Combined Age with Mean Decrease Rates of Total Bilirubin and MELD Score as a Novel and Simple Clinical Predictor on 90-Day Transplant-Free Mortality in Adult Patients with Acute Liver Failure Undergoing Plasma Exchange: A Single-Center Retrospective Study.

Background: Acute liver failure (ALF), previously known as fulminant hepatic failure, has become a common, rapidly progressive, and life-threatening catastrophic hepatic disease in intensive care unit (ICU) due to the continuous increase in drug abuse, viral infection, metabolic insult, and auto-immune cause. At present, plasma exchange (PE) is the main effective alternative treatment for ALF in ICU clinical practice, and high-volume plasma exchange (HVP) has been listed as a grade I recommendation for ALF management in the American Society for Apheresis (ASFA) guidelines. However, no existing models can provide a satisfactory performance for clinical prediction on 90-day transplant-free mortality in adult patients with ALF undergoing PE. Our study aims to identify a novel and simple clinical predictor of 90-day transplant-free mortality in adult patients with ALF undergoing PE. Methods: This retrospective study contained adult patients with ALF undergoing PE from the Medical ICU (MICU) in the Second Affiliated Hospital of Harbin Medical University between January 2017 and December 2020. Baseline and clinical data were collected and calculated on admission to ICU before PE, including gender, age, height, weight, body mass index (BMI), etiology, total bilirubin, direct bilirubin, indirect bilirubin, prothrombin activity, model for end-stage liver disease (MELD) score, and sequential organ failure assessment (SOFA) score. Enrolled adult patients with ALF undergoing PE were divided into a survival group and a death group at discharge and 90 days on account of medical records and telephone follow-up. After each PE, decreased rates of total bilirubin and MELD score and increased rates of prothrombin activity were calculated according to the clinical parameters. In clinical practice, different patients underwent different times of PE, and thus, mean decrease rates of total bilirubin and MELD score and mean increase rate of prothrombin activity were obtained for further statistical analysis. Results: A total of 73 adult patients with ALF undergoing 204 PE were included in our retrospective study, and their transplant-free mortality at discharge and 90 days was 6.85% (5/73) and 31.51% (23/73), respectively. All deaths could be attributed to ALF-induced severe and life-threatening complications or even multiple organ dysfunction syndrome (MODS). Most of the enrolled adult patients with ALF were men (76.71%, 56/73), with a median age of 48.77 years. Various hepatitis virus infections, unknown etiology, auto-immune liver disease, drug-induced liver injury, and acute pancreatitis (AP) accounted for 75.34%, 12.33%, 6.85%, 4.11%, and 1.37% of the etiologies in adult patients with ALF, respectively. Univariate analysis showed a significant difference in age, mean decrease rates of total bilirubin and MELD score mean increase rate of prothrombin activity, decrease rates of total bilirubin and MELD score, and increase rate of prothrombin activity after the first PE between the death group and survival group. Multivariate analysis showed that age and mean decrease rates of total bilirubin and MELD score were closely associated with 90-day transplant-free mortality in adult patients with ALF undergoing PE. The 90-day transplant-free mortality was 1.081, 0.908, and 0.893 times of the original value with each one-unit increase in age and mean decrease rates of total bilirubin and MELD score, respectively. The areas under the receiver operatingcharacteristic (ROC) curve of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 0.689, 0.225, 0.123, and 0.912, respectively. The cut-off values of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 61.50, 3.12, 1.21, and 0.33, respectively. The specificity and sensitivity of combined age with mean decrease rates of total bilirubin and MELD score for predicting 90-day transplant-free mortality in adult patients with ALF undergoing PE were 87% and 14%. Conclusion: Combined age with mean decrease rates of total bilirubin and MELD score as a novel and simple clinical predictor can accurately predict 90-day transplant-free mortality in adult patients with ALF undergoing PE, which is worthy of application and promotion in clinical practice, especially in the identification of potential transplant candidates.

A Standardized Step-by-Step Approach for the Diagnosis and Treatment of Sepsis.

Sepsis is the major culprit of death among critically ill patients who are hospitalized in intensive care units (ICUs). Although sepsis-related mortality is steadily declining year-by-year due to the continuous understanding of the pathophysiological mechanism on sepsis and improvement of the bundle treatment, sepsis-associated hospitalization is rising worldwide. Surviving Sepsis Campaign (SSC) guidelines are continuously updating, while their content is extremely complex and comprehensive for a precisely implementation in clinical practice. As a consequence, a standardized step-by-step approach for the diagnosis and treatment of sepsis is particularly important. In the present study, we proposed a standardized step-by-step approach for the diagnosis and treatment of sepsis using our daily clinical experience and the latest researches, which is close to clinical practice and is easy to implement. The proposed approach may assist clinicians to more effectively diagnose and treat septic patients and avoid the emergence of adverse clinical outcomes.

Effects of acute kidney injury on acute pancreatitis patients' survival rate in intensive care unit: A retrospective study.

BACKGROUND: Acute kidney injury (AKI) is one of the most common acute pancreatitis (AP)-associated complications that has a significant effect on AP, but the factors affecting the AP patients' survival rate remains unclear. AIM: To assess the influences of AKI on the survival rate in AP patients. METHODS: A total of 139 AP patients were included in this retrospective study. Patients were divided into AKI group (n = 72) and non-AKI group (n = 67) according to the occurrence of AKI. Data were collected from medical records of hospitalized patients. Then, these data were compared between the two groups and further analysis was performed. RESULTS: AKI is more likely to occur in male AP patients (P = 0.009). AP patients in AKI group exhibited a significantly higher acute physiologic assessment and chronic health evaluation II score, higher Sequential Organ Failure Assessment score, lower Glasgow Coma Scale score, and higher demand for mechanical ventilation, infusion of vasopressors, and renal replacement therapy than AP patients in non-AKI group (P < 0.01, P < 0.01, P = 0.01, P = 0.001, P < 0.01, P < 0.01, respectively). Significant differences were noted in dose of norepinephrine and adrenaline, duration of mechanical ventilation, maximum and mean values of intra-peritoneal pressure (IPP), maximum and mean values of procalcitonin, maximum and mean serum levels of creatinine, minimum platelet count, and length of hospitalization. Among AP patients with AKI, the survival rate of surgical intensive care unit and in-hospital were only 23% and 21% of the corresponding rates in AP patients without AKI, respectively. The factors that influenced the AP patients' survival rate included body mass index (BMI), mean values of IPP, minimum platelet count, and hospital day, of which mean values of IPP showed the greatest impact. CONCLUSION: AP patients with AKI had a lower survival rate and worse relevant clinical outcomes than AP patients without AKI, which necessitates further attention to AP patients with AKI in surgical intensive care unit.

Mechanisms of Renal-Splenic Axis Involvement in Acute Kidney Injury Mediated by the α7nAChR-NF-κB Signaling Pathway.

This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the α7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the α7nAChR-NF-κB signaling pathway and is involved in the development of AKI.

Effect of initiation of renal replacement therapy on mortality in acute pancreatitis patients.

This study aims to explore effect of initiation of renal replacement therapy (RRT) on mortality in acute pancreatitis (AP) patients. In this study, a total of 92 patients from the surgical intensive care unit (SICU) of the Second Affiliated Hospital of Harbin Medical University who were diagnosed with AP and underwent RRT or not between January 2014 and December 2018 were included in this retrospective study. Demographic and clinical data were obtained on admission to SICU. Patients were divided into early initiation of RRT group (n = 44) and delayed initiation of RRT group (n = 48). Duration of mechanical ventilation (MV), intra-peritoneal pressure, vasopressors infusion, body temperature, procalcitonin, creatinine, platelet counts, length of hospital stay and prognosis were recorded during hospitalization, and then compared between groups. Patients with delayed initiation of RRT exhibited significantly higher APACHE II score, SOFA score and lower GCS score than those with early initiation of RRT (P < 0.001, <0.001,  = 0.04, respectively). No difference in the rest of the baseline data and vasopressors infusion was found. Dose of Norepinephrine, maximum and mean PCT, maximum and mean creatinine, maximum and mean intra-peritoneal pressure, length of hospital stay, prognosis of ICU and hospitalization showed significant difference between groups. Early initiation of RRT may be beneficial for AP patients, which can provide some insight and support for patients' treatment in clinic.

Clinical characteristics of patients with COVID-19 presenting with gastrointestinal symptoms as initial symptoms: Retrospective case series.

BACKGROUND: A large number of pneumonia cases due to coronavirus disease 2019 (COVID-19) have been first reported in China. Meanwhile, the virus is sweeping all around the world and has infected millions of people. Fever and pulmonary symptoms have been noticed as major and early signs of infection, whereas gastrointestinal symptoms were also observed in a significant portion of patients. The clinical investigation of disease onset was underestimated, especially due to the neglection of cases presenting with gastrointestinal symptoms. AIM: To characterize the clinical features of coronavirus-infected patients with gastrointestinal symptoms as initial symptoms. METHODS: This is a retrospective, single-center case series of the general consecutive hospitalized patients with confirmed COVID-19 at Wuhan Union Hospital from February 2, 2020 to February 13, 2020. According to their initial symptoms, these patients were classified into two groups. Patients in group one presented with pulmonary symptoms (PS) as initial symptoms, and group two presented with gastrointestinal symptoms (GS). Epidemiological, demographic, clinical, laboratory, and treatment data were collected for analysis. RESULTS: Among the 50 patients recruited, no patient has been admitted to intensive care units, and no patient died during the study. The duration of hospitalization was longer in the GS group than in the PS group (12.13 ± 2.44 vs 10.00 ± 2.13, P < 0.01). All of the 50 patients exhibited decreased lymphocytes. However, lymphocytes in the GS group were significantly lower compared to those in the PS group (0.94 ± 0.06 vs 1.04 ± 0.15, P < 0.01). Procalcitonin and hs-CRP were both significantly higher in the GS group than in the PS group. Accordingly, the duration of viral shedding was significantly longer in the GS group compared to the PS group (10.22 ± 1.93 vs 8.15 ± 1.87, P < 0.01). CONCLUSION: COVID-19 patients presenting with gastrointestinal symptoms as initial symptoms need more days of viral shedding and hospitalization than the patients presenting with pulmonary symptoms.

Acute right ventricular dysfunction in severe COVID-19 pneumonia.

To investigate the right heart function in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS), a retrospective analysis of 49 COVID-19 patients with ARDS was performed. Patients were divided into severe group and critically-severe group according to the severity of illness. Age-matched healthy volunteers were recruited as a control group. The cardiac cavity diameters, tricuspid annular plane systolic excursion (TAPSE), tricuspid valve regurgitation pressure gradient biggest (TRPG), pulmonary arterial systolic pressure (PASP), maximum inferior vena cava diameter (IVCmax) and minimum diameter (IVCmin), and inferior vena cava collapse index (ICV-CI) were measured using echocardiography. We found that the TAPSE was significantly decreased in pneumonia patients compared to healthy subjects (P < 0.0001), and it was significantly lower in critically-severe patients (P = 0.0068). The TAPSE was less than 17 mm in three (8.6%) severe and five (35.7%) critically-severe patients. In addition, the TAPSE was significantly decreased in severe ARDS patients than in mild ARDS patients. The IVCmax and IVCmin were significantly increased in critically-severe patients compared to healthy subjects and severe patients (P < 0.01), whereas the ICV-CI was significantly decreased (P < 0.05). COVID-19 patients had significantly larger right atrium and ventricle than healthy controls (P < 0.01). The left ventricular ejection fraction (LVEF) in critically-severe patients was significantly lower than that in severe patients and healthy controls (P < 0.05). Right ventricular function was impaired in critically-severe COVID-19 patients. The assessment and protection of the right heart function in COVID-19 patients should be strengthened.

A multi-center cross-sectional study on blood purification among adult patients in intensive care unit in China: a study protocol.

BACKGROUND: Blood purification (BP) is one of the most important rescue measures for patients with critical illness in the intensive care unit (ICU), especially for those with acute kidney injury. The purpose of this nationwide survey was to reveal the real world of current BP practice in different ICUs all over China. This study was designed to be a multi-center cross-sectional study. METHODS: All adult patients (over 18 years of age), who were admitted to ICU and required BP in 35 sub-centers across China were included during 30-day survey period in 2018. Demographic characteristics and clinical data were recorded including the timing of treatment initiation, indications, modality, relative contraindication, establishment of vascular access, selection of filter/membrane, settings, anti-coagulation, executive department, complication, intake, and output. DISCUSSION: This nationwide survey may contribute to reveal the real world of current BP practice in different ICUs all over China. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-EOC-17013119; http://www.chictr.org.cn/showproj.aspx?proj=22487.

Dexmedetomidine protects against lipopolysaccharide-induced sepsis-associated acute kidney injury via an α7 nAChR-dependent pathway.

Acute kidney injury (AKI) is a clinical syndrome that results in severe tubular damage with high morbidity and mortality. However, there is a lack of effective therapy strategies. Therefore, it is critical to develop effective drugs for AKI. Dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist, has neuroprotective, anti-inflammatory and sympatholytic properties. The present study aimed to investigate the effect DEX on attenuating the inflammatory reaction and apoptosis in the kidney tissues of septic mice and to explore its underlying mechanisms. Sepsis-induced AKI mice models were generated via intraperitoneal injection of lipopolysaccaride (LPS). DEX reduced LPS-induced local inflammation and tubular apoptosis, which was aggravated in the pathogenesis of renal dysfunction. Reverse transcription-quantitative polymerase chain reaction and western blot analysis results revealed that the expression of pro-apoptotic genes and inflammatory factors were markedly reduced by DEX pretreatment. Furthermore, the protective role of DEX was markedly inhibited by the α7 nicotinic acetylcholine receptor (nAChR) antagonist α-bungarotoxin. These findings provided novel evidence for the anti-apoptotic and anti-inflammatory effects of DEX in LPS-induced AKI mice through an α7 nAChR-dependent signaling pathway.

[Effects of extracorporeal membrane oxygenation on hemodynamics in acute right heart failure in dogs].

OBJECTIVE: To investigate the effects of extracorporeal membrane oxygenation (ECMO) on the hemodynamics in dogs with acute right heart failure. METHODS: Ten healthy adult male dogs (weighted 20-25 kg) were randomly divided into two groups: acute right heart failure group (n = 5) and ECMO group (n = 5). Under anesthesia, dogs were underwent thoracotomy, then the catheters were placed in the right atrium, right ventricle, and pulmonary artery, for measuring the relevant pressures, including right arterial pressure (RAP), right ventricular pressure (RVP), and pulmonary artery pressure (PAP). The vascular ultrasound probe were placed on the aorta and pulmonary artery for measuring the cardiac output (CO) and pulmonary artery flow rate (QPA). Then, a baseline measurement was acquired. The femoral artery and femoral vein were cannulated and used for the venoarterial extracorporeal membrane oxygenation (VA-ECMO), and then connected to extracorporeal circuit, which was initially primed. The pulmonary artery was progressively ligated to decrease blood flow until QPA was 60%, 40%, and 0% of baseline in both groups. The above flow conditions were respectively maintained for 30 minutes, after which hemodynamic data were collected. RESULTS: The baseline hemodynamic measurements were not different between acute right heart failure group and ECMO group. After ligating the pulmonary artery, compared with baseline, CO (L/min) decreased significantly at 60% and 40% QPA in acute right heart failure group (1.80 ± 0.19, 1.48 ± 0.22 vs. 3.24 ± 0.23, both P < 0.05), and significantly lower than that of ECMO group (60%QPA: 1.80 ± 0.19 vs. 3.24 ± 0.35; 40%QPA: 1.48 ± 0.22 vs. 3.20 ± 0.37, both P < 0.05). CO was not significantly different from baseline in ECMO group at 60%, 40% and 0% QPA (3.24 ± 0.35, 3.20 ± 0.37, 3.12 ± 0.28 vs. 3.44 ± 0.32, all P>0.05). PAP, RAP and RVP (all mm Hg, 1 mm Hg = 0.133 kPa) were significantly elevated in acute right heart failure group at 60% and 40% QPA compared with baseline (PAP: 36.2 ± 5.3, 39.8 ± 5.4 vs. 17.4 ± 2.7; RAP: 11.2 ± 2.8, 12.8 ± 2.6 vs. 4.4 ± 1.7; RVP: 25.6 ± 4.9, 27.8 ± 4.5 vs. 11.6 ± 1.8, all P < 0.05), and significantly higher than those of ECMO group (60%QPA: PAP 36.2 ± 5.3 vs. 23.2 ± 5.2, RAP 11.2 ± 2.8 vs. 6.2 ± 2.3, RVP 25.6 ± 4.9 vs. 15.2 ± 3.5; 40%QPA: PAP 39.8 ± 5.4 vs. 24.4 ± 4.8, RAP 12.8 ± 2.6 vs. 7.0 ± 2.4, RVP 27.8 ± 4.5 vs. 16.8 ± 4.2, all P < 0.05), whereas mean artery pressure (MAP, mm Hg) was significantly lowered compared with that of baseline (81.2 ± 15.8, 62.2 ± 14.4 vs. 128.6 ± 16.4, both P < 0.05), and it was lower than that of ECMO group (60%QPA: 81.2 ± 15.8 vs. 128.0 ± 26.5; 40%QPA: 62.2 ± 14.4 vs. 124.6 ± 25.4, both P < 0.05). At 60%, 40% and 0% QPA in ECMO group, whereas heart rate (HR, beats/min), PAP, RAP and RVP were slightly increased compared with those of baseline (HR: 161.4 ± 14.8, 160.6 ± 13.1, 157.6 ± 11.9 vs. 152.6 ± 14.5; PAP: 23.2 ± 5.2, 24.4 ± 4.8, 25.2 ± 6.2 vs. 18.8 ± 3.4; RAP: 6.2 ± 2.3, 7.0 ± 2.4, 7.6 ± 4.2 vs. 4.6 ± 1.5; RVP: 15.2 ± 3.5, 16.8 ± 4.2, 16.2 ± 3.3 vs. 12.2 ± 2.3), but MAP was slightly decreased (128.0 ± 26.5, 124.6 ± 25.4, 121.2 ± 21.4 vs. 135.8 ± 22.2), however, all differences were not statistically significant (all P>0.05). CONCLUSION: These findings demonstrate that VA-ECMO could be helpful in improving cardiac function, and maintaining stability of hemodynamics in dogs with acute right heart failure.