Construction and evaluation of short-term and long-term mortality risk prediction model for patients with sepsis based on MIMIC-IV database. / 基于MIMIC-IVæž„å»ºåŠè¯„ä¼°è„“æ¯’ç—‡æ‚£è€ è¿‘æœŸå’Œè¿œæœŸæ­»äº¡é£Žé™©é¢„æµ‹æ¨¡åž‹.

OBJECTIVES: Given the high incidence and mortality rate of sepsis, early identification of high-risk patients and timely intervention are crucial. However, existing mortality risk prediction models still have shortcomings in terms of operation, applicability, and evaluation on long-term prognosis. This study aims to investigate the risk factors for death in patients with sepsis, and to construct the prediction model of short-term and long-term mortality risk. METHODS: Patients meeting sepsis 3.0 diagnostic criteria were selected from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and randomly divided into a modeling group and a validation group at a ratio of 7꞉3. Baseline data of patients were analyzed. Univariate Cox regression analysis and full subset regression were used to determine the risk factors of death in patients with sepsis and to screen out the variables to construct the prediction model. The time-dependent area under the curve (AUC), calibration curve, and decision curve were used to evaluate the differentiation, calibration, and clinical practicability of the model. RESULTS: A total of 14 240 patients with sepsis were included in our study. The 28-day and 1-year mortality were 21.45% (3 054 cases) and 36.50% (5 198 cases), respectively. Advanced age, female, high sepsis-related organ failure assessment (SOFA) score, high simplified acute physiology score II (SAPS II), rapid heart rate, rapid respiratory rate, septic shock, congestive heart failure, chronic obstructive pulmonary disease, liver disease, kidney disease, diabetes, malignant tumor, high white blood cell count (WBC), long prothrombin time (PT), and high serum creatinine (SCr) levels were all risk factors for sepsis death (all P<0.05). Eight variables, including PT, respiratory rate, body temperature, malignant tumor, liver disease, septic shock, SAPS II, and age were used to construct the model. The AUCs for 28-day and 1-year survival were 0.717 (95% CI 0.710 to 0.724) and 0.716 (95% CI 0.707 to 0.725), respectively. The calibration curve and decision curve showed that the model had good calibration degree and clinical application value. CONCLUSIONS: The short-term and long-term mortality risk prediction models of patients with sepsis based on the MIMIC-IV database have good recognition ability and certain clinical reference significance for prognostic risk assessment and intervention treatment of patients.

Continuous blood exchange in rats as a novel approach for experimental investigation.

Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases. Consequently, there is an urgent requirement to establish convenient and clinically applicable animal models that can facilitate the exploration of blood exchange therapy mechanisms. Our study conducted continuous WBE in rats through femoral and tail vein catheterization using dual-directional syringe pumps. To demonstrate the applicability of continuous WBE, drug-induced hemolytic anemia (DIHA) was induced through phenylhydrazine hydrochloride (PHZ) injection. Notability, the rats of DIHA + WBE group all survived and recovered within the subsequent period. After the implementation of continuous WBE therapy day (Day 1), the DIHA + WBE group exhibited a statistically significant increase in red blood cells (RBC) (P = 0.0343) and hemoglobin (HGB) levels (P = 0.0090) compared to DIHA group. The rats in the DIHA + WBE group exhibited a faster recovery rate compared to the DIHA group, indicating the successful establishment of a continuous blood exchange protocol. This experimental approach demonstrates not just promising efficacy in the treatment of DIHA and offers a valuable tool for investigating the underlying mechanisms of blood exchange. Furthermore, it has a great potential to the advancement of biomedical research such as drug delivery exploration.

Efficacy of fresh frozen plasma transfusion in decompensated cirrhosis patients with coagulopathy admitted to ICU: a retrospective cohort study from MIMIC-IV database.

We aimed to explore the association between FFP transfusion and outcomes of DC patients with significant coagulopathy. A total of 693 DC patients with significant coagulopathy were analyzed with 233 patients per group after propensity score matching (PSM). Patients who received FFP transfusion were matched with those receiving conventional therapy via PSM. Regression analysis showed FFP transfusion had no benefit in 30-day (HR: 1.08, 95% CI 0.83-1.4), 90-day (HR: 1.03, 95% CI 0.80-1.31) and in-hospital(HR: 1.30, 95% CI 0.90-1.89) mortality, associated with increased risk of liver failure (OR: 3.00, 95% CI 1.78-5.07), kidney failure (OR: 1.90, 95% CI 1.13-3.18), coagulation failure (OR: 2.55, 95% CI 1.52-4.27), respiratory failure (OR: 1.76, 95% CI 1.15-2.69), and circulatory failure (OR: 2.15, 95% CI 1.27-3.64), and even associated with prolonged the LOS ICU (ß: 2.61, 95% CI 1.59-3.62) and LOS hospital (ß: 6.59, 95% CI 2.62-10.57). In sensitivity analysis, multivariate analysis (HR: 1.09, 95%CI 0.86, 1.38), IPTW (HR: 1.11, 95%CI 0.95-1.29) and CAPS (HR: 1.09, 95% CI 0.86-1.38) showed FFP transfusion had no beneficial effect on the 30-day mortality. Smooth curve fitting demonstrated the risk of liver failure, kidney failure and circulatory failure increased by 3%, 2% and 2% respectively, for each 1 ml/kg increase in FFP transfusion. We found there was no significant difference of CLIF-SOFA and MELD score between the two group on day 0, 3, 7, 14. Compared with the conventional group, INR, APTT, and TBIL in the FFP transfusion group significantly increased, while PaO2/FiO2 significantly decreased within 14 days. In conclusion, FFP transfusion had no beneficial effect on the 30-day, 90-day, in-hospital mortality, was associated with prolonged the LOS ICU and LOS hospital, and the increased risk of liver failure, kidney failure, coagulation failure, respiratory failure and circulatory failure events. However, large, multi-center, randomized controlled trials, prospective cohort studies and external validation are still needed to verify the efficacy of FFP transfusion in the future.

The therapeutic efficacy of plasmapheresis for sepsis with multiple organ failure: a propensity score-matched analysis based on the MIMIC-IV database.

BACKGROUND: Despite advancements in sepsis treatment, mortality remains high. Plasmapheresis (PE) targeting multiple pathways simultaneously appears to be a potential treatment option, but evidence is insufficient. We aimed to investigate the efficacy of PE for sepsis with multiple organ failure (MOF). METHOD: Septic patients with MOF were identified from the Medical Information Mart for Intensive Care IV database. Patients who received PE were matched with those receiving conventional therapy via propensity score matching (PSM). Regression analyses evaluated the association between PE and outcomes. The Kaplan-Meier (KM) method was utilized to analyze the survival probability. The generalized additive mixed model investigated early indexes changes' association with treatment modalities and 28-day mortality. RESULTS: 906 septic patients with MOF were enrolled. After PSM, PE and conventional groups consisted of 60 cases each. PE was associated with a reduced risk of 28-day mortality (hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.27-0.94), 1-year mortality (HR: 0.44, 95%CI: 0.26-0.74), and in-hospital mortality (HR: 0.38, 95%CI: 0.20-0.71). KM curves demonstrated significant differences in survival probability between groups. Compared with the conventional group, the sequential organ failure assessment, norepinephrine dosage, prothrombin time, actate dehydrogenase, total bilirubin, white blood cells, and immature granulocytes in the PE group significantly decreased over time, while platelets, red blood cells, and hemoglobin significantly increased over time. CONCLUSIONS: Plasmapheresis demonstrated an association with reduced risks of 28-day, in-hospital and 1-year mortality in septic patients with MOF. Moreover, plasmapheresis might exhibit the potential to improve outcomes by improving organ function, hemodynamics and restoring several indicators such as coagulation, anemia, and inflammation.

Synergistic and Long-Lasting Wound Dressings Promote Multidrug-Resistant Staphylococcus Aureus-Infected Wound Healing.

Background: Multidrug-resistant staphylococcus aureus infected wounds can lead to nonhealing, systemic infections, and even death. Although advanced dressings are effective in protecting, disinfecting, and maintaining moist microenvironments, they often have limitations such as single functionality, inadequate drug release, poor biosafety, or high rates of drug resistance. Methods: Here, a novel wound dressing comprising glycyrrhizic acid (GA) and tryptophan-sorbitol carbon quantum dots (WS-CQDs) was developed, which exhibit synergistic and long-lasting antibacterial and anti-inflammatory effects. We investigated the characterization, mechanical properties, synergistic antibacterial effects, sustained-release properties, and cytotoxicity of GA/WS-CQDs hydrogels in vitro. Additionally, we performed transcriptome sequence analysis to elucidate the antibacterial mechanism. Furthermore, we evaluated the biosafety, anti-inflammatory effects, and wound healing ability of GA/WS-CQDs dressings using an in vivo mouse model of methicillin-resistant staphylococcus aureus (MRSA)-infected wounds. Results: The prepared GA/WS-CQDs hydrogels demonstrated superior anti-MRSA effects compared to common antibiotics in vitro. Furthermore, the sustained release of WS-CQDs from GA/WS-CQDs hydrogels lasted for up to 60 h, with a cumulative release of exceeding 90%. The sustained-released WS-CQDs exhibited excellent anti-MRSA effects, with low drug resistance attributed to DNA damage and inhibition of bacterial biofilm formation. Notably, in vivo experiments showed that GA/WS-CQDs dressings reduced the expression of inflammatory factors (TNF-α, IL-1ß, and IL-6) and significantly promoted the healing of MRSA-infected wounds with almost no systemic toxicity. Importantly, the dressings did not require replacement during the treatment process. Conclusion: These findings emphasize the high suitability of GA/WS-CQDs dressings for MRSA-infected wound healing and their potential for clinical translation.

U-SHAPED ASSOCIATION BETWEEN SERUM CALCIUM LEVELS AND 28-DAY MORTALITY IN PATIENTS WITH SEPSIS: A RETROSPECTIVE ANALYSIS OF THE MIMIC-III DATABASE.

ABSTRACT: Background: Serum calcium levels disorder have been reported to be associated with poor prognosis in different diseases. Studies on the association between serum calcium and outcomes of septic patients remained limited. The aim of this study is to investigate the association between serum calcium and 28-day mortality in septic patients. Method: Patients diagnosed with sepsis in the Medical Information Mart for Intensive Care III database were included. Patients were divided into five groups according to the quintiles of serum calcium levels, and their baseline characteristics were compared. Multivariate Cox regression models were used to assess the association between serum calcium and 28-day mortality. Smooth curve fitting and segmented regression models were used to visualize the association between serum calcium levels and 28-day mortality risk. The 28-day survival probability between five groups was analyzed using Kaplan-Meier curves. Results: A total of 3,016 patients with sepsis were enrolled, and the 28-day mortality rate was 35.64%. After adjusting for confounders, compared with the reference quintile (Q4: 9.00-9.50), the lowest serum calcium level quintile (Q1: 5.70-8.20) was independently associated with an increased risk of 28-day mortality (hazard ratio [HR], 2.12; 95% CI, 1.76-2.56). Smooth spline fitting revealed a U-shaped association between serum calcium and 28-day mortality. When serum calcium was <9.0 mg/dL, 28-day mortality risk increased by 58% per unit decrease in serum calcium (HR, 0.42; 95% CI, 0.37-0.48). When serum calcium was >9.0 mg/dL, the 28-day mortality risk increased by 12% per unit increase in serum calcium (HR, 1.12; 95% CI, 1.04-1.20). Conclusion: A U-shaped association was observed between serum calcium levels and 28-day mortality in septic patients. Lower or higher serum calcium levels were associated with increased risk of 28-day mortality in septic patients.

The effects of plasma to red blood cells transfusion ratio on in-hospital mortality in patients with acute type A aortic dissection.

Background: Blood transfusion is a frequent and necessary practice in acute type A aortic dissection (AAAD) patients, but the effect of plasma/red blood cells (RBCs) ratio on mortality remains unclear. The aim of this study is to investigate the association between plasma/RBCs transfusion ratio and in-hospital mortality in patients with AAAD. Methods: Patients were admitted to Xiangya Hospital of Central South University from January 1, 2016 to December 31, 2021. Clinical parameters were recorded. Multivariate Cox regression model was used to analyze the association between transfusion and in-hospital mortality. We used the smooth curve fitting and segmented regression model to assess the threshold effect between plasma/RBCs transfusion ratio and in-hospital mortality in patients with AAAD. Results: The volumes of RBCs [14.00 (10.12-20.50) unit] and plasma [19.25 (14.72-28.15) unit] transfused in non-survivors were significantly higher than in survivors [RBCs: 8.00 (5.50-12.00) unit]; plasma: [10.35 (6.50-15.22) unit]. Multivariate Cox regression analysis showed plasma transfusion was an independent risk factor of in-hospital mortality. Adjusted HR was 1.03 (95% CI: 0.96-1.11) for RBCs transfusion and 1.08 (95% CI: 1.03-1.13) for plasma transfusion. In the spline smoothing plot, mortality risk increased with plasma/RBCs transfusion ratio leveling up to the turning point 1. Optimal plasma/RBCs transfusion ratio with least mortality risk was 1. When the plasma/RBCs ratio was <1 (adjusted HR per 0.1 ratio: 0.28, 95% CI per 0.1 ratio: 0.17-0.45), mortality risk decreased with the increase of ratio. When the plasma/RBCs ratio was 1-1.5 (adjusted HR per 0.1 ratio: 2.73, 95% CI per 0.1 ratio:1.13-6.62), mortality risk increased rapidly with the increase of ratio. When the plasma/RBCs ratio was >1.5 (adjusted HR per 0.1 ratio: 1.09, 95% CI per 0.1 ratio:0.97-1.23), mortality risk tended to reach saturation, and increased non-significantly with the increase of ratio. Conclusion: A 1:1 plasma/RBCs ratio was associated with the lowest mortality in the patients with AAAD. And non-linear relationship existed between plasma/RBCs ratio and mortality.

High platelet distribution width is an independent risk factor of postoperative pneumonia in patients with type A acute aortic dissection.

Background: Platelet distribution width (PDW), as a widely applied and reliable marker of platelet activation, was associated with adverse outcomes in cardiovascular diseases. However, there is little literature on the relationship between PDW and postoperative pneumonia in patients with type A acute aortic dissection (AAAD). Methods: In this retrospective cohort study, we collected consecutive patients who underwent emergency surgery for AAAD at Xiangya Hospital of Central South University from January 1, 2014 and June 30, 2020. Patients were divided into three tertiles on the basis of the PDW. The independent effect of the PDW on postoperative pneumonia was evaluated using multivariate logistic regression analysis, and smooth curve fitting was performed to visualize the linear relationship between PDW and the risk of postoperative pneumonia in patients with AAAD. Results: A total of 210 patients with AAAD were enrolled and the overall incidence of postoperative pneumonia was 25.24% (n = 53). Multivariate logistic regression revealed that PDW was positively associated with the risk of postoperative pneumonia (OR: 1.07, 95% CI: 1.02-1.13, P < 0.05) after adjusting the confounders. Compared with the lowest PDW tertile, the risk of postoperative pneumonia increased by 1.21-fold in the medium PDW tertile (OR: 2.21, 95% CI: 0.73-6.72) and by 3.16-fold in the highest PDW tertile (OR: 4.16, 95% CI: 1.40-12.33). A straight-line relationship was observed between PDW and postoperative pneumonia risk in smoothing spline fitting. Conclusion: Our findings indicate that high PDW is an independent risk factor of postoperative pneumonia in patients with AAAD. Preoperative PDW may serve as an available indicator of pneumonia, which helps identify AAAD patients with a high risk of postoperative pneumonia.

A novel model forecasting perioperative red blood cell transfusion.

We aimed to establish a predictive model assessing perioperative blood transfusion risk using a nomogram. Clinical data for 97,443 surgery patients were abstracted from the DATADRYAD website; approximately 75% of these patients were enrolled in the derivation cohort, while approximately 25% were enrolled in the validation cohort. Multivariate logical regression was used to identify predictive factors for transfusion. Receiver operating characteristic (ROC) curves, calibration plots, and decision curves were used to assess the model performance. In total, 5888 patients received > 1 unit of red blood cells; the total transfusion rate was 6.04%. Eight variables including age, race, American Society of Anesthesiologists' Physical Status Classification (ASA-PS), grade of kidney disease, type of anaesthesia, priority of surgery, surgery risk, and an 18-level variable were included. The nomogram achieved good concordance indices of 0.870 and 0.865 in the derivation and validation cohorts, respectively. The Youden index identified an optimal cut-off predicted probability of 0.163 with a sensitivity of 0.821 and a specificity of 0.744. Decision curve (DCA) showed patients had a standardized net benefit in the range of a 5-60% likelihood of transfusion risk. In conclusion, a nomogram model was established to be used for risk stratification of patients undergoing surgery at risk for blood transfusion. The URLs of web calculators for our model are as follows: http://www.empowerstats.net/pmodel/?m=11633_transfusionpreiction .

Characterization and utilization of methyltransferase for apramycin production in Streptoalloteichus tenebrarius.

A structurally unique aminoglycoside produced in Streptoalloteichus tenebrarius, Apramycin is used in veterinary medicine or the treatment of Salmonella, Escherichia coli, and Pasteurella multocida infections. Although apramycin was discovered nearly 50 years ago, many biosynthetic steps of apramycin remain unknown. In this study, we identified a HemK family methyltransferase, AprI, to be the 7'-N-methyltransferase in apramycin biosynthetic pathway. Biochemical experiments showed that AprI converted demethyl-aprosamine to aprosamine. Through gene disruption of aprI, we identified a new aminoglycoside antibiotic demethyl-apramycin as the main product in aprI disruption strain. The demethyl-apramycin is an impurity in apramycin product. In addition to demethyl-apramycin, carbamyltobramycin is another major impurity. However, unlike demethyl-apramycin, tobramycin is biosynthesized by an independent biosynthetic pathway in S. tenebrarius. The titer and rate of apramycin were improved by overexpression of the aprI and disruption of the tobM2, which is a crucial gene for tobramycin biosynthesis. The titer of apramycin increased from 2227 ± 320 mg/L to 2331 ± 210 mg/L, while the titer of product impurity demethyl-apramycin decreased from 196 ± 36 mg/L to 51 ± 9 mg/L. Moreover, the carbamyltobramycin titer of the wild-type strain was 607 ± 111 mg/L and that of the engineering strain was null. The rate of apramycin increased from 68% to 87% and that of demethyl-apramycin decreased from 1.17% to 0.34%.

U-shaped relationship between platelet-lymphocyte ratio and postoperative in-hospital mortality in patients with type A acute aortic dissection.

BACKGROUND: The platelet-lymphocyte ratio (PLR), a novel inflammatory marker, is generally associated with increased in-hospital mortality risk. We aimed to investigate the association between PLR and postoperative in-hospital mortality risk in patients with type A acute aortic dissection (AAAD). METHODS: Patients (n = 270) who underwent emergency surgery for AAAD at Xiangya Hospital of Central South University between January 2014 and May 2019 were divided into three PLR-based tertiles. We used multiple regression analyses to evaluate the independent effect of PLR on in-hospital mortality, and smooth curve fitting and a segmented regression model with adjustment of confounding factors to analyze the threshold effect between PLR and in-hospital mortality risk. RESULTS: The overall postoperative in-hospital mortality was 13.33%. After adjusting for confounders, in-hospital mortality risk in the medium PLR tertile was the lowest (Odds ratio [OR] = 0.20, 95% confidence interval [CI] = 0.06-0.66). We observed a U-shaped relationship between PLR and in-hospital mortality risk after smoothing spline fitting was applied. When PLR < 108, the in-hospital mortality risk increased by 10% per unit decrease in PLR (OR = 0.90, P = 0.001). When the PLR was between 108 and 188, the mortality risk was the lowest (OR = 1.02, P = 0.288). When PLR > 188, the in-hospital mortality risk increased by 6% per unit increase in PLR (OR = 1.06, P = 0.045). CONCLUSIONS: There was a U-shaped relationship between PLR and in-hospital mortality in patients with AAAD, with an optimal PLR range for the lowest in-hospital mortality risk of 108-188. PLR may be a useful preoperative prognostic tool for predicting in-hospital mortality risk in patients with AAAD and can ensure risk stratification and early treatment initiation.

Construction of Au-IDE/CFP10-ESAT6 aptamer/DNA-AuNPs MSPQC for rapid detection of Mycobacterium tuberculosis.

Au-IDE/CFP10-ESAT6 aptamer/DNA-AuNPs MSPQC for rapid detection of Mycobacterium tuberculosis was constructed based on specific detection of specific fused antigen CFP10-ESAT6 which secreted only by pathogenic M. tuberculosis in its early culture time. CFP10-ESAT6 aptamer was used as sensor specific probe of CFP10-ESAT6 antigen. Au nanoparticles (NPs) was employed to increase sensor senstivity. The Au-IDE/CFP10-ESAT6 aptamer/DNA-AuNPs electrode probe was prepared by modifying of the complementary DNA-AuNPs on to interdigital array microelectrode with CFP10-ESAT6 aptamer. CFP10-ESAT6 aptamer could specifically catch CFP10-ESAT6 protein and formed a tight complex on the electrode surface and resulted in the DNA-AuNPs fragments fell away from the electrode surface. This change can be sensitively detected by IDE-MSPQC sensor. The detection time was 96.3h. Non-pathogenic Mycobacterium did not affect detection. Compared with conventional methods, this approach was specific, more sensitive, and expected to become a valuable analysis tool for the early detection of M. tuberculosis in clinical sample.