Improved prediction of sepsis-associated encephalopathy in intensive care unit sepsis patients with an innovative nomogram tool.

Background: Sepsis-associated encephalopathy (SAE) occurs as a result of systemic inflammation caused by sepsis. It has been observed that the majority of sepsis patients experience SAE while being treated in the intensive care unit (ICU), and a significant number of survivors continue suffering from cognitive impairment even after recovering from the illness. The objective of this study was to create a predictive nomogram that could be used to identify SAE risk factors in patients with ICU sepsis. Methods: We conducted a retrospective cohort study using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. We defined SAE as a Glasgow Coma Scale (GCS) score of 15 or less, or delirium. The patients were randomly divided into training and validation cohorts. We used least absolute shrinkage and selection operator (LASSO) regression modeling to optimize feature selection. Independent risk factors were determined through a multivariable logistic regression analysis, and a prediction model was built. The performance of the nomogram was evaluated using various metrics including the area under the receiver operating characteristic curve (AUC), calibration plots, Hosmer-Lemeshow test, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: Among the 4,476 sepsis patients screened, 2,781 (62.1%) developed SAE. In-hospital mortality was higher in the SAE group compared to the non-SAE group (9.5% vs. 3.7%, p < 0.001). Several variables were analyzed, including the patient's age, gender, BMI on admission, mean arterial pressure, body temperature, platelet count, sodium level, and use of midazolam. These variables were used to create and validate a nomogram. The nomogram's performance, assessed by AUC, NRI, IDI, and DCA, was found to be superior to the conventional SOFA score combined with delirium. Calibration plots and the Hosmer-Lemeshow test confirmed the accuracy of the nomogram. The enhanced NRI and IDI values demonstrated that our scoring system outperformed traditional diagnostic approaches. Additionally, the DCA curve indicated the practicality of the nomogram in clinical settings. Conclusion: This study successfully identified autonomous risk factors associated with the emergence of SAE in sepsis patients and utilized them to formulate a predictive model. The outcomes of this investigation have the potential to serve as a valuable clinical resource for the timely detection of SAE in patients.

Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway.

BACKGROUND: Lung endothelial barrier injury plays an important role in the pathophysiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) therapy has shown promise in ARDS treatment and restoration of the impaired barrier function. It has been reported that Wnt5a shows protective effects on endothelial cells. Therefore, the study aimed to investigate whether overexpression of Wnt5a could promote the protective effects of MSCs on Lipopolysaccharide (LPS)-induced endothelial cell injury. METHODS: To evaluate the protective effects of MSCs overexpressing Wnt5a, we assessed the migration, proliferation, apoptosis, and angiogenic ability of endothelial cells. We assessed the transcription of protective cellular factors using qPCR and determined the molecular mechanism using Western blot analysis. RESULTS: Overexpression of Wnt5a upregulated the transcription of protective cellular factors in MSCs. Co-culture of MSCWnt5a promoted endothelial migration, proliferation and angiogenesis, and inhibited endothelial cell apoptosis through the PI3K/AKT pathway. CONCLUSIONS: Overexpression of Wnt5a promoted the therapeutic effect of MSCs on endothelial cell injury through the PI3K/AKT signaling. Our study provides a novel approach for utilizing genetically modified MSCs in the transplantation therapy for ARDS.

Association between ICU admission (neutrophil + monocyte)/lymphocyte ratio and 30-day mortality in patients with sepsis: a retrospective cohort study.

BACKGROUND: Sepsis is an important public health issue, and it is urgent to develop valuable indicators to predict the prognosis of sepsis. Our study aims to assess the predictive value of ICU admission (Neutrophil + Monocyte)/lymphocyte ratio (NMLR) on the 30-day mortality of sepsis patients. METHODS: A retrospective analysis was conducted in septic patients, and the data were collected from Medical Information Mart for Intensive Care IV (MIMIC-IV). Univariate and multivariate Cox regression analyses were conducted to investigate the relation between ICU admission NMLR and 30-day mortality. Restricted cubic spline (RCS) was performed to determine the optimum cut-off value of ICU admission NMLR. Survival outcomes of the two groups with different ICU admission NMLR levels were estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: Finally, 7292 patients were recruited in the study, of which 1601 died within 30 days of discharge. The non-survival group had higher ICU admission NMLR values than patients in the survival group (12.24 [6.44-23.67] vs. 8.71 [4.81-16.26], P < 0.001). Univariate and multivariate Cox regression analysis demonstrated that ICU admission NMLR was an independent prognostic predictor on 30-day mortality (Univariate: P < 0.001; multivariate: P = 0.011). The RCS model demonstrated the upturn and non-linear relationship between ICU admission NMLR and 30-day mortality (Nonlinearity: P = 0.0124). According to the KM curve analysis,30-day survival was worse in the higher ICU admission NMLR group than that in the lower ICU admission NMLR group (Log rank test, P < 0.0001). CONCLUSION: The elevated ICU admission NMLR level is an independent risk factor for high 30-day mortality in patients with sepsis.

Association Between ICU admission (Neutrophil + Monocyte)/Lymphocyte Ratio And 30-Day Mortality in Patients with Sepsis: A Retrospective Study from MIMIC-IV.

Background: Sepsis is an important public health issue, and it is urgent to develop valuable indicators to predict the prognosis of sepsis. Our study aims to assess the predictive value of ICU admission (Neutrophil + Monocyte)/lymphocyte ratio (NMLR) on the 30-day mortality of sepsis patients. Methods: A retrospective analysis was conducted in septic patients, and the data were collected from Medical Information Mart for Intensive Care IV (MIMIC-IV). Univariate and multivariate Cox regression analyses were conducted to investigate the relation between ICU admission NMLR and 30-day mortality. Restricted cubic spline (RCS) was performed to determine the optimum cut-off value of ICU admission NMLR. Survival outcomes of the two groups with different ICU admission NMLR levels were estimated using the Kaplan-Meier method and compared by the log-rank test. Results: Finally, 7292 patients were recruited in the study, of which 1601 died within 30 days of discharge. The non-survival group had higher ICU admission NMLR values than patients in the survival group (12.24 [6.44-23.67] vs. 8.71 [4.81-16.26], P < 0.001). Univariate and multivariate Cox regression analysis demonstrated that ICU admission NMLR was an independent prognostic predictor on 30-day mortality (Univariate: P < 0.001; multivariate: P=0.011). The RCS model demonstrated the upturn and non-linear relationship between ICU admission NMLR and 30-day mortality (Nonlinearity: P=0.0124). According to the KM curve analysis,30-day survival was worse in the higher ICU admission NMLR group than that in the lower ICU admission NMLR group (Log rank test, P<0.0001). Conclusion: The elevated ICU admission NMLR level is an independent risk factor for high 30-day mortality in patients with sepsis.

Short-term outcome of total knee replacement in a patient with hemophilia: A case report and review of literature.

BACKGROUND: Hemophilia A is a rare inherited bleeding disorder caused by mutations in the factor VIII gene. This clotting factor plays an intrinsic role in the blood coagulation pathway. Patients with hemophilia may develop orthopedic manifestations such as hemarthrosis, but multiple malunion of fractures over the knee is rare and difficult to treat. CASE SUMMARY: We report a patient with hemophilia A who developed severe knee osteoarthritis along with fracture malunion and nonunion. Total knee replacement was performed using a custom-made modular hinged knee prosthesis (cemented) equipped with extended distal and proximal stems. At 3 years' follow-up, the patient exhibited excellent clinical function and remained satisfied with the surgical outcome. Surgical intervention was accompanied by rigorous coagulation factor replacement. CONCLUSION: This case highlights various unique scenarios specific to individuals with hemophilia and fracture deformity.

Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population.

BACKGROUND: A large proportion of pulmonary embolism (PE) heritability remains unexplained, particularly among the East Asian (EAS) population. Our study aims to expand the genetic architecture of PE and reveal more genetic determinants in Han Chinese. METHODS: We conducted the first genome-wide association study (GWAS) of PE in Han Chinese, then performed the GWAS meta-analysis based on the discovery and replication stages. To validate the effect of the risk allele, qPCR and Western blotting experiments were used to investigate possible changes in gene expression. Mendelian randomization (MR) analysis was employed to implicate pathogenic mechanisms, and a polygenic risk score (PRS) for PE risk prediction was generated. RESULTS: After meta-analysis of the discovery dataset (622 cases, 8853 controls) and replication dataset (646 cases, 8810 controls), GWAS identified 3 independent loci associated with PE, including the reported loci FGG rs2066865 (p-value = 3.81 × 10-14), ABO rs582094 (p-value = 1.16 × 10-10) and newly reported locus FABP2 rs1799883 (p-value = 7.59 × 10-17). Previously reported 10 variants were successfully replicated in our cohort. Functional experiments confirmed that FABP2-A163G(rs1799883) promoted the transcription and protein expression of FABP2. Meanwhile, MR analysis revealed that high LDL-C and TC levels were associated with an increased risk of PE. Individuals with the top 10% of PRS had over a fivefold increased risk for PE compared to the general population. CONCLUSIONS: We identified FABP2, related to the transport of long-chain fatty acids, contributing to the risk of PE and provided more evidence for the essential role of metabolic pathways in PE development.

Overexpression of FoxM1 Enhanced the Protective Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Lipopolysaccharide-Induced Acute Lung Injury through the Activation of Wnt/ß-Catenin Signaling.

Background: Mesenchymal stem cell- (MSC-) based cell and gene therapies have made remarkable progress in alleviating acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the benefits of Forkhead box protein M1 (FoxM1) gene-modified MSCs in the treatment of ALI have not been studied. Methods: We evaluated the therapeutic effects of FoxM1-modified MSCs in ALI mice induced by lipopolysaccharide (LPS) by quantifying the survival rate, lung weight ratio (wet/dry), and contents of bronchoalveolar lavage fluid. In addition, microcomputed tomography, histopathology, Evans Blue assay, and quantification of apoptosis were performed. We also explored the underlying mechanism by assessing Wnt/ß-catenin signaling following the treatment of mice with FoxM1-modified MSCs utilizing the Wnt/ß-catenin inhibitor XAV-939. Results: Compared with unmodified MSCs, transplantation of FoxM1-modified MSCs improved survival and vascular permeability; reduced total cell counts, leukocyte counts, total protein concentrations, and inflammatory cytokines in BALF; attenuated lung pathological impairments and fibrosis; and inhibited apoptosis in LPS-induced ALI/ARDS mice. Furthermore, FoxM1-modified MSCs maintained vascular integrity during ALI/ARDS by upregulating Wnt/ß-catenin signaling, which was partly reversed via a pathway inhibitor. Conclusion: Overexpression of FoxM1 optimizes the treatment action of MSCs on ALI/ARDS by inhibiting inflammation and apoptosis and restoring vascular integrity partially through Wnt/ß-catenin signaling pathway stimulation.

Overexpression of FoxM1 optimizes the therapeutic effect of bone marrow mesenchymal stem cells on acute respiratory distress syndrome.

BACKGROUND: Injury of alveolar epithelial cells and capillary endothelial cells is crucial in the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) are a promising cell source for ALI/ARDS treatment. Overexpression of Fork head box protein M1 (FoxM1) facilitates MSC differentiation into alveolar type II (AT II) cells in vitro. Moreover, FoxM1 has been shown to repair the endothelial barrier. Therefore, this study explored whether overexpression of FoxM1 promotes the therapeutic effect of bone marrow-derived MSCs (BMSCs) on ARDS by differentiation of BMSCs into AT II cells or a paracrine mechanism. METHODS: A septic ALI model was established in mice by intraperitoneal administration of lipopolysaccharide. The protective effect of BMSCs-FoxM1 on ALI was explored by detecting pathological variations in the lung, total protein concentration in bronchoalveolar lavage fluid (BALF), wet/dry (W/D) lung weight ratio, oxidative stress levels, cytokine levels, and retention of BMSCs in the lung. In addition, we assessed whether FoxM1 overexpression promoted the therapeutic effect of BMSCs on ALI/ARDS by differentiating into AT II cells using SPC-/- mice. Furthermore, the protective effect of BMSCs-FoxM1 on lipopolysaccharide-induced endothelial cell (EC) injury was explored by detecting EC proliferation, apoptosis, scratch wounds, tube formation, permeability, and oxidative stress, and analyzing whether the Wnt/ß-catenin pathway contributes to the regulatory mechanism in vitro using a pathway inhibitor. RESULTS: Compared with BMSCs-Vector, treatment with BMSCs-FoxM1 significantly decreased the W/D lung weight ratio, total BALF protein level, lung injury score, oxidative stress, and cytokine levels. With the detected track of BMSCs-FoxM1, we observed a low residency rate and short duration of residency in the lung. Notably, SPC was not expressed in SPC-/- mice injected with BMSCs-FoxM1. Furthermore, BMSCs-FoxM1 enhanced EC proliferation, migration, and tube formation; inhibited EC apoptosis and inflammation; and maintained vascular integrity through activation of the Wnt/ß-catenin pathway, which was partially reversed by XAV-939. CONCLUSION: Overexpression of FoxM1 enhanced the therapeutic effect of BMSCs on ARDS, possibly through a paracrine mechanism rather than by promoting BMSC differentiation into AT II cells in vivo, and prevented LPS-induced EC barrier disruption partially through activating the Wnt/ß-catenin signaling pathway in vitro.

Ghrelin pretreatment enhanced the protective effect of bone marrow-derived mesenchymal stem cell-conditioned medium on lipopolysaccharide-induced endothelial cell injury.

BACKGROUND: Lung endothelial barrier injury plays a crucial role in the pathophysiology of acute respiratory distress syndrome. It has been demonstrated that bone marrow-derived mesenchymal stem cells-conditioned medium (BMSCs-CM) and ghrelin have a protective effect. This study investigated if ghrelin pretreatment enhanced the protective effect of BMSCs-CM on lipopolysaccharide (LPS)-induced endothelial cell injury. METHODS: BMSCs were isolated from rat bone marrow, expanded, then phenotypically tested for mesenchymal stem cell-identifying criteria by flow cytometry. The effects of the conditioned medium derived from ghrelin-pretreated BMSCs (BMSCs-ghrelin-pretreated-CM) on LPS-injured endothelial cells were evaluated by migration, apoptosis, permeability, and pro-inflammatory factor (e.g., tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6) assays in endothelial cells. Further, AKT/GSK3ß pathway activation in endothelial cells was examined by Western blot, and the gene expression profiles of ghrelin-pretreated BMSCs were examined by RNA sequencing. RESULTS: BMSCs-ghrelin-pretreated-CM had a greater protective effect on LPS-induced endothelial cell injury than BMSCs-CM by improving cell migration, alleviating apoptosis, and reducing endothelial permeability and the release of pro-inflammatory factors in endothelial cells. The mechanism is partly related to AKT/GSK3ß pathway activation after BMSCs-ghrelin-pretreated-CM treatment. There were five upregulated candidate genes (Wnt5a [i.e., Wnt Family Member 5A], S100b [i.e., S100 Calcium-Binding Protein B], Bmp2 [i.e., Bone Morphogenetic Protein 2], Id4 [i.e., Inhibitor Of DNA Binding 4], and PTHLH [i.e., Parathyroid Hormone Like Hormone]) in BMSCs after ghrelin treatment, and all were associated with AKT pathway activation and endothelial function. CONCLUSIONS: Ghrelin pretreatment enhanced the protective effect of BMSCs-CM on LPS-induced endothelial cell injury, partly by activating the AKT/GSK3ß pathway.

Ghrelin protects against lipopolysaccharide-induced acute respiratory distress syndrome through the PI3K/AKT pathway.

Pulmonary endothelial barrier dysfunction is a major pathophysiology observed in acute respiratory distress syndrome (ARDS). Ghrelin, a key regulator of metabolism, has been shown to play protective roles in the respiratory system. However, its effects on lipopolysaccharide (LPS)-induced pulmonary endothelial barrier injury are unknown. In this study, the effects of ghrelin on LPS-induced ARDS and endothelial cell injury were evaluated in vivo and in vitro. In vivo, mice treated with LPS (3 mg/kg intranasal application) were used to establish the ARDS model. Annexin V/propidium iodide apoptosis assay, scratch-wound assay, tube formation assay, transwell permeability assay, and Western blotting experiment were performed to reveal in vitro effects and underlying mechanisms of ghrelin on endothelial barrier function. Our results showed that ghrelin had protective effects on LPS-induced ARDS and endothelial barrier disruption by inhibiting apoptosis, promoting cell migration and tube formation, and activating the PI3K/AKT signaling pathway. Furthermore, ghrelin stabilized LPS-induced endothelial barrier function by decreasing endothelial permeability and increasing the expression of the intercellular junction protein vascular endothelial cadherin. LY294002, a specific inhibitor of the PI3K pathway, reversed the protective effects of ghrelin on the endothelial cell barrier. In conclusion, our findings indicated that ghrelin protected against LPS-induced ARDS by impairing the pulmonary endothelial barrier partly through activating the PI3K/AKT pathway. Thus, ghrelin may be a valuable therapeutic strategy for the prevention or treatment of ARDS.

Overexpression of HOXB4 Promotes Protection of Bone Marrow Mesenchymal Stem Cells Against Lipopolysaccharide-Induced Acute Lung Injury Partially Through the Activation of Wnt/ß-Catenin Signaling.

PURPOSE: Pulmonary vascular endothelial cell (EC) injury is recognized as one of the pathological factors of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Bone marrow mesenchymal stem cell (BMSC)-based cytotherapy has attracted substantial attention over recent years as a promising therapeutic approach for ALI/ARDS; however, its use remains limited due to inconsistent efficacy. Currently, gene modification techniques are widely applied to MSCs. In the present study, we aimed to investigate the effect of BMSCs overexpressing Homeobox B4 (HOXB4) on lipopolysaccharide (LPS)-induced EC injury. METHODS: We used LPS to induce EC injury and established EC-BMSC coculture system using transwell chambers. The effect of BMSCs on ECs was explored by detecting EC proliferation, apoptosis, migration, tube formation, and permeability, and determining whether the Wnt/ß-catenin pathway is involved in the regulatory mechanism using XAV-939, inhibitor of Wnt/ ß-catenin. RESULTS: As compared to BMSCWT, BMSCHOXB4 coculture promoted EC proliferation, migration, and tube formation after LPS stimulation and attenuated LPS-induced EC apoptosis and vascular permeability. Mechanistically, BMSCHOXB4 coculture prevented LPS-induced EC injury by activating the Wnt/ß-catenin pathway, which is partially reversible by XAV-939. When cocultured with BMSCHOXB4, pro-inflammatory factors were dramatically decreased and anti-inflammatory factors were greatly increased in the EC medium compared to those in the LPS group (P<0.05). Additionally, when compared to BMSCWT coculture, the BMSCHOXB4 coculture showed an enhanced modulation of IL-6, TNF-α, and IL-10, but there was no statistically significant effect on IL-1ß and IL-4. CONCLUSION: Coculturing of BMSCHOXB4 prevented LPS-induced EC injury by reversing the inactivation of the Wnt/ß-catenin signaling pathway. An in vivo study remains warranted to ascertain whether engraftment of BMSCHOXB4 can be an attractive strategy for the treatment of ALI/ARDS.

Association of Cardiac Troponin T Concentration on Admission with Prognosis in Critically Ill Patients without Myocardial Infarction: A Cohort Study.

PURPOSE: To investigate the association of cardiac Troponin T (cTnT) with prognosis in critically ill patients without myocardial infarction. METHODS: Adult patients admitted to the intensive care units (ICUs) of the Beth Israel Deaconess Medical Center between 2008 and 2019 who were free of myocardial infarction with a length of ICU stay ≥24 hours and available cTnT records within 24 hours before and after ICU admission were included. The association between cTnT on ICU admission and hospital mortality was evaluated by multivariable logistic regression analysis. The discrimination capacity of cTnT on ICU admission for predicting hospital mortality was examined by receiver operating characteristic (ROC) analysis. RESULTS: A total of 2960 patients were included. Elevated cTnT (>0.01 ng/mL) was observed in 2730 (92.23%) patients with a higher hospital mortality compared to normal cTnT (11.21% versus 7.39%, P=0.075). There was no statistically significant association between elevated cTnT on ICU admission and hospital mortality (adjusted odds ratio 1.50, 95% confidence interval (CI) 0.88-2.57). Poor discrimination capacity was found for cTnT on ICU admission to predict hospital mortality (area under the ROC curve 0.48, 95% CI 0.44-0.53). CONCLUSION: cTnT on ICU admission has limited prognostic value in critically ill patients without myocardial infarction.

Sex Differences in Short- and Long-Term Survival Among Critically Ill Patients with Sepsis.

BACKGROUND: Currently, there have been studies showing a correlation between sex differences and prognosis. Nevertheless, the conclusions of clinical studies on sex-based differences are controversial. We aimed to evaluate the effect of sex on the short- and long-term survival of critically ill patients with sepsis. METHODS: We use the critical care database of the healthcare information mart. Cox models were conducted to determine the relationship of 28-day and 1-year mortality with a different sex. Interaction and stratified analyses were conducted to test whether the effect of sex differed across age and sequential organ failure assessment (SOFA) score subgroups. RESULTS: A total of 12,321 patients were enrolled in this study. The Cox regression analysis showed that the 28-day and 1-year mortality rates of female patients were significantly lower than those of male patients by 10% and 8%, respectively (hazard ratio [HR]=0.90, 95% confidence interval [CI] 0.83-0.98, and HR=0.92, 95% CI 0.87-0.97, respectively). The effects of the association between sex and 28-day and 1-year mortality were broadly consistent for age and the SOFA subgroup variables. Only age was observed to have significant interactions in the 1-year mortality (P=0.0177). Compared with male patients, female patients aged <50 years had a long-term survival advantage (HR=0.77, 95% CI 0.62-0.95). In contrast, we did not find sex-based differences in the short- and long-term survival for patients aged ≥50 years. CONCLUSION: In the current retrospective large database review, the 28-day and 1-year mortality were significantly lower in females than in male patients among critically ill patients with sepsis. Notably, there was an interaction between age and sex, and whether female-associated hormones or other contributing factors affect the clinical outcomes of patients with sepsis needs to be further researched.

Association between comorbid diabetes mellitus and prognosis of patients with sepsis in the intensive care unit: a retrospective cohort study.

BACKGROUND: Sepsis patients hospitalized in the intensive care unit (ICU) often have comorbid diabetes mellitus (DM). However, the clinical impact of DM on the clinical outcomes of critically ill sepsis patients has yet to be determined. Therefore, the current study aimed to analyze the association of comorbid DM with the prognosis of sepsis patients in the ICU. METHODS: Data of patients with sepsis and comorbid DM were obtained from a large-scale intensive care database. The primary outcome was 28-day mortality after ICU admission. Associations of comorbid DM with the primary outcome were assessed using a multivariable Cox regression model. Different adjusted models, such as the propensity score method, were used to determine the prognosis of the patients. RESULTS: Overall, 12,321 sepsis patients were enrolled, including 3,509 (28.48%) with comorbid DM. After adjusting and matching, we found that comorbid DM was not an independent risk factor for 28-day mortality in critically ill sepsis patients and was even associated with lower mortality. Propensity score matching showed a dramatically lower 28-day mortality for sepsis patients with comorbid DM in comparison to patients without comorbid DM [hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.77-0.97, P=0.0167]. The relationship of comorbid DM with 28-day mortality was broadly consistent for all subgroup variables. In the stratified analysis, a significant interaction was observed only for glucose concentration (P<0.0001). Patients with comorbid DM and a glucose level of 140-200 mg/dL (7.8-11.1 mmol/L) or ≥200 mg/dL (11.1 mmol/L) had a significantly lower 28-day mortality rate (HR 0.83, 95% CI: 0.71-0.98, P=0.0250 and HR: 0.49, 95% CI: 0.38-0.64, P<0.0001, respectively). CONCLUSIONS: Critically ill patients with sepsis and comorbid DM were not found to have increased 28-day mortality compared to those without comorbid DM, and may even have a lower risk of mortality. Notably, this association remained in the setting of hyperglycemia.

Association of Diabetes and Admission Blood Glucose Levels with Short-Term Outcomes in Patients with Critical Illnesses.

BACKGROUND: Association of diabetes and admission glucose on the short-term prognosis in patients with critical illnesses are currently ambiguous. We aimed to determine whether diabetes and admission glucose affects short-term prognosis of critically ill patients. METHODS: We performed a retrospective analysis of data on 46,476 critically ill patients from the critical care database. Association of diabetes with 28-day mortality was assessed by inverse probability weighting based on the propensity score. Smoothing splines and threshold effect analysis were applied to explore the relationship between admission glucose and clinical outcomes. RESULTS: Of the 33,680 patients enrolled in the study, 8,701 (25.83%) had diabetes. In the main analysis, the 28-day mortality was reduced by 29% (hazard ratio (HR)=0.71, 95% confidence interval (CI) 0.67-0.76) in patients with diabetes compared to those without diabetes. The E-value of 2.17 indicated robustness to unmeasured confounders. Significant interactions were observed for glucose at ICU admission, admission type, and insulin use (Interaction P <0.05). A V-shaped relationship was observed between admission glucose and 28-day mortality in non-diabetic patients, with the lowest 28-day mortality corresponding to a glucose level of 101.75 mg/dl (95% CI 94.64-105.80 mg/dl), and admission hypoglycemia or hyperglycemia should be avoided, especially in patients admitted to the surgical intensive care unit (SICU), cardiac surgery recovery unit (CSRU), and coronary care unit (CCU); for diabetic patients, elevated admission glucose does not appear to be associated with a poor prognosis and perhaps may be beneficial except for CCU and CSRU. CONCLUSION: The non-detrimental effect of diabetes on the short-term prognosis of critically ill patients was further confirmed, which would reduce 28-day mortality by approximately 29%. For non-diabetic patients, the admission glucose level corresponding to the lowest 28-day mortality was 101.75 mg/dl (95% CI 94.64-105.80 mg/dl); however, for diabetics, the appropriate admission glucose threshold remains unresolved.

The Association of Red Blood Cell Distribution Width to Platelet Count Ratio and 28-Day Mortality of Patients with Sepsis: A Retrospective Cohort Study.

BACKGROUND: Sepsis is a life-threatening and inflammatory disease with high morbidity and mortality. Red blood cell distribution width to platelet count ratio (RPR) was known as an inflammatory biomarker and was related to poor outcomes of various diseases. AIM: This study was intended to explore the association between RPR and mortality of sepsis patients. METHODS: A retrospective cohort study was undertaken in patients with sepsis, and the data were collected from a public database called Medical Information Mart for Intensive Care III (MIMIC-III). The primary outcome was 28-day mortality while the secondary outcomes were 90-day mortality and ICU mortality. Multivariable regression analyses, as well as interaction and stratified analyses, were conducted to investigate the relation between RPR and sepsis mortality. RESULTS: In total, we enrolled 7531 patients with 1316 deaths. RPR was independently correlated with 28-day mortality (per 0.1 increase: HR=1.04; 95% CI 1.02-1.06), 90-day mortality (per 0.1 increase: HR=1.04; 95% CI 1.03-1.06) and ICU mortality (per 0.1 increase: OR=1.06; 95% CI 1.02-1.10). Twenty-eight-day survival was worse in the high RPR (≥0.134) group according to the Kaplan-Meier curve analyses (Log rank test, p<0.001). In stratified analyses, Sequential Organ Failure Assessment (SOFA) score and length of ICU stay had interactive effects with the high RPR (≥0.134) group on 28-day mortality. CONCLUSION: RPR is a novel biomarker that indicates poor prognosis of sepsis patients. Clinicians are required to pay more attention to those patients with high RPR.

Association between Body Mass Index and Short-Term Clinical Outcomes in Critically Ill Patients with Sepsis: A Real-World Study.

BACKGROUND: Obesity is now recognized as one of the major public health threats, especially for patients with a critical illness. However, studies regarding whether and how body mass index (BMI) affects clinical outcomes in patients with sepsis are still scarce and controversial. The aim of our study was to determine the effect of BMI on critically ill patients with sepsis. MATERIALS AND METHODS: We performed this study using data from the Medical Information Center for Intensive Care III database. A multivariate Cox regression model was used to assess the independent association of BMI with the primary outcome. RESULTS: A total of 7,967 patients were enrolled in this study. Firstly, we found that the 28-day mortality was reduced by 22% (HR = 0.78, 95% CI 0.69-0.88) and 13% (HR = 0.87, 95% CI 0.78-0.98) for obese and overweight compared to normal weight, respectively. Subsequently, a U-shaped association of BMI with 28-day mortality was observed in sepsis patients, with the lowest 28-day mortality at the BMI range of 30-40 kg/m2. Finally, significant interactions were observed only for sex (P = 0.0071). Male patients with a BMI of 25-30 kg/m2 (HR = 0.74, 95% CI 0.63-0.86) and 30-40 kg/m2 (HR = 0.63, 95% CI 0.53-0.76) had a significantly lower risk of 28-day mortality. CONCLUSIONS: A U-shaped association of BMI with 28-day mortality in critically ill sepsis patients was found, with the lowest 28-day mortality at a BMI range of 30-40 kg/m2. Notably, male patients were protected by a higher BMI more effectively than female patients as males had a significantly lower mortality risk.

Effectiveness of electroacupuncture (EA) for the treatment of urinary incontinence (UI) in patients with spinal cord injury (SCI): A protocol of systematic review of randomized controlled trials.

BACKGROUND: The objective of this study is to examine the effectiveness and safety of electroacupuncture (EA) in the treatment of urinary incontinence (UI) in patients with spinal cord injury (SCI). METHODS: All potential studies will be retrieved from the electronic databases of MEDLINE, EMBASE, Cochrane Library, PsycINFO, Web of Science, CBM, and China National Knowledge Infrastructure from origin of each database up to January 31, 2020. Additionally, we will check other resources, such as Google scholar, dissertations, conference proceedings, and reference lists of included studies. No language and publication date limitations will be considered in the literature resources search. All randomized controlled trials using EA for the treatment of UI in patients with SCI will be included. Two independent investigators will perform study selection, data extraction and study quality assessment. If any conflicts occur, we will invite a third investigator to solve them. Cochrane risk of bias will be used for study quality assessment, and RevMan 5.3 software will be employed for statistical analysis. RESULTS: This study will summarize the most recent evidence to assess the effectiveness and safety of EA for the treatment of UI in patients with SCI. CONCLUSION: The results of this study will provide helpful evidence to determine whether EA is effective and safety for the treatment of UI in patients with SCI or not. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020165562.

A protocol of systematic review and meta-analysis of acupuncture for drug resistant epilepsy.

BACKGROUND: This study aims to appraise the effectiveness and safety of acupuncture for drug resistant epilepsy (DRE). METHODS: We will search all potential randomized controlled trials (RCTs) of acupuncture for patients with DRE from their origin to March 1, 2020: MEDLINE, EMBASE, Cochrane Library, CINAHL, Scopus, WANGFANG, and Chinese Biomedical Literature Database. We will not apply any restrictions to the language and publication date. All RCTs investigating the effectiveness and safety of acupuncture for patients with DRE will be included. Study quality will be appraised by Cochrane risk of bias, and statistical analysis will be scrutinized by RevMan 5.3 software. Whenever possible, a narrative summary to describe study quality and content of the evidence will be performed. RESULTS: This study will provide summarize high quality evidence and will utilize a variety of outcome measurements to verify effectiveness and safety of acupuncture for DRE. CONCLUSION: The results of this study will seek to explore the effectiveness and safety of acupuncture for DRE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020170517.

Efficacy of intrathecal baclofen bolus on neuropathic pain in patients with spinal cord injury: A protocol for systematic review and meta-analysis.

BACKGROUND: This study will explore the efficacy and safety of intrathecal baclofen bolus (IBB) on neuropathic pain (NPP) in patients with spinal cord injury (SCI). METHODS: All potential literatures of IBB on NPP in patients with SCI will be searched from the following electronic databases from inauguration to the January 31, 2020: PUBMED, EMBASE, Cochrane Library, Web of Science, Chinese Scientific Journal Database Information, WANGFANG, and China National Knowledge Infrastructure. In addition, we will search other sources, such as dissertations and reference lists of included trials. There are no restrictions of language and publication status in searching all literature sources. The quality of each eligible trial will be assessed using Cochrane risk of bias tool, and publication bias will be checked using a funnel plot and Egger test. Statistical analysis will be conducted using RevMan 5.3 software. RESULTS: This study will scrutinize the efficacy and safety of IBB on NPP in patients with SCI through pain intensity of NPP, spasticity, walking ability, health-related quality of life, duration of stay at hospital (days), incidence of adverse event, and mortality rate. CONCLUSIONS: The findings of this study will present helpful evidence to judge whether IBB is effective on NPP in patients with SCI or not. STUDY REGISTRATION NUMBER: INPLASY202040192.