Heparin-binding protein as a biomarker for the diagnosis of sepsis in the intensive care unit: a retrospective cross-sectional study in China.

OBJECTIVES: This study aims to investigate the diagnostic value of heparin-binding protein (HBP) in sepsis and develop a sepsis diagnostic model incorporating HBP with key biomarkers and disease-related scores for rapid, and accurate diagnosis of sepsis in the intensive care unit (ICU). DESIGN: Clinical retrospective cross-sectional study. SETTING: A comprehensive teaching tertiary hospital in China. PARTICIPANTS: Adult patients (aged ≥18 years) who underwent HBP testing or whose blood samples were collected when admitted to the ICU. MAIN OUTCOME MEASURES: HBP, C reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), interleukin-6 (IL-6), lactate (LAC), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) score were recorded. RESULTS: Between March 2019 and December 2021, 326 patients were enrolled in this study. The patients were categorised into a non-infection group (control group), infection group, sepsis group and septic shock group based on the final diagnosis. The HBP levels in the sepsis group and septic shock group were 45.7 and 69.0 ng/mL, respectively, which were significantly higher than those in the control group (18.0 ng/mL) and infection group (24.0 ng/mL) (p<0.001). The area under the curve (AUC) value of HBP for diagnosing sepsis was 0.733, which was lower than those corresponding to PCT, CRP and SOFA but higher than those of IL-6, LAC and APACHE II. Multivariate logistic regression analysis identified HBP, PCT, CRP, IL-6 and SOFA as valuable indicators for diagnosing sepsis. A sepsis diagnostic model was constructed based on these indicators, with an AUC of 0.901, a sensitivity of 79.7% and a specificity of 86.9%. CONCLUSIONS: HBP could serve as a biomarker for the diagnosis of sepsis in the ICU. Compared with single indicators, the sepsis diagnostic model constructed using HBP, PCT, CRP, IL-6 and SOFA further enhanced the diagnostic performance of sepsis.

[Predictive value of left ventricular global longitudinal peak strain for the prognosis of septic patients].

OBJECTIVE: To investigate the predictive value of left ventricular global longitudinal peak strain (GLPS) for the prognosis of septic patients. METHODS: A prospective cohort study was conducted. Patients diagnosed with sepsis and admitted to the intensive care unit (ICU) of the First Affiliated Hospital, Sun Yat-sen University from December 2018 to November 2019 were enrolled. The patient characteristics, cardiac ultrasound parameters [left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), four-dimensional ejection fraction (4DEF), GLPS] and cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT)] within 24 hours of ICU admission, organ support therapies, severity of illness, and prognostic indicators were documented. The differences in clinical parameters between patients with varying outcomes during ICU hospitalization were assessed. Pearson correlation analysis was employed to explore the correlation between GLPS and other cardiac systolic parameters, as well as the associations between various cardiac systolic parameters and sequential organ failure assessment (SOFA) score. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive capacity of cardiac ultrasound parameters and cardiac biomarkers for death during ICU hospitalization in septic patients. RESULTS: A total of 50 septic patients were enrolled, with 40 surviving and 10 dying during ICU hospitalization, resulting in a mortality of 20.0%. All patients in the death group were male. Compared with the survival group, the patients in the death group were older, had a higher prevalence of diabetes mellitus, and received continuous renal replacement therapy (CRRT) more frequently, additionally, they exhibited more severe illness and had longer length of ICU stay. The levels of GLPS and cTnT in the death group were significantly elevated as compared with the survival group [GLPS: -7.1% (-8.5%, -7.0%) vs. -12.1% (-15.5%, -10.4%), cTnT (µg/L): 0.07 (0.05, 0.08) vs. 0.03 (0.02, 0.13), both P < 0.05]. However, no statistically significant difference was found in other cardiac ultrasound parameters or cardiac biomarkers between the two groups. Pearson correlation analysis revealed a negative correlation between GLPS and LVEF (r = -0.377, P = 0.014) and 4DEF (r = -0.697, P = 0.000), while no correlation was found with RVEF (r = -0.451, P = 0.069). GLPS demonstrated a positive correlation with SOFA score (r = 0.306, P = 0.033), while LVEF (r = 0.112, P = 0.481), RVEF (r = -0.134, P = 0.595), and 4DEF (r = -0.251, P = 0.259) showed no significant correlation with SOFA score. ROC curve analysis indicated that the area under the ROC curve (AUC) of GLPS for predicting death during ICU hospitalization in septic patients was higher than other cardiac systolic parameters, including LVEF, RVEF, and 4DEF, as well as cardiac biomarkers NT-proBNP and cTnT (0.737 vs. 0.628, 0.556, 0.659, 0.580 and 0.724). With an optimal cut-off value of -14.9% for GLPS, the sensitivity and negative predictive value reached to 100%. CONCLUSIONS: GLPS < -14.9% within 24 hours of ICU admission in septic patients indicated a reduced risk of death risk during ICU hospitalization, while also correlating with the severity of organ dysfunction in this patient population.

Aspirin Therapy and 28-Day Mortality in ICU Patients: A Retrospective Observational Study From Two Large Databases.

PURPOSE: Aspirin is widely used in patients in the intensive care unit (ICU); nonetheless, its effects on these patients remain controversial. This retrospective analysis of data from clinical practice investigated the effects of aspirin on 28-day mortality in ICU patients. METHODS: This retrospective study included data from patients in the Medical Information Mart for Intensive Care (MIMIC)-III database and the eICU-Collaborative Research Database (CRD). Patients aged 18 to 90 years and admitted to the ICU were eligible and were assigned to one of two groups according to whether they were given aspirin during their ICU stay. Multiple imputation was used for patients with >10% missing data. Multivariate Cox models and propensity score analysis were used to estimate the association of aspirin treatment with 28-day mortality among patients admitted to the ICU. FINDINGS: In total, 146,191 patients were enrolled in this study, and 27,424 (18.8%) used aspirin. Aspirin treatment in ICU patients, especially in nonseptic patients, was associated with a lower 28-day all-cause mortality on multivariate Cox analysis (eICU-CRD, hazard ratio [HR] = 0.81, [95% CI, 0.75-0.87]; MIMIC-III, HR = 0.72 [95% CI, 0.68-0.76]). Aspirin treatment was associated with lower 28-day all-cause mortality after propensity score matching (eICU-CRD, HR = 0.80 [95% CI, 0.72-0.88]; MIMIC-III, HR = 0.80 [95% CI, 0.76-0.85]). However, on subgroup analysis, aspirin therapy was not associated with a lower 28-day mortality in patients without systemic inflammatory response syndrome (SIRS) symptoms or with sepsis in either database. IMPLICATIONS: Aspirin treatment during the ICU stay was associated with a significantly reduced 28-day all-cause mortality, particularly in patients with SIRS symptoms but without sepsis. In patients with sepsis and with/without SIRS symptoms, beneficial effects were not clear, or more careful patient selection is required.

Study Protocol of a Multicenter, Randomized, Single-Blind Trial: Efficacy and Safety of Remimazolam Tosylate for Sedation in ICU Patients.

INTRODUCTION: Pharmacodynamic and pharmacokinetic studies in animal experiments and a phase 1 study suggested remimazolam tosylate as an effective and safe sedation/anesthetic agent. However, the effects and safety dose of remimazolam for light sedation in intensive care unit (ICU) patients are not clear and should be confirmed in a phase 2 study. METHODS: Sixty ICU patients requiring sedation treatment and undergoing mechanical ventilation will be enrolled and randomly assigned to a high dose group (HD group, 30 cases) and a low dose group (LD group, 30 cases) in a 1:1 ratio. Patients in both groups will be sedated using remimazolam tosylate in a primary dose of 0.08 mg/kg and a range of 0-2.0 mg/kg/h after randomization. Dose adjustment will be made at the range of every 0.1 mg/kg/h in the LD group and 0.2 mg/kg/h in the HD group to maintain the target Richmond Agitation and Sedation Score (RASS) at - 2 to + 1. The primary outcome will be the proportion of subjects that meet the following conditions: the time within the range of RASS (- 2 to + 1) accounts for 70% of the study drug administration time; without other rescue treatments. Secondary outcomes including the percentage time to reach the sedation goal; the proportion of subjects receiving rescue sedation and/or analgesic, and the mean dose of rescue drug throughout the study period; duration of mechanical ventilation; recovery time to full consciousness and nursing scores. Evaluations of safety including adverse events (AEs), serious AEs, physical examination, laboratory examination, etc. OUTCOME: The results of this study will provide crucial information for the use of remimazolam tosylate for ICU sedation. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05152303.

Population pharmacokinetics and limited sampling strategies of polymyxin B in critically ill patients.

OBJECTIVES: To characterize the pharmacokinetics (PK) of polymyxin B in Chinese critically ill patients. The factors significantly affecting PK parameters are identified, and a limited sampling strategy for therapeutic drug monitoring of polymyxin B is explored. METHODS: Thirty patients (212 samples) were included in a population PK analysis. A limited sampling strategy was developed using Bayesian estimation, multiple linear regression and modified integral equations. Non-linear mixed-effects models were developed using Phoenix NLME software. RESULTS: A two-compartment population PK model was used to describe polymyxin B PK. Population estimates of the volumes of central compartment distribution (V) and peripheral compartment distribution (V2), central compartment clearance (CL) and intercompartmental clearance (Q) were 7.857 L, 12.668 L, 1.672 L/h and 7.009 L/h. Continuous renal replacement therapy (CRRT) significantly affected CL, and body weight significantly affected CL and Q. The AUC0-12h of polymyxin B in patients with CRRT was significantly lower than in patients without CRRT. CL and Q increased with increasing body weight. A limited sampling strategy was suggested using a two-sample scheme with plasma at 0.5h and 8h after the end of infusion (C0.5 and C8) for therapeutic drug monitoring in the clinic. CONCLUSIONS: A dosing regimen should be based on body weight and the application of CRRT. A two-sample strategy for therapeutic drug monitoring could facilitate individualized treatment with polymyxin B in critically ill patients.

HOXB13 facilitates hepatocellular carcinoma progression by activating AKT/mTOR signaling pathway.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the sixth most common malignancies worldwide and is accompanied by high mortality. Homeobox B13 (HOXB13) has been shown to be involved in the development of various cancers. This study aimed to investigate the role of HOXB13 in HCC progression. MATERIALS AND METHODS: The expression of HOXB13 in HCC tumor tissues was analyzed using qRT-PCR and immunohistochemical staining . After overexpression or downregulation of HOXB13 in HCC cell lines, cell proliferation was detected by CCK8 assay and Ki67 staining and cell invasion ability were tested by transwell assay. Western blot assay was applied to analyze the effect of HOXB13 on related signaling pathways. In addition, the role of HOXB13 on HCC in vivo was explored using a HCC mouse model. IF and WB were performed to detect cell proliferation, apoptosis and related protein expression in mice tumor tissues. RESULTS: The results showed that the expression of HOXB13 was significantly increased in HCC tissues compared with adjacent tissues and positively correlated with the tumor stage and survival of HCC patients. Overexpression of HOXB13 promoted the proliferation and invasion of HCC cells and up-regulated the protein expression of AKT, mTOR and MMP2. In contrast, the downregulation of HOXB13 resulted in the opposite results. In vivo experiments, HOXB13 significantly promoted tumor growth in mice bearing HCC by promoting cell proliferation and inhibiting cell apoptosis. CONCLUSIONS: This study suggested that HOXB13 can facilitate HCC progression by activation of the AKT/mTOR signaling pathway. HOXB13 may be a novel target for HCC therapy.

Strategy to small intestine obstruction caused by Crohn's disease on the basis of transnasal ileus tube insertion.

BACKGROUND: Previous studies reported that transnasal ileus tube was a new and useful method for rapid relief of small intestinal obstruction. However, no study reported the impacts of the transnasal ileus tube for Crohn's disease combined with intestinal obstruction. We aimed to describe the strategy to the small intestine obstruction caused by Crohn's disease on the basis of transnasal ileus tube insertion. METHODS: From November 2019 to November 2021, the data of 6 hospitalized patients with CD, diagnosed and conservatively treated in The Second Hospital of Nanjing, were not relived and retrospectively collected. After the insertion of transnasal ileus tube, demographic information, clinical features and treatment data were extracted from medical records. RESULTS: Six Crohn's disease patients with intestinal obstruction were included. Half of them were male. The patients aged from 29 to 70 years. Five patients had chronic intestinal obstruction more than one year. Three patients had intestinal surgery history. One patient had colonic abdominal fistula and anastomotic fistula, when she took intermittent usage of sulfsalazine and steroid. On admission, all the patients had abdominal pain, distention and mass. Five patients had anemia, low albumin and cholinesterase. All CDAI scores were more than 400. Compared to 19 patients with incomplete intestinal obstruction improved by nasogastric decompression tube, 6 patients with intestinal obstruction catheter had significant difference in time for relieving abdominal pain and distension (p = 0.003), time for alleviating abnormal mass (p ≤ 0.01), drainage volume (p = 0.004), and preoperative CDAI score (p = 0.001). Compared with X-ray image before insertion, complete remission of obstruction of 5 patients were observed in intestinal cavity after insertion. After 1-2 months nutrition, all the patients had small intestine resection and ileostomy, half of them underwent colectomy and fistula repair, and 4 patients were performed enterolysis at the same time, the residual small intestine length ranging from 250 to 400 cm. 1 patient had permanent ileostomy;1 patient had abdominal infection after operation. The typical manifestations of acute and chronic inflammation, transmural inflammation, pseudopolyps and serous fiber hyperplasia could be seen in pathological findings of patients 1 to 5. All the patients continued enteral nutrition after surgery. Four patients were treated with infliximab or vedolizumab. CONCLUSION: The current intestinal obstruction catheter which is used to treat patients with Crohn's combined obstruction can afford quick clinical remission, longer nutrition time, and suitable preoperative CDAI score for operation, which is worthy of wildly being used.

Plateletcrit for predicting prognosis in patients with hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloid.

BACKGROUND: Platelet index was reported to be used as a potential prognostic marker in patients with liver fibrosis. We aimed to explore the association between plateletcrit (PCT) and severity of hepatic sinusoidal obstruction syndrome (HSOS). METHODS: Seventy consecutive patients who diagnosed as HSOS by CT and medical history during January 2017-November 2021 were included. All patients were divided into two groups which confirmed as favorable prognosis and poor prognosis on the basis of Child-Turcotte-Pugh score system. The clinical manifestation and laboratory parameters of two groups were retrospectively selected. PCT was evaluated within two groups, and the diagnostic accuracy was evaluated by the area under the receiver operating characteristic curve. RESULTS: The significant difference between the two groups not only in diarrhea, abdominal pain, abdominal distention, urine volume, and skin ecchymosis (p < 0.005), but also in WBC count, NE count, PLT count, TBIL, and D-Dimer (p < 0.005) were found. The PCT level was significantly higher in HSOS patients with poor prognosis (0.169 ± 0.060) than favorable prognosis patients (0.110 ± 0.047). The area under the receiver operating characteristic curve of RDW in predicting poor prognosis was 0.781, with 67.70% sensitivity and 79.5%specificity. CONCLUSIONS: The PCT level was correlated positively with the poor prognosis in HSOS patients. PCT can be a promising indicator for predicting prognosis in HSOS.

Transesophageal echocardiography instead or in addition to transthoracic echocardiography in evaluating haemodynamic problems in intubated critically ill patients.

BACKGROUND: Transesophageal echocardiography (TEE) performed by intensivists is increasingly used in critically ill patients. However, TEE is usually not the preferred monitoring tool, especially when transthoracic echocardiography (TTE) appears to have addressed the clinical problems. As a result, it remains largely unknown whether TEE is a clinically valuable replacement or supplement for TTE as a primary tool in evaluating haemodynamic problems in critically ill surgical patients. The purpose of this study was to assess the diagnostic and therapeutic value of TEE instead or in addition to TTE in critically ill surgical patients with hemodynamic instability. METHODS: A prospective observational study was conducted. A total of 68 consecutive patients were enrolled from December 2016 to February 2018. TEE was routinely performed in addition to TTE, and the imaging data from TTE and TEE were successively disclosed to two different primary physicians, who reported any resulting changes in management. The two physicians were required to reach a consensus if there was any disagreement. The results of the additional TEE examination were compared with the clinical findings and TTE information. The image quality of TTE views was classified as a good (score 2), suboptimal (score 1) or poor view (score 0). According to the scores of TTE images, the patients were divided into two groups: patients with adequate TTE views (score ≥6) and inadequate TTE views (score <6). RESULTS: The results of additional TEE examination were classified into four categories. TEE failed to provide additional information about the initial diagnosis and therapy (class 1) in 26 patients (38.2%). Of the remaining 42 patients (61.8%), TEE instead or in addition to TTE revealed new findings or led to significant changes in therapy, as TTE supplied inadequate information. TEE used in addition to TTE led to a new diagnosis without therapeutic implications (class 2) in 11 patients (16.2%) and made a major clinical contribution leading to a therapeutic change (class 3) in 23 patients (33.8%). TEE used instead of TTE determined the diagnosis and therapy in 8 patients (11.8%) whose haemodynamic problems could not be addressed by TTE (class 4). In total, TEE had critical therapeutic benefits (class 3 and 4) that was not provided by TTE in 31 patients (45.6%). Of particular concern was that TEE had a higher proportion of therapeutic benefits to patients with inadequate TTE views than those with adequate TTE views (54.3% vs. 27.3%, P=0.036). CONCLUSIONS: TEE as a feasible clinical tool is useful for critically ill surgical patients with hemodynamic instability, especially for the patients with inadequate TTE views. TEE instead or in addition to TTE could provide valuable information for diagnosis, which may bring significant therapeutic benefits.

HOXB13 expression is correlated with hepatic inflammatory activity of patients with hepatic fibrosis.

Liver fibrosis is a common pathological process of chronic hepatic injury, preceded by the chronic inflammation. The homeobox B13 (HOXB13) gene, a member of HOX family, plays diverse biological roles in embryonic development, carcinogenesis, and many inflammatory diseases. However, the expression of HOXB13 in chronic liver diseases including hepatic fibrosis remains to be defined. In present study, 55 patients with hepatic fibrosis, 15 patients of hepatocellular carcinoma, and 17 healthy controls were enrolled in this study. Pathological specimens were collected through liver biopsy or surgical resection. The degree of hepatic inflammation (G0-G4) and fibrosis (S0-S4) of hepatic fibrosis was scored based on the modified histology activity index. Intrahepatic HOXB13 expression was analyzed using immunohistochemistry analysis. Compared with healthy subjects, both patients with hepatic fibrosis and patients with hepatocellular carcinoma exhibited significant accumulations of HOXB13+ cells in the liver (p < 0.05). Additionally, the number of HOXB13+ cell was significantly elevated along with the increment of hepatic inflammatory activities, but not fibrosis stages, among these liver fibrosis samples (p < 0.01). Furthermore, the quantity of HOXB13+ cells were also positively correlated with hepatic enzymes, alanine transaminase (r = 0.299, p = 0.041) and aspartate aminotransferase (r = 0.317, p = 0.013) in our cohort of hepatic fibrosis. In conclusion, our study identified a strong hepatic expression of HOXB13 among patients with hepatic fibrosis, which strongly associated with the degree of hepatic inflammatory activity for patients with hepatic fibrosis, suggesting an important role of HOXB13 during the pathogenesis of liver fibrogenesis.

Risk factors and mortality for patients with Bloodstream infections of Klebsiella pneumoniae during 2014-2018: Clinical impact of carbapenem resistance in a large tertiary hospital of China.

BACKGROUND: Bloodstream infection (BSI) caused by Klebsiella pneumoniae (KP), especially carbapenem-resistant KP (CRKP), results in high morbidity and mortality. AIMS: We aim to identify risk factors that associated with the mortality of patients with KP BSI, as well as predictors of developing CRKP BSI. RESULTS: In this retrospective cohort study, we examined 285 inpatients with BSI caused by KP in a tertiary hospital in China between 2014 and 2018, and 46 patients were infected with CRKP. We identified that hematological tumor (odds ratio (OR): 8.359, [95% CI: 2.162-33.721], P=0.002), CRKP isolation (OR: 7.766, [95% CI: 2.796-21.576], P=0.001), chronic lung disease (OR: 5.020, [95% CI: 1.275-19.768], P=0.020), and septic shock (OR: 4.591, [95% CI: 1.686-12.496], P=0.003) were independent risk factors for the death of KP BSI. A 28-day mortality of KP BSI score ranging from 0 to 22 was developed based on the above 4 independent variables. Our scoring system revealed that the 28-day mortality were 9.14%, 35.29%, 38.10 %, 75% and 100% for carriers with a score of 0, 5, 6-10, 11-13 and ≥14, respectively. Additionally, CRKP infection were independently associated with intensive care unit stay (OR: 5.506, [95% CI: 2.258-13.424], P=0.001), exposure to antifungals (OR: 4.679, [95% CI: 2.065-10.063], P=0.001), exposure to fluoroquinolones (OR: 2.892, [95% CI: 1.151-7.267], P=0.020), and the number of isolated bacterial species from the patient ≥ 3 (OR: 2.414, [95% CI: 1.306-4.463], P=0.005). CONCLUSION: Our study may be useful for the reduction of the mortality of patients with KP BSI and the prevention of developing CRKP BSI in hospitals.

Red blood cell distribution width for predicting significant liver inflammation in patients with autoimmune hepatitis.

BACKGROUND: Red blood cell distribution width (RDW) was reported to be associated with the severity of liver diseases. We aimed to investigate the association between RDW and severity of liver inflammation in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Ninety-two consecutive AIH patients who underwent liver biopsy during 2016-2017 were included. Liver histology was evaluated using the Scheuer scoring system. Logistic regression analysis was used to analyze the risk factors for significant inflammation. The diagnostic accuracy was evaluated by the area under the receiver operating characteristic curve. RESULTS: The RDW level was higher in AIH patients with significant inflammation (14.6%, interquartile range: 13.2-16.3%) than in patients with mild inflammation (13.2%, interquartile range: 12.6-13.8%). The RDW level was correlated positively with the grades of liver inflammation (r=0.356, P < 0.001). The area under the receiver operating characteristic curve of RDW in predicting significant inflammation was 0.739 (95% confidential interval: 0.634-0.843, P < 0.001), with 67.80% sensitivity and 75.76% specificity. The diagnostic performance of RDW for significant inflammation was better than alanine aminotransferase (P = 0.003) and immunoglobulin G (P = 0.049). RDW (odds ratio = 1.702, P = 0.001) was identified as an independent predictor for significant inflammation by logistic multivariable analysis. CONCLUSION: The RDW level was correlated positively with the severity of liver inflammation in AIH patients. RDW can be a promising indicator for predicting significant liver inflammation in AIH.