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Sepsis patients in the ICU face heightened mortality risks. There still exist challenges that hinder the development of mortality risk prediction models for sepsis patients. In the ensemble model, the differences between base classifier performance can affect the model accuracy and efficiency, and overlapping sample training will lead to repetitive learning, which reduces the model generalization. To tackle these challenges, we propose an Adaptive Weighted Stacking based on Optimal Weights Selection (AWS-OWS) model. A random sampling without replacement is employed to prevent repetitive learning in base classifiers. Additionally, a weighted function and the gradient descent algorithm is adopted to select optimal weights for base classifiers, enhancing the performance of stacking model. The MIMIC-IV dataset is used for model training and internal testing, and the independent samples from MIMIC-III are used for external validation. The results show that AWS-OWS achieves the best AUC of 0.88 in the internal test, with a threefold reduction in computation time compared to standard stacking. In external validation, it also demonstrates good model generalization. AWS-OWS significantly improves the prediction performance and model efficiency, facilitates the identification of high-risk patients with sepsis and supports clinicians in determining appropriate management and treatment strategies. [ABSTRACT FROM AUTHOR]

Activation of the Toll-like receptor 4 (TLR4) by bacterial endotoxins in macrophages plays a crucial role in the pathogenesis of sepsis. However, the mechanism underlying TLR4 activation in macrophages is still not fully understood. Here, we reveal that upon lipopolysaccharide (LPS) stimulation, lysine acetyltransferase CBP is recruited to the TLR4 signalosome complex leading to increased acetylation of the TIR domains of the TLR4 signalosome. Acetylation of the TLR4 signalosome TIR domains significantly enhances signaling activation via NF-κB rather than IRF3 pathways. Induction of NF-κB signaling is responsible for gene expression changes leading to M1 macrophage polarization. In sepsis patients, significantly elevated TLR4-TIR acetylation is observed in CD16+ monocytes combined with elevated expression of M1 macrophage markers. Pharmacological inhibition of HDAC1, which deacetylates the TIR domains, or CBP play opposite roles in sepsis. Our findings highlight the important role of TLR4-TIR domain acetylation in the regulation of the immune responses in sepsis, and we propose this reversible acetylation of TLR4 signalosomes as a potential therapeutic target for M1 macrophages during the progression of sepsis. Synopsis: Activation of macrophage TLR4 by bacterial endotoxins is important for the progression of sepsis, but the underlying mechanisms remain unknown. This study demonstrates that lipopolysaccharide (LPS) stimulation induces acetylation of the TLR4 signalosome TIR domains, which plays an important role in M1 macrophage polarization. LPS induces CBP-mediated acetylation of the TIR domains of TLR4, Mal, and MyD88 in the TLR4 signalosome complex. TIR domain acetylation in the TLR4 complex enhances NF-κB activation, leading to pro-inflammatory gene expression in M1 macrophages during sepsis. Inhibition of the primary TIR domain acetyltransferase CBP or deacetylase HDAC1 has opposite effects on the progression of sepsis. LPS-induced acetylation of the TLR4 complex TIR domains induces NF-κB signaling, leading to macrophage polarization. [ABSTRACT FROM AUTHOR]

Introduction: Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice. Methods: Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP. Results: Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1β (IL-1β), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-α, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%). Conclusion: FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a common disease associated with neonatal and infant mortality, and for diagnosis, blood culture is currently the gold standard method, but it has a low positivity rate and requires more than 2 days to develop. Meanwhile, unfortunately, the specific biomarkers for the early and timely diagnosis of sepsis in infants and for the determination of the severity of this disease are lacking in clinical practice. Methods: Samples from 18 sepsis infants with comorbidities, 25 sepsis infants without comorbidities, and 25 infants with noninfectious diseases were evaluated using a serum metabolomics approach based on liquid chromatography‒mass spectrometry (LC‒MS) technology. Differentially abundant metabolites were screened via multivariate statistical analysis. In addition, least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analyses were conducted to identify the key metabolites in infants with sepsis and without infections. The random forest algorithm was applied to determine key differentially abundant metabolites between sepsis infants with and without comorbidities. Receiver operating characteristic (ROC) curves were generated for biomarker value testing. Finally, a metabolic pathway analysis was conducted to explore the metabolic and signaling pathways associated with the identified differentially abundant metabolites. Results: A total of 189 metabolites exhibited significant differences between infectious infants and noninfectious infants, while 137 distinct metabolites exhibited differences between septic infants with and without comorbidities. After screening for the key differentially abundant metabolites using LASSO and SVM-RFE analyses, hexylamine, psychosine sulfate, LysoPC (18:1 (9Z)/0:0), 2,4,6-tribromophenol, and 25-cinnamoyl-vulgaroside were retained for the diagnosis of infant sepsis. ROC curve analysis revealed that the area under the curve (AUC) was 0.9200 for hexylamine, 0.9749 for psychosine sulfate, 0.9684 for LysoPC (18:1 (9Z)/0:0), 0.7405 for 2,4,6-tribromophenol, 0.8893 for 25-cinnamoyl-vulgaroside, and 1.000 for the combination of all metabolites. When the septic infants with comorbidities were compared to those without comorbidities, four endogenous metabolites with the greatest importance were identified using the random forest algorithm, namely, 12-oxo-20-trihydroxy-leukotriene B4, dihydrovaltrate, PA (8:0/12:0), and 2-heptanethiol. The ROC curve analysis of these four key differentially abundant metabolites revealed that the AUC was 1 for all four metabolites. Pathway analysis indicated that phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and porphyrin metabolism play important roles in infant sepsis. Conclusion: Serum metabolite profiles were identified, and machine learning was applied to identify the key differentially abundant metabolites in septic infants with comorbidities, septic infants without comorbidities, and infants without infectious diseases. The findings obtained are expected to facilitate the early diagnosis of sepsis in infants and determine the severity of the disease. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a common disease associated with neonatal and infant mortality, and for diagnosis, blood culture is currently the gold standard method, but it has a low positivity rate and requires more than 2 days to develop. Meanwhile, unfortunately, the specific biomarkers for the early and timely diagnosis of sepsis in infants and for the determination of the severity of this disease are lacking in clinical practice. Methods: Samples from 18 sepsis infants with comorbidities, 25 sepsis infants without comorbidities, and 25 infants with noninfectious diseases were evaluated using a serum metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) technology. Differentially abundant metabolites were screened via multivariate statistical analysis. In addition, least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analyses were conducted to identify the key metabolites in infants with sepsis and without infections. The random forest algorithm was applied to determine key differentially abundant metabolites between sepsis infants with and without comorbidities. Receiver operating characteristic (ROC) curves were generated for biomarker value testing. Finally, a metabolic pathway analysis was conducted to explore the metabolic and signaling pathways associated with the identified differentially abundant metabolites. Results: A total of 189 metabolites exhibited significant differences between infectious infants and noninfectious infants, while 137 distinct metabolites exhibited differences between septic infants with and without comorbidities. After screening for the key differentially abundant metabolites using LASSO and SVM-RFE analyses, hexylamine, psychosine sulfate, LysoPC (18:1 (9Z)/0:0), 2,4,6-tribromophenol, and 25-cinnamoyl-vulgaroside were retained for the diagnosis of infant sepsis. ROC curve analysis revealed that the area under the curve (AUC) was 0.9200 for hexylamine, 0.9749 for psychosine sulfate, 0.9684 for LysoPC (18: 1 (9Z)/0:0), 0.7405 for 2,4,6-tribromophenol, 0.8893 for 25-cinnamoylvulgaroside, and 1.000 for the combination of all metabolites. When the septic infants with comorbidities were compared to those without comorbidities, four endogenous metabolites with the greatest importance were identified using the random forest algorithm, namely, 12-oxo-20-trihydroxy-leukotriene B4, dihydrovaltrate, PA (8:0/12:0), and 2-heptanethiol. The ROC curve analysis of these four key differentially abundant metabolites revealed that the AUC was 1 for all four metabolites. Pathway analysis indicated that phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and porphyrin metabolism play important roles in infant sepsis. Conclusion: Serum metabolite profiles were identified, and machine learning was applied to identify the key differentially abundant metabolites in septic infants with comorbidities, septic infants without comorbidities, and infants without infectious diseases. The findings obtained are expected to facilitate the early diagnosis of sepsis in infants and determine the severity of the disease. [ABSTRACT FROM AUTHOR]

Background Sepsis and pneumonia in the elderly comprise a significant portion of medical admissions. Chloramphenicol has been used in Israel for treatment of bacterial infections, without evidence regarding its efficacy and safety. Objectives We aimed to examine whether chloramphenicol was associated with similar outcomes to ceftriaxone, for treatment of sepsis and pneumonia in the elderly with dementia and functional disability. Methods Patients over 75, with dementia and functional disability, admitted to the internal medicine ward at Beilinson Hospital between 2011 and 2021, with community-acquired aspiration pneumonia or sepsis of undetermined source were included. Patients with mild dementia and independent in their activities of daily living were excluded. Primary outcome was 30- and 90-day all-cause mortality. A propensity-weighted multivariable model was constructed using inverse probability of treatment weighting. Results were expressed as OR with 95% CI. Results In total, 1558 patients were included: 512 treated with chloramphenicol and 1046 with ceftriaxone. The cohort consisted of elderly patients (mean age 87 ± 6.2 years) with comorbidities; 30- and 90-day all-cause mortality were similar [222/512 (43.3%) versus 439/1046 (41.9%) P  = 0.602, and 261/512 (50.9%) versus 556/1046 (53.1%) P  = 0.419, respectively]. Propensity-weighted, logistic multivariable analysis for 30- and 90-day all-cause mortality revealed similar mortality rates for chloramphenicol and ceftriaxone (OR 1.049 95% CI 0.217–1.158, OR 0.923 95% CI 0.734–1.112, respectively). Conclusion In this retrospective cohort of elderly debilitated patients hospitalized with pneumonia and sepsis, we found no difference in 30- and 90-day mortality between those treated with chloramphenicol or ceftriaxone. Further studies should determine the efficacy and safety of chloramphenicol in this population. [ABSTRACT FROM AUTHOR]

Purpose: Urinary sepsis is the leading cause of mortality in the setting of endourological procedures for stone treatment such as URS and PCNL; renal stones themselves may be a source of infection. Aim of this study is to determine the diagnostic accuracy of stone cultures (SC) collected during URS and PCNL in predicting post-operative septic complications, compared to preoperative bladder urine culture (BUC). Methods: We performed a systematic review (SR) of literature according to the PRISMA guidelines; Literature quality was evaluated according to The Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I) assessment tool. A univariate meta-analysis (MA) was used to estimate pooled log odds ratio of BUC and SC, respectively. Results: Overall, 14 studies including 3646 patients met the inclusion criteria. Eight studies reported data from PCNL only; three from URS only; three from both URS and PCNL. Stone cultures showed a higher sensitivity (0.52 vs 0.32) and higher positive predictive value (0.28 vs 0.21) in predicting post-operative sepsis, compared to bladder urine cultures. The pool-weighted logarithmic odd risk (LOR) for BUC was 2.30 (95% CI 1.51–3.49, p < 0.001); the LOR for stone cultures (SC) in predicting post-operative sepsis was 5.79 (95% CI 3.58–9.38, p < 0.001). Conclusion: The evidence from this SR and MA suggests that intraoperative SC from stone fragments retrieved during endourological procedures are better predictors of the likelihood of occurrence of post-operative sepsis compared to pre-operative BUC. Therefore, SC should be a standard of care in patients undergoing endourological interventions. [ABSTRACT FROM AUTHOR]

Purpose: To create a machine-learning model for estimating the likelihood of post-retrograde intrarenal surgery (RIRS) sepsis. Methods: All consecutive patients with kidney stone(s) only undergoing RIRS in 16 centers were prospectively included (January 2022–August 2023). Inclusion criteria: adult, renal stone(s) only, CT scan (within three months), mid-stream urine culture (within 10 days). Exclusion criteria: concomitant ureteral stone, bilateral procedures. In case of symptomatic infection/asymptomatic bacteriuria, patients were given six days of antibiotics according to susceptibility profiles. All patients had antibiotics prophylaxis. Variables selected for the model: age, gender, age-adjusted Charlson Comorbidity Index, stone volume, indwelling preoperative bladder catheter, urine culture, single/multiple stones, indwelling preoperative stent/nephrostomy, ureteric access sheath, surgical time. Analysis was conducted using Python programming language, with Pandas library and machine learning models implemented using the Scikit-learn library. Machine learning algorithms tested: Decision Tree, Random Forest, Gradient Boosting. Overall performance was accurately estimated by K-Fold cross-validation with three folds. Results: 1552 patients were included. There were 20 (1.3%) sepsis cases, 16 (1.0%) septic shock cases, and three more cases (0.2%) of sepsis-related deaths. Random Forest model showed the best performance (precision = 1.00; recall = 0.86; F1 score = 0.92; accuracy = 0.92). A web-based interface of the predictive model was built and is available at https://emabal.pythonanywhere.com/ Conclusions: Our model can predict post-RIRS sepsis with high accuracy and might facilitate patient selection for day-surgery procedures and identify patients at higher risk of sepsis who deserve extreme attention for prompt identification and treatment. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening organ dysfunction caused by a disorder in the regulation of a body's response to infection. If sepsis is not recognized at an early stage and treatment is not started, it can lead to septic shock, multiple organ failure, and death. Sepsis diagnostics, traditionally based on the clinical picture and the detection of etiologically significant microorganisms in the blood and foci, has been improved in recent years through the search for and the implementation of various biomarkers. One of promising sepsis biomarkers is 3-(4-hydroxyphenyl)lactic acid (4-HPLA). In this work, an amperometric sensor modified with a molecularly imprinted polymer (MIP) of hydroxyphenyllactic acid is developed, and a fundamental possibility of determining 4-HPLA in model aqueous solutions using this sensor is demonstrated. Molecularly imprinted polymers are widely used in substance separation processes and in the fabrication of selective sensors. Among a variety of selective materials, polyimides are of particular interest. In this regard, MIP sensors with imprints of 4-hydroxyphenyllactic acid were developed based on a copolymer of 1,2,4,5-benzenetracarboxylic acid with 4,4'-diaminodiphenyl oxide. The sensors are obtained in two stages (stage I at 80°C, stage II at 180°C) using the non-covalent imprinting method. The high selectivity of the MIP sensors with respect to the target molecules was established. The analytical range of the acid is 0.0002−0.2 mg/L. The experimentally established limit of detection for 4-hydroxyphenyllactic acid is 4.5 × 10–5 mg/L. [ABSTRACT FROM AUTHOR]

Background: In recent years, some studies classified patients with sepsis and predicted their mortality by using some evaluation scales. Several studies reported significant differences in the predictive values of several tools, and the non‐uniformity of the cut‐off value. Aim: To determine and compare the prognostic accuracy of Sequential Organ Failure Assessment (SOFA) score, Modified Early Warning Score (MEWS), and Systemic Inflammatory Response Syndrome (SIRS) criteria in predicting the mortality of patients with sepsis. Methods: This study comprised of systematic literature review and meta‐analysis according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses. We searched PubMed, Embase, Web of Science and Cochrane Library databases from their establishment to July 31, 2022. The research articles published in the index journals provide sufficient data (true positive, false positive, true negative, and false negative results) for patients with sepsis. The combined sensitivity and specificity of the 95% confidence interval (CI) were calculated using the bivariate random effect model (BRM). The hierarchical overall subject working characteristics (HSROC) curve was drawn to evaluate the accuracy of the overall prognosis. Results: Data of 55 088 patients from 32 studies were included in this meta‐analysis. SOFA had an intermediate sensitivity of 0.73 (95% CI: 0.67–0.78) and a specificity of 0.70 (0.63–0.76). SIRS criteria had the highest sensitivity of 0.75 (0.66–0.82) and the lowest specificity of 0.40 (0.29–0.52). MEWS had the lowest sensitivity of 0.49 (0.40–0.59) and the highest specificity of 0.82 (0.78–0.86). Conclusions: Among SOFA, MEWS, and SIRS criteria, SOFA showed moderate sensitivity and specificity for predicting mortality in patients with sepsis, the highest sensitivity of SIRS and the strongest specificity of MEWS for predicting mortality in patients with sepsis. The future research direction is to combine the relevant indicators of MEWS and SIRS to develop a measurement tool with high reliability and validity. Relevance to clinical practice: The review provides useful insights into the prognostic accuracy of different assessment tools in predicting mortality in sepsis patients, which will help clinicians choose the most appropriate tool for early identification and treatment of sepsis. The findings may also contribute to the development of more accurate and reliable prognostic models for sepsis. [ABSTRACT FROM AUTHOR]

Sepsis is common and expensive, and evidence suggests that sepsis order sets may help to improve care. Very incomplete evidence exists regarding the effects of sepsis order sets on the value of care produced by hospitals or the societal costs of sepsis care. In patients hospitalized for sepsis, is the receipt a of a sepsis order set vs no order set associated with improved value of care, defined as decreased hospital mortality, decreased hospital direct variable costs, and decreased societal spending on hospitalizations? This retrospective cohort study included patients discharged with sepsis International Classification of Diseases, Tenth Revision, codes over 2 years from a large integrated delivery system. Using a propensity score, sepsis order set users were matched to nonusers to study the association between sepsis order set use and the value of care from the hospital and societal perspective. The association between order set receipt and hospital mortality, direct variable cost, and hospital revenue also were examined in a priori defined subgroups of sepsis severity and hospital mortality. The study included 97,249 patients, with 52,793 patients (54%) receiving the sepsis order set. The propensity score match analysis included 55,542 patients, with 27,771 patients in each group. Recipients of the sepsis order set showed a 3.3% lower hospital mortality rate and a $1,487 lower median direct variable total cost (P <. 01 for both). Median payer-neutral reimbursement (ie, PNR), a proxy for hospital revenue and thus societal costs, was $465 lower for sepsis order set users (P <. 01). Receipt of the sepsis order set was associated with a $1,022 increase in contribution margin, the difference between direct variable costs and PNR per patient. Receipt of the sepsis order set was associated with improved value of care, from both a hospital and societal perspective. [Display omitted] [ABSTRACT FROM AUTHOR]

OBJECTIVES: Significant practice variation exists in the amount of resuscitative IV fluid given to patients with sepsis. Current research suggests equipoise between a tightly restrictive or more liberal strategy but data is lacking on a wider range of resuscitation practices. We sought to examine the relationship between a wide range of fluid resuscitation practices and sepsis mortality and then identify the primary driver of this practice variation. DESIGN: Retrospective analysis of the Premier Healthcare Database. SETTING: Six hundred twelve U.S. hospitals. PATIENTS: Patients with sepsis and septic shock admitted from the emergency department to the ICU from January 1, 2016, to December 31, 2019. INTERVENTIONS: The volume of resuscitative IV fluid administered before the end of hospital day-1 and mortality. MEASUREMENTS AND MAIN RESULTS: In total, 190,682 patients with sepsis and septic shock were included in the analysis. Based upon patient characteristics and illness severity, we predicted that physicians should prescribe patients with sepsis a narrow mean range of IV fluid (95% range, 3.6-4.5 L). Instead, we observed wide variation in the mean IV fluids administered (95% range, 1.7-7.4 L). After splitting the patients into five groups based upon attending physician practice, we observed patients in the moderate group (4.0 L; interquartile range [IQR], 2.4-5.1 L) experienced a 2.5% reduction in risk-adjusted mortality compared with either the very low (1.6 L; IQR, 1.0-2.5 L) or very high (6.1 L; IQR, 4.0-9.0 L) fluid groups p < 0.01). An analysis of within- and betweenhospital IV fluid resuscitation practices showed that physician variation within hospitals instead of practice differences between hospitals accounts for the observed variation. CONCLUSIONS: Individual physician practice drives excess variation in the amount of IV fluid given to patients with sepsis. A moderate approach to IV fluid resuscitation is associated with decreased sepsis mortality and should be tested in future randomized controlled trials. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the metabolomic profiles associated with different immune activation states in sepsis patients. DESIGN: Subgroup analysis of the PROVIDE (a Personalized Randomized trial of Validation and restoration of Immune Dysfunction in severe infections and Sepsis) prospective clinical study. SETTING: Results of the PROVIDE study showed that patients with sepsis may be classified into three states of immune activation: 1) macrophage-activation-like syndrome (MALS) characterized by hyperinflammation, sepsis-induced immunoparalysis, and 3) unclassified or intermediate patients without severe immune dysregulation. PATIENTS OR SUBJECTS: Two hundred ten patients from 14 clinical sites in Greece meeting the Sepsis-3 definitions with lung infection, acute cholangitis, or primary bacteremia. INTERVENTIONS: During our comparison, we did not perform any intervention. MEASUREMENTS AND MAIN RESULTS: Untargeted metabolomics analysis was performed on plasma samples from 210 patients (a total of 1394 products). Differential abundance analysis identified 221 significantly different metabolites across the immune states. Metabolites were enriched in pathways related to ubiquinone biosynthesis, tyrosine metabolism, and tryptophan metabolism when comparing MALS to immunoparalysis and unclassified patients. When comparing MALS to unclassified, 312 significantly different metabolites were found, and pathway analysis indicated enrichment in multiple pathways. Comparing immunoparalysis to unclassified patients revealed only two differentially regulated metabolites. CONCLUSIONS: Findings suggest distinct metabolic dysregulation patterns associated with different immune dysfunctions in sepsis: the strongest metabolic dysregulation is associated with MALS. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Sepsis survivors have greater healthcare use than those surviving hospitalizations for other reasons, yet factors associated with greater healthcare use in this population remain ill-defined. Rural Americans are older, have more chronic illnesses, and face unique barriers to healthcare access, which could affect postsepsis healthcare use. Therefore, we compared healthcare use and expenditures among rural and urban sepsis survivors. We hypothesized that rural survivors would have greater healthcare use and expenditures. DESIGN, SETTING, AND PATIENTS: To test this hypothesis, we used data from 106,189 adult survivors of a sepsis hospitalization included in the IBM MarketScan Commercial Claims and Encounters database and Medicare Supplemental database between 2013 and 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified hospitalizations for severe sepsis and septic shock using the International Classification of Diseases, 9th Edition (ICD-9) or 1CD-10 codes. We used Metropolitan Statistical Area classifications to categorize rurality. We measured emergency department (ED) visits, inpatient hospitalizations, skilled nursing facility admissions, primary care visits, physical therapy visits, occupational therapy visits, and home healthcare visits for the year following sepsis hospitalizations. We calculated the total expenditures for each of these categories. We compared outcomes between rural and urban patients using multivariable regression and adjusted for covariates. After adjusting for age, sex, comorbidities, admission type, insurance type, U.S. Census Bureau region, employment status, and sepsis severity, those living in rural areas had 17% greater odds of having an ED visit (odds ratio [OR] 1.17; 95% CI, 1.13-1.22; p < 0.001), 9% lower odds of having a primary care visit (OR 0.91; 95% CI, 0.87-0.94; p < 0.001), and 12% lower odds of receiving home healthcare (OR 0.88; 95% CI, 0.84-0.93; p < 0.001). Despite higher levels of ED use and equivalent levels of hospital readmissions, expenditures in these areas were 14% (OR 0.86; 95% CI, 0.80-0.91; p < 0.001) and 9% (OR 0.91; 95% CI, 0.87-0.96; p < 0.001) lower among rural survivors, respectively, suggesting these services may be used for lower-acuity conditions. CONCLUSIONS: In this large cohort study, we report important differences in healthcare use and expenditures between rural and urban sepsis survivors. Future research and policy work is needed to understand how best to optimize sepsis survivorship across the urban-rural continuum. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether mortality differed between initial invasive mechanical ventilation (IMV) or noninvasive ventilation (NIV) followed by delayed IMV in immunocompromised patients with sepsis. DESIGN: Retrospective analysis using the National Data Center for Medical Service claims data in China from 2017 to 2019. SETTING: A total of 3530 hospitals across China. PATIENTS: A total of 36,187 adult immunocompromised patients with sepsis requiring ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital mortality. Patients were categorized into NIV initiation or IMV initiation groups based on first ventilation. NIV patients were further divided by time to IMV transition: no transition, immediate (= 1 d), early (2-3 d), delayed (4-7 d), or late (= 8 d). Mortality was compared between groups using weighted Cox models. Over the median 9-day follow-up, mortality was similar for initial NIV versus IMV (adjusted hazard ratio [HR] 1.006; 95% CI, 0.959-1.055). However, among NIV patients, a longer time to IMV transition is associated with stepwise increases in mortality, from immediate transition (HR 1.65) to late transition (HR 2.51), compared with initial IMV. This dose-response relationship persisted across subgroups and sensitivity analyses. CONCLUSIONS: Prolonged NIV trial before delayed IMV transition is associated with higher mortality in immunocompromised sepsis patients ultimately intubated. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the frequency of and risk factors for increased postsepsis healthcare utilization compared with pre-sepsis healthcare utilization. DESIGN: Retrospective observational cohort study. SETTING: Years 2016-2019 MarketScan Commercial and Medicaid Database. PATIENTS: Children (0-18 yr) with sepsis treated in a U.S. hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured the frequency of and risk factors for increased healthcare utilization in the 90 days post- vs. presepsis hospitalization. We defined increased healthcare utilization as an increase of at least 3 days in the 90 days post-hospitalization compared with the 90 days pre-hospitalization based on outpatient, emergency department, and inpatient hospitalization. We identified 2801 patients hospitalized for sepsis, of whom 865 (30.9%) had increased healthcare utilization post-sepsis, with a median (interquartile range [IQR]) of 3 days (1-6 d) total in the 90 days pre-sepsis and 10 days (IQR, 6-21 d) total in the 90 days post-sepsis (p < 0.001). In multivariable models, the odds of increased healthcare use were higher for children with longer lengths of hospitalization (> 30 d adjusted odds ratio [aOR], 4.35; 95% CI, 2.99-6.32) and children with preexisting complex chronic conditions, specifically renal (aOR, 1.47; 95% CI, 1.02-2.12), hematologic/immunologic (aOR, 1.34; 95% CI, 1.03-1.74), metabolic (aOR, 1.39; 95% CI, 1.08-1.79), and malignancy (aOR, 1.89; 95% CI, 1.38-2.59). CONCLUSIONS: In this nationally representative cohort of children who survived sepsis hospitalization in the United States, nearly one in three had increased healthcare utilization in the 90 days after discharge. Children with hospitalizations longer than 30 days and complex chronic conditions were more likely to experience increased healthcare utilization. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Pediatric sepsis-associated acute kidney injury (AKI) often requires continuous renal replacement therapy (CRRT), but limited data exist regarding patient characteristics and outcomes. We aimed to describe these features, including the impact of possible dialytrauma (i.e., vasoactive requirement, negative fluid balance) on outcomes, and contrast them to nonseptic patients in an international cohort of children and young adults receiving CRRT. DESIGN: A secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), an international, multicenter, retrospective study. SETTING: Neonatal, cardiac and PICUs at 34 centers in nine countries from January 1, 2015, to December 31, 2021. PATIENTS: Patients 0-25 years old requiring CRRT for AKI and/or fluid overload. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1016 patients, 446 (44%) had sepsis at CRRT initiation and 650 (64%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (defined as a composite of death, renal replacement therapy [RRT] dependence, or > 25% decline in estimated glomerular filtration rate from baseline at 90 d from CRRT initiation). Septic patients were less likely to liberate from CRRT by 28 days (30% vs. 38%; p < 0.001) and had higher rates of MAKE-90 (70% vs. 61%; p = 0.002) and higher mortality (47% vs. 31%; p < 0.001) than nonseptic patients; however, septic survivors were less likely to be RRT dependent at 90 days (10% vs. 18%; p = 0.011). On multivariable regression, pre-CRRT vasoactive requirement, time to negative fluid balance, and median daily fluid balance over the first week of CRRT were not associated with MAKE-90; however, increasing duration of vasoactive requirement was independently associated with increased odds of MAKE-90 (adjusted OR [aOR], 1.16; 95% CI, 1.05-1.28) and mortality (aOR, 1.20; 95% CI, 1.1-1.32) for each additional day of support. CONCLUSIONS: Septic children requiring CRRT have different clinical characteristics and outcomes compared with those without sepsis, including higher rates of mortality and MAKE-90. Increasing duration of vasoactive support during the first week of CRRT, a surrogate of potential dialytrauma, appears to be associated with these outcomes. [ABSTRACT FROM AUTHOR]

Background: Comorbidities are similarly associated with short‐term mortality for COVID‐19, acute respiratory distress syndrome (ARDS) and sepsis in intensive care unit (ICU) patients, but their adjusted frequencies at admission are unknown. Thus, we aimed to evaluate the adjusted distribution, reported as odds ratios, of known risk factors (i.e., age, sex and comorbidities) for ICU admission between COVID‐19, sepsis and ARDS patients in this nationwide registry‐based study. Methods: In this cohort study, we included adult patients admitted to Swedish ICUs with COVID‐19 (n = 7382) during the pandemic and compared them to patients admitted to ICU with sepsis (n = 22,354) or ARDS (n = 2776) during a pre‐COVID‐19 period. The main outcomes were the adjusted odds for comorbidities, sex, and age in multivariable logistic regression on diagnostic categories in patients admitted to ICU, COVID‐19 or sepsis and COVID‐19 or ARDS. Results: We found that most comorbidities, as well as age, had a stronger association with sepsis admission than COVID‐19 admission with the exception of male sex, type 2 diabetes mellitus, and asthma that were more strongly associated with COVID‐19 admission, while no difference was seen for chronic renal failure and obesity. For COVID‐19 and ARDS admission most risk factors were more strongly associated with ARDS admission except for male sex, type 2 diabetes mellitus, chronic renal failure, and obesity which were more strongly associated with COVID‐19 admission, whereas hypertension, chronic obstructive pulmonary disease and asthma were not different. Conclusions: Patients admitted to ICU with sepsis or ARDS carry a heavier burden of comorbidity and high age than patients admitted with COVID‐19. This is likely caused by a combination of: (1) respiratory failure in COVID‐19 being less dependent on comorbidities than in other forms of ARDS, and the cause of critical illness in other infections causing sepsis and (2) COVID‐19 patients being deferred admission in situations where patients with the other syndromes were admitted. [ABSTRACT FROM AUTHOR]

Background: The average treatment effect (ATE) reported by most randomised clinical trials provides estimates of treatment effects for the theoretical, non‐existent average patient. However, ATE may not accurately reflect the outcomes for all subsets of the trial population; some individuals may benefit from the intervention, while others experience worse outcomes or no effect at all. Heterogeneity of treatment effect (HTE) is the non‐random and explainable variation in the magnitude or direction of a treatment effect among individuals within a population. Predictive approaches to HTE seek to provide estimates of which treatment of choice is better suited for the individual patient, using regression and/or machine learning techniques. This scoping review aims to investigate the extent to which such predictive approaches to HTE are applied to data from trials on sepsis or septic shock as well as the results of these analyses. Methods: The planned review will be conducted in accordance with the PRISMA extension for scoping reviews. We will search Medline, EMBASE, Central, Cinahl and Google Scholar for studies on sepsis or septic shock in which HTE was analysed using predictive approaches. We plan to chart data regarding trial characteristics, patient demographics, disease severity, interventions, outcomes of interest and ATEs, type of predictive approach for the HTE analysis, results from HTE analysis and whether HTE analysis would change an ATE‐based trial conclusion. Results: Studies included in the scoping review will be presented as narrative summaries, supplemented with descriptive statistics of quantitative data. Conclusion: The planned scoping review will systematically investigate, summarise and delineate the existing evidence of analysis of HTE in trials on sepsis or septic shock patients as well as their findings, when performed using predictive approaches. [ABSTRACT FROM AUTHOR]

• We report data on immunocompromised ICU patients with intra-abdominal infections. • Compared to an immunocompetent cohort in a large multinational cohort study. • Community-acquired infections were less frequent and septic shock more frequent. • Mortality was not higher. • Risk factors for death are septic shock and source control failure. We compared epidemiology of intra-abdominal infection (IAI) between immunocompromised and non-immunocompromised ICU patients and identified risk factors for mortality. We performed a secondary analysis on the " AbSeS " database, a prospective, observational study with IAI patients from 309 ICUs in 42 countries. Immunocompromised status was defined as either neutropenia or prolonged corticosteroids use, chemotherapy or radiotherapy in the past year, bone marrow or solid organ transplantation, congenital immunodeficiency, or immunosuppressive drugs use. Mortality was defined as ICU mortality at any time or 28-day mortality for those discharged earlier. Associations with mortality were assessed by logistic regression. The cohort included 2589 patients of which 239 immunocompromised (9.2 %), most with secondary peritonitis. Among immunocompromised patients, biliary tract infections were less frequent, typhlitis more frequent, and IAIs were more frequently healthcare-associated or early-onset hospital-acquired compared with immunocompetent patients. No difference existed in grade of anatomical disruption, disease severity, organ failure, pathogens, and resistance patterns. Septic shock was significantly more frequent in the immunocompromised population. Mortality was similar in both groups (31.1% vs. 28.9 %; p = 0.468). Immunocompromise was not a risk factor for mortality (OR 0.98, 95 % CI 0.66–1.43). Independent risk factors for mortality among immunocompromised patients included septic shock at presentation (OR 6.64, 95 % CI 1.27–55.72), and unsuccessful source control with persistent inflammation (OR 5.48, 95 % CI 2.29–12.57). In immunocompromised ICU patients with IAI, short-term mortality was similar to immunocompetent patients, despite the former presented more frequently with septic shock, and septic shock and persistent inflammation after source control were independent risk factors for death. [ABSTRACT FROM AUTHOR]

• An improvement in mortality in sepsis patients with early administration of antibiotics at 3 and 6 hrs but not at 1hr. • Our findings do not support the current guideline recommendations to administer antibiotics to sepsis patients with shock within 1 hour of diagnosis. • Antibiotics should be administered within 3 hrs of sepsis recognition and/or ED arrival. To evaluate whether the timing of initial antibiotic administration in patients with sepsis in hospital affects mortality. This systematic review and meta-analysis included studies from inception up to 19 May 2022. Interventional and observational studies including adult human patients with suspected or confirmed sepsis and reported time of antibiotic administration with mortality were included. Data were extracted by two independent reviewers. Summary estimates were calculated by using random-effects model. The primary outcome was mortality. We included 42 studies comprising 190,896 patients with sepsis. Pooled data showed that the OR for patient mortality who received antibiotics ≤1 hr was 0.83 (95 %CI: 0.67 to 1.04) when compared with patients who received antibiotics >1hr. Significant reductions in the risk of death in patients with earlier antibiotic administration were observed in patients ≤3 hrs versus >3 hrs (OR: 0.80, 95 %CI: 0.68 to 0.94) and ≤6 hrs vs 6 hrs (OR: 0.57, 95 %CI: 0.39 to 0.82). Our findings show an improvement in mortality in sepsis patients with early administration of antibiotics at <3 and <6 hrs. Thus, these results suggest that antibiotics should be administered within 3 hrs of sepsis recognition or ED arrival regardless of the presence or absence of shock. [ABSTRACT FROM AUTHOR]

High concentrations of immunoglobulins, bioactive peptides, and growth factors are found in bovine colostrum (BC), the milk produced by cows in the first few days after parturition. Various biological functions make it increasingly used to provide nutritional support and immune protection to the offspring of many species, including humans. These biological functions include cell growth stimulation, anti-infection, and immunomodulation. The primary components and biological functions of colostrum were reviewed in the literature, and the authors also looked at its latent effects on the growth and development of neonates as well as on conditions such as infections, necrotizing enterocolitis, short bowel syndrome, and feeding intolerance. The importance of BC in neonatal nutrition, immune support, growth and development, and gut health has been demonstrated in a number of experimental and animal studies. BC has also been shown to be safe at low doses without adverse effects in newborns. BC supplementation has been shown to be efficient in preventing several disorders, including rotavirus diarrhea, necrotizing enterocolitis, and sepsis in animal models of prematurity and some newborn studies. Therefore, BC supplementation should be considered in cases where maternal milk is insufficient or donor milk is unavailable. The optimal age, timing, dosage, and form of BC administration still require further investigation. [ABSTRACT FROM AUTHOR]

The article discusses the critical need to address maternal sepsis as a prominent cause of maternal morbidity and mortality worldwide. Topics include the background of maternal sepsis, detailing its impact on pregnant and postpartum women; diagnostic approaches to improve early detection and outcomes; and management strategies within obstetric critical care, emphasizing timely intervention and multidisciplinary care.

Objective To compare the risk of severe maternal morbidity (SMM) from the delivery admission to 42 days' postdischarge among persons with sickle cell disease (SCD) to those without SCD. Study Design This retrospective cohort study included deliveries ≥20 weeks' gestation at an urban safety net hospital in Atlanta, GA from 2011 to 2019. The exposure was SCD diagnosis. The outcome was a composite of SMM from the delivery admission to 42 days' postdischarge. SMM indicators as defined by the Centers for Disease Control and Prevention were identified using the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes; transfusion of blood products and sickle cell crisis were excluded. Results Of N = 17,354 delivery admissions, n = 92 (0.53%) had SCD. Persons with SCD versus without SCD had an increased risk of composite SMM (15.22 vs. 2.29%, p < 0.001), acute renal failure (6.52 vs. 0.71%, p < 0.001), acute respiratory distress syndrome (4.35 vs. 0.17%, p < 0.001), puerperal cerebrovascular disorders (3.26 vs. 0.10%, p < 0.001), sepsis (4.35 vs. 0.42%, p < 0.01), air and thrombotic embolism (5.43 vs. 0.10%, p < 0.001), and ventilation (2.17 vs. 0.09%, p < 0.01). Ultimately, those with SCD had an approximately 6-fold higher incidence risk ratio of SMM, which remained after adjustment for confounders (adjusted incidence risk ratio [aIRR]: 5.96, 95% confidence interval [CI]: 3.4–9.19, p < 0.001). Persons with SCD in active vaso-occlusive crisis at the delivery admission had an approximately 9-fold higher risk of SMM up to 42 days' postdischarge compared with those with SCD not in crisis at the delivery admission (incidence: 25.71 vs. 8.77%, p < 0.05; aIRR: 8.92, 95% CI: 4.5–10.04, p < 0.05). Among those with SCD, SMM at the delivery admission was primarily related to renal and cerebrovascular events, whereas most postpartum SMM was related to respiratory events or sepsis. Conclusion SCD is significantly associated with an increased risk of SMM during the delivery admission and through 42 days' postdischarge. Active crisis at delivery further increases the risk of SMM. Key Points Sickle cell disease was associated with an approximately 6-fold increased risk of SMM. Active vaso-occlusive crisis at delivery was associated with an approximately 9-fold increased risk of SMM. 48% of SMM events in persons with SCD occurred postpartum and were respiratory- or sepsis-related. [ABSTRACT FROM AUTHOR]

Introduction: Most patients on extracorporeal membrane oxygenation (ECMO) decease during therapy on the system. However, the actual causes of death have not been studied sufficiently. This study analyses the etiology, prevalence, and risk factors for the outcome variable death during ongoing ECMO for all patients and divided according to venoarterial (VA) or venovenous (VV) support. Methods: We retrospectively analysed all patients receiving ECMO support at our institution between March 2006 to January 2021. Only the patients deceased during ongoing support were included. Results: 2016 patients were placed on VA (n = 1168; 58%) or VV (n = 848; 42%) ECMO; 759 patients (37.7%) deceased on support. The causes of death differed between the support types: VA ECMO patients mostly died from cerebral ischemia (34%), low-cardiac output (LCO; 24.1%) and multi-organ failure (MOF; 21.6%), whereas in VV ECMO cases, refractory respiratory failure (28.2%), and sepsis (20.4%) dominated. Multivariate regression analysis revealed cardiopulmonary resuscitation (CPR) and acidosis prior to ECMO as risk factors for dying on VA ECMO, while high inotropic doses pre-ECMO, a high fraction of inspired oxygen on day 1, elevated lactate dehydrogenase, and international normalized ratio levels lead to an unfavourable outcome in VV ECMO patients. Conclusion: Even in highly experienced centers, ECMO mortality remains high and occurs mainly on support or 24 h after its termination. The causes of death differ between VV and VA ECMO, depending on the underlying diseases responsible for the need of extracorporeal support. [ABSTRACT FROM AUTHOR]

Several investigations have been carried out to explore the genetic association of TLR4 codon variants, specifically Asp299Gly and Thr399Ile, and susceptibility to sepsis, but the results have been contradictory. The present study aimed to conduct a meta‐analysis to draw a definitive conclusion regarding the role of TLR4 genetic variants (Asp299Gly and Thr399Ile) in sepsis. A thorough literature search was conducted using the PubMed, Scopus, and Science Direct databases. The inclusion and exclusion criteria were established to ensure the accuracy of the data. The Comprehensive Meta‐Analysis Software v4 was utilized to perform the meta‐analysis and related analyses. A total of 13 studies were analyzed, including 2328 sepsis cases and 2495 healthy controls for the TLR4 Asp299Gly variant. Eight studies provided genotype data for the rs4986791 polymorphism. The Asp299Gly variant showed a marginal protective effect in the allele (p = 0.08, odds ratio = 0.71) and dominant (p = 0.09, odds ratio = 0.71) genetic models, although it was not statistically significant. The trial sequential analysis indicated that further case–control studies are necessary to draw definitive conclusions about the TLR4 polymorphisms in sepsis. The TLR4 Asp299Gly variant may have a protective effect against sepsis. However, additional research with larger sample sizes across diverse populations is required to validate this finding. [ABSTRACT FROM AUTHOR]

Background: The peripheral perfusion index (PI) reflects microcirculatory blood flow perfusion and indicates the severity and prognosis of sepsis. Method: The cohort comprised 208 patients admitted to the intensive care unit (ICU) with infection, among which 117 had sepsis. Demographics, medication history, ICU variables, and laboratory indexes were collected. Primary endpoints were in-hospital mortality and 28-day mortality. Secondary endpoints included organ function variables (coagulation function, liver function, renal function, and myocardial injury), lactate concentration, mechanical ventilation time, and length of ICU stay. Univariate and multivariate analyses were conducted to assess the associations between the PI and clinical outcomes. Sensitivity analyses were performed to explore the associations between the PI and organ functions in the sepsis and nonsepsis groups. Result: The PI was negatively associated with in-hospital mortality (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.55), but was not associated with 28-day mortality. The PI was negatively associated with the coagulation markers prothrombin time (PT) (β −0.36, 95% CI −0.59 to 0.13) and activated partial thromboplastin time (APTT) (β −1.08, 95% CI −1.86 to 0.31), and the myocardial injury marker cardiac troponin I (cTnI) (β −2085.48, 95% CI −3892.35 to 278.61) in univariate analysis, and with the PT (β −0.36, 95% CI −0.60 to 0.13) in multivariate analysis. The PI was negatively associated with the lactate concentration (β −0.57, 95% CI −0.95 to 0.19), mechanical ventilation time (β −23.11, 95% CI −36.54 to 9.69), and length of ICU stay (β −1.28, 95% CI −2.01 to 0.55). Sensitivity analyses showed that the PI was significantly associated with coagulation markers (PT and APTT) and a myocardial injury marker (cTnI) in patients with sepsis, suggesting that the associations between the PI and organ function were stronger in the sepsis group than the nonsepsis group. Conclusion: The PI provides new insights for assessing the disease severity, short-term prognosis, and organ function damage in ICU patients with sepsis, laying a theoretical foundation for future research. [ABSTRACT FROM AUTHOR]

Objective: Vitamin K (VK) is commonly prescribed for pediatric sepsis-induced coagulopathy without trial-derived evidence to support its use for this indication. The purpose of this study was to characterize national prescribing trends for VK in this population. Patients and Methods: This is a multicenter retrospective cohort study using the Pediatric Health Information System registry including children 0 to 17 years of age hospitalized for sepsis in the pediatric intensive care unit from January 2016 through December 2022. The primary outcome was overall, annual, and center-specific VK prescribing rates. Descriptive data included demographics, length of stay, and rates of VK deficiency, hepatic insufficiency, red blood cell (RBC) transfusion, venous thromboembolism (VTE), and mortality. VK prescribing trends were assessed using Joinpoint regression. Descriptive statistics employed included Wilcoxon rank-sum, student's t, and chi-square tests. Results: Of the 31 221 encounters studied, 4539 (14.6%) were prescribed VK (median center-specific rate: 14.2%; interquartile range [IQR]: 8.8-21%) with a linear annual trend decreasing from 17.3% in 2016 to 13.3% in 2022 (−0.6%/year, r 2 =.661). Those prescribed VK had greater rates of hepatic dysfunction (20.5% vs 3.1%), RBC transfusion (26.5% vs 11.2%), VTE (12.5% vs 4.6%), mortality (17.1% vs 4.4%), and median length of stay (16 [IQR: 8-33] vs 8 [4-15] days) (all P <.001). VK deficiency was diagnosed in 0.2% of encounters. Conclusions: In this multicenter retrospective cohort, VK prescribing was common among critically ill children diagnosed with sepsis. Phased trials are needed to demonstrate clinical efficacy and safety for VK in this population. [ABSTRACT FROM AUTHOR]

Neutropenic sepsis (NS) is one of the leading causes of death among patients with hematologic malignancies. Identifying its predictive factors is fundamental for early detection. Few studies have evaluated the predictive factors in relation to microbial infection confirmation, which is clinically important for initiating sepsis treatment. This study aimed to determine whether selected biomarkers (i.e., body temperature, C-reactive protein, albumin, procalcitonin), treatment-related characteristics (i.e., diagnosis, duration of neutropenia, treatment modality), and infection-related characteristics (i.e., infection source, causative organisms) can predict NS in patients with hematologic malignancies. We also aimed to identify the optimal predictive cutoff points for these parameters. This retrospective case–control study used the data from a total of 163 patients (58 in the sepsis group and 105 in the non-sepsis group). We collected data with reference to the day of specimen collection, with which microbial infection was confirmed. Multiple logistic regression was used to determine predictive risk factors and the area under the curve (AUC) of the receiver operating characteristic for the optimal predictive cutoff points. The independent predictors of NS were average body temperature during a fever episode and procalcitonin level. The odds for NS rose by 9.97 times with every 1°C rise in average body temperature (95% confidence interval, CI [1.33, 75.05]) and by 2.09 times with every 1 ng/mL rise in the procalcitonin level (95% CI [1.08, 4.04]). Average body temperature (AUC = 0.77, 95% CI [0.68, 0.87]) and procalcitonin levels (AUC = 0.71, 95% CI [0.59, 0.84]) have fair accuracy for predicting NS, with the optimal cutoff points of 37.9°C and 0.55 ng/mL, respectively. This study found that average body temperature during a fever episode and procalcitonin are useful in predicting NS. Thus, nurses should carefully monitor body temperature and procalcitonin levels in patients with hematologic malignancies to detect the onset of NS. [ABSTRACT FROM AUTHOR]

Purpose: To discern whether reduced infection rates were attributed to antiseptic solutions or mechanical rectal irrigation. Patients and Methods: After receiving ethical approval, the study included patients who underwent transrectal prostate biopsy due to elevated PSA or abnormal digital rectal examination findings, and prostate cancer under active surveillance, at Tepecik Training and Research Hospital between April 2022 and June 2023. Standard antibiotic prophylaxis was administered. Patients were randomized into three equal groups according to the rectal irrigation strategy. Results: Overall complications occurred in 4%. Despite distinct cleaning agents, there was no significant difference in infection rates (p = 0.780) or fever incidence (p = 0.776). Pathological analyses revealed comparable outcomes (p = 0.764). Conclusion: The study challenges the prevailing belief that antiseptic solutions are indispensable for infection prevention, as saline demonstrated similar efficacy. Limitations include data gaps from potential external hospital visits and absent rectal microorganism swab culture. While TRUS-PB remains the gold standard, this study suggests that mechanically cleansing the rectal mucosa with saline—a cost-effective, side-effect-free alternative—may be a viable infection prevention method, particularly beneficial for patients with antiseptic allergies. The findings prompt a reconsideration of the necessity of antiseptic solutions in TRUS-PB, offering an alternative approach to mitigate infectious complications. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy and safety of retrograde double J stent (RDJS) placement in the management of complicated obstructive uropathy caused by urolithiasis. Patients and Methods: An observational study done at a tertiary center was implemented in which a total of 27 patients (10 males, 17 females) with average age of 48.74 years (range: 15–88) who underwent RDJS or percutaneous nephrostomy (PCN) between 2017 and 2021 due to complicated obstruction caused by urolithiasis were included. Results: A total of 27 patients (10 males, 17 females) with average age of 48.74 years (range: 15–88) who underwent kidney decompression between 2017 and 2021 due to complicated unilateral or bilateral kidney obstruction caused by ureteral stones were included. Twenty-two patients (81.48%) underwent successful RDJS placement, two patients had RDJS placement then PCN was also placed, and two patients underwent PCN placement. Three patients needed an intensive care unit "ICU" after intervention, two of them were in the ICU before intervention. All septic parameters were normalized within a short period postoperatively. Two patients with failed previous ureteroscopy had a successful RDJS placement. Conclusion: Retrograde DJS placement is a feasible option in the management of complicated cases of obstructive uropathy caused by urolithiasis. Short hospitalization period, low rate of complications and better quality of life are the most prominent advantages of RDJS placement. In the hands of experienced surgeons, RDJS should be offered as the first choice of decompression for obstructive uropathy caused by urolithiasis. [ABSTRACT FROM AUTHOR]

To investigate the protective mechanisms of hydrogen sulfide (H 2 S) in sepsis-induced acute kidney injury (SAKI), we conducted an in vivo study using a SAKI mouse model induced by intraperitoneal lipopolysaccharide (LPS) injection. Following 6 h of LPS injection, levels of tumor necrosis factor-alpha (TNF-α) and blood urea nitrogen (Bun) were significantly elevated in mouse plasma. In the kidneys of SAKI mice, expression of H 2 S-generating enzymes cysteinyl-tRNA synthetase (CARS), cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) was markedly downregulated, while glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R-like endoplasmic reticulum kinase/protein kinase R-like endoplasmic reticulum kinase (p-PERK/PERK), and B-cell lymphoma-2 recombinant protein X/B-cell lymphoma-2 (Bax/Bcl2) expression was significantly upregulated. H 2 S improved renal function and attenuated renal histopathological changes in SAKI mice, thereby alleviating LPS-induced endoplasmic reticulum stress (ERS). Additionally, it inhibited the expression of p-PERK/PERK and Bax/Bcl2. After inhibiting CSE activity with dl -propargylglycine (PPG i. p.), the renal tissue pathology in LPS-induced AKI mice was further exacerbated, leading to enhanced activation of the PERK/Bax-Bcl2 pathway. Our findings suggest that endogenous H 2 S influences the pathogenesis of SAKI, while exogenous H 2 S protects against LPS-induced AKI by inhibiting the PERK/Bax-Bcl2 pathway involved in ERS. • The lack of endogenous hydrogen sulfide generation is the cause of SAKI in sepsis. • Exogenous hydrogen sulfide treatment inhibits ER stress and improves SAKI. • Exogenous hydrogen sulfide improves SAKI by suppressing ER stress through inhibition of the PERK/Bax-Bcl2 pathway. [ABSTRACT FROM AUTHOR]

Sepsis is one of the major causes of morbidity and mortality in burn patients. However, the optimal timing of admission which can minimize the probability of sepsis is still unclear. This study aims to determine the optimal time period of admission for severely burned patients and find out the possible reasons for it. 185 victims to the Kunshan factory aluminum dust explosion accident, which happened on August 2nd, 2014, were studied. The optimal cutpoint for continuous variables in survival models was determined by means of the maximally selected rank statistic. Univariate and multivariate analyses were further conducted to verify that admission time was not a risk factor for sepsis. Subgroup analyses were performed to find out possible contributing factors for the result. The cutoff point for admission time was determined as seven hours, which was supported by the survival curve (p < 0.001). Multivariate analysis showed that, in our study population, delayed admission time was not a risk factor for sepsis (HR = 0.610, 95 %CI = 0.415 - 0.896, p = 0.012). Subgroup analyses showed that "Tracheotomy before admission" (p = 0.002), "Whole blood transfusion" (p < 0.001), "Hemodynamic instability before admission" (p = 0.02), "Has a burn department in the hospital" (p = 0.009), "Has a burn ICU in the hospital" (p < 0.001), "Acute heart failure (AHF)" (p = 0.05), "acute respiratory distress syndrome (ARDS)" (p = 0.05) and "GI bleeding" (p = 0.04) were all statistically significant. In our study population, we found that delayed admission time was not a risk factor associated with a reduced incidence of sepsis among severely burned patients. This might be attributed to variations in prehospital treatments (whole blood transfusion and tracheotomy), whether the hospital had a burn department/ICU, and certain complications (AHF, ARDS and GI bleeding). It can be inferred that early prehospital care plays a crucial role in reducing sepsis risk among severe burn patients. • Seven hours post-injury is key to reducing sepsis risk in severe burn cases. • Hospital facilities, especially burn units, crucially impact sepsis prognosis. • Complications such as AHF, ARDS, and GI bleeding significantly affect sepsis risk. [ABSTRACT FROM AUTHOR]

Summary: Background: Re‐exploration following caesarean birth and the associated maternal morbidity has not been investigated in the UK. Our aims were to determine the national incidence and identify the associated risk factors. Methods: We conducted a prospective observational case–control study across 194 UK consultant‐led maternity units in women whose caesarean birth was complicated by a re‐exploration. Independent factors for re‐exploration were analysed using multivariable multi‐level mixed effects logistic regression. Results: Over the study period (1 June 2021 and 31 May 2022) 238,423 caesarean births were recorded across the UK of which 187 women underwent re‐exploration, giving an incidence of one re‐exploration per 1282 caesarean births (95%CI 1:1099–1:1471). Haemorrhage (124/187, 66.3%) and sepsis (31/187, 16.6%) were the most common findings at re‐exploration. Median (IQR [range]) time interval to re‐exploration following the caesarean birth was 1 (0–4 [0–28]) day. Mechanical ventilation was required in 34 (18.6%) women, cardiac arrest was reported in 5 (2.7%) and 3 (1.6%) women died. Independent preceding factors associated with a re‐exploration included: receipt of blood transfusion (adjusted OR (95%CI) 8.25 (2.66–25.61)); use of a general anaesthetic (adjusted OR (95%CI) 3.33 (1.61–6.88)); pre‐eclampsia (adjusted OR (95%CI) 3.27 (1.55–6.91)); black ethnicity (adjusted OR (95%CI) 3.14 (1.39–7.11)); postpartum haemorrhage (adjusted OR (95%CI) 2.82 (1.81–4.37)); use of anticoagulants or antiplatelet drugs pre‐caesarean birth (adjusted OR (95%CI) 2.26 (1.35–3.81)); and emergency caesarean birth (adjusted OR (95%CI) 1.89 (1.01–3.57)). Conclusion: Re‐exploration following caesarean birth in the UK is uncommon but is associated with significant maternal morbidity and mortality. These study findings will help guide informed consent and encourage appropriate surveillance of high‐risk women postpartum. [ABSTRACT FROM AUTHOR]

Independent risk factors for sepsis‐associated acute kidney injury (S‐AKI) patients include elevated lactate levels, but the specific mechanism remains unclear. Recently, An et al. discovered that excessive acetylation and inactivation of PDHA1 lead to overproduction of lactate, resulting in mitochondrial fragmentation, ATP depletion, excessive mtROS production, and mitochondrial apoptosis, thereby exacerbating AKI in sepsis. Therefore, understanding the pathophysiological processes of mitochondrial function and lactate generation in SAKI is essential and can aid in the development of novel therapeutic strategies. This review elucidates the pathological mechanisms of mitochondrial autophagy and dynamics in AKI. We also discuss the sources of lactate in SAKI and some consequences of lactonization, which may provide new strategies for improving renal injury and delaying the progression of these diseases. [ABSTRACT FROM AUTHOR]