Trimatch comparison of the prognosis of hypochloremia, normolchloremia and hyperchloremia in patients with septic shock.

BACKGROUND: Septic shock is a lethal disease, and identifying high-risk patients through noninvasive and widely available biomarkers can help improve global outcomes. While the clinical impact of chloride levels on critically ill patients remains unclear, this study aims to investigate the association between hypochloremia and mortality following ICU admission among septic shock patients. METHODS: This is an analysis of data stored in the databases of Medical Information Mart for Intensive Care IV (MIMIC-IV). The initial chloride levels were classified ashypochloremia, normal chloraemia, and hyperchloraemia. A multivariate logistic regression model was applied, adjusting for age, lactate, pH, PO2, urine volume, RDW, creatinine, and liver disease, to assess the association between the three categories of chloride levels and mortality. RESULTS: Of 3726 patients included in the study, 470 patients (12.6%) had hypochloremia on ICU admission. During the follow-up period, 1120 (33.5%) patients died. Hypochloremia was significantly associated with increased mortality and the incidence of AKI after adjusting for several variables. CONCLUSIONS: Hypochloremia is independently associated with higher hospital mortality, AKI incidence among septic shock patients. However, further high-quality research is necessary to establish the precise relationship between hypochloremia and septic shock prognosis.

A nomogram prediction of pressure injury in critical ill patients: A retrospective cohort study.

Pressure injury (PI) is still a significant public health problem to be solved. Accurate prediction can lead to timely prophylaxis and therapy. However, the currently used Braden score shows insufficient predictive validity. We aimed to develop a nomogram to predict PI development in critically ill patients. We extracted data from Medical Information Mart for Intensive Care-IV v1.0. Variable selection was based on univariate logistic regression and all-subset regression. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of the nomogram and Braden score. Decision curve analysis (DCA) was performed to identify and compare the clinical usefulness between the nomogram model and Braden score. We have developed a novel and practical nomogram that accurately predicts pressure ulcers. The AUC of the new model was better than that of the Braden score (P < .001). DCA showed that the nomogram model had a better net benefit than the Braden score at any given threshold. This finding needs to be confirmed by external validation as well as multicentre prospective studies.

Phospho-Tyr705 of STAT3 is a therapeutic target for sepsis through regulating inflammation and coagulation.

BACKGROUND: Sepsis is an infection-induced aggressive and life-threatening organ dysfunction with high morbidity and mortality worldwide. Infection-associated inflammation and coagulation promote the progression of adverse outcomes in sepsis. Here, we report that phospho-Tyr705 of STAT3 (pY-STAT3), not total STAT3, contributes to systemic inflammation and coagulopathy in sepsis. METHODS: Cecal ligation and puncture (CLP)-induced septic mice were treated with BP-1-102, Napabucasin, or vehicle control respectively and then assessed for systemic inflammation, coagulation response, lung function and survival. Human pulmonary microvascular endothelial cells (HPMECs) and Raw264.7 cells were exposed to lipopolysaccharide (LPS) with pharmacological or genetic inhibition of pY-STAT3. Cells were assessed for inflammatory and coagulant factor expression, cell function and signaling. RESULTS: Pharmacological inhibition of pY-STAT3 expression by BP-1-102 reduced the proinflammatory factors, suppressed coagulation activation, attenuated lung injury, alleviated vascular leakage and improved the survival rate in septic mice. Pharmacological or genetic inhibition of pY-STAT3 diminished LPS-induced cytokine production in macrophages and protected pulmonary endothelial cells via the IL-6/JAK2/STAT3, NF-κB and MAPK signaling pathways. Moreover, the increase in procoagulant indicators induced by sepsis such as tissue factor (TF), the thrombin-antithrombin complex (TAT) and D-Dimer were down-regulated by pY-STAT3 inhibition. CONCLUSIONS: Our results revealed a therapeutic role of pY-STAT3 in modulating the inflammatory response and defective coagulation during sepsis. Video Abstract.

Elevated serum iron level is a predictor of prognosis in ICU patients with acute kidney injury.

BACKGROUND: Accumulation of iron is associated with oxidative stress, inflammation, and regulated cell death processes that contribute to the development of acute kidney injury (AKI). We aimed to investigate the association between serum iron levels and prognosis in intensive care unit (ICU) patients with AKI. METHODS: A total of 483 patients with AKI defined as per the Kidney Disease: Improving Global Guidelines were included in this retrospective study. The data was extracted from the single-centre Medical Information Mart for Intensive Care III database. AKI patients with serum iron parameters measured upon ICU admission were included and divided into two groups (low group and high group). The prognostic value of serum iron was analysed using univariate and multivariate Cox regression analysis. RESULTS: The optimal cut-off value for serum iron was calculated to be 60 µg/dl. Univariable Cox regression analysis showed that serum iron levels were significantly correlated with prognosis of AKI patients. After adjusting for possible confounding variables, serum iron levels higher than 60 µg/dl were associated with increases in 28-day (hazard [HR] 1.832; P <  0.001) and 90-day (HR 1.741; P <  0.001) mortality, as per multivariable Cox regression analysis. CONCLUSIONS: High serum iron levels were associated with increased short- and long-term mortality in ICU patients with AKI. Serum iron levels measured upon admission may be used for predicting prognosis in AKI patients.

Assessing the impact of transfusion thresholds in patients with septic acute kidney injury: a retrospective study.

Background: Sepsis is a severe condition that often leads to complications such as acute kidney injury, which significantly increases morbidity and mortality rates. Septic AKI (S-AKI) is common in ICU patients and is associated with poor outcomes. However, there is no consensus on the optimal transfusion threshold for achieving the best clinical results. This retrospective study aims to investigate the relationship between different transfusion thresholds during hospitalization and the prognosis of septic AKI. Methods: Data from patients with S-AKI was extracted from MIMIC-IV. Based on the lowest hemoglobin level 24 h before transfusion, patients were divided into high-threshold (≥7 g/L) and low-threshold (<7 g/L) groups. We compared the outcomes between these two groups, including hospital and ICU mortality rates as primary outcomes, and 30 days, 60 days, and 90 days mortality rates, as well as duration of stay in ICU and hospital as secondary outcomes. Results: A total of 5,654 patients were included in our study. Baseline characteristics differed significantly between the two groups, with patients in the low-threshold group generally being younger and having higher SOFA scores. After performing propensity score matching, no significant differences in survival rates were found between the groups. However, patients in the low-threshold group had a longer overall hospital stay. Conclusion: A lower transfusion threshold does not impact the mortality rate in S-AKI patients, but it may lead to a longer hospital stay.

Value of early critical care transthoracic echocardiography for patients undergoing mechanical ventilation: a retrospective study.

OBJECTIVES: To evaluate whether early intensive care transthoracic echocardiography (TTE) can improve the prognosis of patients with mechanical ventilation (MV). DESIGN: A retrospective cohort study. SETTING: Patients undergoing MV for more than 48 hours, based on the Medical Information Mart for Intensive Care III (MIMIC-III) database and the eICU Collaborative Research Database (eICU-CRD), were selected. PARTICIPANTS: 2931 and 6236 patients were recruited from the MIMIC-III database and the eICU database, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality from the date of ICU admission, days free of MV and vasopressors 30 days after ICU admission, use of vasoactive drugs, total intravenous fluid and ventilator settings during the first day of MV. RESULTS: We used propensity score matching to analyse the association between early TTE and in-hospital mortality and sensitivity analysis, including the inverse probability weighting model and covariate balancing propensity score model, to ensure the robustness of our findings. The adjusted OR showed a favourable effect between the early TTE group and in-hospital mortality (MIMIC: OR 0.78; 95% CI 0.65 to 0.94, p=0.01; eICU-CRD: OR 0.76; 95% CI 0.67 to 0.86, p<0.01). Early TTE was also associated with 30-day mortality in the MIMIC database (OR 0.71, 95% CI 0.57 to 0.88, p=0.001). Furthermore, those who had early TTE had both more ventilation-free days (only in eICU-CRD: 23.48 vs 24.57, p<0.01) and more vasopressor-free days (MIMIC: 18.22 vs 20.64, p=0.005; eICU-CRD: 27.37 vs 28.59, p<0.001) than the control group (TTE applied outside of the early TTE and no TTE at all). CONCLUSIONS: Early application of critical care TTE during MV is beneficial for improving in-hospital mortality. Further investigation with prospectively collected data is required to validate this relationship.

A narrative review of driving pressure as a monitoring indicator during mechanical ventilation with spontaneous breathing.

The mortality of acute respiratory distress syndrome (ARDS) remains high, and mechanical ventilation (MV) is an essential means of treatment. During MV, people realize the benefits of spontaneous breathing and the disadvantages of uncontrolled spontaneous breathing. Current methods of monitoring spontaneous breathing include oesophageal manometry, P0.1, and diaphragm function monitoring. However, these methods have limitations and deficiencies. The driving pressure is a new indicator that reflects the strain of the lung, which indicates the volumetric injury of the lung and is independently associated with mortality in ARDS patients. Moreover, in recent studies, driving pressure monitoring has been shown to be feasible in assisted support ventilation. This review summarizes the current state of spontaneous breathing and examines whether it is convenient to monitor driving pressure during spontaneous breathing to achieve lung protection ventilation.

Red blood cell distribution width is associated with mortality risk in patients with acute respiratory distress syndrome based on the Berlin definition: A propensity score matched cohort study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder of the lungs and is associated with oxidative damage. However, red blood cell distribution width (RDW), as an indicator of body response to inflammation and oxidative stress, has not been studied for its relationship with ARDS as diagnosed by the Berlin definition. OBJECTIVES: To examine the value of RDW in predicting the prognosis of in patients with ARDS. METHODS: This is a retrospective study based on the Medical Information Mart for Intensive Care III (MIMIC-III) database. Berlin-defined ARDS patients using mechanical ventilation for more than 48 hours were selected using structured query language. The primary statistical methods were propensity score matching and sensitivity analysis, including an inverse probability weighting model to ensure the robustness of our findings. RESULTS: A total of 529 intensive care unit (ICU) patients with ARDS according to the Berlin definition were enrolled in the study. The adjusted OR showed an adverse effect between the higher RDW group and 30-day mortality [OR 2.33, 95% CI (1.15-4.75), P=0.019]. However, we found that length of ICU stay was not related to RDW (P=0.167), and in the anaemia group, RDW was poorly predictive of 30-day mortality (P=0.307). CONCLUSION: In unselected ARDS patients, higher RDW was associated with higher 30-day mortality rate. Further investigation is required to validate this relationship with prospectively collected data.

The association of coagulation indicators with in-hospital mortality and 1-year mortality of patients with sepsis at ICU admissions: A retrospective cohort study.

BACKGROUND: Coagulation activation is the host's response to pathogens during sepsis and is considered to be one of the reasons for tissue damage and multiple organ failure. This study is designed to evaluate whether the alterations of coagulation indicators are related to in-hospital mortality and 1-year mortality of patients with sepsis. METHOD: Data of all 2258 patients were extracted from the database Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III). The relationship between the in-hospital mortality of patients with sepsis and coagulation indicators was analyzed with a receiver operating characteristic (ROC) curve analysis and logistic regression model. Effects of coagulation indicators on patients' 1-year mortality were determined by using a Cox hazard regression model, and clinical experience or quintiles were used to classify the activated partial thromboplastin time (APTT) to determine the cutoff values to explore segmentation effects. RESULT: International normalized ratio (INR) was positively associated with hospital mortality of patients with sepsis after adjusting confounders with an odds ratio (OR) of 1.86 [95% confidence interval (CI), 1.37-2.52], and a hazard ratio (HR) of 1.465[95%CI(1.24-1.74)] for 1-year mortality, respectively. 1-year mortality of patients with sepsis demonstrated a U-shaped relationship with APTT, ranging from 25 to 37, indicating the lowest risk. The adjusted HR (95% CI) values for 1-year mortality of septic patients with risk values <25 and >37 were 1.493 (1.02, 2.19) and 1.379 (1.06, 1.79), respectively. CONCLUSION: Increased INR in critically ill septic patients is related to greater in-hospital mortality and 1-year mortality. A U-shaped relationship was found between APTT and 1-year mortality of patients with sepsis.

Gene Cloning and Tissue Expression Analysis of a PR-5 Thaumatin-Like Protein in Phellinus weirii-Infected Douglas-Fir.

ABSTRACT In western North America, Douglas-fir (Pseudotsuga menziesii) is the most economically important conifer species susceptible to laminated root rot caused by Phellinus weirii. While attempting to internally sequence an endochitinase found to be up-regulated in P. weirii-infected Douglas-fir roots, we obtained overlapping peptide fragments showing 28% similarity with a PR-5 thaumatin-like protein (TLP) designated PmTLP (Pm for Pseudotsuga menziesi). A rabbit polyclonal antibody was reared against a synthetic peptide composed of a 29-amino-acid-long, conserved, internal sequence of PmTLP and purified by immunoaffinity. Western immunoblot analysis of infected roots of 24-year-old coastalfir showed significantly higher amounts of PmTLP (P < 0.01) closest to the point of P. weirii inoculation and infection than in uninfected regions of the same root. The antibody was also used to screen for PmTLP in roots of 25-year-old interior Douglas-firs naturally infected with a related pathogen, Armillaria ostoyae, and results showed significantly higher levels of PmTLP in bark tissues adjacent to infection (P < 0.05) than in uninfected tissue. Using polymerase chain reaction (PCR)-based cloning, the cDNA of PmTLP was shown to have a 702-bp open reading frame with a signal peptide cleavage site at 155 bp corresponding to a 29-amino-acid-long residue prior to the start of the N-terminal. Based on the deduced amino acid sequence, the molecular mass of the putative PmTLP was calculated to be 21.0 kDa with an isoelectric point of 3.71. Alignment analysis of PmTLP cDNA with a representative genomic DNA PCR sequence showed presence of one intron of variable size, within the coding region. The induction of PmTLP at the site of root infection and its presence in needle tissue suggests a general role for this protein in adaptation to stress and may be part of an integrated defense response initiated by the host to impede further pathogen spread.

Characterization of Pin m III cDNA in western white pine.

Maximum accumulation of Pin m III protein in western white pine (Pinus monticola Dougl. ex D. Don) needles occurred during the winter months. To characterize Pin m III, an expression cDNA library from poly(A)+ mRNA of needles was immunoscreened and the full length cDNA was cloned. An open reading frame of 486 bases encodes a protein of 161 amino acid residues with a molecular mass of 18 kD and a predicted isoelectric point of 5.5. The deduced amino acid sequence had some similarities (37%) with an intracellular pathogenesis-related (PR) protein from garden asparagus (Asparagus officinalis L.) and the major pollen allergen from white birch (Betula verrucosa J. F. Ehrh.), which are members of the ribonuclease-like PR-10 family. Phylogenetic analysis provided circumstantial evidence that Pin m III may be grouped with intracellular PRs from asparagus and potato (Solanum tuberosum L.), while the allergens formed another subgroup. Northern analysis showed that the Pin m III gene was preferentially expressed during cold acclimation with the highest expression in the fall and winter months, preceding the peak of Pin m III protein accumulation. Tissue specificity expression analysis indicated that the gene was strongly expressed in roots and twigs. Higher amounts of the homologous protein (Pin l I) and its transcript accumulated in sugar pine (Pinus lambertiana Dougl.) needles infected with blister rust compared with healthy needles.

Cloning and characterization of a cDNA of cro rI from the white pine blister rust fungus Cronartium ribicola.

White pine blister rust (WPBR) is caused by the fungus Cronartium ribicola which has five spore stages on two unrelated hosts, the five-needle pines and Ribes spp. Recently, during the molecular analysis of the proteins and genes involved in host-pathogen interaction, the WPBR fungal protein Cro rI was identified in infected white pine tissues. To further characterize Cro rI, an expression cDNA library from poly(A)(+) mRNA of C. ribicola axenic mycelial culture was constructed and immunoscreened and the cDNA was cloned. Sequence analysis indicated an open reading frame of 462 bases, which encodes a protein of 153 amino acid residues with a molecular mass of 16.7 kDa and a predicted isoelectric point (pI) of 8.93. Based on the N-terminal amino acid sequences of Cro rI, the secreted portion of Cro rI protein should be 136 amino acids long with several putative posttranslational modification sites and a molecular mass of 14.8 kDa. The predicted pI for the secreted portion was 9.34. The predicted N-terminal signal peptide was 17 amino acids long. The N-terminal 42-amino acid sequence of the predicted mature protein (secreted portion) was identical to the amino terminal sequence of Cro rI that was previously determined. Southern blot hybridizations indicated that the C. ribicola genome contained at least two copies of the cro rI gene. Isolation of the genomic PCR fragment, which was approximately 400 bp longer than the cDNA, and subsequent cloning and sequencing analyses confirmed that there were three introns within the coding regions. Western immunoblot analyses revealed that Cro rI protein accumulated in large amounts only in the infected white pine tissues while no trace was detectable in the alternate Ribes stage or the five different spores, suggesting a critical role of Cro rI in the haploid stage of the fungus (in pine). The translocation of Cro rI was only found to occur in cankered trees, and not in the young infected seedlings. The implications of Cro rI in pathogenesis are discussed.