Shenhuangdan decoction alleviates sepsis-induced lung injury through inhibition of GSDMD-mediated pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis-induced lung injury is closely associated with it remarkable morbidity and mortality. Shenhuangdan (SHD) decoction, a traditional Chinese medicine prescription, has been clinically proven to be an effective treatment for sepsis. However, the mechanism of SHD decoction in treating sepsis remains unclear. AIM OF THE STUDY: This study aimed to evaluate the therapeutic effect of SHD decoction on sepsis-induced lung injury and its underlying mechanism. MATERIALS AND METHODS: In this study, we established a mouse model of sepsis by cecum ligation and puncture (CLP) surgery. Firstly, seven-day survival analysis and histological staining of lung tissue were used to evaluate the therapeutic effect of SHD decoction on lung injury in septic mice. Multifactor microarray was used to detect cytokine expression changes in serum and bronchoalveolar lavage fluid (BALF). Subsequently, the main components in medicated serum of SHD decoction were inspected by Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The material basis of SHD decoction and potential interaction mechanisms were analysed by systemic pharmacology. To confirm the reliability of network pharmacology for predicting outcomes, we used molecular docking techniques to identify interactions between the core components and targets of SHD. Finally, TUNEL staining, immunofluorescence and western blotting were used to explore the mechanism of SHD decoction through the inhibition of GSDMD-mediated pyroptosis in septic mice. RESULTS: SHD was found to be effective in reducing the mortality and alleviating lung pathological damage in septic mice. Multifactor microarray results showed that SHD can reduce the expression of inflammation factors (IL-18, IL-1ß, IL-5, IL-6 and TNF-α) in serum and BALF of septic mice. There were 22 major blood-entry components detected by UPLC-MS/MS. Then, combined with the network pharmacological analysis, it is evident that the main components of SHD for sepsis are Renshen-ginsenoside Rh2, Danshen-tanshinone IIA and Dahuang-rhein. The main targets were IL-1ß and caspase-1, which were related to GSDMD-mediated pyroptosis signalling pathway. Molecular docking exhibited that Renshen-ginsenoside Rh2, Danshen-tanshinone IIA and Dahuang-rhein can closely bind to GSDMD, IL-1ß and caspase-1. In addition, TUNEL staining and immunohistochemistry demonstrated that SHD alleviated the expression of GSDMD protein. The western blotting showed that SHD significantly inhibited the protein expression levels of NLRP3, GSDMD, GSDMD-N, cleved caspase-1, caspase-1 and ASC in lung tissue. CONCLUSIONS: Our study revealed that SHD improves CLP-induced lung injury by blocking the GSDMD-mediated pyroptosis signalling pathway in septic mice. This study provides evidence to support that SHD had a potential therapeutic effect on sepsis.

Protocolos gerenciados por enfermeiros para identificação precoce da sepse: revisão de escopo / Nurse-managed protocols for early identification of sepsis: a scoping review / Protocolos administrados por enfermeros para la identificación temprana de la sepsis: revisión del alcance

Objetivo: mapear os protocolos assistenciais utilizados por enfermeiros para identificação precoce da sepse no ambiente hospitalar. Método: trata-se de uma revisão de escopo ancorada nas recomendações do Joanna Briggs Institute, desenvolvida em sete bases de dados. A busca e seleção ocorreu em 17 de julho de 2021, utilizando os descritores: sepse, protocolos de enfermagem, avaliação de enfermagem e cuidados de enfermagem. Resultados: a amostra foi composta de seis estudos, destacaram-se os protocolos implementados por projetos de melhoria de qualidade e utilização sistemas eletrônicos de alerta para deterioração clínica. Conclusão: protocolos assistenciais impulsionam a aderência dos profissionais às recomendações oficiais para o manejo da sepse no ambiente hospitalar e o desenvolvimento de cuidados de enfermagem baseados em evidências, contribuindo para melhorar os indicadores de qualidade e reduzir a mortalidade entre pacientes com sepse.

Objective: to map the care protocols used by nurses for the early identification of sepsis in the hospital environment. Method: this is a scope review anchored in the recommendations of the Joanna Briggs Institute, developed in seven databases. The search and selection took place on July 17, 2021, using the descriptors: sepsis, nursing protocols, nursing assessment and nursing care. Results: the sample consisted of six studies, highlighting the protocols implemented by quality improvement projects and the use of electronic warning systems for clinical deterioration. Conclusion: care protocols boost professionals' adherence to official recommendations for the management of sepsis in the hospital environment and the development of evidence-based nursing care, contributing to improve quality indicators and reduce mortality among patients with sepsis.

Objetivo: mapear los protocolos de atención utilizados por las enfermeras para identificar de forma temprana la sepsis en el ambiente hospitalario. Método: se trata de una revisión de alcance anclada en las recomendaciones del Instituto Joanna Briggs, desarrollada en siete bases de datos. La búsqueda y selección se realizó el 17 de julio de 2021, utilizando los descriptores: sepsis, protocolos de enfermería, evaluación de enfermería y cuidados de enfermería. Resultados: la muestra estuvo compuesta por seis estudios, se destacaron los protocolos implementados por los proyectos de mejora de la calidad y utilización de sistemas electrónicos de alerta con respecto al deterioro clínico. Conclusión: los protocolos asistenciales impulsan la adherencia de los profesionales a las recomendaciones oficiales para el manejo de la sepsis en el ámbito hospitalario y el desarrollo de cuidados de enfermería basados en evidencias, contribuyendo a mejorar los indicadores de calidad y reducir la mortalidad entre los pacientes con sepsis.

Comparing Long-Term Prognosis in Chronic Critically Ill Patients: A Case Series Study of Medical versus Surgical Sepsis.

Background and Objectives: Chronic critical illness (CCI) is a syndrome characterized by persistent organ dysfunction that requires critical care therapy for ≥14 days. Sepsis and respiratory failure constitute the two primary causes of CCI. A better understanding of this patient population and their clinical course may help to risk-stratify them early during hospitalization. Our objective was to identify whether the source of sepsis (medical versus surgical) affected clinical trajectory and prognosis in patients developing CCI. Materials and Methods: We describe a cohort of patients having acute respiratory failure and sepsis and requiring critical care therapy in the medical (MICU) or surgical (SICU) critical care units for ≥14 days. Given the relative infrequency of CCI, we use a case series design to examine mortality, functional status, and place of residence (home versus non-home) at one year following their index hospitalization. Results: In medical patients developing CCI (n = 31), the severity of initial organ dysfunction, by SOFA score, was significantly associated with the development of CCI (p = 0.002). Surgical patients with CCI (n = 7) experienced significantly more ventilator-free days within the first 30 days following sepsis onset (p = 0.004), as well as less organ dysfunction at day 14 post-sepsis (p < 0.0001). However, one-year mortality, one-year functional status, and residency at home were not statistically different between cohorts. Moreover, 57% of surgical patients and 26% of medical patients who developed CCI were living at home for one year following their index hospitalization (p = 0.11). Conclusions: While surgical patients who develop sepsis-related CCI experience more favorable 30-day outcomes as compared with medical patients, long-term outcomes do not differ significantly between groups. This suggests that reversing established organ dysfunction and functional disability, regardless of etiology, is more challenging compared to preventing these complications at an earlier stage.

Current Trends for Delirium Screening within the Emergency Department.

Delirium is an acute neurological disorder that involves attention and cognition. It is associated with a high risk of morbidity and mortality among older people (>65 years old). In the context of the Emergency Department (ED), it is frequently experienced by patients but often not recognized. Literature studies have identified some screening instruments for an initial evaluation of delirium. Most of these tools have not been validated yet in the context of emergencies, but, in other settings, they were very useful for assessing and maximizing the recognition of this condition among older patients. We conducted a review of the literature, including randomized control trials, clinical and observational studies, and research studies published in recent years, confirming that most of the screening tools for delirium used in the intensive care unit (ICU) or the geriatric department have not been tested in the ED, and the ideal timing and form of the delirium assessment process for older adults have not been defined yet. The aim of our review is to summarize the updated evidence about the screening tools for delirium in the context of the ED, due to the fact that overcrowding of the ED and the stressful condition of emergency situations (that contribute to the onset of delirium) could expose older patients to a high risk of complications and mortality if delirium is not promptly recognized. In conclusion, we support the evidence that delirium is a current and real condition that emergency physicians have to face daily, and we are aware that more research is needed to explore this field in order to improve the overall outcomes of older patients admitted to the ED.

Clinical Sepsis Phenotypes in Critically Ill Patients.

Sepsis, defined as the life-threatening dysregulated host response to an infection leading to organ dysfunction, is considered as one of the leading causes of mortality worldwide, especially in intensive care units (ICU). Moreover, sepsis remains an enigmatic clinical syndrome, with complex pathophysiology incompletely understood and a great heterogeneity both in terms of clinical expression, patient response to currently available therapeutic interventions and outcomes. This heterogeneity proves to be a major obstacle in our quest to deliver improved treatment in septic critical care patients; thus, identification of clinical phenotypes is absolutely necessary. Although this might be seen as an extremely difficult task, nowadays, artificial intelligence and machine learning techniques can be recruited to quantify similarities between individuals within sepsis population and differentiate them into distinct phenotypes regarding not only temperature, hemodynamics or type of organ dysfunction, but also fluid status/responsiveness, trajectories in ICU and outcome. Hopefully, we will eventually manage to determine both the subgroup of septic patients that will benefit from a therapeutic intervention and the correct timing of applying the intervention during the disease process.

Management of Sepsis and Septic Shock: What Have We Learned in the Last Two Decades?

Sepsis is a clinical syndrome encompassing physiologic and biological abnormalities caused by a dysregulated host response to infection. Sepsis progression into septic shock is associated with a dramatic increase in mortality, hence the importance of early identification and treatment. Over the last two decades, the definition of sepsis has evolved to improve early sepsis recognition and screening, standardize the terms used to describe sepsis and highlight its association with organ dysfunction and higher mortality. The early 2000s witnessed the birth of early goal-directed therapy (EGDT), which showed a dramatic reduction in mortality leading to its wide adoption, and the surviving sepsis campaign (SSC), which has been instrumental in developing and updating sepsis guidelines over the last 20 years. Outside of early fluid resuscitation and antibiotic therapy, sepsis management has transitioned to a less aggressive approach over the last few years, shying away from routine mixed venous oxygen saturation and central venous pressure monitoring and excessive fluids resuscitation, inotropes use, and red blood cell transfusions. Peripheral vasopressor use was deemed safe and is rising, and resuscitation with balanced crystalloids and a restrictive fluid strategy was explored. This review will address some of sepsis management's most important yet controversial components and summarize the available evidence from the last two decades.

Bacteremia in Patients with Sepsis in the ICU: Does It Make a Difference?

Sepsis (and septic shock) is on of the most common causes of death worldwide. Bacteremia often, but not necessarily, occurs in septic patients, but the impact of true bacteremia on a patient's clinical characteristics and outcome remains unclear. The main aim of this study was to compare the characteristics and outcome of a well-defined cohort of 258 septic patients with and without bacteremia treated in the intensive care unit (ICU) of a tertiary center hospital in Prague, Czech Republic. As expected, more frequently, bacteremia was present in patients without previous antibiotic treatment. A higher proportion of bacteremia was observed in patients with infective endocarditis as well as catheter-related and soft tissue infections in contrast to respiratory sepsis. Multivariant analysis showed increased severity of clinical status and higher Charlson comorbidity index (CCI) as variables with significant influence on mortality. Bacteremia appears to be associated with higher mortality rates and length of ICU stay in comparison with nonbacteremic counterparts, but this difference did not reach statistical significance. The presence of bacteremia, apart from previous antibiotic treatment, may be related to the site of infection.

A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction.

HMGB1 is a key late inflammatory mediator upregulated during air-pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays a significant role in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 levels may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution-induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense against air-pollution-induced oxidative stress and lung damage. Here, a standardized botanical antioxidant composition from Scutellaria baicalensis and Acacia catechu was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis. Murine models of disorders, including hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized. The effect of the botanical composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed cultured macrophages. Analyses, such as hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, Western blot analysis for proteins, including extracellular HMGB1, and bacterial counts in the lungs and airways, were performed. Statistically significant decreases in mortality (50%), proinflammatory cytokines (TNF-α, IL-1ß, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage fluid (BALF), and increased bacterial clearance from airways and lungs; reduced airway total protein, and decreased extracellular HMGB1 were observed in in vivo studies. A statistically significant 75.9% reduction in the level of extracellular HMGB1 and an increase in phagocytosis were observed in cultured macrophages. The compilations of data in this report strongly suggest that the botanical composition could be indicated for oxidative-stress-induced lung damage protection, possibly through attenuation of increased extracellular HMGB1 accumulation.

Nano-Biotechnology for Bacteria Identification and Potent Anti-bacterial Properties: A Review of Current State of the Art.

Sepsis is a critical disease caused by the abrupt increase of bacteria in human blood, which subsequently causes a cytokine storm. Early identification of bacteria is critical to treating a patient with proper antibiotics to avoid sepsis. However, conventional culture-based identification takes a long time. Polymerase chain reaction (PCR) is not so successful because of the complexity and similarity in the genome sequence of some bacterial species, making it difficult to design primers and thus less suitable for rapid bacterial identification. To address these issues, several new technologies have been developed. Recent advances in nanotechnology have shown great potential for fast and accurate bacterial identification. The most promising strategy in nanotechnology involves the use of nanoparticles, which has led to the advancement of highly specific and sensitive biosensors capable of detecting and identifying bacteria even at low concentrations in very little time. The primary drawback of conventional antibiotics is the potential for antimicrobial resistance, which can lead to the development of superbacteria, making them difficult to treat. The incorporation of diverse nanomaterials and designs of nanomaterials has been utilized to kill bacteria efficiently. Nanomaterials with distinct physicochemical properties, such as optical and magnetic properties, including plasmonic and magnetic nanoparticles, have been extensively studied for their potential to efficiently kill bacteria. In this review, we are emphasizing the recent advances in nano-biotechnologies for bacterial identification and anti-bacterial properties. The basic principles of new technologies, as well as their future challenges, have been discussed.

Use of Peak Glucose Level and Peak Glycemic Gap in Mortality Risk Stratification in Critically Ill Patients with Sepsis and Prior Diabetes Mellitus of Different Body Mass Indexes.

Sepsis remains a critical concern in healthcare, and its management is complicated when patients have pre-existing diabetes and varying body mass indexes (BMIs). This retrospective multicenter observational study, encompassing data from 15,884 sepsis patients admitted between 2012 and 2017, investigates the relationship between peak glucose levels and peak glycemic gap in the first 3 days of ICU admission, and their impact on mortality. The study reveals that maintaining peak glucose levels between 141-220 mg/dL is associated with improved survival rates in sepsis patients with diabetes. Conversely, peak glycemic gaps exceeding 146 mg/dL are linked to poorer survival outcomes. Patients with peak glycemic gaps below -73 mg/dL also experience inferior survival rates. In terms of predicting mortality, modified Sequential Organ Failure Assessment-Peak Glycemic Gap (mSOFA-pgg) scores outperform traditional SOFA scores by 6.8% for 90-day mortality in overweight patients. Similarly, the modified SOFA-Peak Glucose (mSOFA-pg) score demonstrates a 17.2% improvement over the SOFA score for predicting 28-day mortality in underweight patients. Importantly, both mSOFA-pg and mSOFA-pgg scores exhibit superior predictive power compared to traditional SOFA scores for patients at high nutritional risk. These findings underscore the importance of glycemic control in sepsis management and highlight the potential utility of the mSOFA-pg and mSOFA-pgg scores in predicting mortality risk, especially in patients with diabetes and varying nutritional statuses.

Endotoxin activity trend and multi-organ dysfunction in critically ill patients with septic shock, who received Polymyxin-B hemadsorption: A multicenter, prospective, observational study.

BACKGROUND: The baseline endotoxin activity (EAT0) may predict the outcome of critically ill septic patients who receive Polymyxin-B hemadsorption (PMX-HA), however, the clinical implications of specific EA trends remain unknown. METHODS: Subgroup analysis of the prospective, multicenter, observational study EUPHAS2. We included 50 critically ill patients with septic shock and EAT0 ≥ 0.6, who received PMX-HA. The primary outcome of the study was the EA and SOFA score progression from T0 to 120 h afterwards (T120). Secondary outcomes included the EA and SOFA score progression in whom had EA at 48 h (EAT48) < 0.6 (EA responders, EA-R) versus who had not (EA non-responders, EA-NR). RESULTS: Septic shock was mainly caused by 27 abdominal (54%) and 17 pulmonary (34%) infections, predominantly due to Gram negative bacteria (39 patients, 78%). The SAPS II score was 67.5 [52.8-82.3] and predicted a mortality rate of 75%. Between T0 and T120, the EA decreased (p < 0.001), while the SOFA score and the Inotropic Score (IS) improved (p < 0.001). In comparison with EA-NR (18 patients, 47%), the EA-R group (23 patients, 53%) showed faster IS improvement and lower requirement of continuous renal replacement therapy (CRRT) during the ICU stay. Overall hospital mortality occurred in 18 patients (36%). CONCLUSIONS: In critically ill patients with septic shock and EAT0 ≥ 0.6 who received PMX-HA, EA decreased and SOFA score improved over 120 h. In whom high EA resolved within 48 h, IS improvement was faster and CRRT requirement was lower compared with patients with EAT48 ≥ 0.6.

Risk factors of concurrent urinary sepsis in patients with diabetes mellitus comorbid with upper urinary tract calculi.

BACKGROUND: Urinary sepsis is frequently seen in patients with diabetes mellitus (DM) complicated with upper urinary tract calculi (UUTCs). Currently, the known risk factors of urinary sepsis are not uniform. AIM: To analyze the risk factors of concurrent urinary sepsis in patients with DM complicated with UUTCs by logistic regression. METHODS: We retrospectively analyzed 384 patients with DM complicated with UUTCs treated in People's Hospital of Jincheng between February 2018 and May 2022. The patients were screened according to the inclusion and exclusion criteria, and 204 patients were enrolled. The patients were assigned to an occurrence group (n = 78) and a nonoccurrence group (n = 126). Logistic regression was adopted to analyze the risk factors for urinary sepsis, and a risk prediction model was established. RESULTS: Gender, age, history of lumbago and abdominal pain, operation time, urine leukocytes (U-LEU) and urine glucose (U-GLU) were independent risk factors for patients with concurrent urinary sepsis (P < 0.05). Risk score = 0.794 × gender + 0.941 × age + 0.901 × history of lumbago and abdominal pain - 1.071 × operation time + 1.972 × U-LEU + 1.541 × U-GLU. The occurrence group had notably higher risk scores than the nonoccurrence group (P < 0.0001). The area under the curve of risk score for forecasting concurrent urinary sepsis in patients was 0.801, with specificity of 73.07%, sensitivity of 79.36% and Youden index of 52.44%. CONCLUSION: Sex, age, history of lumbar and abdominal pain, operation time, ULEU and UGLU are independent risk factors for urogenic sepsis in diabetic patients with UUTC.

IL-1ß-pretreated bone mesenchymal stem cell-derived exosomes alleviate septic endoplasmic reticulum stress via regulating SIRT1/ERK pathway.

Background: Endoplasmic reticulum (ER) plays a crucial role in the development of organ injury caused by sepsis. Therefore, it is highly important to devise strategies that specially target ER stress for the treatment of sepsis. Previous research has shown that priming chemokines can enhance the therapeutic effects of mesenchymal stem cells (MSCs). In this study, we aimed to investigate the function and mechanism of exosomes derived from MSCs that were pretreated with IL-1ß (IB-exos) in the context of septic ER stress. Methods: Mouse bone MSCs were preconditioned with or without IL-1ß and the supernatant was used for exosome extraction. In vitro sepsis cell mode was induced by treating HUVECs with LPS, while in vivo sepsis model was established through cecal ligation and puncture (CLP) operation in mice. Cell viability, apoptosis, motility, and tube formation were assessed using the EDU proliferation assay, flow cytometry analysis, migration assay, and tube formation assay, respectively. The molecular mechanism was investigated using ELISA, qRT-PCR, Western blot, and immunofluorescence staining. Results: Pretreatment with IL-1ß enhanced the positive impact of MSC-exos on the viability, apoptosis, motility, and tube formation ability of HUVECs. The administration of LPS or CLP increased ER stress response, but this effect was blocked by the treatment of IB-exos. Additionally, IB-exos reversed the inhibitory effects of LPS or CLP on the expression levels of SIRT1 and ERK phosphorylation. Knockdown of SIRT1 counteracted the effects of IB-exos on HUVEC cellular function and ER stress. In a mouse model, the injection of IB-exos mitigated sepsis-induced lung injury by inhibiting ER stress response through the activation of SIRT1. Conclusion: IB-exos have been found to alleviate sepsis-induced lung injury via inhibiting ER stress through the SIRT1/ERK pathway. These findings indicated that IB-exos could potentially be used as a strategy to mitigate lung injury caused by sepsis.

Assessment of implementation methods in sepsis: study protocol for a cluster-randomized hybrid type 2 trial.

BACKGROUND: Sepsis is the leading cause of intensive care unit (ICU) admission and ICU death. In recognition of the burden of sepsis, the Surviving Sepsis Campaign (SSC) and the Institute for Healthcare Improvement developed sepsis "bundles" (goals to accomplish over a specific time period) to facilitate SSC guideline implementation in clinical practice. Using the SSC 3-h bundle as a base, the Centers for Medicare and Medicaid Services developed a 3-h sepsis bundle that has become the national standard for early management of sepsis. Emerging observational data, from an analysis conducted for the AIMS grant application, suggest there may be additional mortality benefit from even earlier implementation of the 3-h bundle, i.e., the 1-h bundle. METHOD: The primary aims of this randomized controlled trial are to: (1) examine the effect on clinical outcomes of Emergency Department initiation of the elements of the 3-h bundle within the traditional 3 h versus initiating within 1 h of sepsis recognition and (2) examine the extent to which a rigorous implementation strategy will improve implementation and compliance with both the 1-h bundle and the 3-h bundle. This study will be entirely conducted in the Emergency Department at 18 sites. A secondary aim is to identify clinical sepsis phenotypes and their impact on treatment outcomes. DISCUSSION: This cluster-randomized trial, employing implementation science methodology, is timely and important to the field. The hybrid effectiveness-implementation design is likely to have an impact on clinical practice in sepsis management by providing a rigorous evaluation of the 1- and 3-h bundles. FUNDING: NHLBI R01HL162954. TRIAL REGISTRATION: ClinicalTrials.gov NCT05491941. Registered on August 8, 2022.

LncRNA CASC9 enhances the stability of SOCS-1 by combining with FUS to alleviate sepsis-induced liver injury.

BACKGROUND: Liver injury plays a major role in the development of sepsis. Liver damage after sepsis is an independent risk factor for multiple organ failure and death. Cancer susceptibility candidate 9 (CASC9) exerts a protective effect on sepsis-induced acute lung injury (ALI). However, the role and underlying mechanism haven't been fully evaluated. METHODS: Animal and cell models of sepsis were established in vivo and in vitro experiments. The histological and apoptosis analyses of liver tissues were tested by hematoxylin-eosin (HE) staining and terminal dUTP nick end labeling (TUNEL) assay, respectively. Serum levels of inflammatory cytokines were detected via using an enzyme-linked immunosorbent assay (ELISA). The expressions of CASC9, suppressor of cytokine signaling (SOCS)-1, Bcl-2, Bax, Bad, and caspase3 were measured by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to examine cell viability and apoptosis, respectively. RNA immunoprecipitation (RIP) and RNA-pull down assay were used to verify the binding relationships among CASC9, SOCS-1 and FUS. RESULTS: CASC9 and SOCS-1 were lowly expressed in animal and cell models of sepsis liver injury. CASC9 or SOCS-1 overexpression could inhibit cell apoptosis upon lipopolysaccharide (LPS) induction. Meanwhile, the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6 and IL-8 were reduced by CASC9 or SOCS-1 overexpression in LPS-induced LO2 cells. Mechanistically, CASC9 interacted with fused in sarcoma (FUS) to stabilize the mRNA of SOCS-1. SOCS-1 silencing antagonized the effects of CASC9 on improving sepsis liver injury. CONCLUSION: CASC9 overexpression ameliorated the sepsis-induced liver injury, and the probable underlying mechanism may be that CASC9 stabilized the SOCS-1 mRNA by interacting with FUS.

Association between stillbirth and severe maternal morbidity.

BACKGROUND: Severe maternal morbidity has been increasing in the past few decades. Few studies have examined the risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries. OBJECTIVE: This study aimed to examine the prevalence and risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries during delivery hospitalization as a primary outcome and during the postpartum period as a secondary outcome. STUDY DESIGN: This was a retrospective cohort study using birth and fetal death certificate data linked to hospital discharge records from California (2008-2018), Michigan (2008-2020), Missouri (2008-2014), Pennsylvania (2008-2014), and South Carolina (2008-2020). Relative risk regression analysis was used to examine the crude and adjusted relative risks of severe maternal morbidity along with 95% confidence intervals among individuals with stillbirths vs individuals with live-birth deliveries, adjusting for birth year, state of residence, maternal sociodemographic characteristics, and the obstetric comorbidity index. RESULTS: Of the 8,694,912 deliveries, 35,012 (0.40%) were stillbirths. Compared with individuals with live-birth deliveries, those with stillbirths were more likely to be non-Hispanic Black (10.8% vs 20.5%); have Medicaid (46.5% vs 52.0%); have pregnancy complications, including preexisting diabetes mellitus (1.1% vs 4.3%), preexisting hypertension (2.3% vs 6.2%), and preeclampsia (4.4% vs 8.4%); have multiple pregnancies (1.6% vs 6.2%); and reside in South Carolina (7.4% vs 11.6%). During delivery hospitalization, the prevalence rates of severe maternal morbidity were 791 cases per 10,000 deliveries for stillbirths and 154 cases per 10,000 deliveries for live-birth deliveries, whereas the prevalence rates for nontransfusion severe maternal morbidity were 502 cases per 10,000 deliveries for stillbirths and 68 cases per 10,000 deliveries for live-birth deliveries. The crude relative risk for severe maternal morbidity was 5.1 (95% confidence interval, 4.9-5.3), whereas the adjusted relative risk was 1.6 (95% confidence interval, 1.5-1.8). For nontransfusion severe maternal morbidity among stillbirths vs live-birth deliveries, the crude relative risk was 7.4 (95% confidence interval, 7.0-7.7), whereas the adjusted relative risk was 2.0 (95% confidence interval, 1.8-2.3). This risk was not only elevated among individuals with stillbirth during the delivery hospitalization but also through 1 year after delivery (severe maternal morbidity adjusted relative risk, 1.3; 95% confidence interval, 1.1-1.4; nontransfusion severe maternal morbidity adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3). CONCLUSION: Stillbirth was found to be an important contributor to severe maternal morbidity.

The polarization of M2 macrophages can be adjusted to alleviate renal injury by methylprednisolone in sepsis-AKI.

Acute kidney injury in sepsis patients has an extreme mortality rate in clinical. It obviously seems that immune cells, for example, macrophages are involved with this process. Macrophages, as highly important immune cells, play a significant role in the development of human kidney diseases. But the specific role of macrophages in this process is still unclear. Under different timeline points, we surprisingly found that macrophages had the most dynamic changes in acute kidney injury immune cells. Based on macrophages' functions, they are primarily classified into M1 macrophages (pro-inflammatory) and M2 macrophages (anti-inflammatory). The polarization of M2 macrophages is closely associated with the seriousness of sepsis-induced kidney injury, but how to modulate their polarization to alleviate sepsis-associated renal damage remains unknown. We discovered that the polarization of M2 macrophages after methylprednisolone injection can significantly alleviate acute kidney injury by reducing secreted cytokine. This study suggests that the proportion of macrophage subtypes can be regulated by methylprednisolone to alleviate acute kidney injury in sepsis to provide a new sight for a clinical to provide a promising strategy for renal injury caused.

Probiotics in septic acute kidney injury, a double blind, randomized control trial.

INTRODUCTION: During acute kidney injury (AKI) due to sepsis, the intestinal microbiota changes to dysbiosis, which affects the kidney function recovery (KFR) and amplifies the injury. Therefore, the administration of probiotics could improve dysbiosis and thereby increase the probability of KFR. METHODS: In this double-blind clinical trial, patients with AKI associated with sepsis were randomized (1:1) to receive probiotics or placebo for 7 consecutive days, with the objectives of evaluate the effect on KFR, mortality, kidney replacement therapy (KRT), urea, urine volume, serum electrolytes and adverse events at day 7. RESULTS: From February 2019 to March 2022, a total of 92 patients were randomized, 48 to the Probiotic and 44 to Placebo group. When comparing with placebo, those in the Probiotics did not observe a higher KFR (HR 0.93, 0.52-1.68, p = 0.81), nor was there a benefit in mortality at 6 months (95% CI 0.32-1.04, p = 0.06). With probiotics, urea values decreased significantly, an event not observed with placebo (from 154 to 80 mg/dl, p = 0.04 and from 130 to 109 mg/dl, p = 0.09, respectively). Urinary volume, need for KRT, electrolyte abnormalities, and adverse events were similar between groups. (ClinicalTrial.gov NCT03877081) (registered 03/15/2019). CONCLUSION: In AKI related to sepsis, probiotics for 7 consecutive days did not increase the probability of KFR, nor did other variables related to clinical improvement, although they were safe.