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Abstract Background The process of assessing and allocating nursing staff, as well as evaluating performance, relies heavily on nursing workload, which is strongly associated with patient safety outcomes. Nevertheless, most previous studies have utilized cross-sectional data collection methods, which limit the precision of workload prediction. Static workload models do not incorporate longitudinal changes in influential factors, potentially resulting in delayed or erroneous nursing management decisions and ultimately causing imbalances in nurses’ workload. Aim To employ machine learning algorithms to facilitate the dynamic prediction of nursing workload on the basis of patient characteristics. Methods This prospective cohort quantitative study was conducted between March 2019 and August 2021 in two general hospitals located in China. Data on the characteristics of 133 patients over the course of 1339 hospital days, as well as direct nursing time, were collected. A longitudinal investigation of nursing workload was carried out, applying multiple linear regression to identify measurable factors that significantly impact nursing workload. Additionally, machine learning methods were applied to dynamically predict the nursing time needed for each patient. Results The mean direct nursing workload varied greatly across hospitalizations. Significant factors contributing to increased care needs included complications, comorbidities, body mass index (BMI), income, history of past illness, simple clinical score (SCS), and activities of daily living (ADL). The predictive performance improved through machine learning, with the random forest model demonstrated the best performance (root mean square error (RMSE): 1148.38; coefficient of determination (R2): 0.74; mean square error (MSE): 1318744.64). Conclusions The variability in nursing workload during hospitalization is influenced primarily by patient self-care capacity, complications, and comorbidities. The random forest algorithm, a machine learning algorithm, effectively handles a wide range of features, such as patient characteristics, complications, comorbidities, and other factors. This algorithm has demonstrated good performance in predicting workload. Implications for nursing management This study introduces a quantitative model designed to evaluate nursing workload throughout the duration of hospitalization. By employing the model, nursing managers can consider multiple factors that impact workload comprehensively, resulting in enhanced comprehension and interpretation of workload variations. Through the application of a random forest algorithm for workload prediction, nursing managers can anticipate and estimate workload in a proactive and precise manner, thereby facilitating more efficient human resource planning.

Sensorineural hearing loss (SNHL) is characterized by a compromised cochlear perception of sound waves. Major risk factors for SNHL include genetic mutations, exposure to noise, ototoxic medications, and the aging process. Previous research has demonstrated that inflammation, oxidative stress, apoptosis, and autophagy, which are detrimental to inner ear cells, contribute to the pathogenesis of SNHL; however, the precise mechanisms remain inadequately understood. The endoplasmic reticulum (ER) plays a key role in various cellular processes, including protein synthesis, folding, lipid synthesis, cellular calcium and redox homeostasis, and its homeostatic balance is essential to maintain normal cellular function. Accumulation of unfolded or misfolded proteins in the ER leads to endoplasmic reticulum stress (ERS) and activates the unfolded protein response (UPR) signaling pathway. The adaptive UPR has the potential to reestablish protein homeostasis, whereas the maladaptive UPR, associated with inflammation, oxidative stress, apoptosis, and autophagy, can lead to cellular damage and death. Recent evidence increasingly supports the notion that ERS-mediated cellular damage responses play a crucial role in the initiation and progression of various SNHLs. This article reviews the research advancements on ERS in SNHL, with the aim of elucidating molecular biological mechanisms underlying ERS in SNHL and providing novel insights for the treatment.

ABSTRACT The mechanisms behind the high inflammatory state and immunocompromise in severe sepsis remain unclear. While microbiota’s role in immune regulation is known, the impact of pulmonary microbiota on sepsis progression is not fully understood. This study aims to investigate pulmonary microbial characteristics in septic patients and their relationship with host immune-related genes and clinical features. Fifty-four sepsis patients were divided into the immunocompromised host (ICH) group (n = 18) and the control group (n = 36). Bronchoalveolar lavage fluid (BALF) was analyzed using metagenomic next-generation sequencing (mNGS) to assess the pulmonary microbiome, and transcriptomic sequencing evaluated host gene expression. The pulmonary microbiota network in the ICH group showed notable alterations. Symbiotic bacteria like Streptococcus salivarius and Streptococcus oralis were key taxa in the control group. In contrast, opportunistic pathogens such as Campylobacter concisus and Prevotella melaninogenica, typically linked to infections in various body sites, dominated in the ICH group. Transcriptomic analysis revealed differential genes between the two groups. The downregulated differential genes in the ICH group were primarily enriched in pathways related to T-cell activation and the Type I interferon signaling pathway, both crucial for the immune system. Further correlation analysis identified significant associations between certain microbes and host genes, as well as clinical indicators, particularly with species like Campylobacter concisus, Streptococcus salivarius, Streptococcus oralis, and several species of Veillonella. These findings suggest that alterations in the pulmonary microbiome, especially the presence of opportunistic pathogens, may contribute to immune dysregulation in immunocompromised septic patients, warranting further research to explore causal relationships.IMPORTANCERecent research has substantiated the significant role of microbiota in immune regulation, which could influence high inflammatory state and immunocompromise in patients with severe sepsis, as well as provide new opportunities for acute lung injury induced by sepsis diagnosis and treatment. Our study identified some potential critical microbes (Campylobacter concisus and several species of Veillonella), which were correlated with immune-related genes and might be the novel target to regulate immunotherapy in sepsis.

Abstract Background Sepsis is a common and severe disease with a high mortality rate in intensive care unit (ICU). The hemoglobin (HGB) level is a key parameter for oxygen supply in sepsis. Although HGB is associated with the progression of inflammation in sepsis patients, its role as a marker following sepsis treatment remains unclear. Here, we studied the correlation between early temporal changes in HGB levels and long-term mortality rates in septic patients. Method In this retrospective study of data on patients with sepsis from the Medical Information Mart for Intensive Care (MIMIC) IV database, the outcome was long-term mortality. Patients were divided based on the cut-off of the HGB percentage for receiver operating characteristic (ROC) curve calculation. Kaplan–Meier (KM) survival curves and Cox proportional hazards regression models were used to analyse the associations between groups and outcomes. Propensity score matching (PSM) was used to verify the results. Results In this study, 2042 patients with sepsis and changes in HGB levels at day 4 after admission compared to day 1 were enrolled and divided into two groups: group 1 (n = 1147) for those with reduction of HGB

Abstract Background Flexible hybrid teaching has become the new normal of basic medical education in the postepidemic era. Identifying ways to improve the quality of curriculum teaching and achieve high-level talent training is a complex problem that urgently needs to be solved. Over the course of the past several semesters, the research team has integrated design thinking (DT) into undergraduate teaching to identify, redesign and solve complex problems in achieving curriculum teaching and professional talent training objectives. Methods This study is an observational research. A total of 156 undergraduate stomatology students from Jining Medical University in 2021 were selected to participate in two rounds of online flipped teaching using the design thinking EDIPT (empathy, definition, idea, prototype, and test) method. This approach was applied specifically to the chapters on the respiratory system and female reproductive system. Data collection included student questionnaires, teacher-student interviews, and exam scores. GraphPad Prism software was used for data analysis, and the statistical method was conducted by multiple or unpaired t test. Results According to the questionnaire results, the flipped classroom teaching design developed using design thinking methods received strong support from the majority of students, with nearly 80% of students providing feedback that they developed multiple abilities during the study process. The interview results indicated that teachers generally believed that using design thinking methods to understand students' real needs, define teaching problems, and devise instructional design solutions, along with testing and promptly adjusting the effectiveness through teaching practices, played a highly positive role in improving teaching and student learning outcomes. A comparison of exam scores showed a significant improvement in the exam scores of the class of 2021 stomatology students in the flipped teaching chapters compared to the class of 2020 stomatology students, and this difference was statistically significant. However, due to the limitation of the experimental chapter scope, there was no significant difference in the overall course grades. Conclusion The study explores the application of design thinking in histology and embryology teaching, revealing its positive impact on innovative teaching strategies and students' learning experience in medical education. Online flipped teaching, developed through design thinking, proves to be an effective and flexible method that enhances student engagement and fosters autonomous learning abilities.

Abstract Background The current study aims to explore the relationship between tumor necrosis factor‐α (TNF‐α) polymorphism and the risk of primary nephrotic syndrome (PNS). Methods A total of 250 PNS patients were selected for this study, as well as 300 volunteers serving as the control group. TNF‐α polymorphism were assessed using the polymerase chain reaction‐restriction fragment length polymorphism method. In addition, a meta‐analysis was conducted to analyze previously published literature on this topic. Results No significant differences were observed in the genotypes frequency or alleles frequency among the study populations. Meta‐analysis results revealed a positive association between TNF‐α rs1800629 polymorphism and allele contrast in African populations (p = 0), homozygote comparison (p = .007), heterozygote comparison (p = .026), recessive genetic model (p = .011), and dominant genetic model (p = .000). Conclusions TNF‐α rs1800629 polymorphism does not appear to confer any increased risk for PNS.

Abstract The authors of the manuscript ‘Complementary and alternative medicine - practice, attitudes, and knowledge among healthcare professionals in New Zealand: an integrative review’ [1] disagree with the assertion by McDowell et al. that our manuscript has extrapolation errors.

Abstract Background Phenylephrine (PE) and norepinephrine (NE) may be used to maintain adequate blood pressure and tissue perfusion in patients with septic shock, but the effect of NE combined with PE (NE-PE) on mortality remains unclear. We hypothesized that NE-PE would not inferior to NE alone for all-cause hospital mortality in patients with septic shock. Methods This single-center, retrospective cohort study included adult patients with septic shock. According to the infusion type, patients were divided into the NE-PE or NE group. Multivariate logistic regression, propensity score matching and doubly robust estimation were used to analyze the differences between groups. The primary outcome was the all-cause hospital mortality rate after NE-PE or NE infusion. Results Among 1, 747 included patients, 1, 055 received NE and 692 received NE-PE. For the primary outcome, the hospital mortality rate was higher in patients who received NE-PE than in those who received NE (49.7% vs. 34.5%, p

Abstract Background Acute myocardial infarction (AMI) and cancer are diseases with high morbidity and mortality worldwide, bringing a serious economic burden, and they share some risk factors. The purpose of this study was to determine the effect of cancer on the all-cause in-hospital mortality of patients with AMI. Methods This multicenter retrospective study analyzed patients with AMI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and eICU Collaborative Research Database (eICU-CRD) in the United States. Patients were divided into two groups based on whether they had concomitant malignant cancer: cancer and noncancer groups. The outcome was all-cause in-hospital mortality. The association between the two groups and their outcomes were analyzed using Kaplan–Meier and Cox proportional-hazards regression models. Propensity score matching (PSM) and propensity score based inverse probability of treatment weighting (IPTW) were used to further adjust for confounding variables to verify the stability of the results. Results The study included 3,034 and 5,968 patients with AMI from the MIMIC-IV database and the eICU-CRD, respectively. Kaplan–Meier survival curves indicated that the probability of in-hospital survival was lower in patients with cancer than in those without cancer. After adjusting for potential confounding variables using multivariable Cox proportional hazards regression, the risk of all-cause in-hospital mortality was significantly higher in the cancer than the noncancer group, and the HR (95% CI) values for the cancer group were 1.56(1.22,1.98) and 1.35(1.01,1.79) in the MIMIC-IV database and the eICU-CRD, respectively. The same results were obtained after using PSM and IPTW, which further verified the results. Conclusions Among the patients with AMI, the all-cause in-hospital mortality risk of those with cancer was higher than those without cancer. Therefore, when treating such patients, comprehensive considerations should be made from a multidisciplinary perspective involving cardiology and oncology, with the treatment plan adjusted accordingly.

Objective This study aimed to investigate the work engagement of clinical nursing teachers and examine whether psychological capital and perceived supervisor social support mediates the association between role stress and work engagement among clinical nursing teachers.Design A cross-sectional study design was used.Setting This study was conducted in five tertiary hospitals affiliated with medical universities in Shandong Province, China.Participants A total of 412 clinical nursing teachers were recruited out of which 406 completed the questionnaires effectively.Methods Questionnaires were administered offline and the items consisted of social demographic characteristics, scale related to role stress, psychological capital, perceived supervisor social support and work engagement. T-tests, one-way analysis of variance and Pearson’s correlation analysis were conducted using SPSS, and mediation analysis was performed using structural equation modelling.Results The work engagement scores of clinical nursing teachers were high, with an average score of 4.76±0.69. Structural equation modelling showed a good fit of the data to the hypothesised model. Role stress did not directly affect work engagement (β=0.057, p>0.001). However, a strong indirect effect of role stress on work engagement (β=−0.373, p

Abstract Background Sepsis still threatens the lives of more than 300 million patients annually and elderly patients with sepsis usually have a more complicated condition and a worse prognosis. Existing studies have shown that both Hematocrit (HCT) and albumin (ALB) can be used as potential predictors of sepsis, and their difference HCT-ALB has a significant capacity to diagnose infectious diseases. Currently, there is no relevant research on the relationship between HCT-ALB and the prognosis of elderly sepsis patients. Therefore, this study aims to explore the association between HCT-ALB and mortality in elderly patients with sepsis. Methods This study was a multi-center retrospective study based on the Medical Information Mart for Intensive Care (MIMIC-IV) database and the eICU Collaborative Research Database (eICU-CRD) in elderly patients with sepsis. The optimal HCT-ALB cut-off point for ICU mortality was calculated by the Youden Index based on the eICU-CRD dataset, and multivariate logistic regressions were conducted to explore the association between HCT-ALB and ICU/hospital mortality in the two databases. Subgroup analyses were performed for different parameters and comorbidity status. Results The number of 16,127 and 3043 elderly sepsis patients were selected from two large intensive care databases (eICU-CRD and MIMIC-IV, respectively) in this study. Depending on the optimal cut-off point, patients in both eICU-CRD and MIMIC-IV were independently divided into low HCT-ALB (

Abstract Background Elderly patients with sepsis have many comorbidities, and the clinical reaction is not obvious. Thus, clinical treatment is difficult. We planned to use the laboratory test results and comorbidities of elderly patients with sepsis from a large-scale public database Medical Information Mart for Intensive Care (MIMIC) IV to build a random survival forest (RSF) model and to evaluate the model’s predictive value for these patients. Methods Clinical information of elderly patients with sepsis in MIMIC IV database was collected retrospectively. Machine learning (RSF) was used to select the top 30 variables in the training cohort to build the final RSF model. The model was compared with the traditional scoring systems SOFA, SAPSII, and APSIII. The performance of the model was evaluated by C index and calibration curve. Results A total of 6,503 patients were enrolled in the study. The top 30 important variables screened by RSF were used to construct the final RSF model. The new model provided a better C-index (0.731 in the validation cohort). The calibration curve described the agreement between the predicted probability of RSF model and the observed 30-day survival. Conclusions We constructed a prognostic model to predict a 30-day mortality risk in elderly patients with sepsis based on machine learning (RSF algorithm), and it proved superior to the traditional scoring systems. The risk factors affecting the patients were also ranked. In addition to the common risk factors of vasopressors, ventilator use, and urine output. Newly added factors such as RDW, type of ICU unit, malignant cancer, and metastatic solid tumor also significantly influence prognosis.

Abstract Background The efficacy of moxibustion in treating rheumatoid arthritis is recognized, but its molecular mechanism is still unclear. This study aimed to characterize the molecular map and potential key genes in the process of different moxibustion warm at Zusanli acupoint treatment of adjuvant arthritis (AA) model. Methods AA rat model was induced by complete Freund’s adjuvant (CFA) and then accessed by foot swelling and thermal hyperalgesia test. Transcriptome sequencing, series test of cluster (STC) and weighted gene co-expression network analysis (WGCNA) were used in this study. Results CFA-induced inflammation, foot swelling, and pain in AA rats were significantly improved by moxibustion warm. Differentially expressed genes (DEGs) were screened in nine different comparison groups and a total of 4535 DEGs were identified, and these DEGs were preferentially clustered in inflammatory and immune-related pathways, such as MAPK signaling pathway. Only 1 DEG of heat shock protein 90, alpha (cytosolic), class A member 1 (Hsp90aa1) was shared in comparison groups of model with moxibustion treatment. STC analysis also revealed that Hsp90aa1 was increased in AA model, but decreased after 37 °C moxibustion intervention, and constantly decreased after 42 °C moxibustion treatment. GO and KEGG pathway analysis revealed that these genes enriched in inflammatory and immune-related pathways. Moreover, WGCNA identified that violet module was positively correlated with model temperature while negatively correlated with control, and the paleturquoise module was positively correlated with model. The violet and paleturquoise module gene were significantly enriched in MAPK signaling pathway. Importantly, Hsp90aa1 also played a central role in the violet module by interacting with multiple proteins. Conclusions Moxibustion warm improved AA in rat, and we obtained the transcriptome profile and excavate a critical gene of Hsp90aa1, and provided insight into gene signatures for moxibustion warm at Zusanli acupoint in AA rat.

Abstract Background Lung infection is a common cause of sepsis, and patients with sepsis and lung infection are more ill and have a higher mortality rate than sepsis patients without lung infection. We constructed a nomogram prediction model to accurately evaluate the prognosis of and provide treatment advice for patients with sepsis and lung infection. Methods Data were retrospectively extracted from the Medical Information Mart for Intensive Care (MIMIC-III) open-source clinical database. The definition of Sepsis 3.0 [10] was used, which includes patients with life-threatening organ dysfunction caused by an uncontrolled host response to infection, and SOFA score ≥ 2. The nomogram prediction model was constructed from the training set using logistic regression analysis, and was then internally validated and underwent sensitivity analysis. Results The risk factors of age, lactate, temperature, oxygenation index, BUN, lactate, Glasgow Coma Score (GCS), liver disease, cancer, organ transplantation, Troponin T(TnT), neutrophil-to-lymphocyte ratio (NLR), and CRRT, MV, and vasopressor use were included in the nomogram. We compared our nomogram with the Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score II (SAPSII), the nomogram had better discrimination ability, with areas under the receiver operating characteristic curve (AUROC) of 0.743 (95% C.I.: 0.713–0.773) and 0.746 (95% C.I.: 0.699–0.790) in the training and validation sets, respectively. The calibration plot indicated that the nomogram was adequate for predicting the in-hospital mortality risk in both sets. The decision-curve analysis (DCA) of the nomogram revealed that it provided net benefits for clinical use over using the SOFA score and SAPSII in both sets. Conclusion Our new nomogram is a convenient tool for accurate predictions of in-hospital mortality among ICU patients with sepsis and lung infection. Treatment strategies that improve the factors considered relevant in the model could increase in-hospital survival for these ICU patients.

Abstract Background Simulation has been widely used in the teaching of pre-licensed nursing students and has shown positive results. However, there is limited evidence regarding the application of a comprehensive nursing course with simulation for Associated Degree in Nursing (ADN)-prepared nurses with different work experience times. Therefore, this study aimed to evaluate the satisfaction, self-confidence, and perceptions of scenario simulation among Chinese nurses in a comprehensive nursing skills course in an RN-BSN program. Methods A single-group post-test approach was used in the current study. Participants that completed a comprehensive nursing skills course with simulation in an RN-BSN program were enrolled. Results The mean satisfaction, self-confidence, educational practice, and simulation designs scores were rated highly. Self-confidence (p = 0.002), active learning (p = 0.020), collaboration (p = 0.030), support (p = 0.008), and problem-solving (p = 0.007) were significantly higher among students with more work experience compared to those with less experience. Then, four themes were analyzed: enthusiasm for learning, ability to experience different feelings during role-play, hybrid teaching format, and simulation fidelity. Conclusions Results demonstrated that a comprehensive nursing skills course with simulation might improve Chinese ADN-prepared nurses’ satisfaction and self-confidence in learning. Nurses with work experience gave a high rate to the scenario simulation, demonstrating that simulation can be widely applicable for students with different characteristics. Finally, the teaching strategy in the present study can be applied to more RN-BSN programs.

Background: To identify the distinct trajectories of the Sequential Organ Failure Assessment (SOFA) scores at 72 h for patients with sepsis in the Medical Information Mart for Intensive Care (MIMIC)-IV database and determine their effects on mortality and adverse clinical outcomes. Methods: A retrospective cohort study was carried out involving patients with sepsis from the MIMIC-IV database. Group-based trajectory modeling (GBTM) was used to identify the distinct trajectory groups for the SOFA scores in patients with sepsis in the intensive care unit (ICU). The Cox proportional hazards regression model was used to investigate the relationship between the longitudinal change trajectory of the SOFA score and mortality and adverse clinical outcomes. Results: A total of 16,743 patients with sepsis were included in the cohort. The median survival age was 66 years (interquartile range: 54–76 years). The 7-day and 28-day in-hospital mortality were 6.0% and 17.6%, respectively. Five different trajectories of SOFA scores according to the model fitting standard were determined: group 1 (32.8%), group 2 (30.0%), group 3 (17.6%), group 4 (14.0%) and group 5 (5.7%). Univariate and multivariate Cox regression analyses showed that, for different clinical outcomes, trajectory group 1 was used as the reference, while trajectory groups 2–5 were all risk factors associated with the outcome (P < 0.001). Subgroup analysis revealed an interaction between the two covariates of age and mechanical ventilation and the different trajectory groups of patients’ SOFA scores (P < 0.05). Conclusion: This approach may help identify various groups of patients with sepsis, who may be at different levels of risk for adverse health outcomes, and provide subgroups with clinical importance.

Abstract Background Sepsis-associated acute kidney injury (S-AKI) is a common and life-threatening complication in hospitalized and critically ill patients. This condition is an independent cause of death. This study was performed to investigate the correlation between the trajectory of urine output within 24 h and S-AKI. Methods Patients with sepsis were studied retrospectively based on the Medical Information Mart for Intensive Care IV. Latent growth mixture modeling was used to classify the trajectory of urine output changes within 24 h of sepsis diagnosis. The outcome of this study is AKI that occurs 24 h after sepsis. Cox proportional hazard model, Fine–Gray subdistribution proportional hazard model, and doubly robust estimation method were used to explore the risk of AKI in patients with different trajectory classes. Results A total of 9869 sepsis patients were included in this study, and their 24-h urine output trajectories were divided into five classes. The Cox proportional hazard model showed that compared with class 1, the HR (95% CI) values for classes 3, 4, and 5 were 1.460 (1.137–1.875), 1.532 (1.197–1.961), and 2.232 (1.795–2.774), respectively. Competing risk model and doubly robust estimation methods reached similar results. Conclusions The trajectory of urine output within 24 h of sepsis patients has a certain impact on the occurrence of AKI. Therefore, in the early treatment of sepsis, close attention should be paid to changes in the patient's urine output to prevent the occurrence of S-AKI.

Abstract Background The use of dobutamine in patients with sepsis is questionable currently. As the benefit of dobutamine in septic patients is unclear, we aimed to evaluate whether the use of dobutamine was associated with decreased hospital mortality in sepsis patients. Methods Based on the analysis of MIMIC III public database, we performed a big-data, real world study. According to the use of dobutamine or not, patients were categorized as the dobutamine group or non dobutamine group.We used propensity score matched (PSM) analysis to adjust for confoundings. The primary outcome was hospital mortality. Results In the present study, after screening 38,605 patients, 2826 patients with sepsis were included. 121 patients were in dobutamine group and 2165 patients were in non dobutamine group. Compared with patients in non-dobutamine group, patients in dobutamine group had a lower MAP, higher HR, higher RR, higher severity of illness scores. 72 of 121 patients (59.5%) in the dobutamine group and 754 of 2165 patients (34.8%) in the non-dobutamine group died in the hospital, which resulted in a significant between-group difference (OR 1.56, 95% CI 1.01–2.40; P = 0.000). For the secondary outcomes, patients in dobutamine group received more MV use, more renal replacement therapy use, had longer ICU stay durations and more cardiac arrhythmias than those in non-dobutamine group. After adjusting for confoundings between groups by PSM analysis, hospital mortality was consistently higher in dobutamine group than that in non-dobutamine group (60.2% vs. 49.4%, OR 1.55, 95% CI 1.01–2.37; P = 0.044). Conclusions Among patients with sepsis, our study showed that the use of dobutamine was not associated with decreased hospital mortality. Further large scale, randomized controlled studies are warrented to confirm our findings.

Abstract Background Early and timely fluid treatment or resuscitation are the basic measures for the active treatment of sepsis. Our aim is to further explore the relationship between fluid balance and prognosis in patients with sepsis on a daily basis for 5 days. Methods Sepsis patients in eICU Collaborative Research Database were divided into the negative balance group (NB/−) and the positive balance group (PB/+) according to daily fluid balance. The primary outcome was in-hospital mortality. Survival differences between the groups were analyzed by using Cox regression. Then dose-response relationship between fluid balance and in-hospital mortality was studied using restricted cubic splines (RCSs). Furthermore, patients with fluid balance data for the previous three consecutive days were selected and divided into eight groups (“+/+/+”, “+/+/−”, “+/ −/−”, “+/ −/+”, “−/ −/−”, “−/ −/+”, “−/+/+”, and “−/+/−”). Kaplan–Meier curves and Cox regression were used to show the survival difference between groups. Results Our study, which included 19,557 patients in a multicenter database, showed that positive fluid balances on days 1, 2, and 3 after sepsis diagnosis were associated with poor prognosis with the HRs of 1.29 (1.20,1.40), 1.13 (1.01,1.27), and 1.25 (1.08,1.44), respectively, while the fluid balance on days 4 and 5 had no effect on the primary outcome. Then RCSs showed an overall trend that the risk of in-hospital mortality on days 1, 2, and 3 increased with increasing fluid balance. For three consecutive days of fluid balance, we studied 9205 patients and Kaplan–Meier curves revealed survival differences among patients in the eight groups. The cox model demonstrated that compared with the “+/+/+” group, the “+/ −/−”, “−/ −/−”, “−/ −/+”, “−/+/+”, and “−/+/−” groups had a lower risk of in-hospital mortality, with HRs of 0.65 (0.45,0.93), 0.72 (0.60,0.86), 0.63 (0.43,0.93), 0.69 (0.48,0.98), and 0.63 (0.42,0.96), respectively. Conclusions In patients with sepsis, positive fluid balance on days 1, 2, and 3 was associated with adverse outcomes. For patients with fluid balance for three consecutive days, the “+/−/−”, “−/ −/−”, “−/−/+”, “−/+/+”, and “−/+/−” groups were less likely to die in hospital than the “+/+/+” group.

Protein-based hydrogels hold a high content of water in their three-dimensional (3D) network structure and exhibit innate biological activities as well as soft tissue-like mechanical properties, resulting in being highly applicable to various tissue engineering fields. However, precisely controlling the 3D porous structure of protein-based hydrogels remains a challenging task, and understanding the influence of their porous structure on physical properties and cellular responses is crucial for tissue engineering applications. In this study, we prepared highly ordered gelatin methacryloyl hydrogels with regular interconnected pores and traditional bulk hydrogels with irregular pores to evaluate their differences in physiochemical properties and cellular behaviors. Highly ordered gelatin methacryloyl hydrogels exhibited a high degree of compliance owing to their sponge-like structure whereas gelatin methacryloyl bulk hydrogels exhibited relatively higher moduli but were brittle due to a densely packed structure. The highly ordered gelatin methacryloyl hydrogels with interconnected pores supported higher cell viability (about 100%) due to an efficient flux of oxygen and nutrients compared to the dense bulk hydrogels showing cell viability (around 80%). Also, cells in the highly ordered gelatin methacryloyl hydrogels displayed a more stretched morphology compared to those in the gelatin methacryloyl bulk hydrogels that exhibited a more round morphology during the cell culture period.

Ischemic stroke (IS) has been associated with an impairment in glymphatic function. Xuefu Zhuyu Decoction (XFZYD) is widely used in the prevention and treatment of ischemic stroke. We hypothesized that Xuefu Zhuyu decoction pretreatment could attenuate early neurological deficits after ischemic stroke by enhancing the function of the glymphatic system. To prove our hypothesis, we carried out temporary middle cerebral artery occlusion and reperfusion surgery on C57BL/6 mice and then measured neurological score, infarct size and performed hematoxylin-eosin staining to assess stroke outcomes after 24 h of reperfusion. Subsequently, we injected fluorescent tracers in to the cisterna magna and evaluated tracer distribution in coronal brain sections. The polarization of aquaporin-4 (AQP4), colocalization of aquaporin-4, α-dystroglycan, β-dystroglycan and agrin were determined by immunofluorescence. Our research showed that pretreatment with Xuefu Zhuyu decoction significantly alleviated neurological scores, neurological deficits and pathological abnormalities in a mouse model of ischemic stroke. Importantly, Xuefu Zhuyu decoction pretreatment enhanced cerebrospinal fluid influx, protected aquaporin-4 depolarization and promoted the colocalization of aquaporin-4 with its anchoring proteins in the brain. Our findings highlight novel mechanisms underlying the neuroprotective effect of Xuefu Zhuyu decoction pretreatment on ischemic stroke-induced brain damage through the glymphatic system. Xuefu Zhuyu decoction pretreatment may offer a promising approach to slow the onset and progression of ischemic stroke.

Summary: Sepsis-associated acute kidney injury (S-AKI) is very common and early prediction is beneficial. This study aiming to develop an accurate ensemble model to predict the risk of S-AKI based on easily available clinical information. Patients with sepsis from the United States (US) database Medical Information Mart for Intensive Care-IV were used as a modeling cohort to predict the occurrence of AKI by combining Support Vector Machine, Random Forest, Neural Network, and Extreme Gradient Boost as four first-level learners via stacking algorithm. The external validation databases were the eICU Collaborative Research Database from US and Critical Care Database comprising infection patients at Zigong Fourth People’s Hospital from China, whose AUROC values for the ensemble model 48–12 h before the onset of AKI were 0.774–0.788 and 0.756–0.813, respectively. In this study, an ensemble model for early prediction of S-AKI onset was developed and it demonstrated good performance in multicenter external datasets.

BackgroundSepsis is a serious disease with high clinical morbidity and mortality. Despite the tremendous advances in medicine and nursing, treatment of sepsis remains a huge challenge. Our purpose was to explore the effects of shock index (SI) trajectory changes on the prognosis of patients within 24 h after the diagnosis of sepsis.MethodsThis study was based on Medical Information Mart for Intensive Care IV (MIMIC- IV). The effects of SI on the prognosis of patients with sepsis were investigated using C-index and restricted cubic spline (RCS). The trajectory of SI in 24 h after sepsis diagnosis was classified by latent growth mixture modeling (LGMM). Cox proportional hazard model, double robust analysis, and subgroup analysis were conducted to investigate the influence of SI trajectory on in-hospital death and secondary outcomes.ResultsA total of 19,869 patients were eventually enrolled in this study. C-index showed that SI had a prognostic value independent of Sequential Organ Failure Assessment for patients with sepsis. Moreover, the results of RCS showed that SI was a prognostic risk factor. LGMM divided SI trajectory into seven classes, and patients with sepsis in different classes had notable differences in prognosis. Compared with the SI continuously at a low level of 0.6, the SI continued to be at a level higher than 1.0, and the patients in the class whose initial SI was at a high level of 1.2 and then declined had a worse prognosis. Furthermore, the trajectory of SI had a higher prognostic value than the initial SI.ConclusionBoth initial SI and trajectory of SI were found to be independent factors that affect the prognosis of patients with sepsis. Therefore, in clinical treatment, we should closely monitor the basic vital signs of patients and arrive at appropriate clinical decisions on basis of their change trajectory.

BackgroundType 2 diabetes leads to an increase in the prevalence of lipid abnormalities, which increases the risk of cardiovascular disease. Therefore, current guidelines generally recommend the use of moderate or high-intensity statins in patients with type 2 diabetes. There are still few studies on the overall risk benefit balance of statins for acute myocardial infarction (AMI) patients with diabetes. Compared with other types of lipid-lowering drugs, the advantage of statins for the prognosis of patients with AMI has not yet been determined. We investigated the effects of statins and non-statins on intensive care unit (ICU) and inpatient mortality in patients with AMI and diabetes.MethodsThis study retrospectively collected all patients with AMI and diabetes in the Medical Information Mart Intensive Care-IV database. We assessed ICU and in-hospital mortality rates during hospitalization in both groups. The clinical end point was in-hospital mortality and ICU mortality. Kaplan-Meier and Cox proportional-hazards regression models were applied to analyze the correlation between the two groups and the outcomes.ResultsData on 1,315 patients with AMI and diabetes were collected, among which 1,211 used statins during hospitalization. The overall in-hospital mortality of patients with AMI and diabetes was 17.2%, and the total ICU mortality was 12.6%. The in-hospital mortality was lower for the statin group than for the non-statin group (13.9% and 55.8%, respectively). Kaplan-Meier survival curves demonstrated that survival probability was higher in the statin group than in the non-statin group. In the cohort without hyperlipidemia, the statin group had lower risks of ICU death (HR = 0.12, 95% CI = 0.04–0.40) and in-hospital death (HR = 0.36, 95% CI = 0.16–0.84) compared with the non-statin group.ConclusionsStatins can significantly reduce ICU and in-hospital mortality rates in patients with AMI and diabetes. Even in the population without hyperlipidemia, statins can still reduce the mortality in patients with AMI and diabetes.

Peanut seeds are susceptible to Aspergillus flavus infection, which has a severe impact on the peanut industry and human health. However, the molecular mechanism underlying this defense remains poorly understood. The aim of this study was to analyze the changes in differentially expressed genes (DEGs) and differential metabolites during A. flavus infection between Zhonghua 6 and Yuanza 9102 by transcriptomic and metabolomic analysis. A total of 5768 DEGs were detected in the transcriptomic study. Further functional analysis showed that some DEGs were significantly enriched in pectinase catabolism, hydrogen peroxide decomposition and cell wall tissues of resistant varieties at the early stage of infection, while these genes were differentially enriched in the middle and late stages of infection in the nonresponsive variety Yuanza 9102. Some DEGs, such as those encoding transcription factors, disease course-related proteins, peroxidase (POD), chitinase and phenylalanine ammonialyase (PAL), were highly expressed in the infection stage. Metabolomic analysis yielded 349 differential metabolites. Resveratrol, cinnamic acid, coumaric acid, ferulic acid in phenylalanine metabolism and 13S-HPODE in the linolenic acid metabolism pathway play major and active roles in peanut resistance to A. flavus. Combined analysis of the differential metabolites and DEGs showed that they were mainly enriched in phenylpropane metabolism and the linolenic acid metabolism pathway. Transcriptomic and metabolomic analyses further confirmed that peanuts infected with A. flavus activates various defense mechanisms, and the response to A. flavus is more rapid in resistant materials. These results can be used to further elucidate the molecular mechanism of peanut resistance to A. flavus infection and provide directions for early detection of infection and for breeding peanut varieties resistant to aflatoxin contamination.

Abstract Background The prevalence of CAM use is increasing. This integrative review investigated New Zealand healthcare professionals’ practice of, attitudes toward, and knowledge about complementary and alternative medicine (CAM). Methods Literature search was conducted in four databases from inception to April 2020. Studies were included if they reported results from primary data collection on practice of, attitudes toward, or knowledge about CAM amongst New Zealand healthcare professionals. Results Eleven studies (two of ‘high-quality’, seven of ‘moderate-quality’, and two of ‘low-quality’) were identified with 2060 healthcare professionals including general practitioners (GPs), nurses, midwives, pharmacists, physiotherapists, and medical specialists. New Zealand healthcare professionals were generally positive regarding CAM use, but have concerns on the scientific evidence, regulation, safety, financial costs of CAM, and encourage an evidence-based CAM practice and stronger CAM regulation. Findings indicated that around 25% of GPs practise CAM, and 82.3% refer patients to CAM practitioners. When treating pregnant women, 48.4% of physiotherapists practise acupuncture, and 37.3% of midwives recommend CAM. GPs believe that acupuncture is the most helpful CAM modality, and most commonly practiced and referred patients to acupuncture. Up to 58% of GPs and Plunket nurses wanted to receive further education on CAM, and up to 66.7% GPs favour the idea CAM should be included in medical curriculums. Conclusions Nine of the 11 included studies were of moderate to high quality, thus enhancing the reliability of the review findings. In order to better manage CAM in New Zealand New Zealand clinical settings, there is a need to invest in CAM research and education, and enhance CAM regulation. This review is a first step in developing an evidence base to offer insights for further development of effective CAM policies regarding safety, efficacy, regulation and integration in New Zealand.

BackgroundAlthough there has been a large amount of research focusing on medical image classification, few studies have focused specifically on the portable chest X-ray. To determine the feasibility of transfer learning method for detecting atelectasis with portable chest X-ray and its application to external validation, based on the analysis of a large dataset.MethodsFrom the intensive care chest X-ray medical information market (MIMIC-CXR) database, 14 categories were obtained using natural language processing tags, among which 45,808 frontal chest radiographs were labeled as “atelectasis,” and 75,455 chest radiographs labeled “no finding.” A total of 60,000 images were extracted, including positive images labeled “atelectasis” and positive X-ray images labeled “no finding.” The data were categorized into “normal” and “atelectasis,” which were evenly distributed and randomly divided into three cohorts (training, validation, and testing) at a ratio of about 8:1:1. This retrospective study extracted 300 X-ray images labeled “atelectasis” and “normal” from patients in ICUs of The First Affiliated Hospital of Jinan University, which was labeled as an external dataset for verification in this experiment. Data set performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and positive predictive values derived from transfer learning training.ResultsIt took 105 min and 6 s to train the internal training set. The AUC, sensitivity, specificity, and accuracy were 88.57, 75.10, 88.30, and 81.70%. Compared with the external validation set, the obtained AUC, sensitivity, specificity, and accuracy were 98.39, 70.70, 100, and 86.90%.ConclusionThis study found that when detecting atelectasis, the model obtained by transfer training with sufficiently large data sets has excellent external verification and acculturate localization of lesions.

BackgroundAnti-Embolism (AE) devices therapy is an additional antithrombotic treatment that is effective in many venous diseases, but the correlations between this medical compression therapy and cardiovascular arterial disease or comorbid diabetes mellitus (DM) are still controversial. In this study we investigated the association between compression therapy and intensive care unit (ICU) mortality in patients with a first acute myocardial infarction (AMI) diagnosis complicated with type II DM.MethodsThis retrospective cohort study analyzed all patients with AMI and type II DM in the Medical Information Mart for Intensive Care-IV database. We extracted the demographics, vital signs, laboratory test results, comorbidities, and scoring system results of patients from the first 24 h after ICU admission. The outcomes of this study were 28-day mortality and ICU mortality. Analyses included Kaplan–Meier survival analysis, Cox proportional-hazards regression, and subgroup analysis.ResultsThe study included 985 eligible patients with AMI and type II DM, of who 293 and 692 were enrolled into the no-AE device therapy and AE device therapy groups, respectively. In the multivariate analysis, compared with no-AE device therapy, AE device therapy was a significant predictor of ICU mortality (HR = 0.48, 95% CI = 0.24–0.96, P = 0.039) and 28-day mortality (HR = 0.50, 95% CI = 0.27–0.90, P = 0.021). In addition to age, gender and coronary artery bypass grafting surgery, there were no significant interactions of AE device therapy and other related risk factors with ICU mortality and 28-day mortality in the subgroup analysis.ConclusionsSimple-AE-device therapy was associated with reduced risks of ICU mortality and 28-day mortality, as well as an improvement in the benefit on in-hospital survival in patients with AMI complicated with type II DM.

Objective Congestive heart failure (CHF) is a clinical syndrome in which the heart disease progresses to a severe stage. Early diagnosis and risk assessment of death of patients with CHF are critical to prognosis and treatment. The purpose of this study was to establish a nomogram that predicts the in-hospital death of patients with CHF in the intensive care unit (ICU).Design A retrospective observational cohort study.Setting and participants Data for the study were from 30 411 patients with CHF in the Medical Information Mart for Intensive Care database and the eICU Collaborative Research Database (eICU-CRD).Primary outcome In-hospital mortality.Methods Univariate logistic regression analysis was used to select risk factors associated with in-hospital mortality of patients with CHF, and multivariate logistic regression was used to build the prediction model. Discrimination, calibration and clinical validity of the model were evaluated by AUC, calibration curve, Hosmer-Lemeshow χ2 test and decision curve analysis, respectively. Finally, data from 15 503 patients with CHF in the multicentre eICU-CRD were used for external validation of the established nomogram.Results The inclusion criteria were met by 15 983 subjects, whose in-hospital mortality rate was 12.4%. Multivariate analysis determined that the independent risk factors were age, race, norepinephrine, dopamine, phenylephrine, vasopressin, mechanical ventilation, intubation, hepatic failure (HepF), heart rate, respiratory rate, temperature, systolic blood pressure (SBP), anion gap (AG), blood urea nitrogen (BUN), creatinine, chloride, mean corpuscular volume (MCV), red blood cell distribution width (RDW) and white cell count (WCC). The C-index of the nomogram (0.767, 95% CI 0.759 to 0.779) was superior to that of the traditional Sequential Organ Failure Assessment, Acute Physiology Score III and Get With The Guidelines Heart Failure scores, indicating its discrimination power. Calibration plots demonstrated that the predicted results are in good agreement with the observed results. The decision curves of the derivation and validation sets both had net benefits.Conclusion The 20 independent risk factors for in-hospital mortality of patients with CHF were age, race, norepinephrine, dopamine, phenylephrine, vasopressin, mechanical ventilation, intubation, HepF, heart rate, respiratory rate, temperature, SBP, AG, BUN, creatinine, chloride, MCV, RDW and WCC. The nomogram, which included these factors, accurately predicted the in-hospital mortality of patients with CHF. The novel nomogram has the potential for use in clinical practice as a tool to predict and assess mortality of patients with CHF in the ICU.

Background: In intensive care units (ICUs), the morbidity and mortality of ventilator-associated pneumonia (VAP) are relatively high, and this condition also increases medical expenses for mechanically ventilated patients, which will seriously affect the prognoses of critically ill patients. The purpose of this study was to determine the impact of bronchoscopy on the prognosis of patients with VAP undergoing invasive mechanical ventilation (IMV).Methods: This was a retrospective study based on patients with VAP from the Medical Information Mart for Intensive Care IV database. The outcomes were ICU and in-hospital mortality. Patients were divided based on whether or not they had undergone bronchoscopy during IMV. Kaplan-Meier (KM) survival curves and Cox proportional-hazards regression models were used to analyze the association between groups and outcomes. Propensity score matching (PSM) and propensity score based inverse probability of treatment weighting (IPTW) were used to further verify the stability of the results. The effect of bronchoscopy on prognosis was further analyzed by causal mediation analysis (CMA).Results: This study enrolled 1,560 patients with VAP: 1,355 in the no-bronchoscopy group and 205 in the bronchoscopy group. The KM survival curve indicated a significant difference in survival probability between the two groups. The survival probabilities in both the ICU and hospital were significantly higher in the bronchoscopy group than in the no bronchoscopy group. After adjusting all covariates as confounding factors in the Cox model, the HRs (95% CI) for ICU and in-hospital mortality in the bronchoscopy group were 0.33 (0.20–0.55) and 0.40 (0.26–0.60), respectively, indicating that the risks of ICU and in-hospital mortality were 0.67 and 0.60 lower than in the no-bronchoscopy group. The same trend was obtained after using PSM and IPTW. CMA showed that delta-red blood cell distribution width (RDW) mediated 8 and 7% of the beneficial effects of bronchoscopy in ICU mortality and in-hospital mortality.Conclusion: Bronchoscopy during IMV was associated with reducing the risk of ICU and in-hospital mortality in patients with VAP in ICUs, and this beneficial effect was partially mediated by changes in RDW levels.

Background: Ventilator-associated pneumonia (VAP) is a common infection complication in intensive care units (ICU). It not only prolongs mechanical ventilation and ICU and hospital stays, but also increases medical costs and increases the mortality risk of patients. Although many studies have found that thiamine supplementation in critically ill patients may improve prognoses, there is still no research or evidence that thiamine supplementation is beneficial for patients with VAP. The purpose of this study was to determine the association between thiamine and the prognoses of patients with VAP.Methods: This study retrospectively collected all patients with VAP in the ICU from the Medical Information Mart for Intensive Care-IV database. The outcomes were ICU and in-hospital mortality. Patients were divided into the no-thiamine and thiamine groups depending upon whether or not they had received supplementation. Associations between thiamine and the outcomes were tested using Kaplan-Meier (KM) survival curves and Cox proportional-hazards regression models. The statistical methods of propensity-score matching (PSM) and inverse probability weighting (IPW) based on the XGBoost model were also applied to ensure the robustness of our findings.Results: The study finally included 1,654 patients with VAP, comprising 1,151 and 503 in the no-thiamine and thiamine groups, respectively. The KM survival curves indicated that the survival probability differed significantly between the two groups. After multivariate COX regression adjusted for confounding factors, the hazard ratio (95% confidence interval) values for ICU and in-hospital mortality in the thiamine group were 0.57 (0.37, 0.88) and 0.64 (0.45, 0.92), respectively. Moreover, the results of the PSM and IPW analyses were consistent with the original population.Conclusion: Thiamine supplementation may reduce ICU and in-hospital mortality in patients with VAP in the ICU. Thiamine is an inexpensive and safe drug, and so further clinical trials should be conducted to provide more-solid evidence on whether it improves the prognosis of patients with VAP.

Sleep contributes to the maintenance of overall health and well-being. There are a growing number of patients who have headache disorders that are significantly affected by poor sleep. This is a paradoxical relationship, whereby sleep deprivation or excess sleep leads to a worsening of headaches, yet sleep onset also alleviates ongoing headache pain. Currently, the mechanism of action remains controversial and poorly understood. The glymphatic system is a newly discovered perivascular network that encompasses the whole brain and is responsible for removing toxic proteins and waste metabolites from the brain as well as replenishing nutrition and energy. Recent studies have suggested that glymphatic dysfunction is a common underlying etiology of sleep disorders and headache pain. This study reviews the current literature on the relationship between the glymphatic system, sleep, and headaches, discusses their roles, and proposes acupuncture as a non-invasive way to focus on the glymphatic function to improve sleep quality and alleviate headache pain.

Objective: This study analyzed the association of gastric acid secretion inhibitors (GASIs) [including proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs)] with the occurrence of ventilator-associated pneumonia (VAP) and in-hospital mortality in patients who received invasive mechanical ventilation (IMV).Method: Patients who received IMV and used GASI were included based on records in the MIMIC-IV database. The relationships of GASIs with VAP and the in-hospital mortality were determined using univariate and multivariate logistic regression analyses. Also, the effects of GASIs in some subgroups of the population were further analyzed.Results: A total of 18,669 patients were enrolled, including 9191 patients on H2RAs only, 6921 patients on PPIs only, and 2557 were on a combination of the two drugs. Applying logistic regression to the univariate and multivariate models revealed that compared with H2RAs, PPIs had no significant effect on the incidence of VAP, and the combination of H2RAs and PPIs was a risk factor for VAP. Compared with H2RAs, univariate logistic regression revealed that, PPIs and combine the two drugs were both risk factors for in-hospital mortality, but multivariate logistic regression showed that they were not significantly associated with in-hospital mortality. In subgroup analysis, there were interaction in different subgroups of age, PCO2, myocardial infarct, congestive heart failure (P for interaction

Background: Capsaicin (CAP) has an anti-obesity effect that has been shown to involve the transient receptor potential vanilloid-1 (TRPV1) channel. Importantly, recent studies in high fat diet (HFD)-fed mice show that CAP also alters gut microbiota composition and causes weight loss in HFD-fed mice. Many studies have suggested that short-chain fatty acids (SCFAs) mediate the links between diet, gut microbiota, and fat storage. Objective: The present study investigated whether CAP exerted its anti-obesity effect through changes in the composition of gut microbiota and SCFAs, and whether the TRPV1 contributes to CAP’s effects against obesity in HFD-fed mice. Design: C57BL/6J (TRPV1+/+) and B6.129X1-Trpv1tm1Jul/J (TRPV1-/-) mice were respectively divided into three groups (n = 6),that is SLD, HFD-fed, and CAP (2 mg/kg, po) +HFD fed and were administered respective treatment for 12 weeks. Results: We observed significantly lower weight gain and food intake, triglyceride, cholesterol, glucose, and insulin levels in HFD+CAP-fed TRPV1knockout (KO) mice compared to the HFD-fed KO mice, though this effect was more obvious in wild-type (WT) mice. CAP increased the numbers of Akkermansia, Prevotella, Bacteroides, Odoribacter, Allobaculum, Coprococcus, and S24-7, and reduced the numbers of Desulfovibrio, Escherichia, Helicobacter, and Sutterella in the HFD+CAP-fed WT and KO mice compared with HFD-fed WT and KO mice. CAP increased the relative abundances of SCFAs producing the bacterial species, which increased intestinal acetate and propionate concentrations, which were beneficial in prevention and treatment of obesity. Conclusions: Results from our study indicate that the reduced food intake and anti-obesity effect of CAP had been observed regardless of TRPV1 channel activation, and which is mediated by changes in the gut microbiota populations and SCFAs concentrations.

BackgroundVancomycin can effectively inhibit Gram-positive cocci and is widely used in critically ill patients. This study utilized a large public database to explore the effect of patients' first vancomycin trough concentration (FVTC) on the occurrence of acute kidney injury (AKI) and mortality after receiving vancomycin treatment in intensive care unit (ICU).MethodsCritically ill patients who used vancomycin in the Medical Information Mart for Intensive Care (MIMIC) IV have been retrospectively studied. The outcomes included the occurrence of AKI during the use of vancomycin or within 72 h of withdrawal, ICU mortality and hospital mortality. Restricted cubic splines (RCS) were used to analyze the linear relationship between FVTC and the outcomes. Multivariate logistic/Cox regression analysis was used to analyze the association between patient's FVTC and the occurrence of AKI, ICU mortality, and in-hospital mortality.ResultsThe study ultimately included 3,917 patients from the MIMIC-IV database who had been treated with vancomycin for more than 48 h. First of all, the RCS proved the linear relationship between FVTC and the outcomes. After controlling for all covariates as confounders in logistic/Cox regression, FVTC was a risk factor with the occurrence of AKI (OR: 1.02; 95% CI: 1.01–1.04), ICU mortality (HR: 1.02; 95% CI: 1.01–1.03), and in-hospital mortality (HR: 1.02; 95% CI: 1.01–1.03). Moreover, patients were divided into four groups in the light of the FVTC value: group1 ≤ 10 mg/L, 10 20 mg/L. Categorical variables indicated that group 3 and group 4 had a significant relationship on the occurrence of AKI [group 3: (OR: 1.36; 95% CI: 1.02–1.81); group 4: (OR: 1.76; 95% CI: 1.32–2.35)] and ICU mortality [group 3: (HR: 1.47; 95% CI: 1.03–2.09); group 4: (HR: 1.87; 95% CI: 1.33–2.62)], compared to group 1, while group 4 had a significant effect on in-hospital mortality (HR: 1.48; 95% CI: 1.15–1.91).ConclusionsFVTC is associated with the occurrence of AKI and increased ICU and in-hospital mortality in critically ill patients. Therefore, in clinical practice, patients in intensive care settings receiving vancomycin should be closely monitored for FVTC to prevent drug-related nephrotoxicity and reduce patient mortality.

Introduction: Liver cirrhosis is caused by the development of various acute and chronic liver diseases. Esophageal varices is a common and serious complication of liver cirrhosis during decompensation. Despite the development of various treatments, the prognosis for liver cirrhosis with esophageal varices (LCEV) remains poor. We aimed to establish and validate a nomogram for predicting in-hospital death in LCEV patients.Methods: Data on LCEV patients were extracted from the Medical Information Mart for Intensive Care III and IV (MIMIC-III and MIMIC-IV) database. The patients from MIMIC-III were randomly divided into training and validation cohorts. Training cohort was used for establishing the model, validation and MIMIC-IV cohorts were used for validation. The independent prognostic factors for LCEV patients were determined using the least absolute shrinkage and selection operator (LASSO) method and forward stepwise logistic regression. We then constructed a nomogram to predict the in-hospital death of LCEV patients. Multiple indicators were used to validate the nomogram, including the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow test, integrated discrimination improvement (IDI), net reclassification index (NRI), and decision curve analysis (DCA).Results: Nine independent prognostic factors were identified by using LASSO and stepwise regressions: age, Elixhauser score, anion gap, sodium, albumin, bilirubin, international normalized ratio, vasopressor use, and bleeding. The nomogram was then constructed and validated. The AUC value of the nomogram was 0.867 (95% CI = 0.832–0.904) in the training cohort, 0.846 (95% CI = 0.790–0.896) in the validation cohort and 0.840 (95% CI = 0.807–0.872) in the MIMIC-IV cohort. High AUC values indicated the good discriminative ability of the nomogram, while the calibration curves and the Hosmer-Lemeshow test results demonstrated that the nomogram was well-calibrated. Improvements in NRI and IDI values suggested that our nomogram was superior to MELD-Na, CAGIB, and OASIS scoring system. DCA curves indicated that the nomogram had good value in clinical applications.Conclusion: We have established the first prognostic nomogram for predicting the in-hospital death of LCEV patients. The nomogram is easy to use, performs well, and can be used to guide clinical practice, but further external prospective validation is still required.

Objective To construct a nomogram based on the Sequential Organ Failure Assessment (SOFA) that is more accurate in predicting 30-, 60-, and 90-day mortality risk in patients with sepsis. Methods Data from patients with sepsis were retrospectively collected from the Medical Information Mart for Intensive Care (MIMIC) database. Included patients were randomly divided into training and validation cohorts. Variables were selected using a backward stepwise selection method with Cox regression, then used to construct a prognostic nomogram. The nomogram was compared with the SOFA model using the concordance index (C-index), area under the time-dependent receiver operating characteristics curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA). Results A total of 5240 patients were included in the study. Patient’s age, SOFA score, metastatic cancer, SpO 2 , lactate, body temperature, albumin, and red blood cell distribution width were included in the nomogram. The C-index, AUC, NRI, IDI, and DCA of the nomogram showed that it performs better than the SOFA alone. Conclusion A nomogram was established that performed better than the SOFA in predicting 30-, 60-, and 90-day mortality risk in patients with sepsis.

Abstract Background The effect of high-flow nasal cannula (HFNC) therapy in patients after planned extubation remains inconclusive. We aimed to perform a rigorous and comprehensive systematic meta-analysis to robustly quantify the benefits of HFNC for patients after planned extubation by investigating postextubation respiratory failure and other outcomes. Method We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Library from inception to August 2018. Two researchers screened studies and collected the data independently. Randomized controlled trials (RCTs) and crossover studies were included. The main outcome was postextubation respiratory failure. Results Ten studies (seven RCTs and three crossover studies; HFNC group: 856 patients; Conventional oxygen therapy (COT) group: 852 patients) were included. Compared with COT, HFNC may significantly reduce postextubation respiratory failure (RR, 0.61; 95% CI, 0.41, 0.92; z = 2.38; P = 0.02) and respiratory rates (standardized mean differences (SMD), − 0.70; 95% CI, − 1.16, − 0.25; z = 3.03; P = 0.002) and increase PaO2 (SMD, 0.30; 95% CI, 0.04, 0.56; z = 2.23; P = 0.03). There were no significant differences in reintubation rate, length of ICU and hospital stay, comfort score, PaCO2, mortality in ICU and hospital, and severe adverse events between HFNC and COT group. Conclusions Our meta-analysis demonstrated that compared with COT, HFNC may significantly reduce postextubation respiratory failure and respiratory rates, increase PaO2, and be safely administered in patients after planned extubation. Further large-scale, multicenter studies are needed to confirm our results.

Background: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in patients in intensive care unit (ICU). The therapeutic value of glucocorticoids (GCs) in the prognosis of ARDS remains controversial. The aim of this research is studying the impacts of GCs treatment on ARDS patients in ICU.Methods: We retrospectively studied 2,167 ARDS patients whose data were collected from the public eICU Collaborative Research Database, among which 254 patients who received glucocorticoid (GCs) treatment were 1:1 matched by propensity matching analysis (PSM). The primary outcome was ICU mortality. Every oxygenation index (PaO2/FiO2) measurement before death or ICU discharge was recorded. A joint model (JM) which combined longitudinal sub-model (mixed-effect model) and time-to-event sub-model (Cox regression model) by trajectory functions of PaO2/FiO2 was conducted to determine the effects of GCs treatment on both ICU mortality and PaO2/FiO2 level and further PaO2/FiO2's effect on event status. The marginal structural cox model (MSCM) adjusted the overall PaO2/FiO2 of patients to further validate the results.Results: The result of the survival sub-model showed that GCs treatment was significantly associated with reduced ICU mortality in ARDS patients [HR (95% CI) = 0.642 (0.453, 0.912)], demonstrating that GCs treatment was a protective factor of ICU mortality. In the longitudinal sub-model, GCs treatment was not correlated to the PaO2/FiO2. After adjusted by the JM, the HR of GCs treatment was 0.602 while GCs was still not significantly related to PaO2/FiO2 level. The JM-induced association showed that higher PaO2/FiO2 was a significant protective factor of mortality in ARDS patients and the HR was 0.991 which demonstrated that one level increase of PaO2/FiO2 level decreased 0.9% risk of ICU mortality. MSCM results also show that GCs can improve the prognosis of patients.Conclusion: Rational use of GCs can reduce the ICU mortality of ARDS patients in ICU. In addition to the use of GCs treatment, clinicians should also focus on the shifting trend of PaO2/FiO2 level to provide better conditions for patients' survival.

Background: Diabetes mellitus (DM) has a high morbidity and mortality worldwide, and it is a risk factor for cardiovascular diseases. Non-diabetic stress hyperglycemia is common in severely ill patients, and it could affect prognosis. This study aimed to analyze the influence of different blood glucose levels on prognosis from the perspective of stress hyperglycemia by comparing them with normal blood glucose levels and those of patients with DM.Methods: A retrospective study of 1,401 patients in coronary care unit (CCU) from the critical care database called Medical Information Mart for Intensive Care IV was performed. Patients were assigned to the following groups 1–4 based on their history of DM, random blood glucose, and HbA1c levels: normal blood glucose group, moderate stress hyperglycemia group, severe stress hyperglycemia group and DM group. The main outcome of this study was 30- and 90-day mortality rates. The associations between groups and outcomes were analyzed using Kaplan–Meier survival analysis, Cox proportional hazard regression model and competing risk regression model.Results: A total of 1,401 patients in CCU were enrolled in this study. The Kaplan–Meier survival curve showed that group 1 had a higher survival probability than groups 3 and 4 in terms of 30- and 90-day mortalities. After controlling the potential confounders in Cox regression, groups 3 and 4 had a statistically significant higher risk of both mortalities than group 1, while no difference in mortality risk was found between groups 2 and 1. The hazard ratios [95% confidence interval (CI)] of 30- and 90-day mortality rates for group 3 were 2.77(1.39,5.54) and 2.59(1.31,5.12), respectively, while those for group 4 were 1.92(1.08,3.40) and 1.94(1.11,3.37), respectively.Conclusions: Severe stress hyperglycemia (≥200 mg/dL) in patients without DM in CCU may increase the risk of short-term death, which is greater than the prognostic effect in patients with diabetes. Patients with normal blood glucose levels and moderate stress hyperglycemia (140 mg/dL ≤ RBG

Background: Urinary tract infection (UTI) is one of the common causes of sepsis. However, nomograms predicting the sepsis risk in UTI patients have not been comprehensively researched. The goal of this study was to establish and validate a nomogram to predict the probability of sepsis in UTI patients.Methods: Patients diagnosed with UTI were extracted from the Medical Information Mart for Intensive Care III database. These patients were randomly divided into training and validation cohorts. Independent prognostic factors for UTI patients were determined using forward stepwise logistic regression. A nomogram containing these factors was established to predict the sepsis incidence in UTI patients. The validity of our nomogram model was determined using multiple indicators, including the area under the receiver operating characteristic curve (AUC), correction curve, Hosmer-Lemeshow test, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision-curve analysis (DCA).Results: This study included 6,551 UTI patients. Stepwise regression analysis revealed that the independent risk factors for sepsis in UTI patients were congestive heart failure, diabetes, liver disease, fluid electrolyte disorders, APSIII, neutrophils, lymphocytes, red blood cell distribution width, urinary protein, urinary blood, and microorganisms. The nomogram was then constructed and validated. The AUC, NRI, IDI and DCA of the nomogram all showed better performance than traditional APSIII score. The calibration curve and Hosmer-Lemeshow test results indicate that the nomogram was well-calibrated. Improved NRI and IDI values indicate that our nomogram scoring system is superior to other commonly used ICU scoring systems. The DCA curve indicates that the DCA map of the nomogram has good clinical application ability.Conclusion: This study identified the independent risk factors of sepsis in UTI patients and used them to construct a prediction model. The present findings may provide clinical reference information for preventing sepsis in UTI patients.

Objectives. The purpose of this study was to determine whether there is a dose-response relationship between body mass index (BMI) and all-cause mortality in patients after coronary revascularization. Methods. The MIMIC-III database (version 1.4) was used as the sample population. For variables with less than 10% of values missing, we used the mice package of R software for multiple imputations. Cox regression was used to determine the risk factors of all-cause mortality in patients. RCSs were used to observe the relationship between BMI and all-cause mortality. Additional subgroup and sensitivity analyses were also performed to explore whether the conclusion can be applied to specific groups. Results. Both univariate and multivariate Cox models indicated that the mortality risk was lower for overweight patients than for normal-weight patients (P

The increasing utilization of wood-based products raises new demands for improved durability, for example an enhanced liquid repellence. Superhydrophobic or superamphiphobic surfaces have been widely fabricated. Less attention has been paid to such modifications on wood and the changes of its hygroscopic or solvoscopic properties. In this work, wood veneers were surface modified by hydrophobized silicone nanofilaments. Results revealed that the surface-modified wood showed a superamphiphobic behavior, i.e. it repelled water, ethylene glycol and hexadecane with contact angles greater than 150° and roll-off angles of less than 10°. Most importantly, a plastron effect was observed when the surface-modified wood was submerged in water, ethylene glycol or hexadecane, which reduced the liquid sorption rate and extent to various degrees. By comparing the measured permeabilities and the estimated diffusive mass flux and supported by Hansen solubility parameters and the degrees of swelling, it is concluded that diffusion is the major cause for the liquid uptake in the surface-modified wood. Moreover, the interaction between the liquid and the modified layer (the solubility of the liquid in the modified layer) also needs to be considered, especially in hexadecane.

Background: Post-stroke cognitive impairment (PSCI) is commonest clinical disorder in which peripheral cholinergic activity is important. Oleuropein (OLP) is polyphenol is present in olive oil. Here we evaluated the effect of OLP in cognitive dysfunction rats in post cerebral stroke model. Methods: The post cerebral stroke cognitive dysfunction PSD rat model was created by occlusion of transient middle cerebral artery. The rats were divided into 6 groups named, Sham + Vehicle, Sham + OLP (50 mg/kg), PSD rats + Vehicle, PSD rats + OLP (20, 50 or 100 mg/kg). The spatial learning was assessed by Morris water maze (MWM). The expression of choline acetyltransferase (ChAT), acetylcholine (ACH), extent of histone acetylation and phosphorylation of cAMP response element-binding protein (CREB) were evaluated by Western blot assay and immunofluorescence staining. Results: Treatment of OLP at various doses showed higher number of spontaneous and rewarded alterations and lesser percentage bias compared to vehicle treated PSD rats. OLP resulted in decreased levels of ChAT and ACH, whereas the degree of histone acetylation and phosphorylation of CREB improved in dose dependent pattern. Conclusion: treatment of OLP improved PSCI via increasing the phosphorylation of CREB and histone acetylation, thus attenuating cholinergic activity.

Abstract Background The risk of ventilator-associated pneumonia (VAP) is reduced when postpyloric enteral nutrition (EN) is administered compared to when gastric EN is administered in specific populations. In the present study, we tested the hypothesis that postpyloric EN is superior to gastric EN in reducing the incidence of VAP in elderly patients (age ≥ 75 years) who are admitted to the intensive care unit (ICU) and require mechanical ventilation. Methods We performed a single-center randomized clinical trial involving elderly patients (age ≥ 75 years) who were admitted to the ICU and required mechanical ventilation. The patients were randomly assigned to either the postpyloric EN group or the gastric EN group. The primary outcome was the VAP rate. Results Of the 836 patients screened, 141 patients were included in the study (70 in the postpyloric EN group and 71 in the gastric EN group). The patients in the postpyloric EN group were 82.0 (75.0–99.0) years old (male 61.4%), and those in the gastric EN group were 82.0 (75.0–92.0) years old (male 63.4%). The Acute Physiology and Chronic Health Evaluation II scores were 28.09 ± 6.75 in the postpyloric EN group and 27.80 ± 7.60 in the gastric EN group (P = 0.43). VAP was observed in 8 of 70 patients (11.4%) in the postpyloric EN group and in 18 of 71 patients (25.4%) in the gastric EN group, which resulted in a significant between-group difference (OR 0.38, 95% CI 0.15–0.94; P = 0.04). In the postpyloric EN group, there were significant reductions in vomiting (12 patients in the postpyloric EN group vs 29 patients in the gastric EN group; OR 0.30, 95% CI 0.14–0.65; P = 0.002) and abdominal distension (18 patients in the postpyloric EN group vs 33 patients in the gastric EN group; OR 0.40, 95% CI 0.20–0.81; P = 0.01). No significant differences were observed between the two groups regarding mortality and other secondary outcomes. Conclusions Our study demonstrated that, compared with gastric EN, postpyloric EN reduced the VAP rate among elderly patients who were admitted to the ICU and required mechanical ventilation. Trial registration Chinese Clinical Trial Registry, ChiCTR-IPR-16008485. Registered on 17 May 2016.

Abstract Background Acute respiratory failure (ARF) is a common and life-threatening medical emergency in patients admitted to the hospital. Currently, there is a lack of large-scale evidence on the use of high-flow nasal cannulas (HFNC) in patients with ARF. In this systematic review and meta-analysis, we evaluated whether there were differences between HFNC therapy and conventional oxygen therapy (COT) for treating patients with ARF. Methods The EMBASE, Medline, and Wanfang databases and the Cochrane Library were searched. Two investigators independently collected the data and assessed the quality of each study. Randomized controlled trials that compared HFNC therapy with COT in patients with ARF were included. RevMan 5.3 was used to conduct the meta-analysis. Results Four studies that involved 703 patients with ARF were included, with 371 patients in the HFNC group and 332 patients in the COT group. In the overall estimates, there were no significant differences between the HFNC and COT groups in the rates of escalation of respiratory support (RR, 0.68; 95% CI, 0.37, 1.27; z = 1.20, P = 0.23), intubation (RR, 0.74; 95% CI, 0.55, 1.00; z = 1.95, P = 0.05), mortality (RR, 0.82; 95% CI, 0.36, 1.88; z = 0.47, P = 0.64), or ICU transfer (RR, 1.09; 95% CI, 0.57, 2.09; z = 0.26, P = 0.79) during ARF treatment. However, the subgroup analysis showed that HFNC therapy may decrease the rate of escalation of respiratory support (RR, 0.71; 95% CI, 0.53, 0.97; z = 2.15, P = 0.03) and the intubation rate (RR, 0.71; 95% CI, 0.53, 0.97; z = 2.15, P = 0.03) when ARF patients were treated with HFNC therapy for ≥24 h compared with COT. Conclusions HFNC therapy was similar to COT in ARF patients. The subgroup analysis showed that HFNC therapy may decrease the rate of escalation of respiratory support and the intubation rate when ARF patients were treated with HFNC for ≥24 h compared with COT. Further high-quality, large-scale studies are needed to confirm our results.