personalized therapy, and studying how to improve long-term rehabilitation and quality of life for survivors.
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Coronaviruses are single-stranded RNA viruses that are common in animals. In the past 20 years, there have been three large-scale epidemics of coronaviruses, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease (COVID). Heart disease is an independent risk factor for severe COVID. At the same time, SARS-CoV-2 infection is often complicated with myocardial injury, which is closely related to poor prognosis. The receptors of SARS coronavirus are angiotensin-converting enzyme 2 (ACE2) and CD209L, among which ACE2 is the main receptor, and ACE2 is abundant in the heart. The receptor of MERS-coronavirus is dipeptide peptidase 4 (DPP4), which is not expressed in myocardial cells, but existed in vascular endothelial cells and blood. These receptors are important factors for the myocardial injury caused by coronavirus infection.
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Animals , COVID-19 , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , Endothelial Cells , Peptidyl-Dipeptidase A/geneticsABSTRACT
The global coronavirus disease 2019 epidemic is still in a pandemic state. Aging population with underlying diseases is prone to become severe, and have a higher mortality. The treatment capacity of the critical care department directly determines the treatment success rate of critical illness. At present, there is still a certain gap between domestic and foreign countries in intensive care unit (ICU), which is not only in the allocation of medical staff, but also in the beds and settings. The current medical model cannot fully meet the needs of development. The experience and lessons of many major public health emergencies suggested that " dual track of peace and war" approach in discipline construction of critical care is the best medical model. Following the concept of "combination of peace and war", strengthening the discipline construction of critical care department in municipal and district designated hospitals, allocating reasonable standard ICU, step-down ICU and combat readiness ICU, establishing rapid response team, and strengthening regular training and scientific management may be the key measures to deal with the epidemic.
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BACKGROUND@#Vancomycin treatment failure against vancomycin-susceptible gram-positive cocci is not rare in the intensive care unit (ICU). One of the reasons for this is the substandard drug trough concentration. We aimed to examine the hypothesis that the target serum concentration could be reached earlier with a loading dose of vancomycin.@*METHODS@#This retrospective cohort study was conducted at our ICU between June 2018 and June 2020 and involved patients who were suspected of having, or confirmed to have, gram-positive cocci infection and treated with vancomycin. One group of the patients was administered a loading dose of vancomycin (loading group) and compared with the group that did not receive a loading dose (control group). The baseline characteristics, vancomycin serum concentrations, and clinical outcomes were collected and analyzed.@*RESULTS@#Fifty-five patients were finally included, of which 29 received a loading dose of vancomycin. The serum concentration of vancomycin before the second dose was significantly higher for the loading group than for the control group (10.3 ± 6.1 mg/L vs. 5.7 ± 4.4 mg/L, P = 0.002). The results for both groups were similar before the fifth dose (12.4 ± 7.3 mg/L vs. 10.3 ± 6.3 mg/L in the loading and the control groups, respectively; P = 0.251). The 28-day mortality was lower for the loading group than for the control group (6.7% vs. 34.6% in the loading and control groups, respectively; P = 0.026). No significant differences were observed in serum creatinine (Cr) concentrations of the two groups.@*CONCLUSION@#With the loading dose of vancomycin, the target serum concentration of vancomycin may be reached earlier without increasing the risk of acute kidney injury.@*TRIAL REGISTRATION@#https://www.chictr.org.cn; ChiCTR2000035369.
Subject(s)
Humans , Anti-Bacterial Agents/therapeutic use , Creatinine , Intensive Care Units , Retrospective Studies , VancomycinABSTRACT
Prone position ventilation has become an important part of lung protective ventilation in acute respiratory distress syndrome (ARDS) patients. Timely and appropriate implementation can improve the mortality of such patients. The same is true for patients with critical coronavirus disease 2019 (COVID-19) patients, but safety assessment, control of implementation details and prevention of complications still need to be further standardized during the practical procedure of prone position ventilation. The purpose of this paper is to explain the specific requirements and key points of prone position ventilation in critical COVID-19 patients, in order to promote the application of prone position ventilation in the treatment of patients with critical COVID-19 and reduce the occurrence of related complications.
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ImportanceHeart injury can be easily induced by viral infection such as adenovirus and enterovirus. However, whether coronavirus disease 2019 (COVID-19) causes heart injury and hereby impacts mortality has not yet been fully evaluated. ObjectiveTo explore whether heart injury occurs in COVID-19 on admission and hereby aggravates mortality later. Design, Setting, and ParticipantsA single-center retrospective cohort study including 188 COVID-19 patients admitted from December 25, 2019 to January 27, 2020 in Wuhan Jinyintan Hospital, China; follow up was completed on February 11, 2020. ExposuresHigh levels of heart injury indicators on admission (hs-TNI; CK; CK-MB; LDH; -HBDH). Main Outcomes and MeasuresMortality in hospital and days from admission to mortality (survival days). ResultsOf 188 patients with COVID-19, the mean age was 51.9 years (standard deviation: 14.26; range: 21[~]83 years) and 119 (63.3%) were male. Increased hs-TnI levels on admission tended to occur in older patients and patients with comorbidity (especially hypertension). High hs-TnI on admission ([≥] 6.126 pg/mL), even within the clinical normal range (0[~]28 pg/mL), already can be associated with higher mortality. High hs-TnI was associated with increased inflammatory levels (neutrophils, IL-6, CRP, and PCT) and decreased immune levels (lymphocytes, monocytes, and CD4+ and CD8+ T cells). CK was not associated with mortality. Increased CK-MB levels tended to occur in male patients and patients with current smoking. High CK-MB on admission was associated with higher mortality. High CK-MB was associated with increased inflammatory levels and decreased lymphocytes. Increased LDH and -HBDH levels tended to occur in older patients and patients with hypertension. Both high LDH and -HBDH on admission were associated with higher mortality. Both high LDH and -HBDH were associated with increased inflammatory levels and decreased immune levels. hs-TNI level on admission was negatively correlated with survival days (r= -0.42, 95% CI= -0.64[~]-0.12, P=0.005). LDH level on admission was negatively correlated with survival days (r= -0.35, 95% CI= -0.59[~]-0.05, P=0.022). Conclusions and RelevanceHeart injury signs arise in COVID-19, especially in older patients, patients with hypertension and male patients with current smoking. COVID-19 virus might attack heart via inducing inflammatory storm. High levels of heart injury indicators on admission are associated with higher mortality and shorter survival days. COVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, because COVID-19 is never just confined to respiratory injury. Key pointsO_ST_ABSQuestionC_ST_ABSDoes coronavirus disease 2019 (COVID-19) cause heart injury and hereby impact mortality? FindingsIn this retrospective cohort study including 188 patients with COVID-19, patients with high levels of high-sensitivity cardiac troponin I (hs-TNI) on admission had significantly higher mortality (50.0%) than patients with moderate or low levels of hs-TNI (10.0% or 9.1%). hs-TNI level on admission was significantly negatively correlated with survival days (r= -0.42, 95% CI= -0.64[~]-0.12, P=0.005). MeaningCOVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, in order to maximally prevent or rescue heart injury-related mortality in COVID-19.
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Continuous renal replacement therapy (CRRT) has become an effective multiple organ support therapy instead of single renal replacement as initially expected, and it is widely used in intensive care unit (ICU). After the outbreak of coronavirus disease 2019 (COVID-19), a series of expert recommendation or consensus have been developed to diagnose and treat the disease, including CRRT in acute kidney injury (AKI) and hyper inflammatory response. However, CRRT in COVID-19 is extraordinarily different from regular one due to different pathophysiology and infectious clinical scenarios. Accordingly, the paper aims to elaborate the similarities and differences between CRRT in COVID-19 and routine treatment in terms of safety and accessibility, indications and timing, clinical operation, anticoagulation, fluid management, prevention and control of infectious diseases, etc.
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To investigate the value of renal resistive index (RRI) in early predictor and discriminator of severe acute pancreatitis (SAP)-related acute kidney injury (AKI). Methods A retrospective observational study was conducted. SAP patients complicated with AKI (within 1 week of onset) and admitted to intensive care unit (ICU) of Ruijin Hospital Shanghai Jiaotong University School of Medicine from January 2016 to June 2019 were enrolled. The RRI within 24 hours admission was measured. Clinical data such as acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), intra-abdominal pressure (IAP), arterial blood lactate (Lac), oxygenation index (PaO2/FiO2), base excess (BE), serum creatinine (SCr), urine output, norepinephrine (NE) and RRI were collected. Within 24 hours and 7 days after ICU admission, patients were grouped according to AKI classification criteria of Kidney Disease: Improving Global Outcomes (KDIGO), and the differences of relevant parameters were statistically analyzed. Influence factors of AKI grading were screened by Logistic regression analysis. Pearson correlation analysis was used to analyze the correlation between RRI and other parameters. The predictive value of RRI for AKI classification was analyzed by receiver operating characteristic (ROC) curve. Results A total 57 patients were included, with an average age of (54.6±13.5) years old, and APACHEⅡscore of 21.8±5.6. Within 24 hours, the number of patients suffered from stage 1-3 AKI were 19 (33.3%), 18 (31.6%) and 20 (35.1%), respectively. On day 7, the number of patients suffered from stage 0-3 AKI were 21 (36.9%), 8 (14.0%), 9 (15.8%) and 19 (33.3%), respectively. The higher APACHEⅡ score, CVP, IAP, Lac, NE dosage and RRI were found in the group with higher AKI grades, especially in the group with stage 3 AKI on day 7. RRI of patients with stage 3 AKI was significantly higher than that of patients with stage 1 and 2 AKI within 24 hours (0.74±0.04 vs. 0.65±0.05, 0.68±0.05, both P < 0.05). Similarly, RRI of patients with stage 2 and 3 AKI were significantly higher than that of patients with stage 0 and 1 AKI on day 7 (0.70±0.04, 0.74±0.04 vs. 0.65±0.05, 0.66±0.05, all P < 0.05). Multivariate Logistic regression analysis showed that RRI was an independent factor of AKI classification [odds ratio (OR) = 3.15, 95% confidence interval (95%CI) = 1.09-9.04, P < 0.05], and IAP and CVP also had significant impacts on AKI grading [OR value was 2.11 (95%CI = 1.16-4.22), 3.78 (95%CI = 1.21-12.90), both P < 0.05]. ROC curve analysis showed that the area under curve (AUC) of RRI for predicting AKI ≥2 stage was 0.87 (P < 0.05); the cut-off ﹥ 0.71, sensitivity was 71% and specificity was 83%. The correlation analysis showed that RRI was positively correlated to a certain extent with IAP and lactic acid (r1 = 0.49, r2 = 0.39, both P < 0.05). Conclusion High RRI on ICU admission was a significant predictor for development of severe AKI during the first week, and RRI can help predict the tendency of AKI in SAP.
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Objective To investigate the role and mechanism of ulinastatin on the hyper-permeability of vascular endothelial cell induced by matrix metalloproteinase-9 (MMP-9). Methods Human umbilical vein endothelial cells (HUVEC) were cultured in vitro to establish a complete monolayer vascular endothelial cell model. The monolayer vascular endothelial cells were randomly divided into three groups: blank control group [phosphate buffered saline (PBS) added], MMP-9 model group (1 mg/L MMP-9 added) and ulinastatin group (1 mg/L MMP-9 and 1 000 kU/L ulinastatin added). The permeability of monolayer vascular endothelial cells was measured by fluorescein isothiocyanate (FITC)-labeled dextran (FD40) leaking method; the soluble vascular endothelial cells calcium dependent adherin (VE-cadherin) concentration in culture solution was determined by enzyme linked immunosorbent assay (ELISA);the protein expression levels of zonular occlusion protein-1 or tight junction (ZO-1), VE-cadherin, claudin-5 were detected by Western Blot and immunofluorescence methods. Results Compared with the blank control group, the permeability of vascular endothelial cells in MMP-9 model group was significantly increased [(cm2/h, ×10-2):3.35±0.56 vs. 0.94±0.06, P < 0.05]; the concentrations of soluble VE-cadherin in the Transwell upper and lower chambers were increased significantly [upper chamber (μg/L): 5.02±0.40 vs. 3.83±0.42, lower chamber (μg/L):4.92±1.05 vs. 3.24±1.24, both P < 0.05]; the protein expression levels of ZO-1, VE-cadherin and claudin-5 were significantly decreased [ZO-1/β-actin: 0.152±0.067 vs. 0.262±0.090, VE-cadherin/β-actin: 0.137±0.048 vs. 0.246±0.094, claudin-5/β-actin: 0.148±0.062 vs. 0.336±0.119, all P < 0.05], and obvious rupture sites appeared in their fluorescent patterns, and fluorescent particles were significantly reduced; compared with MMP-9 model group, the permeability of vascular endothelial cells in ulinastatin group was significantly decreased [(cm2/h, ×10-2): 1.80±0.34 vs. 3.35±0.56, P < 0.05]; the soluble VE-cadherin concentrations were significantly reduced in upper and lower chambers than those in the MMP-9 model group [upper chamber (μg/L): 4.41±0.37 vs. 5.02±0.40, lower chamber (μg/L):3.85±1.04 vs. 4.92±1.05, both P < 0.05], the expressions of endothelial junction protein were significantly increased in ulinastatin group (ZO-1/β-actin: 0.229±0.097 vs. 0.152±0.067, VE-cadherin/β-actin: 0.236±0.089 vs. 0.137±0.048, claudin-5/β-actin: 0.262±0.101 vs. 0.148±0.062, all P < 0.05], and the continuity of their fluorescent patterns and fluorescent particles were both increased. Conclusion The in vitro experiment showed that the hyper-permeability of vascular endothelial cells induced by MMP-9 can be attenuated by ulinastatin through decreasing the destruction of VE-cadherin and maintaining the protein expression levels of ZO-1, VE-cadherin and claudin-5 in vascular endothelial cells.
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Intestinal?barrier?act?as?the?crucial?defender?against?pathogen?invasion,?and?is?indispensable?in?maintaining?tissue?homeostasis?both?locally?and?systemically.?Severe?disease?can?lead?to?impaired?intestinal?barrier.?In?addition?to?cause?a?variety?of?gastrointestinal?diseases,?intestinal?barrier?damage?can?also?worsen?the?disease?progression?in?critically?ill?patients.?Innate?lymphoid?cells?(ILCs)?is?a?group?of?newly?defined?innate?immune?cells?which?have?some?characteristics?as?adaptive?immune?cells.?Group?3?innate?lymphoid?cells?(ILC3),?which?mainly?reside?at?gut?associate?mucosal?tissue,?have?been?reported?to?play?a?critical?role?in?maintaining?intestinal?barrier?function.?After?a?brief?introduction?about?its?origination?and?classification,?we?will?focus?on?function?of?ILC3?physiologically?and?pathologically,?and?provide?a?new?theoretical?basis?for?maintaining?intestinal?barrier?function?under?pathological?conditions?in??this?review.
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Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.
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OBJECTIVE@#To investigate the diagnostic value of Hepcidin as a sepsis biomarker in critically ill adults.@*METHODS@#An observational study was conducted. The patients with suspected or proven infection admitted to intensive care unit (ICU) of Zhoupu Hospital Affiliated to Shanghai University of Medicine and Health Sciences from March 2016 to November 2017 were enrolled. According to the third international consensus definitions for sepsis and septic shock (Sepsis-3), the patients were divided into non-sepsis group and sepsis group, and the septic patients were subdivided into general sepsis subgroup and septic shock subgroup according to the severity of disease. The differences in serum Hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC), neutrophil granulocytes (NEUT) and lactic acid (Lac) within 1 hour after ICU admission between non-sepsis and sepsis groups and among the sepsis subgroups were compared. The acute physiology and chronic health evaluation II (APACHE II) within 24 hours after ICU admission and sequential organ failure score (SOFA) were recorded, and the mortality rate was followed up for 28 days. Receiver operation characteristic curve (ROC) was used to evaluate and compare the diagnostic value of Hepcidin and PCT, CRP, WBC for sepsis. Logistic regression model was used to estimate the association between Hepcidin and sepsis. Spearman correlation analysis was used to analyze the correlation between Hepcidin and other parameters of sepsis patients.@*RESULTS@#A total of 183 patients were enrolled, 93 in the non-sepsis group and 90 in the sepsis group (48 with general sepsis and 42 with septic shock). (1) The levels of Hepcidin, IL-6, TNF-α, PCT, Lac in serum, and APACHE II and SOFA scores in the sepsis group were significantly higher than those in the non-sepsis group. ROC analysis showed that the area under the ROC curve (AUC) of Hepcidin and PCT for sepsis diagnosis were 0.865 [95% confidence interval (95%CI) = 0.807-0.911] and 0.848 (95%CI = 0.788-0.897), respectively, without statistical significance (Z = 0.443, P = 0.657). Furthermore, the AUC of Hepcidin for sepsis diagnosis was significantly higher than that of the conventional biomarkers CRP and WBC [AUC was 0.530 (95%CI = 0.455-0.604) and 0.527 (95%CI = 0.452-0.601), respectively] with statistical significance (both P < 0.01). When Hepcidin > 54.00 μg/L, its sensitivity for sepsis diagnosis was 95.56%, specificity was 66.67%, positive and negative predictive value was 73.51% and 93.94%, respectively. Parallel test was conducted for combination of Hepcidin and PCT, which showed that the AUC was 0.885, and the sensitivity and negative predictive value was significantly improved to 98.96% and 98.36%, respectively. Logistic regression analysis demonstrated that after adjusted for PCT, Hepcidin > 54.00 μg/L was also associated with sepsis independently, with odds ratio (OR) of 1.011 (95%CI = 1.008-1.015, P < 0.001), indicating that Hepcidin and PCT were not completely overlapped in the diagnosis of sepsis. (2) With the increase in infection severity, serum Hepcidin, PCT, IL-6, TNF-α, Lac, APACHE II, SOFA score and 28-day mortality all showed an increasing trend in patients. There was a significantly positive correlation between Hepcidin and IL-6, TNF-α, PCT, APACHE II, and SOFA in the sepsis patients (r value was 0.526, 0.449, 0.591, 0.359, and 0.374, respectively, all P < 0.01), but no correlation was found between Hepcidin and Lac (r = 1.104, P > 0.05).@*CONCLUSIONS@#Serum Hepcidin is a useful biomarker for the diagnosis of sepsis, and it is correlated to the severity of the sepsis. The combination of Hepcidin and PCT can improve the accuracy of diagnosis of sepsis.@*CLINICAL TRIAL REGISTRATION@#China Clinical Trial Registration Center, ChiCTR-DDD-16008522.
Subject(s)
Adult , Humans , Biomarkers , C-Reactive Protein , Calcitonin , Calcitonin Gene-Related Peptide , China , Critical Illness , Hepcidins , Prognosis , Protein Precursors , ROC Curve , SepsisABSTRACT
Objective@#To investigate the diagnostic value of Hepcidin as a sepsis biomarker in critically ill adults.@*Methods@#An observational study was conducted. The patients with suspected or proven infection admitted to intensive care unit (ICU) of Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences from March 2016 to November 2017 were enrolled. According to the third international consensus definitions for sepsis and septic shock (Sepsis-3), the patients were divided into non-sepsis group and sepsis group, and the septic patients were subdivided into general sepsis subgroup and septic shock subgroup according to the severity of disease. The differences in serum Hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC), neutrophil granulocytes (NEUT) and lactic acid (Lac) within 1 hour after ICU admission between non-sepsis and sepsis groups and among the sepsis subgroups were compared. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) within 24 hours after ICU admission and sequential organ failure score (SOFA) were recorded, and the mortality rate was followed up for 28 days. Receiver operation characteristic curve (ROC) was used to evaluate and compare the diagnostic value of Hepcidin and PCT, CRP, WBC for sepsis. Logistic regression model was used to estimate the association between Hepcidin and sepsis. Spearman correlation analysis was used to analyze the correlation between Hepcidin and other parameters of sepsis patients.@*Results@#A total of 183 patients were enrolled, 93 in the non-sepsis group and 90 in the sepsis group (48 with general sepsis and 42 with septic shock).① The levels of Hepcidin, IL-6, TNF-α, PCT, Lac in serum, and APACHEⅡand SOFA scores in the sepsis group were significantly higher than those in the non-sepsis group. ROC analysis showed that the area under the ROC curve (AUC) of Hepcidin and PCT for sepsis diagnosis were 0.865 [95% confidence interval (95%CI) = 0.807-0.911] and 0.848 (95%CI = 0.788-0.897), respectively, without statistical significance (Z = 0.443, P = 0.657). Furthermore, the AUC of Hepcidin for sepsis diagnosis was significantly higher than that of the conventional biomarkers CRP and WBC [AUC was 0.530 (95%CI = 0.455-0.604) and 0.527 (95%CI = 0.452-0.601), respectively] with statistical significance (both P < 0.01). When Hepcidin > 54.00 μg/L, its sensitivity for sepsis diagnosis was 95.56%, specificity was 66.67%, positive and negative predictive value was 73.51% and 93.94%, respectively. Parallel test was conducted for combination of Hepcidin and PCT, which showed that the AUC was 0.885, and the sensitivity and negative predictive value was significantly improved to 98.96% and 98.36%, respectively. Logistic regression analysis demonstrated that after adjusted for PCT, Hepcidin > 54.00 μg/L was also associated with sepsis independently, with odds ratio (OR) of 1.011 (95%CI = 1.008-1.015, P < 0.001), indicating that Hepcidin and PCT were not completely overlapped in the diagnosis of sepsis. ② With the increase in infection severity, serum Hepcidin, PCT, IL-6, TNF-α, Lac, APACHEⅡ, SOFA score and 28-day mortality all showed an increasing trend in patients. There was a significantly positive correlation between Hepcidin and IL-6, TNF-α, PCT, APACHEⅡ, and SOFA in the sepsis patients (r value was 0.526, 0.449, 0.591, 0.359, and 0.374, respectively, all P < 0.01), but no correlation was found between Hepcidin and Lac (r = 1.104, P > 0.05).@*Conclusions@#Serum Hepcidin is a useful biomarker for the diagnosis of sepsis, and it is correlated to the severity of the sepsis. The combination of Hepcidin and PCT can improve the accuracy of diagnosis of sepsis.@*Clinical trial registration@#China Clinical Trial Registration Center, ChiCTR-DDD-16008522.
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Objective To observe apoptosis and proliferation of intestinal epithelial cells and to explore the mechanism of protective effects of rhubarb monomers on intestinal epithelial cells in septic rats.Methods Eighty male Sprague-Dawley (SD) rats (230-250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP).After surgical preparation,rats were randomly (ramdom number) divided into 8 groups (n =10 each):a sham group (A) [normal saline (NS) gavage];a sepsis group (B) (NS gavage);group C (ip dexamethasone 0.5 mg/kg immediately after CLP) (C);and rhubarb monomer 100 mg/kg in NS treated groups including:rhein group (D),emodin group (E),3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid group (F),1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose group (G),and 3,8-dihydroxy-1-methyl-anthraquione group (H).Animals were sacrificed 24 hrs after treatment.Intestinal histopathology,apoptosis (TUNEL) and proliferation of intestinal epithelial cells (proliferating cell nuclear antigen,PCNA) were measured.Multiple comparisons were carried out with one-way analysis of variance (ANOVA).Results Histopathology revealed injury to the intestinal mucosal villi induced by sepsis in group B compared with group A.The injury was significantly ameliorated in groups C,D,E,F,G,and H compared with group B.The apoptosis index in group B was significantly higher than that in group A (P < 0.05) and the apoptosis index in groups C,D,E,F,G,and H was significantly lower than that in group B (P < 0.05).The PCNA positive index in group B was significantly lower than that in group A (P < 0.05),but was significantly higher in groups C,D,E,F,G,and H than that in group B (P < 0.05).Conclusion Rhubarb monomers can promote the proliferation of mucosal cells and prevent apoptosis of intestinal mucosal cells.In addition,rhubarb monomers may play a role in protecting the intestinal barrier function.
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ObjectiveTo investigate the correlation between procalcitonin (PCT), C-reactive protein (CRP) and acute physiology and chronic health evaluationⅡ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score, and to investigate the value in assessment of PCT and CRP in prognosis in patients with sepsis.Methods Clinical data of patients admitted to intensive care unit (ICU) of Changzheng Hospital Affiliated to the Second Military Medical University from January 2011 to June 2014 were retrospectively analyzed. 201 sepsis patients who received PCT and CRP tests, and evaluation of APACHEⅡ score and SOFA score were enrolled. The values of PCT, CRP, APACHEⅡ score and SOFA score between survivals (n = 136) and non-survivals (n = 65) were compared. The values of PCT and CRP among groups with different APACHEⅡ scores and SOFA scores were compared. The relationships between PCT, CRP and APACHEⅡ score and SOFA score were analyzed by Spearman correlation analysis. Receiver operating characteristic (ROC) curve was plotted to assess the prognostic value of PCT and CRP for prognosis of patients with sepsis.Results Compared with survival group, the values of PCT [μg/L: 11.03 (19.17) vs. 1.39 (2.61), Z= -4.572,P 20, the value of PCT was 1.45 (2.62), 1.96 (9.04), and 7.41 (28.9)μg/L, respectively, and the value of CRP was 57.50 (83.40), 59.00 (119.70), and 77.60 (120.00) mg/L, respectively. When SOFA score was 0-5, 6-10, and> 10, the value of PCT was respectively 1.43 (3.09), 3.41 (9.75), and 5.43 (29.60)μg/L, and the value of CRP was 49.30 (86.20), 76.00 (108.70), and 75.60 (118.10) mg/L, respectively. There was significant difference in PCT between any two groups with different APACHEⅡ and SOFA scores (P< 0.05 orP<0.01), but no significant differences in CRP were found. The area under the ROC curve (AUC) of PCT for prognosis was significantly greater than that of CRP [0.872 (95% confidence interval 0.811-0.943) vs. 0.512 (95% confidence interval 0.427-0.612),P< 0.001]. When the cut-off value of PCT was 3.36μg/L, the sensitivity was 66.8%, and the specificity was 45.4%. When the cut-off value of CRP was 44.50 mg/L, the sensitivity was 82.2%, and the specificity was 80.3%.Conclusions Compared with CRP, PCT was more significantly correlated with APACHEⅡ score and SOFA score. PCT can be a better indicator for evaluation of degree of severity, and also prognosis in sepsis patients.
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<p><b>BACKGROUND</b>Surfactant protein A (SP-A) contributes to the regulation of sepsis-induced acute lung injury. In a previous study, we demonstrated the expression and localization of SP-A in the kidneys. The present study evaluated the effect of SP-A on lipopolysaccharide (LPS)-induced tumor necrosis factor-a (TNF-α) expression and its underlying mechanisms in the human renal tubular epithelial (HK-2) cells.</p><p><b>METHODS</b>Indirect immunofluorescence assay was used to detect SP-A distribution and expression in HK-2 cells. HK-2 cells were treated with various concentrations of LPS (0, 0.1, 1, 2, 5, and 10 mg/L) for 8 hours and with 5 mg/L LPS for different times (0, 2, 4, 8, 16, and 24 hours) to determine the effects of LPS on SP-A and TNF-α expression. Then, HK-2 cells were transfected with SP-A siRNA to analyze nuclear factor κB (NF-κB) P65 and TNF-α expression of HK-2 cells after LPS-treatment.</p><p><b>RESULTS</b>Indirect immunofluorescence assay revealed that SP-A is localized to the membrane and cytoplasm of HK-2 cells. Interestingly, SP-A1/SP-A2 and TNF-a expression were found to be significantly increased in HK-2 cells upon LPS treatment. Transfection of LPS-treated HK-2 cells with SP-A siRNA resulted in significant increases in the levels of NF-κB P65 protein and TNF-α mRNA and protein compared to those in non-transfected LPS-treated HK-2 cells.</p><p><b>CONCLUSION</b>SP-A plays an important role in protecting cells against sepsis-induced acute kidney injury by inhibiting NF-κB activity to modulate LPS-induced increase in TNF-α expression.</p>
Subject(s)
Humans , Cell Line , Epithelial Cells , Cell Biology , Metabolism , Fluorescent Antibody Technique, Indirect , Kidney Tubules, Proximal , Cell Biology , Lipopolysaccharides , Pharmacology , Pulmonary Surfactant-Associated Protein A , Metabolism , Pharmacology , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
<p><b>BACKGROUND</b>Comorbidity is one of the most important determinants of short-term and long-term outcomes in septic patients. Charlson's weighted index of comorbidities (WIC) and the chronic health score (CHS), which is a component of the acute physiology and chronic health evaluation (APACHE) II, are two frequently-used measures of comorbidity. In this study, we assess the performance of WIC and CHS in predicting the hospital mortality of intensive care unit (ICU) patients with sepsis.</p><p><b>METHODS</b>A total of 338 adult patients with sepsis were admitted to a multisystem ICU between October 2010 and August 2012. Clinical data were collected, including age, gender, underlying diseases, key predisposing causes, severity-of-sepsis, and hospital mortality. The APACHE II, CHS, acute physiology score (APS), sequential organ failure assessment (SOFA) and WIC scores were assessed within the first 24 hours of admission. Univariate and multiple Logistic regression analyses were used to compare the performance of WIC and CHS. The area under the receiver operating characteristic curve (AUC) was used to predict hospital mortality over classes of risk.</p><p><b>RESULTS</b>Of all the enrolled patients, 224 patients survived and 114 patients died. The surviving patients had significantly lower WIC, CHS, APACHE II, and SOFA scores than the non-surviving patients (P < 0.05). Combining WIC or CHS with other administrative data showed that the hospital mortality was significantly associated with age, severe sepsis, key predisposing causes such as pneumonia, a history of underlying diseases such as hypertension and congestive cardiac failure, and WIC, CHS and APS scores (P < 0.05). The AUC for the hospital mortality were 0.564 (95% confidence interval (CI) 0.496-0.631) of CHS, 0.663 (95% CI 0.599-0.727) of WIC, 0.770 (95% CI 0.718-0.822) of APACHE II, 0.856 (95% CI 0.815-0.897) of the CHS combined with other administrative data, and 0.857 (95% CI 0.817-0.897) of the WIC combined with other administrative data. The diagnostic value of WIC was better than that of CHS (P = 0.0015).</p><p><b>CONCLUSIONS</b>The WIC and CHS scores might be independent determinants for hospital mortality among ICU patients with sepsis. WIC might be an even better predictor of the mortality of septic patients with comorbidities than CHS.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , APACHE , Comorbidity , Organ Dysfunction Scores , Sepsis , Mortality , Pathology , Severity of Illness IndexABSTRACT
Objective To predict the risk of 28-day mortality in septic patients in intensive care unit (ICU) with the combination of Weighted index of comorbidities (WIC) and sepsis-related organ failure assessment (SOFA) score.Methods The clinical data of adult severe sepsis/septic shock patients in Department of Emergency Medicine of Changzheng Hospital and Department of Critical Care Medicine of Jinan Military General Hospital from October 2011 to February 2013 were analyzed retrospectively.The etiological factor,past history,having severe sepsis or not were recorded.Age score,WIC score,acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and SOFA score were calculated at or 24 hours after admission.The logistic regression was used and the receiver operating characteristic curve (ROC curve) was drawn to calculate the patients' outcome.Results In 310 enrolled patients,223 (71.9%) patients survived and 87 (28.1%) died.Univariate analysis showed that the P values of the age score,WIC score,APACHE Ⅱ score and SOFA score,chronic cardiac insufficiency,type 2 diabetes,cerebrovascular disease,tumor,multiple injury,pulmonary infection and having severe sepsis or not were all less than 0.2.The above 11 variables were put into the multivariate logistic regression equation 1,of which predicted probability was reserved.It revealed that 5 variables were independently associated with 28-day prognosis,of which influence power in descending order were SOFA score [odds ratio (OR) =1.308,95% confidence interval (95% CI):1.158-1.478,P=0.000],having severe sepsis or not (OR =0.206,95% CI:0.100-0.424,P=0.000),APACHE Ⅱ score (OR =1.090,95%CI:1.021-1.164,P=0.010),WICscore (OR=1.441,95%CI:1.067-1.947,P=0.017),agescore (OR=1.228,95%CI:1.027-1.468,P=0).024),the Walswere 18.554,18.369,6.725,5.662,5.067,respectively.The 3 variables,age score,WIC score and SOFA score,were brought into the multivariate logistic regression equation 2,of which predicted probability was reserved too.It revealed that age score (OR=1.330,95%CI:1.145-1.546,P=0.000),WIC score (OR =1.496,95% CI:1.145-1.546,P=0.000) and SOFA score (OR =1.429,95% CI:1.303-1.567,P=0.000),were independently associated with the septic patients' 28-day prognosis.There was no significant difference in the area under receiver operating characteristic curve (AUC) between the SOFA score and APACHE Ⅱ score (0.784 vs.0.780,Z=0.014,P=0.989).However,compared with APACHE Ⅱ score,the AUC of equation 1 (0.888) and 2 (0.851) were much more (Z=4.333,P=0.000; Z=2.669,P=0.008).Conclusion The sensitivity of 28-day prognosis by WIC score was improved greatly with the combination of SOFA score and age score.
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Objective To investigate the effects of rhubarb on the expression of glucocorticoids receptor (GR)and peripheral blood lymphocytes in burning-induced septic rats. Methods Sixty-six male healthy Sprague-Dawley(SD)rats were randomly divided into sham operated control group(n=18),sepsis model group(n=24) and rhubarb treatment group(n=24),each group was further randomly divided into 12,24 and 72 hours subgroups according to different time points. The model of scald sepsis was replicated by scald injury induced by boiling water at the rat back accounting for 30% total body surface area(Ⅲ grade of scald),and administration of endotoxin (5 mg/kg)into the peritoneal cavity 12 hours after scald injury. After the successful establishment of septic models, the rats in the rhubarb treatment group were immediately infused with 50 mg/kg rhubarb powder dissolved in 1 mL saline through a gastric tube,while the rats in sham operated control group and sepsis model group received saline by the same way as a substitute for rhubarb. The the binding capacity of GR of peripheral blood leucocyte and binding activity of GR of hepatocyte were analyzed by radiation ligands binding assay. The CD4+,CD8+as well as CD4+/CD8+ ratio in peripheral blood lymphocytes were detected by flow cytometer. Results The binding capacity of GR of peripheral blood leucocyte and binding activity of GR of hepatocyte were significantly decreased in a time-dependent manner in sepsis model group compared to those of the sham operated control group,while in the rhubarb treatment group they were increased in a time-dependent manner after interference of rhubarb, and they were higher than those in the model group at the same time points〔leukocyte GR binding capacity (locus/cell)at 12,24,72 hours :1 515.38±300.44,1 859.63±258.26,1 890.50±307.88 vs. 1 122.63±225.39, 1 008.88±150.41,724.38±91.19;hepatocyte GR binding capacity(fmol/mg):210.19±26.26,258.01±20.98, 283.38±38.21 vs. 153.11±30.07, 129.83±26.89, 94.08±14.30, all P<0.01〕. Compared with the sham operated control group,the CD4+ and CD8+ were decreased in various degrees at 12 hours and 24 hours in the septic group, at 24 hours the differences being statistically significant (P<0.01 and P<0.05). CD4+/CD8+ratios were decreased significantly at all time points,the differences were statistically significant at 24 hours and 72 hours(both P<0.01). The CD4+ T cell and CD4+/CD8+ ratio at all the time points were increased at various degrees in the rhubarb treatment group,and the differences from those in the sepsis model group at 24 hours and 72 hours were statistically significant (1.58±0.69, 1.56±0.49 vs. 1.02±0.41, 1.01±1.68, both P<0.01). Conclusion Rhubarb can modulate the binding capacity of GR of peripheral blood leucocyte and the binding activity of GR of hepatocyte,and via its influence on the number of peripheral leucocytes,the immune dysfunction in the sepsis processes is improved.
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Objective To estimate the validity of Charlson' s weighted index of comorbidities (WIC) used to predicting 28-day mortality among ICU pneumonia patients with underlying diseases.Methods Aretrospective analysis of 160 adult patients with pneumonia admitted to a multi-discipline ICU of Shanghai Changzheng hospital between October 2010 and February 2012 was carried out.Clinical data were collected including age,gender,community acquired pneumonia (CAP) or hospital acquired pneumonia (HAP),underlying diseases,severity-of-sepsis,and 28-day mortality.WIC scores,acute physiology and chronic health evaluation (APACHE) Ⅱ,and sepsis related organ failure assessment (SOFA) were assessed within the first 24 hours after admission.Logistic regression analyses were used to evaluate the predictors for outcome.The receiver operating characteristic curve (ROC) was used to compare the performance of these scores between different methods.Results Of 160 enrolled patients,76 (48.8%) were CAP,82 (51.2%) HAP,and 106 (66.3%) male,54 (33.7%) female,and 99 (61.9%) patients survived and 61 (38.1%) died.The average age was (62.4 ± 17.3) years old.Compared with survivors,WIC,APACHE Ⅱ and SOFA scores were significantly higher in death group (P < 0.05).The multivariate logistic regression revealed that risk of death depends predominantly on age (OR =1.049,95% CI:1.011-1.088,P =0.011),WIC (OR =1.725,95% CI:1.194-2.492,P =0.004),APACHE Ⅱ score (OR =1.175,95%CI:1.058-1.305,P =0.003),SOFA score (OR =1.277,95% CI:1.048-1.556,P =0.015),presence of ARDS (OR =0.081,95% CI:0.008-0.829,P =0.034),and complicated with severe sepsis (OR =0.149,95% CI:0.232-0.622,P =0.004).The area under the receiver operating characteristics curve in predicting mortality was 0.639 (0.547-0.730) for the WIC,0.782 (0.709-0.856) for APACHE Ⅱ score,0.79 (0.714-0.866) for SOFA score and 0.842 (0.777-0.907) for the merger of three.Conclusions In pneumonia patients of ICU,WIC is a useful approach to predicting 28-day mortality,and the risk of death significantly depends on co-morbidities.