INTRODUCTION:The impact of continuous renal replacement therapy (CRRT) with oXiris hemofilter (oXiris CRRT) on sepsis outcomes remain controversial. We aimed to investigate the association between the oXiris CRRT and subsequent outcomes in adult patients with septic shock. METHODS:This single-center, retrospective cohort study included adult patients with septic shock, who were admitted to the intensive care unit (ICU) of our tertiary referral hospital between 2019 and 2023, and underwent at least one CRRT session. Patients were categorized into two groups based on the initially hemofilter used (oXiris group vs. M100 group). A 1:1 propensity score matching was performed to compare the primary outcome 28-day vasopressor-free days. RESULTS:Of 465 patients who met all eligibility criteria, 69 cases in the oXiris group were matched with 69 individuals in the M100 group. Compared with the M100 group, the use of oXiris CRRT was associated with longer 28-day vasopressor-free days (24 vs. 19 days, P = 0.04), shorter CRRT duration (72 vs. 117 h, P = 0.03), and a greater reduction in SOFA scores (-2 vs. 1, P = 0.004). However, competing risk analysis indicated no significant between-group difference in the cumulative incidence of vasopressor weaning after accounting for the competing risk of ICU mortality. Furthermore, no significant between-group differences were observed in changes in lactate, PCT, or IL-6 levels, fluid balance, ICU or hospital length of stay (LOS), or short-term mortality. CONCLUSIONS:In this cohort of septic shock patients undergoing CRRT, unadjusted analyses demonstrated potential improvements in hemodynamic stability and organ function following oXiris therapy. Nevertheless, these preliminary signals were not confirmed by competing risk analysis of the primary outcome. Therefore, the clinical impacts of oXiris CRRT observed in the present study must be viewed cautiously, well-designed prospective investigations are warranted to verify its definitive therapeutic value.

Background: Severe infections in intensive care units (ICUs) pose a significant challenge, substantially contributing to morbidity and mortality, and thus making their early diagnosis critical. Traditional pathogen culture methods have longer turnaround times (TATs) and limited sensitivity, potentially missing key pathogens (viruses or atypical organisms). Next-generation sequencing (NGS) has shorter TAT, emerging as a promising technology for rapid, broad-spectrum pathogen detection. This study aimed to compare the diagnostic performance of NGS against traditional pathogen culture methods in ICU patients and to explore the impact of positive NGS results on patient outcomes. Methods: This retrospective observational study analyzed data of patients admitted to the ICU of Zhongnan Hospital of Wuhan University between April 2021 and April 2023. Patient demographics (gender and age), clinical data (admission reason, infection details, underlying diseases, ICU treatments, Sequential Organ Failure Assessment score, and Acute Physiology and Chronic Health Evaluation II score), and results from paired NGS and pathogen cultures performed on various samples (predominantly bronchoalveolar lavage fluid [BALF] and blood) were obtained. Inflammatory markers were also recorded. Statistical analyses were performed to compare detection rates, pathogen spectrum, and TATs between NGS and culture methods. Furthermore, agreement rates were calculated, and multivariate logistic regression was used to assess the influence of various factors, including NGS positivity, on 28-day mortality. Results: Overall, 601 clinical cases were included. The overall pathogen detection rate for NGS was 8.9%, which was significantly higher compared to 45.1% for culture. NGS identified viruses in 34.4%, bacteria in 7.5%, fungi in 4.3%, and atypical pathogens in 8.0% of cases, while culture primarily detected bacteria and fungi in 36.9% and 9.0% of cases, respectively. The TAT for NGS was significantly shorter than for culture (P < 0.001), particularly for blood samples. Positive agreement between the methods was highest in BALF samples (55.2%), while negative agreement was highest in blood samples (45.9%). NGS showed a significantly better ability to detect common pathogens than culture (P < 0.001). Importantly, multivariate logistic regression analysis revealed that NGS positivity was an independent risk factor for 28-day mortality (P < 0.05). Conclusion: In critically ill ICU patients, NGS demonstrates a superior diagnostic yield, detecting a broader range of pathogens, including unculturable ones, with a significantly faster TAT compared to traditional pathogen culture methods. Furthermore, a positive NGS result is independently associated with increased 28-day mortality, underscoring the clinical relevance of the pathogens identified using this advanced technique.

Sepsis-associated acute kidney injury (SA-AKI) is a severe condition with high mortality rates and a lack of specific treatments. Dendrobine (DEN) has shown diverse pharmacological effects across different diseases. Nonetheless, its impact on SA-AKI remains unexplored. This study aimed to investigate DEN's therapeutic potential in SA-AKI and elucidate its mechanism of action. In vivo, SA-AKI models were induced through cecal ligation and puncture or lipopolysaccharide (LPS) administration, while in vitro model was established using LPS-stimulated HK-2 cells. We found that pre-treatment with DEN reduced levels of inflammation-related cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), and improved kidney function in SA-AKI both in vitro and in vivo. RNA-seq analysis unveiled the critical role of mitophagy in DEN treatment for SA-AKI. We observed an initial increase in mitophagy-related proteins such as PINK1, PARKIN, and LC3B/A, peaking at 8 h post-LPS stimulation, followed by a subsequent decline. Additionally, we demonstrated that DEN upregulated the expression of mitophagy-associated proteins in both in vitro and in vivo SA-AKI models. Notably, we found that carbonyl cyanide 3-chlorophenylhydrazone (CCCP) increased LC3B/A levels in DEN treatment for SA-AKI, whereas Mdivi-1 counteracted the effect of DEN on PINK1, PARKIN, and LC3B/A. These findings demonstrated that DEN enhances mitophagy through the activation of PINK1/PARKIN-mediated pathways, thus mitigating SA-AKI.

Sepsis remains a leading cause of global mortality, primarily driven by microvascular collapse stemming from severe vascular endothelial injury. Within this pathology, the dramatic depletion of Apolipoprotein A1 (ApoA1) and its carrier, high-density lipoprotein (HDL), is a hallmark feature. Despite being recognized as a prognostic biomarker, a comprehensive understanding of the ApoA1/HDL axis as an active participant and therapeutic target in endothelial protection remains fragmented. This review systematically synthesizes current evidence to reframe the ApoA1/HDL axis from a passive indicator to a master regulator of endothelial homeostasis in sepsis. We first delineate the strong correlation between reduced ApoA1/HDL levels and endothelial damage across various infections. Subsequently, we dissect its protective triad of mechanisms: potent anti-inflammatory actions, preservation of endothelial barrier integrity, and restoration of microvascular flow. Furthermore, we explore the emerging interplay between ApoA1 and exosomes, a novel aspect of its regulatory function. Finally, the translational potential of ApoA1-based therapies, including mimetic peptides and recombinant HDL, is evaluated. By providing an integrated mechanistic framework, this review highlights the ApoA1 as a critical therapeutic target and offers a roadmap for developing novel, endothelium-centric treatments for sepsis.

Background:Malnutrition poses a significant public health challenge, particularly as the global population ages. However, there is a notable lack of comprehensive literature analyzing the global burden of malnutrition among the elderly. Methods:Data on nutritional deficiencies indicators-prevalence, incidence, and disability-adjusted life years (DALYs)-for individuals aged 70 and older were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) database from 1990 to 2021. The estimated annual percentage change (EAPC) was used to assess trends in malnutrition burden. Predictions for new cases over the next 25 years were also made. Results:In 2021, over 97.60 million cases of malnutrition among the elderly were reported globally, a 1.2-fold increase from 44.36 million cases in 1990. The global prevalence rate of malnutrition has decreased with an EAPC of -0.32%. Women experienced more cases than men but had a lower prevalence rate. Furthermore, in high socio-demographic index (SDI) regions, both prevalence rate and DALYs rates increased from 1990 to 2021, with EAPCs of 0.33% and 1.34%, respectively. The burden of malnutrition in the elderly was negatively correlated with SDI. Predictions from 2022 to 2046 estimated approximately 29.64 million new cases of malnutrition by 2046, despite a declining incidence rate. Conclusion:Despite a decline in malnutrition prevalence rate and DALYs rate since 1990, the burden remains high, particularly in high SDI regions where rates have increased. With a projected rise in new cases, effective prevention and management strategies are urgently needed to support the health of older adults.

Background: Despite numerous studies assessing bundled interventions to enhance hand hygiene compliance (HHC), compliance rates persist at suboptimal levels. Our objective was to employ Kotter's Change Model (KCM) to enhance HHC and conduct a comprehensive process evaluation among medical staff within the intensive care unit (ICU). Methods: KCM was implemented at the ICU of Zhongnan Hospital of Wuhan University from March 2018 to August 2021, with a 41-month longitudinal monitoring of HHC. The primary outcome focused on the absolute monthly change in HHC. Secondary outcomes encompassed the HHC characteristics across different phases, varying trends in HHC concerning different hand hygiene opportunities and occupations, quarterly incidences of central line-associated bloodstream infections (CLABSI) and catheter-associated urinary tract infections (CAUTI). Results: This study included 20,222 hand hygiene actions and 24,195 opportunities. The overall HHC was 83.58 % (95 %CI, 83.11 %-84.04 %). Following the KCM implementation, HHC surged from 35.71 % (95 % CI, 22.99 %-50.83 %) to 87.75 % (95 % CI, 85.53 %-89.67 %), reflecting a notable increase of 145.73 %. The most rapid growth in HHC occurred post-patient contact, elevating from 35.29 % to 89.8 %. Despite escalating patient numbers and treatment complexities annually, the quarterly rates of CLABSI (0 %o -3.53 %o ) and CAUTI (0.96 %o-4.26 %o ) remained consistently low. Conclusion: Utilizing KCM systematically alters healthcare providers' perception of hand hygiene, fostering an environment that advocates for and sustains improved HHC among ICU personnel. Implications for clinical practice: The Kotter's change model can be an effective framework for healthcare organizations to systematically improve and maintain hand hygiene compliance among healthcare providers, which can in turn help reduce healthcare-associated infections.

The replacement intervals for infusion sets may differ among healthcare institutions, which may have an impact on the occurrence of central line-associated bloodstream infections (CLABSI). Nevertheless, there exists a limited amount of high-quality evidence available to assist clinicians in determining the most suitable replacement intervals for infusion sets. Therefore, the objective of this trial is to compare the efficacy of 24-h and 96-h replacement intervals for infusion sets on CLABSI among critically ill adults who have central venous access devices. This is a multicenter, parallel-group randomized controlled trial that will investigate the effect of infusion set replacement intervals on CLABSI in adult patients admitted to intensive care units (ICUs). The study will enroll 1240 participants who meet the inclusion criteria, which includes being 18 years or older, expected to stay in the ICU for longer than 96 h, and in need of central venous access. Participants will be randomly assigned to either a control group receiving a 96-h replacement interval or a treatment group receiving a 24-h replacement interval. The primary outcome of this trial is the rate of CLABSI within 28 days after randomization. This is the first randomized controlled trial to investigate the effects of infusion set replacement at 24-h and 96-h intervals on CLABSI in ICU patients. ClinicalTrials.gov identifier, NCT05359601.

Background The lack of transparency is a prevalent issue among the current machine-learning (ML) algorithms utilized for predicting mortality risk. Herein, we aimed to improve transparency by utilizing the latest ML explicable technology, SHapley Additive exPlanation (SHAP), to develop a predictive model for critically ill patients.Methods We extracted data from the Medical Information Mart for Intensive Care IV database, encompassing all intensive care unit admissions. We employed nine different methods to develop the models. The most accurate model, with the highest area under the receiver operating characteristic curve, was selected as the optimal model. Additionally, we used SHAP to explain the workings of the ML model.Results The study included 21 395 critically ill patients, with a median age of 68 years (interquartile range, 56-79 years), and most patients were male (56.9%). The cohort was randomly split into a training set (N = 16 046) and a validation set (N = 5349). Among the nine models developed, the Random Forest model had the highest accuracy (87.62%) and the best area under the receiver operating characteristic curve value (0.89). The SHAP summary analysis showed that Glasgow Coma Scale, urine output, and blood urea nitrogen were the top three risk factors for outcome prediction. Furthermore, SHAP dependency analysis and SHAP force analysis were used to interpret the Random Forest model at the factor level and individual level, respectively.Conclusion A transparent ML model for predicting outcomes in critically ill patients using SHAP methodology is feasible and effective. SHAP values significantly improve the explainability of ML models. Key messages What is already known on this topic? The lack of transparency is a prevalent issue among the current machine-learning (ML) algorithms utilized for predicting mortality risk. What this study adds? We successfully developed a high-performance ML model for the prediction of in-hospital mortality in critically ill patients (accuracy: 87.62%; area under the receiver operating characteristic curve: 0.89), and utilized a latest ML interpretable technology called SHapley Additive exPlanation, to increase model transparency. How this study might affect research, practice, or policy? Our findings could assist healthcare providers in identifying high-risk factors contributing to mortality in daily clinical practice. This, in turn, could help optimize the alignment of care goals and improve healthcare resource utilization.

Background This study aimed to explore the correlation between hyperglycemia at intensive care unit (ICU) admission and the incidence of acute kidney injury (AKI) in patients after cardiac surgery. Methods We conducted a retrospective cohort study, in which clinical data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Adults (≥18 years) in the database who were admitted to the cardiovascular intensive care unit after cardiac surgery were enrolled. The primary outcome was the incidence of AKI within 7 days following ICU admission. Secondary outcomes included ICU mortality, hospital mortality, ICU length of stay, and the 28-day and 90-day mortality. Multivariable Cox regression analysis was used to assess the association between ICU-admission hyperglycemia and AKI incidence within 7 days of ICU admission. Different adjustment strategies were used to adjust for potential confounders. Patients were divided into three groups according to their highest blood glucose levels recorded within 24 h of ICU admission: no hyperglycemia (<140 mg/dL), mild hyperglycemia (140–200 mg/dL), and severe hyperglycemia (≥200 mg/dL). Results Of the 6905 included patients, 2201 (31.9%) were female, and the median (IQR) age was 68.2 (60.1–75.9) years. In all, 1836 (26.6%) patients had severe hyperglycemia. The incidence of AKI within 7 days of ICU admission, ICU mortality, and hospital mortality was significantly higher in patients with severe admission hyperglycemia than those with mild hyperglycemia or no hyperglycemia (80.3% vs. 73.6% and 61.2%, respectively; 2.8% vs. 0.9% and 1.9%, respectively; and 3.4% vs. 1.2% and 2.5%, respectively; all P <0.001). Severe hyperglycemia was a risk factor for 7-day AKI (Model 1: hazard ratio [HR]=1.4809, 95% confidence interval [CI]: 1.3126 to 1.6707; Model 2: HR=1.1639, 95% CI: 1.0176 to 1.3313; Model 3: HR=1.2014, 95% CI: 1.0490 to 1.3760; all P <0.050). Patients with normal glucose levels (glucose levels <140 mg/dL) had a higher 28-day mortality rate than those with severe hyperglycemia (glucose levels ≥200 mg/dL) (4.0% vs. 3.8%, P <0.001). Conclusions In post-cardiac surgery patients, severe hyperglycemia within 24 h of ICU admission increases the risk of 7-day AKI, ICU mortality, and hospital mortality. Clinicians should be extra cautious regarding AKI among patients with hyperglycemia at ICU admission after cardiac surgery.

Magnesium imbalances commonly exist in septic patients. However, the association of serum magnesium levels with mortality in septic patients remains uncertain. Herein, we elucidated the association between serum magnesium and all-cause mortality in septic patients from American and Chinese cohorts by analyzing data from 9099 patients in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and 1727 patients from a university-affiliated hospital' intensive care unit in China. Patients in both cohorts were categorized into five groups based on serum magnesium quintiles from the MIMIC-IV dataset. Patients with higher serum magnesium levels exhibited an increased risk of 28-day mortality in both cohorts. The restricted cubic spline (RCS) curves revealed a progressively elevated risk of 28-day mortality with increasing serum magnesium in MIMIC-IV cohort, while a J-shaped correlation was observed in institutional cohort. Our findings have validated the association between high serum magnesium and high mortality in sepsis across different races and medical conditions. Serum magnesium levels might be useful in identifying septic patients at higher mortality risk.

Damage to renal tubular epithelial cells (RTECs) signaled the onset and progression of sepsis-associated acute kidney injury (SA-AKI). Recent research on mitochondria has revealed that mitophagy plays a crucial physiological role in alleviating injury to RTECs and it is suppressed progressively by the inflammation response in SA-AKI. However, the mechanism by which inflammation influences mitophagy remains poorly understood. We examined how macrophage migration inhibitory factor (MIF), a pro-inflammatory protein, influences the PINK1-Parkin pathway of mitophagy by studying protein-protein interactions when MIF was inhibited or overexpressed. Surprisingly, elevated levels of MIF were found to directly bind to PINK1, disrupting its interaction with Parkin. This interference hindered the recruitment of Parkin to mitochondria and impeded the initiation of mitophagy. Furthermore, this outcome led to significant apoptosis of RTECs, which could, however, be reversed by an MIF inhibitor ISO-1 and/or a new mitophagy activator T0467. These findings highlight the detrimental impact of MIF on renal damage through its disruption of the interaction between PINK1 and Parkin, and the therapeutic potential of ISO-1 and T0467 in mitigating SA-AKI. This study offers a fresh perspective on treating SA-AKI by targeting MIF and mitophagy.

Background Capillary refill time (CRT) is defined as the time taken for color to return to an external capillary bed after pressure is applied to cause blanching. Recent studies demonstrated the benefits of CRT in guiding fluid therapy for sepsis. However, lack of consistency among physicians in how to perform and interpret CRT has led to a low interobserver agreement for this assessment tool, which prevents its availability in sepsis clinical settings. Objective To give physicians a concise overview of CRT and explore recent evidence on its reliability and value in the management of sepsis. Research design A narrative review. Results This narrative review summarizes the factors affecting CRT values, for example, age, sex, temperature, light, observation techniques, work experience, training level and differences in CRT measurement methods. The methods of reducing the variability of CRT are synthesized. Based on studies with highly reproducible CRT measurements and an excellent inter-rater concordance, we recommend the standardized CRT assessment method. The threshold of normal CRT values is discussed. The application of CRT in different phases of sepsis management is summarized. Conclusions Recent data confirm the value of CRT in critically ill patients. CRT should be detected by trained physicians using standardized methods and reducing the effect of ambient-related factors. Its association with severe infection, microcirculation, tissue perfusion response, organ dysfunction and adverse outcomes makes this approach a very attractive tool in sepsis. Further studies should confirm its value in the management of sepsis. Implications for clinical practice As a simple assessment, CRT deserves more attention even though it has not been widely applied at the bedside. CRT could provide nursing staff with patient’s microcirculatory status, which may help to develop individualized nursing plans and improve the patient’s care quality and treatment outcomes.

Acute lung injury (ALI) has received considerable attention in intensive care owing to its high mortality rate. It has been demonstrated that the selective alpha7 nicotinic acetylcholine receptor agonist Gainesville Tokushima scientists (GTS)-21 is promising for treating ALI caused by lipopolysaccharides (LPS). However, the precise underlying mechanism remains unknown. This study aimed to investigate the potential efficacy of GTS-21 in the treatment of ALI. We developed mouse models of ALI and alveolar epithelial type II cells (AT2s) injury following treatment with LPS and different polarized macrophage supernatants, respectively. Pathological changes, pulmonary edema, and lung compliance were assessed. Inflammatory cells count, protein content, and pro-inflammatory cytokine levels were analysed in the bronchoalveolar lavage fluid. The expression of angiotensin-converting enzyme (ACE), ACE2, syndecan-1 (SDC-1), heparan sulphate (HS), heparanase (HPA), exostosin (EXT)-1, and NF-κB were tested in lung tissues and cells. GTS-21-induced changes in macrophage polarization were verified in vivo and in vitro. Polarized macrophage supernatants with or without recombination a disintegrin and metalloproteinase-17 (ADAM-17) and small interfering (si)RNA ADAM-17 were used to verify the role of ADAM-17 in AT2 injury. By reducing pathological alterations, lung permeability, inflammatory response, ACE/ACE2 ratio, and glycocalyx shedding, as well as by downregulating the HPA and NF-κB pathways and upregulating EXT1 expression in vivo, GTS-21 significantly diminished LPS-induced ALI compared to that of the LPS group. GTS-21 significantly attenuated macrophage M1 polarization and augmented M2 polarization in vitro and in vivo. The destructive effects of M1 polarization supernatant can be inhibited by GTS-21 and siRNA ADAM-17. GTS-21 exerted a protective effect against LPS-induced ALI, which was reversed by recombinant ADAM-17. Collectively, GTS-21 alleviates LPS-induced ALI by attenuating AT2s ACE/ACE2 ratio and glycocalyx shedding through the inhibition of macrophage M1 polarization derived ADAM-17.

The development of intensive care medicine is inseparable from the diversified monitoring data. Intensive care medicine has been closely integrated with data since its birth. Critical care research requires an integrative approach that embraces the complexity of critical illness and the computational technology and algorithms that can make it possible. Considering the need of standardization of application of big data in intensive care, Intensive Care Medicine Branch of China Health Information and Health Care Big Data Society, Standard Committee has convened expert group, secretary group and the external audit expert group to formulate Chinese Experts’ Consensus on the Application of Intensive Care Big Data (2022). This consensus makes 29 recommendations on the following five parts: Concept of intensive care big data, Important scientific issues, Standards and principles of database, Methodology in solving big data problems, Clinical application and safety consideration of intensive care big data. The consensus group believes this consensus is the starting step of application big data in the field of intensive care. More explorations and big data based retrospective research should be carried out in order to enhance safety and reliability of big data based models of critical care field.

Acute kidney injury (AKI) is a common complication in patients supported by extracorporeal membrane oxygenation (ECMO). Vasoactive-Inotropic Score (VIS) serves as an indicator of the extent of cardiovascular drug support provided. Our objective is to assess the relationship between the VIS and ECMO-associated AKI (EAKI). This single-center retrospective study extracted adult patients treated with ECMO between August 2016 and September 2022 from an intensive care unit (ICU) in a university hospital. A total of 126 patients requiring ECMO support were included in the study, of which 76% developed AKI. Multivariate logistic regression analysis identified VIS-max Day1 (odds ratio [OR]: 1.025, 95% confidence interval [CI]: 1.007-1.044, p = 0.006), VIS-max Day2 (OR: 1.038, 95% CI: 1.007-1.069, p = 0.015), VIS-mean Day1 (OR: 1.048, 95% CI: 1.013-1.084, p = 0.007), and VIS-mean Day2 (OR: 1.059, 95% CI: 1.014-1.107, p = 0.010) as independent risk factors for EAKI. VIS-max Day1 showing the best predictive effect (Area under the receiver operating characteristic curve (AUROC): 0.80, sensitivity: 71.87%, specificity: 80.00%) for EAKI with a cutoff value of 33.33. Surprisingly, VIS-mean Day2 was also excellent at predicting 7 day mortality (AUROC: 0.77, sensitivity: 87.50%, specificity: 56.38%) with a cutoff value of 8.67. In conclusion, VIS could independently predict EAKI and 7 day mortality in patients with ECMO implantation, which may help clinicians to recognize the poor prognosis in time for early intervention.

Objectives: This observational study was conducted to investigate capillary refill time (CRT) during the early phase of ICU admission in relationship with microvascular flow alteration and outcome in critically ill patients. Design: Prospective, observational, pilot study. Setting: ICU in a university hospital. Patients: Two hundred eighty-two critically ill adult patients admitted to the ICU. Interventions: None. Measurements and Main Results: All patients underwent simultaneous measurements by CRT and sidestream dark field imaging within 24 hours of ICU admission. Other clinical data such as demographic characteristics, hemodynamics, laboratory values, treatment, and physiologic parameters were also included simultaneously. Microcirculatory measurements were performed at 10.2 ± 5.7 hours after ICU admission. Of the 282 included patients, 106 (37.6%) were female, the median (interquartile range) age was 63 years (53–74 yr), and the median Sequential Organ Failure Assessment (SOFA) score was 5 (2–7). The primary finding was the association between CRT and simultaneous the condition of peripheral circulation (microvascular flow index [MFI]: r = –0.4430, p < 0.001; proportion of perfused vessels: r = –0.3708, p < 0.001; heterogeneity index: r = 0.4378, p < 0.001; perfused vessel density: r = –0.1835, p = 0.0020; except total vessel density: p = 0.9641; and De Backer score: p = 0.5202) in critically ill patients. In addition, this relationship was also maintained in subgroups. Microcirculatory flow abnormalities, 28-day mortality, and SOFA score appeared to be more severe for increasing CRT. In a multivariable analysis, prolonged CRT was independently associated with microvascular flow abnormalities (MFI < 2.6; odds ratio [OR], 1.608; 95% CI, 2.1–10.2; p < 0.001). Similarly, multivariable analysis identified CRT as an independent predictor of 28-day mortality (OR, 1.296; 95% CI, 1.078–1.558; p = 0.006). Conclusions: In our ICU population, a single-spot prolonged CRT was independently associated with abnormal microcirculation and increased mortality.

IntroductionRestored cardiopulmonary function is efficiently achieved by utilizing extracorporeal membrane oxygenation (ECMO). Nevertheless, the incidence of Clostridioides difficile infection (CDI) associated with ECMO is relatively uncommon.Case presentationIn this report, we present the case of a 59-year-old male with severe chest pain due to acute myocardial infarction, subsequently necessitating ECMO support. During the first day of hospitalization, pulmonary infections were observed, and piperacillin-tazobactam was prescribed for 7 days at low dosages. However, the patient developed severe diarrhea 4 days later. After ruling out common pathogens, we suspected the occurrence of CDI and performed genetic testing for C. difficile toxin, confirming our diagnosis. The prescription of vancomycin resulted in slight improvement, while fecal microbiota transplantation (FMT) proved to be more effective.ConclusionIn this case, temporary application of ECMO was applied, and the anti-infective treatment relied on the use of antibiotics at short-term, low-dose, and low CDI risk. Hence, the occurrence of CDI was considered an uncommon event, which may serve as a reference for future cases.

Sepsis-induced acute kidney injury (S-AKI) is highly lethal, and effective drugs for treatment are scarce. Previously, we reported the robust therapeutic efficacy of fibroblastic reticular cells (FRCs) in sepsis. Here, we demonstrate the ability of FRC-derived exosomes (FRC-Exos) to improve C57BL/6 mouse kidney function following cecal ligation and puncture-induced sepsis. In vivo imaging confirmed that FRC-Exos homed to injured kidneys. RNA-Seq analysis of FRC-Exo-treated primary kidney tubular cells (PKTCs) revealed that FRC-Exos influenced PKTC fate in the presence of lipopolysaccharide (LPS). FRC-Exos promoted kinase PINK1-dependent mitophagy and inhibited NLRP3 inflammasome activation in LPS-stimulated PKTCs. To dissect the mechanism underlying the protective role of Exos in S-AKI, we examined the proteins within Exos by mass spectrometry and found that CD5L was the most upregulated protein in FRC-Exos compared to macrophage-derived Exos. Recombinant CD5L treatment in vitro attenuated kidney cell swelling and surface bubble formation after LPS stimulation. FRCs were infected with a CD5L lentivirus to increase CD5L levels in FRC-Exos, which were then modified in vitro with the kidney tubular cell targeting peptide LTH, a peptide that binds to the biomarker protein kidney injury molecule-1 expressed on injured tubule cells, to enhance binding specificity. Compared with an equivalent dose of recombinant CD5L, the modified CD5L-enriched FRC-Exos selectively bound PKTCs, promoted kinase PINK-ubiquitin ligase Parkin-mediated mitophagy, inhibiting pyroptosis and improved kidney function by hindering NLRP3 inflammasome activation, thereby improving the sepsis survival rate. Thus, strategies to modify FRC-Exos could be a new avenue in developing therapeutics against kidney injury.