Nomogram predictive model for in-hospital mortality risk in elderly ICU patients with urosepsis.

BACKGROUND: Urinary tract infection (UTI) is a common cause of sepsis. Elderly patients with urosepsis in intensive care unit (ICU) have more severe conditions and higher mortality rates owing to factors such as advanced age, immunosenescence, and persistent host inflammatory responses. However, comprehensive studies on nomograms to predict the in-hospital mortality risk in elderly patients with urosepsis are lacking. This study aimed to construct a nomogram predictive model to accurately assess the prognosis of elderly patients with urosepsis and provide therapeutic recommendations. METHODS: Data of elderly patients with urosepsis were extracted from the Medical Information Mart for Intensive Care (MIMIC) IV 2.2 database. Patients were randomly divided into training and validation cohorts. A predictive nomogram model was constructed from the training set using logistic regression analysis, followed by internal validation and sensitivity analysis. RESULTS: This study included 1,251 patients. LASSO regression analysis revealed that the Glasgow Coma Scale (GCS) score, red cell distribution width (RDW), white blood count (WBC), and invasive ventilation were independent risk factors identified from a total of 43 variables studied. We then created and verified a nomogram. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) of the nomogram were superior to those of the traditional SAPS-II, APACHE-II, and SOFA scoring systems. The Hosmer-Lemeshow test results and calibration curves suggested good nomogram calibration. The IDI and NRI values showed that our nomogram scoring tool performed better than the other scoring systems. The DCA curves showed good clinical applicability of the nomogram. CONCLUSIONS: The nomogram constructed in this study is a convenient tool for accurately predicting in-hospital mortality in elderly patients with urosepsis in ICU. Improving the treatment strategies for factors related to the model could improve the in-hospital survival rates of these patients.

Early persistent exposure to high CVP is associated with increased mortality and AKI in septic shock: A retrospective study.

PURPOSE: This study's objective was to investigate the association between exposure to different intensities of central venous pressure (CVP) over time in patients with septic shock with 28-day mortality and acute kidney injury (AKI). MATERIALS AND METHODS: We obtained data from the AmsterdamUMCdb, which includes data on patients ≥18 years old with septic shock undergoing CVP monitoring. The primary outcome was mortality by day 28. Piecewise exponential additive mixed models were used to estimate the strength of the association over time. RESULTS: 9668 patients were included in the study. They exhibited 8.2% overall mortality at 28 days and 41.1% AKI incidence. Daily time-weighted average CVP was strongly associated with increased mortality at 28 days, primarily within 24 h of ICU admission. The mortality rate of patients was lowest when the CVP was 6-12 cmH2O. When the time of high CVP (TWA-CVP >12 cmH2O) exposure within the first 24 h was >5 h, the risk of death increased by 2.69-fold. Additionally, patients exposed to high CVP had a significantly increased risk of developing AKI. CONCLUSIONS: The optimal CVP range for patients with septic shock within 24 h of ICU admission is 6-12 cmH2O. Mortality increased when patients were exposed to high CVP for >5 h.

The catalytic core of DEMETER guides active DNA demethylation in Arabidopsis.

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, but how it is recruited to these differing chromatin landscapes is unknown. The C-terminal half of DME consists of 3 conserved regions required for catalysis in vitro. We show that this catalytic core guides active demethylation at endogenous targets, rescuing dme developmental and genomic hypermethylation phenotypes. However, without the N terminus, heterochromatin demethylation is significantly impeded, and abundant CG-methylated genic sequences are ectopically demethylated. Comparative analysis revealed that the conserved DME N-terminal domains are present only in flowering plants, whereas the domain architecture of DME-like proteins in nonvascular plants mainly resembles the catalytic core, suggesting that it might represent the ancestral form of the 5mC DNA glycosylase found in plant lineages. We propose a bipartite model for DME protein action and suggest that the DME N terminus was acquired late during land plant evolution to improve specificity and facilitate demethylation at heterochromatin targets.

Dynamic DNA Methylation in Plant Growth and Development.

DNA methylation is an epigenetic modification required for transposable element (TE) silencing, genome stability, and genomic imprinting. Although DNA methylation has been intensively studied, the dynamic nature of methylation among different species has just begun to be understood. Here we summarize the recent progress in research on the wide variation of DNA methylation in different plants, organs, tissues, and cells; dynamic changes of methylation are also reported during plant growth and development as well as changes in response to environmental stresses. Overall DNA methylation is quite diverse among species, and it occurs in CG, CHG, and CHH (H = A, C, or T) contexts of genes and TEs in angiosperms. Moderately expressed genes are most likely methylated in gene bodies. Methylation levels decrease significantly just upstream of the transcription start site and around transcription termination sites; its levels in the promoter are inversely correlated with the expression of some genes in plants. Methylation can be altered by different environmental stimuli such as pathogens and abiotic stresses. It is likely that methylation existed in the common eukaryotic ancestor before fungi, plants and animals diverged during evolution. In summary, DNA methylation patterns in angiosperms are complex, dynamic, and an integral part of genome diversity after millions of years of evolution.

Physical activity, sedentary behavior, and risk of sepsis: a two-sample mendelian randomization study.

Objective: This investigation aimed to explore the potential causal relationship between physical activity, sedentary behavior and the risk of sepsis. Methods: Using a two-sample Mendelian randomization approach, this study evaluated the association between physical activity (including moderate to vigorous physical activity [MVPA], vigorous physical activity [VPA], and accelerometer assessed physical activity) and sedentary behaviors (including television watching, computer use, and driving) with the risk of sepsis. This assessment was based on whole-genome association study data from the UK Biobank and the FinnGen database. Causal inferences were estimated using inverse variance-weighted, weighted median, and MR-Egger methods. Sensitivity analyses were performed using Cochran's Q test, the MR-Egger intercept test, and the leave-one-out method. Results: The risk of sepsis was significantly inversely associated with genetically predicted MVPA (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.24-0.93, P = 0.0296) and VPA alone (OR 0.19, 95% CI 0.04-0.87, P = 0.0324). Conversely, prolonged driving time showed a significant positive association with the risk of sepsis (OR 3.99, 95% CI 1.40-11.40, P = 0.0097). Conclusion: This study provides preliminary evidence of a causal relationship between MVPA and VPA and a reduced risk of sepsis, while prolonged sedentary behaviors such as driving are positively associated with an increased risk of sepsis. These findings provided essential scientific evidence for the development of effective sepsis prevention strategies.

Development and validation of potential phenotypes of serum electrolyte disturbances in critically ill patients and a Web-based application.

BACKGROUND: Electrolyte disturbances are highly heterogeneous and severely affect the prognosis of critically ill patients. Our study was to determine whether data-driven phenotypes of seven electrolytes have prognostic relevance in critically ill patients. METHODS: We extracted patient information from three large independent public databases, and clustered the electrolyte distribution of ICU patients based on the extreme value, median value and coefficient of variation of electrolytes. Three plausible clinical phenotypes were calculated using K-means clustering algorithm as the basic clustering method. MIMIC-IV was considered a training set, and two others have been designated as verification set. The robustness of the model was then validated from different angles, providing dynamic and interactive visual charts for more detailed characterization of phenotypes. RESULTS: 15,340, 12,445 and 2147 ICU patients with electrolyte records during early ICU stay in MIMIC-IV, eICU-CRD and AmsterdamUMCdb were enrolled. After clustering, three reasonable and interpretable phenotypes are defined as α, ß and γ according to the order of clusters. The α and γ phenotype, with significant differences in electrolyte distribution and clinical variables, higher 28-day mortality and longer length of ICU stay (p < 0.001), was further demonstrated by robustness analysis. The α phenotype has significant kidney injury, while the ß phenotype has the best prognosis. In addition, the assignment methods of the three phenotypes were developed into a web-based tool for further verification and application. CONCLUSIONS: Three different clinical phenotypes were identified that correlated with electrolyte distribution and clinical outcomes. Further validation and characterization of these phenotypes is warranted.

Construction and validation of a nomogram prediction model for the progression to septic shock in elderly patients with urosepsis.

Background: Septic shock is a clinical syndrome characterized by the progression of sepsis to a severe stage. Elderly patients with urosepsis in the intensive care unit (ICU) are more likely to progress to septic shock. This study aimed to establish and validate a nomogram model for predicting the risk of progression to septic shock in elderly patients with urosepsis. Methods: We extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). The MIMIC-IV dataset was split into a training set for model development and an internal validation set to assess model performance. Further external validation was performed using a distinct dataset sourced from the eICU-CRD. Predictors were screened using least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analyses. The evaluation of model performance included discrimination, calibration, and clinical usefulness. Results: The study demonstrated that the Glasgow Coma Scale (GCS), white blood count (WBC), platelet, blood urea nitrogen (BUN), calcium, albumin, congestive heart failure (CHF), and invasive ventilation were closely associated with septic shock in the training cohort. Nomogram prediction, utilizing eight parameters, demonstrated strong predictive accuracy with area under the curve (AUC) values of 0.809 (95 % CI 0.786-0.834), 0.794 (95 % CI 0.756-0.831), and 0.723 (95 % CI 0.647-0.801) in the training, internal validation, and external validation sets, respectively. Additionally, the nomogram demonstrated a promising calibration performance and significant clinical usefulness in both the training and validation sets. Conclusion: The constructed nomogram is a reliable and practical tool for predicting the risk of progression to septic shock in elderly patients with urosepsis. Its implementation in clinical practice may enhance the early identification of high-risk patients, facilitate timely and targeted interventions to mitigate the risk of septic shock, and improve patient outcomes.

Canagliflozin attenuates post-resuscitation myocardial dysfunction in diabetic rats by inhibiting autophagy through the PI3K/Akt/mTOR pathway.

This study investigated the effects of canagliflozin on myocardial dysfunction after cardiac arrest and cardiopulmonary resuscitation in diabetic rats and the underlying mechanisms. Male rats with type 2 diabetes mellitus (T2DM) were subjected to a modified epicardial fibrillation model. Pretreatment with canagliflozin (10 mg/kg/day) for four weeks improved ATP levels, post-resuscitation ejection fraction, acidosis, and hemodynamics. Canagliflozin also reduced myocardial edema, mitochondrial damage and, post-resuscitation autophagy levels. In vitro analyses showed that canagliflozin significantly reduced reactive oxygen species and preserved mitochondrial membrane potential. Using the PI3K/Akt pathway inhibitor Ly294002, canagliflozin was shown to attenuate hyperautophagy and cardiac injury induced by high glucose and hypoxia-reoxygenation through activation of the PI3K/Akt/mTOR pathway. This study highlights the therapeutic potential of canagliflozin in post-resuscitation myocardial dysfunction in diabetes, providing new insights for clinical treatment and experimental research.

Shenfu injection alleviate gut ischemia/reperfusion injury after severe hemorrhagic shock through improving intestinal microcirculation in rats.

Background: Shenfu (SF) injection, a traditional Chinese medication, would improve microcirculation in cardiogenic shock and infectious shock. This study was aimed to explore the therapeutic potential of the SF injection in gut ischemia-reperfusion (I/R) injury after severe hemorrhagic shock (SHS) and resuscitation. Furthermore, we also investigated the optimal adm？ inistration timing. Methods: Twenty-four male SD rats were randomly divided into four groups: Sham group (sham, n = 6), Control group (n = 6), SF injection group (SF, n = 6), and Delayed Shenfu injection administration group (SF-delay, n = 6). In SHS and resuscitation model, rats were induced by blood draw to a mean arterial pressure (MAP) of 40 ± 5 mmHg within 1 h and then maintained for 40 min; HR, MAP 'were recorded, microcirculation index [De Backer score, perfused small vessel density (PSVD), total vessel density (TVD), microcirculation flow index score (MFI), flow heterogeneity index (HI)] were analyzed. The blood gas index was detected, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), malondialdehyde (MDA) were measured by ELISA; ZO-1, and claudin-1 were measured by Western blotting. In addition, hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining pathological sections of the intestinal mucosal tissues were also performed. Results: SF injection increased the MAP, relieved the metabolic acidosis degree associated with the hypoperfusion, and improved the intestinal microcirculatory density and perfusion quality after I/R injury. The expression of DAO, MDA in intestinal tissue, and plasma IL-6, TNF-α significantly decreased in the SF injection group compared to the control group. The concentration of ZO-1 and claudin-1 is also higher in the SF injection group. In addition, the HE and PAS staining results also showed that SF injection could decrease mucosal damage and maintain the structure. In the SF-delay group, the degree of intestinal tissue damage was intermediate between that of the control group and SF injection group. Conclusions: SF injection protect the intestine from I/R injury induced by SHS and resuscitation, the mechanism of which might be through improving intestinal microcirculation, reducing the excessive release of inflammatory factors and increasing intestinal mucosal permeability. Furthermore, the protection effect is more pronounced if administration during the initial resuscitation phase.

Interpretable machine learning model for early prediction of 28-day mortality in ICU patients with sepsis-induced coagulopathy: development and validation.

OBJECTIVE: Sepsis-induced coagulopathy (SIC) is extremely common in individuals with sepsis, significantly associated with poor outcomes. This study attempted to develop an interpretable and generalizable machine learning (ML) model for early predicting the risk of 28-day death in patients with SIC. METHODS: In this retrospective cohort study, we extracted SIC patients from the Medical Information Mart for Intensive Care III (MIMIC-III), MIMIC-IV, and eICU-CRD database according to Toshiaki Iba's scale. And the overlapping in the MIMIC-IV was excluded for this study. Afterward, only the MIMIC-III cohort was randomly divided into the training set, and the internal validation set according to the ratio of 7:3, while the MIMIC-IV and eICU-CRD databases were considered the external validation sets. The predictive factors for 28-day mortality of SIC patients were determined using recursive feature elimination combined with tenfold cross-validation (RFECV). Then, we constructed models using ML algorithms. Multiple metrics were used for evaluation of performance of the models, including the area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), accuracy, sensitivity, specificity, negative predictive value, positive predictive value, recall, and F1 score. Finally, Shapley Additive Explanations (SHAP), Local Interpretable Model-Agnostic Explanations (LIME) were employed to provide a reasonable interpretation for the prediction results. RESULTS: A total of 3280, 2798, and 1668 SIC patients were screened from MIMIC-III, MIMIC-IV, and eICU-CRD databases, respectively. Seventeen features were selected to construct ML prediction models. XGBoost had the best performance in predicting the 28-day mortality of SIC patients, with AUC of 0.828, 0.913 and 0.923, the AUPRC of 0.807, 0.796 and 0.921, the accuracy of 0.785, 0.885 and 0.891, the F1 scores were 0.63, 0.69 and 0.70 in MIMIC-III (internal validation set), MIMIC-IV, and eICU-CRD databases. The importance ranking and SHAP analyses showed that initial SOFA score, red blood cell distribution width (RDW), and age were the top three critical features in the XGBoost model. CONCLUSIONS: We developed an optimal and explainable ML model to predict the risk of 28-day death of SIC patients 28-day death risk. Compared with conventional scoring systems, the XGBoost model performed better. The model established will have the potential to improve the level of clinical practice for SIC patients.

Histone H1 affects gene imprinting and DNA methylation in Arabidopsis.

Imprinting, i.e. parent-of-origin expression of alleles, plays an important role in regulating development in mammals and plants. DNA methylation catalyzed by DNA methyltransferases plays a pivotal role in regulating imprinting by silencing parental alleles. DEMETER (DME), a DNA glycosylase functioning in the base-excision DNA repair pathway, can excise 5-methylcytosine from DNA and regulate genomic imprinting in Arabidopsis. DME demethylates the maternal MEDEA (MEA) promoter in endosperm, resulting in expression of the maternal MEA allele. However, it is not known whether DME interacts with other proteins in regulating gene imprinting. Here we report the identification of histone H1.2 as a DME-interacting protein in a yeast two-hybrid screen, and confirmation of their interaction by the in vitro pull-down assay. Genetic analysis of the loss-of-function histone h1 mutant showed that the maternal histone H1 allele is required for DME regulation of MEA, FWA and FIS2 imprinting in Arabidopsis endosperm but the paternal allele is dispensable. Furthermore, we show that mutations in histone H1 result in an increase of DNA methylation in the maternal MEA and FWA promoter in endosperm. Our results suggest that histone H1 is involved in DME-mediated DNA methylation and gene regulation at imprinted loci.

LONO1 encoding a nucleoporin is required for embryogenesis and seed viability in Arabidopsis.

Early embryogenesis in Arabidopsis (Arabidopsis thaliana) is distinguished by a predictable pattern of cell divisions and is a good system for investigating mechanisms of developmental pattern formation. Here, we identified a gene called LONO1 (LNO1) in Arabidopsis in which mutations can abolish the first asymmetrical cell division of the zygote, alter planes and number of cell divisions in early embryogenesis, and eventually arrest embryo development. LNO1 is highly expressed in anthers of flower buds, stigma papilla of open flowers, and embryo and endosperm during early embryogenesis, which is correlated with its functions in reproductive development. The homozygous lno1-1 seed is not viable. LNO1, a homolog of the nucleoporin NUP214 in human (Homo sapiens) and Nup159 in yeast (Saccharomyces cerevisiae), encodes a nucleoporin protein containing phenylalanine-glycine repeats in Arabidopsis. We demonstrate that LNO1 can functionally complement the defect in the yeast temperature-sensitive nucleoporin mutant nup159. We show that LNO1 specifically interacts with the Arabidopsis DEAD-box helicase/ATPase LOS4 in the yeast two-hybrid assay. Furthermore, mutations in AtGLE1, an Arabidopsis homolog of the yeast Gle1 involved in the same poly(A) mRNA export pathway as Nup159, also result in seed abortion. Our results suggest that LNO1 is a component of the nuclear pore complex required for mature mRNA export from the nucleus to the cytoplasm, which makes LNO1 essential for embryogenesis and seed viability in Arabidopsis.

Acetaldehyde dehydrogenase 2 activation attenuates sepsis-induced brain injury through NLRP3 inflammasome regulation.

OBJECTIVE: Acetaldehyde dehydrogenase 2 (ALDH2) plays an important part in neuroprotection; however, its effect on sepsis-induced brain injury is nuclear. Our aim is to investigate the potential effect and mechanism of ALDH2 in this condition. METHODS: We established an animal model using cecal ligation and perforation (CLP). Twenty-four rats were divided into sham group (n = 6), CLP group (n = 6), CLP + Alda-1 group (n = 6) and CLP + Cyanamide (CYA) group (n = 6). Vital signs were monitored, and arterial blood gas analysis, hippocampal histological staining and ALDH2 activity analysis were conducted. Western blot analysis and enzyme-linked immunosorbent assays were also carried out. Lipopolysaccharide (LPS)-treated HT22 cells were employed as an in vitro model of sepsis-induced brain injury, with and without pretreatment with Alda-1 or CYA, to further examine the potential mechanisms. Real-time quantitative polymerase chain reaction and western blot were used to determine the levels of pyrin domain-containing 3 (NLRP3) inflammasome. RESULTS: We found hippocampal cell injury in the CLP group (p < 0.05), with decreased ALDH2 activity (p < 0.05) and suspected overexpression of NLRP3/caspase-1 axis (p < 0.05). In the group pretreated with Alda-1, there were increased ALDH2 activity (p < 0.05), decreased hippocampal cell damage (p < 0.05), and reduced protein levels of NLRP3, apoptosis-associated speck like protein containing a caspase recruitment domain (ASC), cleaved caspase-1 and Gasdermin D (GSDMD) (p < 0.05). The levels of interleukin 18 (IL-18) and interleukin 1ß (IL-1ß) were also reduced (p < 0.05). In the group pretreated with CYA, ALDH2 activity was further declined, the cell injury grade increased, and the elevated levels of pyroptosis-related proteins aggravated (p < 0.05). LPS treatment decreased the cell viability and ALDH2 activity of the HT22 cells (p < 0.05), along with increased mRNA levels of the NLRP3 inflammasome, as well as IL-1ß and IL-18 (p < 0.05). Western blot further revealed elevated levels of NLRP3, ASC, cleaved caspase-1 and GSDMD (p < 0.05). In the LPS+Alda-1 group, there were increased cell viability (p < 0.05), elevated ALDH2 activity (p < 0.05), and reduced levels of NLRP3 inflammasome and pyroptosis-related proteins (p < 0.05). In the CYA+LPS group, cell viability and ALDH2 activity were further declined (p < 0.05), while levels of NLRP3 /caspase-1 axis were increased (p < 0.05). CONCLUSIONS: The activation of ALDH2 can attenuate sepsis-induced brain injury, hypothetically through regulation of the NLRP3/caspase-1 signaling pathway. Therefore, ALDH2 could potentially be considered as a new therapeutic target for the treatment of sepsis-induced brain injury.

The association of diastolic arterial pressure and heart rate with mortality in septic shock: a retrospective cohort study.

BACKGROUND: The effects of diastolic arterial pressure (DAP) and heart rate (HR) on the prognosis of patients with septic shock are unclear, and whether these effects persist over time is unknown. We aimed to investigate the relationship between exposure to different intensities of DAP and HR over time and mortality at 28 days in patients with septic shock. METHODS: In this cohort study, we obtained data from the Medical Information Mart for Intensive Care IV, which includes the data of adult patients (≥ 18 years) with septic shock who underwent invasive blood pressure monitoring. We excluded patients who received extracorporeal membrane oxygenation (ECMO) or glucocorticoids within 48 h of ICU admission. The primary outcome was mortality at 28 days. Piece-wise exponential additive mixed models were used to estimate the strength of the associations over time. RESULTS: In total, 4959 patients were finally included. The median length of stay in the ICU was 3.2 days (IQR: 1.5-7.1 days), and the mortality in the ICU was 12.9%, with a total mortality at 28 days of 15.9%. After adjustment for baseline and time-dependent confounders, both daily time-weighted average (TWA) DAP and HR were associated with increased mortality at 28 days and strong association, mainly in the early to mid-stages of the disease. The results showed that mortality in patients with septic shock was lowest at a DAP of 50-70 mm Hg and an HR of 60-90 beats per minute (bpm). Throughout, a significant increase in the risk of death was found with daily exposure to TWA-DAP ≤ 40 mmHg (hazard ratio 0.99, 95% confidence interval (CI) 0.94-1.03) or TWA-HR ≥ 100 bpm (hazard ratio 1.16, 95% CI 1.1-1.21). Cumulative and interactive effects of harmful exposure (TWA-DAP ≤ 40 mmHg and TWA-HR ≥ 100 bpm) were also observed. CONCLUSION: The optimal ranges for DAP and HR in patients with septic shock are 50-70 mmHg and 60-90 bpm, respectively. The cumulative and interactive effects of exposure to low DAP (≤ 40 mmHg) and tachycardia (≥ 100 bpm) were associated with an increased risk of death.

A randomized controlled trial of Baduanjin exercise to reduce the risk of atherosclerotic cardiovascular disease in patients with prediabetes.

To investigate the effectiveness of long-term Baduanjin and aerobic training on the 10-year risk of atherosclerotic cardiovascular disease in prediabetic patients. This study was single-blind randomized controlled trial. A total of 98 participants with prediabetes were randomly divided into three groups: the BDJ (n = 34), AT (n = 32), and control (n = 32) groups. Participants in the BDJ and AT groups underwent one year of supervised group exercise, consisting of 60 min/session every other day. The primary outcomes were metabolic control and the 10-year risk of ASCVD. The secondary outcome was a change in blood glucose status. After the intervention, various metabolic indexes were significantly improved in the two exercise groups relative to the control group and baseline measurements (p < 0.05). Compared with no exercise, BDJ and AT had significant preventive and protective effects against the risk of ASCVD in patients with prediabetes (p < 0.001). The overall effects of the two exercise groups were similar (p > 0.05). Long-term BDJ training can effectively reduce the risk of type 2 diabetes mellitus (T2DM) and its cardiovascular complications in prediabetic patients. The effect of BDJ is similar to that of moderate-intensity aerobic exercise.

A Nomogram With Six Variables Is Useful to Predict the Risk of Acquiring Carbapenem-Resistant Microorganism Infection in ICU Patients.

Background: Carbapenem-resistant microorganism (CRO) transmission in the medical setting confers a global threat to public health. However, there is no established risk prediction model for infection due to CRO in ICU patients. This study aimed to develop a nomogram to predict the risk of acquiring CRO infection in patients with the first ICU admission and to determine the length of ICU stay (ICU-LOS) and 28-day survival. Methods: Patient data were retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV) database based on predetermined inclusion and exclusion criteria. A CRO was defined as a bacterium isolated from any humoral microbial culture that showed insensitivity or resistance to carbapenems. The characteristics of CRO and non-CRO patients in the first ICU admission were compared. Propensity score matching was applied to balance the differences between the CRO and non-CRO cohorts. Kaplan-Meier curves were constructed to determine the 28-day survival rate and ICU-LOS. Furthermore, after randomization of the CRO cohort into the training and validation sets, a predictive nomogram was constructed based on LASSO regression and Logistic regression analysis, and its performance was verified by internal validation. Results: Overall, 4531 patients who had first ICU admission as recorded in MIMIC-IV were enrolled, 183 (4.04%) of whom were diagnosed with CRO infection. Moreover, CRO infection was independently associated with 28-day survival and ICU-LOS in ICU patients. Parameters eligible for inclusion in this nomogram were male sex, hemoglobin-min, temperature-max, use of a peripherally inserted central catheter line, dialysis treatment, and use of carbapenems. This nomogram showed a better performance as indicated by the area under the receiver operating characteristic curve values of 0.776 (95% confidence interval [CI] 0.667-0.750) and 0.723 (95% CI 0.556-0.855) in the training and validation sets, respectively, in terms of predicting the risk of acquiring CRO infection. Conclusions: CRO infection was independently associated with ICU-LOS and 28-day survival in patients with first ICU admission. The nomogram showed the best prediction of the risk of acquiring CRO infection in ICU patients. Based on the nomogram-based scoring, we can management the risk factors and guide individualized prevention and control of CRO.

Influence of the Initial Neutrophils to Lymphocytes and Platelets Ratio on the Incidence and Severity of Sepsis-Associated Acute Kidney Injury: A Double Robust Estimation Based on a Large Public Database.

Background: Acute kidney injury (AKI) is a frequent consequence of sepsis and has been linked to poor prognosis. In critically ill patients, the ratio of neutrophils to lymphocytes and platelets (N/LP) has been confirmed as an inflammation-related marker connected with the development of renal dysfunction. However, the effect of the N/LP ratio on the initiation and development of AKI in patients with sepsis remained unclear. The purpose of this study was to determine if the N/LP ratio on intensive care unit (ICU) admission was associated with the occurrence of sepsis-associated AKI (S-AKI) and severe AKI. Methods: Adult septic patients from the Medical Information Mart for Intensive Care-IV database were screened and classified into three categories (low, middle, or high) based on their N/LP ratio quartiles. The Cox proportional hazard and competing risk models were used to determine the risk of S-AKI in various N/LP groups, whilst the logistic regression model and restricted cubic splines (RCS) analysis were employed to investigate the link between N/LP ratios and the occurrence of severe AKI. Finally, we did a doubly robust estimation, a subgroup analysis, and a sensitivity analysis to determine the findings' robustness. Results: We categorized 485, 968, and 485 septic patients into three groups based on their N/LP ratios: low, intermediate, and high. According the Cox proportional hazard model, the hazard rate (95% CI) for those in the middle and high N/LP groups on the incidence of S-AKI were 1.30(1.07, 1.58) and 1.27(1.02, 1.59), respectively, as compared to those in the low N/LP group. And the Fine-Gray proportional subdistribution hazards model indicated that mortality was not a substantial competing risk for S-AKI. Additionally, multivariate logistic regression revealed that the risk of severe AKI increased 1.83 fold in the high group compared to the low group. The RCS result also suggested that the probability of severe AKI rose significantly when N/LP > 9.5. The consistency of these findings was confirmed using doubly robust estimation. However, subgroup and sensitivity analyses revealed that the association between N/LP and the incidence of S-AKI, severe AKI varied considerably between different populations and diagnostic criteria. Conclusion: A raised initial N/LP level may induce the development of S-AKI and severe AKI within 7 days after ICU admission in septic patients. These influences were enhanced in elder, male, septic shock, and those with poor health condition. Furthermore, high NLP was more strongly connected to the risk of S-AKI and severe AKI in sepsis patients on the urine output-based AKI criteria than on the serum creatinine-based criteria.

Loss of linker histone H1 in the maternal genome influences DEMETER-mediated demethylation and affects the endosperm DNA methylation landscape.

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the central cell genome prior to fertilization. This epigenetic reconfiguration of the female gamete companion cell establishes gene imprinting in the endosperm and is essential for seed viability. DME demethylates small and genic-flanking transposons as well as intergenic and heterochromatin sequences, but how DME is recruited to these loci remains unknown. H1.2 was identified as a DME-interacting protein in a yeast two-hybrid screen, and maternal genome H1 loss affects DNA methylation and expression of selected imprinted genes in the endosperm. Yet, the extent to which H1 influences DME demethylation and gene imprinting in the Arabidopsis endosperm has not been investigated. Here, we showed that without the maternal linker histones, DME-mediated demethylation is facilitated, particularly in the heterochromatin regions, indicating that H1-bound heterochromatins are barriers for DME demethylation. Loss of H1 in the maternal genome has a very limited effect on gene transcription or gene imprinting regulation in the endosperm; however, it variably influences euchromatin TE methylation and causes a slight hypermethylation and a reduced expression in selected imprinted genes. We conclude that loss of maternal H1 indirectly influences DME-mediated demethylation and endosperm DNA methylation landscape but does not appear to affect endosperm gene transcription and overall imprinting regulation.

Association of Blood Glucose Level and Glycemic Variability With Mortality in Sepsis Patients During ICU Hospitalization.

Background: There was considerable debate regarding the effect of mean blood glucose (MBG) and glycemic variability (GV) on the mortality of septic patients. This retrospective cohort study aimed to assess the association between MBG and GV with ICU mortality of sepsis patients and to explore the optimal MBG range. Methods: Sepsis patients were enrolled from the Medical Information Mart for Intensive Care IV database (MIMIC-IV). MBG and glycemic coefficient of variation (GluCV) were, respectively, calculated to represent the overall glycemic status and GV during ICU stay. The associations between MBG, GluCV, and ICU mortality of the septic patients were assessed by using multivariate logistic regression in different subgroups and the severity of sepsis. Restricted cubic splines evaluated the optimal MBG target. Results: A total of 7,104 adult sepsis patients were included. The multivariate logistic regression results showed that increased MBG and GluCV were significantly correlated with ICU mortality. The adjusted odds ratios were 1.14 (95% CI 1.09-1.20) and 1.05 (95% CI 1.00-1.12). However, there was no association between hyperglycemia and ICU mortality among diabetes, liver disease, immunosuppression, and hypoglycemia patients. And the impact of high GluCV on ICU mortality was not observed in those with diabetes, immunosuppression, liver disease, and non-septic shock. The ICU mortality risk of severe hyperglycemia (≧200 mg/dl) and high GluCV (>31.429%), respectively, elevated 2.30, 3.15, 3.06, and 2.37, 2.79, 3.14-folds in mild (SOFA ≦ 3), middle (SOFA 3-7), and severe group (SOFA ≧ 7). The MBG level was associated with the lowest risk of ICU mortality and hypoglycemia between 120 and 140 mg/dl in the subgroup without diabetes. For the diabetic subset, the incidence of hypoglycemia was significantly reduced when the MBG was 140-190 mg/dl, but a glycemic control target effectively reducing ICU mortality was not observed. Conclusion: MBG and GluCV during the ICU stay were associated with all-cause ICU mortality in sepsis patients; however, their harms are not apparent in some particular subgroups. The impact of hyperglycemia and high GV on death increased with the severity of sepsis. The risk of ICU mortality and hypoglycemia in those with no pre-existing diabetes was lower when maintaining the MBG in the range of 120-140 mg/dl.

Efficacy and safety of abdominal paracentesis drainage on patients with acute pancreatitis: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis of the efficacy and safety of abdominal paracentesis drainage (APD) in patients with acute pancreatitis (AP) when compared with conventional 'step-up' strategy based on percutaneous catheter drainage (PCD). DESIGN: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, Cochrane Library, MEDLINE (OVID), China National Knowledge Infrastructure and Wanfang Database were electronically searched to collect cohort studies and randomised controlled trials (RCTs) from inception to 25 July 2020. Studies related to comparing APD with conventional 'step-up' strategy based on PCD were included. OUTCOMES: The primary outcome was all-cause mortality. The secondary outcomes were the rate of organ dysfunction, infectious complications, hospitalisation expenses and length of hospital stay. RESULTS: Five cohort studies and three RCTs were included in the analysis. Compared with the conventional 'step-up' method, pooled results suggested APD significantly decreased all-cause mortality during hospitalisation (cohort studies: OR 0.48, 95% CI 0.26 to 0.89 and p=0.02), length of hospital stay (cohort studies: standard mean difference (SMD) -0.31, 95% CI -0.53 to -0.10 and p=0.005; RCTs: SMD -0.45, 95% CI -0.64 to -0.26 and p<0.001) and hospitalisation expenses (cohort studies: SMD -2.49, 95% CI -4.46 to -0.51 and p<0.001; RCTs: SMD -0.67, 95% CI -0.89 to -0.44 and p<0.001). There was no evidence to prove that APD was associated with a higher incidence of infectious complications. However, the incidence of organ dysfunction between cohort studies and RCTs subgroup slightly differed (cohort studies: OR 0.66, 95% CI 0.34 to 1.28 and p=0.22; RCTs: OR 0.58, 95% CI 0.35 to 0.98 and p=0.04). CONCLUSIONS: The findings suggest that early application of APD in patients with AP is associated with reduced all-cause mortality, expenses during hospitalisation and the length of stay compared with the 'step-up' strategy without significantly increasing the risk of infectious complications. These results must be interpreted with caution because of the limited number of included studies as well as a larger dependence on observational trials. PROSPERO REGISTRATION NUMBER: CRD42020168537.