Conocimiento en estudiantes de enfermería sobre sepsis quirúrgico / Knowledge in nursing students about surgical sepsis

Objetivo: Determinar el nivel de conocimiento de los estudiantes de enfermería de la Universidad Técnica de Ambato sobre sepsis quirúrgica. Material y método: La presente investigación tiene un diseño de desarrollo observacional, de tipo descriptivo, cohorte transversal, con un enfoque cuantitativo, ya que el nivel de cono-cimiento se verá representado mediante tablas y gráficos para des-cribir la problemática del periodo octubre 2023 febrero 2024. Re-sultados: Se evidencia un alto porcentaje de respuestas incorrectas por cada ítem por parte de los estudiantes. La categoría Nivel de Conocimiento sobre Definición de Sepsis, fue respondida de ma-nera incorrecta con un porcentaje del 83,9%, la categoría Nivel de Conocimiento sobre Diagnóstico de Sepsis obtuvo 51,7% y, por úl-timo, la Nivel de Conocimiento sobre Tratamiento de Sepsis con el 29,2%. Conclusiones: El nivel de conocimiento de los estudiantes sobre Sepsis Quirúrgica es malo, debido a que existe una subesti-mación de la gravedad de la sepsis como afección potencialmente mortal, lo que puede traer un impacto negativo en los pacientes[AU]

Objective: Determine the level of knowledge of nursing students at the Technical University of Ambato about surgical sepsis. Mate-rials and methods: This research has an observational, descriptive, transversal development design, with a quantitative approach since the level of knowledge will be represented through tables and gra-phs to describe the problems of the period October 2023-February 2024. Results: A high percentage of incorrect answers for each item by the students is evident. The category Level of Knowledge about Definition of Sepsis was answered incorrectly with a percentage of 83.9%, the category Level of Knowledge about Diagnosis of Sepsis obtained 51.7% and, finally, the category Level of Knowledge about Treatment of Sepsis. Sepsis with 29.2%. Conclusions: The level of knowledge of students about Surgical Sepsis is poor because there is an underestimation of the severity of sepsis as a potentially fatal condition, which can have a negative impact on patients[AU]

Objetivo: Determinar o nível de conhecimento dos estudantes de enfermagem da Universidade Técnica de Ambato sobre sepse ci-rúrgica. Material e método: Esta pesquisa possui desenho de coor-te observacional, descritivo, transversal, com abordagem quantita-tiva, uma vez que o nível de conhecimento será representado por meio de tabelas e gráficos para descrever o problema no período de outubro de 2023 a fevereiro de 2024. Resultados: Uma parada. É evidente o percentual de respostas incorretas para cada item por parte dos alunos. A categoria Nível de Conhecimento sobre Defi-nição de Sepse foi respondida incorretamente com percentual de 83,9%, a categoria Nível de Conhecimento sobre Diagnóstico de Sepse obteve 51,7% e por fim, a categoria Nível de Conhecimen-to sobre Tratamento de Sepse com 29,2%. Conclusões: O nível de conhecimento dos estudantes sobre a Sepse Cirúrgica é baixo, pois há uma subestimação da gravidade da sepse como uma condição potencialmente fatal, que pode ter um impacto negativo nos pa-cientes[AU]

Risk factors for acute kidney injury in preterm neonates after noncardiac surgery: a single-center retrospective cohort study.

Postoperative acute kidney injury (AKI) is a common complication that is associated with chronic kidney disease, early postsurgical mortality, and prolonged hospital stays. Preterm neonates who undergo surgery are at risk factors for AKI due to underdeveloped kidneys. To date, little is known about the incidence and perioperative risk factors for AKI in preterm neonates undergoing noncardiac surgery. Preterm neonates who underwent noncardiac surgery between January May 1, 2020, and February 28, 2023, were enrolled in the trial according to the inclusion criteria. Both multivariable and logistic regression analyses were used to analyze the associations between characteristic data and AKI. In total, 106 preterm neonates met the inclusion criteria, and 25 preterm neonates (23.6%) developed postoperative AKI. Multivariate analysis revealed that the factors associated with AKI were gestational age < 32 weeks [OR: 4.88; 95% CI (1.23-19.42)], preoperative sepsis [OR: 3.98; 95% CI (1.29-12.28)], and intraoperative hypotension [OR: 3.75; 95% CI (1.26-11.15)]. Preterm neonates who developed AKI were more likely to have longer hospital length of stays (38 [18,69] days vs. 21[12,46]) and higher medical costs (93,181.6 [620450.0,173,219.0] ï¿¥ vs. 58,134.6 [31015.1,97,224,1) ï¿¥ than neonates who did not develop AKI. Preterm neonates who underwent noncardiac surgery had a high incidence of AKI. Independent risk factors for AKI in preterm neonates who underwent noncardiac surgery were low gestational age, preoperative sepsis, and intraoperative hypotension. Preterm neonates who developed AKI were more likely to have longer hospital stays and higher medical costs.

Medicinal evaluation and molecular docking study of osajin as an anti-inflammatory, antioxidant, and antiapoptotic agent against sepsis-associated acute kidney injury in rats.

Despite efforts to find effective drugs for sepsis-associated acute kidney injury (SA-AKI), mortality rates in patients with SA-AKI have not decreased. Our study evaluated the protective effects of isoflavone osajin (OSJ) on SA-AKI in rats by targeting inflammation, oxidative stress, and apoptosis, which represent the cornerstones in the pathophysiological mechanism of SA-AKI. Polymicrobial sepsis was induced in rats via the cecal ligation and puncture (CLP) technique. Markers of oxidative stress were evaluated in kidney tissues using biochemical methods. The expression of interleukin-33 (IL-33), 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, and kidney injury molecule-1 (KIM-1) was evaluated as indicators of inflammation, DNA damage, apoptosis, and SA-AKI respectively in the kidney tissues using immunohistochemical and immunofluorescent detection methods. The CLP technique significantly (p < 0.001) increased lipid peroxidation (LPO) levels and significantly (p < 0.001) decreased the activities of superoxide dismutase and catalase in kidney tissues. In the renal tissues, strong expression of IL-33, 8-OHdG, caspase-3, and KIM-1 was observed with severe degeneration and necrosis in the tubular epithelium and intense interstitial nephritis. In contrast, the administration of OSJ significantly (p < 0.001) reduced the level of LPO, markedly improved biomarkers of antioxidant status, decreased the levels of serum creatinine and urea, lowered the expression of IL-33, 8-OHdG, caspase-3, and KIM-1 and alleviated changes in renal histopathology. A promising binding score was found via a molecular docking investigation of the OSJ-binding mode with mouse IL-33 (PDB Code: 5VI4). Therefore, OSJ protects against SA-AKI by suppressing the IL-33/LPO/8-OHdG/caspase-3 pathway and improving the antioxidant system.

Neuroinflammation in the medullary visceral zone exert a powerful impaction on the systemic inflammation in sepsis through cholinergic anti-inflammatory pathway.

To investigate whether sepsis-induced neuroinflammation of medulla visceral zone (MVZ) predominates the systemic inflammation through cholinergic anti-inflammatory pathway (CAP), and to explore the effect of central anti-inflammation on systemic inflammation. 112 adult Sprague-Dawley male rats were randomly divided into sepsis experimental group (n = 56) and neuroinflammation experimental group (n = 56). The two experimental groups were individually randomly divided into control group (n = 8), model group (n = 16), central anti-inflammatory group (n = 16) and vagus transection group (n = 16). Rats in two control groups were administered with saline at the dose of 6 mL/kg intraperitoneally or with 25 µL artificial cerebrospinal fluid injected into forth ventricle once a day for 3 days. Rats in two model groups were administered with Lipopolysaccharide (LPS) at the dose of 6 mg/kg intraperitoneally or with 25 µg/25 µL LPS injected into forth ventricle once a day for 3 days. Rats in two central anti-inflammatory groups were fed with 10 mg/mL minocycline sucrose solution as the only water source for 4 days prior to be treated as the model groups of their own, and feeding style was continued until the end of the experiment. Rats in the two vagus transection groups were undergone right vagotomy and 7 days of adaptive feeding prior to be treated as the same as those in the central anti-inflammatory group of their own. The Murine Sepsis Score (MSS), mortality rate and heat rate variability (HRV) were recorded during the last 3 days of intervention. Then the rats were sacrificed and blood samples were collected for ELISA analysis to detect the serum level of inflammatory cytokines such as TNF-α, IL-6, and IL-10. The expression of TNF-α and IL-6 in medulla oblongata were analyzed by Western blot. The correlation and regression analysis among the expression levels of cytokines in medulla oblongata, HRV indexes and serum inflammatory cytokines were performed. The mortality rate and MSS of the sepsis model group and the MVZ's neuroinflammation model group were significantly higher than those of their own control group, and the central anti-inflammation reduced the mortality rate and MSS scores of the two model groups, while the right vagotomy abolished the effect of central anti-inflammatory. In the sepsis model group and the MVZ's neuroinflammation model group, the levels of TNF-α, IL-6, and other cytokines in serum and MVZ were significantly increased, and HRV indexes (SDNN, RMSSD, LF, HF, LF/HF) were significantly decreased (P = 0.000). Central anti-inflammatory treatment reversed the above changes. However, right vagotomy abolished the central anti-inflammatory effect. Correlation and regression analysis showed that there was a significant linear correlation among the expression of inflammatory factors in MVZ, the indexes of HRV and the levels of serum cytokines. Our study shows that sepsis-induced MVZ's neuroinflammation exert a powerful influence on the systemic inflammation through CAP in sepsis. Central anti-inflammation effectively improves systemic inflammation through inhibiting MVZ's neuroinflammation in sepsis. The time domain and frequency domain indexes of HRV can reflect the regulatory effect of CAP and the degree of inflammation of MVZ, which may be potentially used to monitor the condition and treatment effectiveness of sepsis patients.

Association of triglyceride-glucose index and delirium in patients with sepsis: a retrospective study.

OBJECTIVE: It is well known that glucose and lipid metabolism disorders and insulin resistance are common in sepsis, which affect the occurrence and prognosis of multiple organ dysfunction in septic patients. Previous study reported the predictive value of triglyceride-glucose index (TyG), a clinical indicator for insulin resistance, in postoperative delirium patients. However, it remains unclear whether the TyG index is a novel predictive biomarker for sepsis-associated delirium. The aim of this study is to explore the relationship between TyG index and the risk of delirium in patients with sepsis. METHODS: Adult septic patients were identified from the MIMIC-IV database and divided into four groups based on the mean value of TyG. The primary outcome was the incidence of delirium. The association between TyG and the risk of developing delirium was evaluated by restricted cubic spline (RCS), multivariate logistic regression and subgroup analysis. Propensity Score Matching (PSM) method was used to balance the baseline data. RESULTS: A total of 3,331 septic patients were included in the analysis, and further divided into four groups: Q1 (TyG ≤ 8.67), Q2 (8.67 < TyG ≤ 9.08), Q3 (9.08 < TyG ≤ 9.61), and Q4 (TyG > 9.61). The RCS curves demonstrated a non-linear positive relationship between TyG index and the risk of developing delirium, and an optimal cut-of value 9.09 was recommended. After balancing the baseline information by PSM, patients in the TyG > 9.09 group had a significant higher incidence of delirium compared with those in the TyG ≤ 9.09 group. In logistic regression analysis, TyG > 9.09 was significantly associated with lower risk of developing delirium in both original cohort (OR 1.54-1.78, all P < 0.001) and the PSM cohort (OR 1.41-1.48, all P < 0.001). No association was found between the TyG index and mortality (all P > 0.05). In subgroup analysis, our findings were consistent (all OR > 1 in all subgroups). CONCLUSION: Our study demonstrated an independent association between TyG index and increased risk of delirium in septic patients, indicating that TyG index can serve as a biomarker for delirium in sepsis.

Fluid management for sepsis-induced hypotension in patients with advanced chronic kidney disease: a secondary analysis of the CLOVERS trial.

BACKGROUND: Early fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD. METHODS: This post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.73 m2 or history of end-stage renal disease on chronic dialysis) from the crystalloid liberal or vasopressor early resuscitation in sepsis (CLOVERS) trial. The primary endpoint was death from any cause before discharge home by day 90. RESULTS: Of 1563 participants enrolled in the CLOVERS trial, 196 participants had advanced CKD (45% on chronic dialysis), with 92 participants randomly assigned to the restrictive treatment group and 104 assigned to the liberal fluid group. Death from any cause before discharge home by day 90 occurred significantly less often in the restrictive fluid group compared with the liberal fluid group (20 [21.7%] vs. 41 [39.4%], HR 0.5, 95% CI 0.29-0.85). Participants in the restrictive fluid group had more vasopressor-free days (19.7 ± 10.4 days vs. 15.4 ± 12.6 days; mean difference 4.3 days, 95% CI, 1.0-7.5) and ventilator-free days by day 28 (21.0 ± 11.8 vs. 16.5 ± 13.6 days; mean difference 4.5 days, 95% CI, 0.9-8.1). CONCLUSIONS: In patients with advanced CKD and sepsis-induced hypotension, an early restrictive fluid strategy, prioritizing vasopressor use, was associated with a lower risk of death from any cause before discharge home by day 90 as compared with an early liberal fluid strategy. TRIAL REGISTRATION: NCT03434028 (2018-02-09), BioLINCC 14149.

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Sepsis-induced myocardial depression (SIMD), a common complication of sepsis, is one of the main causes of death in patients with sepsis. The pathogenesis of SIMD is complicated, and the process of SIMD remains incompletely understood, with no single or definitive mechanism fully elucidated. Notably, pyroptosis, as a pro-inflammatory programmed cell death, is characterized by Gasdermin-mediated formation of pores on the cell membrane, cell swelling, and cell rupture accompanied by the release of large amounts of inflammatory factors and other cellular contents. Mechanistically, pyroptosis is mainly divided into the canonical pathway mediated by caspase-1 and the non-canonical pathway mediated by caspase-4/5/11. Pyroptosis has been confirmed to participate in various inflammation-associated diseases. In recent years, more and more studies have shown that pyroptosis is also involved in the occurrence and development of SIMD. This article reviews the molecular mechanisms of pyroptosis and its research progress in SIMD, aiming to provide novel strategies and targets for the treatment of SIMD.

Prognostication of the development of septic complications in children with burn injuries.

OBJECTIVE: Aim: To determine the prognostic criteria for the development of septic complications in children with thermal injury. PATIENTS AND METHODS: Materials and Methods: A single-center retrospective-prospective cohort study included a retrospective analysis of 98 medical histories of children of different ages with severe burns who were treated from 2007 to 2017. A prospective study was conducted among children (n=63) from 1 to 5 years old, who received various degrees severity burn injury, according to an open comparative method in the period from 2018 to 2021. RESULTS: Results: Indicators of a high risk of developing sepsis were burns by flames of any etiology, damage severity index ≥75 units, total burn surface ≥25 %, deep burn area ≥ 5%. The threshold value of procalcitonin (PCT) ≥ 0.86 ng/ml on the 1st-3rd day and PCT > 0.51 ng/ml on the 7th day of burn disease, had a prognostic value for assessing the probability of sepsis. On the 1st day of hospitalization, the development of sepsis was predicted if the C-reactive protein (CRP) value was higher than 6.98 ng/ml, on the 3rd - the CRP level was above 7.43 ng/ml, on the 7th day - above 7.28 ng/ml. CONCLUSION: Conclusions: Based on the obtained data, we selected the criteria with the best prognostic characteristics, which allows us to predict and prevent the development of sepsis in the early stages of burn disease in children.

Diagnostic Accuracy of Serum Procalcitonin to Diagnose Sepsis in Advanced Solid Tumor Patients with Fever.

BACKGROUND: Diagnosis of infection in advanced solid tumor patients can be challenging since signs and symptoms might be overlapping due to paraneoplastic condition. Delay diagnosis of existing infection can lead to more severe conditions and increased mortality. Procalcitonin (PCT) has been used to support the diagnosis of bacterial infection and sepsis. Unfortunately, PCT also increases in malignancy even without an infection. We investigated the diagnostic accuracy of PCT in advanced solid tumor patients with fever to diagnose sepsis. METHODS: A cross-sectional study was conducted in solid advanced tumor patients with fever patients who were admitted to Cipto Mangunkusumo Hospitals, Indonesia between June 2016 and April 2018. Sepsis was defined using 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference criteria. The diagnostic accuracy of PCT was determined using the receiver operating characteristic (ROC) curve. RESULTS: A total of 194 subjects were enrolled in this study. 60.3% were female with a mean age of 49.47±12.87 years old. 143 patients (73.7%) with advanced solid tumors. Among this latter group, 39 patients (27%) were sepsis. The ROC curve showed that the levels of PCT for sepsis in advanced solid tumor patients with fever were in the area under the curve (AUC) 0.853 (95%CI 0.785 - 0.921). The Cut-off of PCT in advanced solid tumor patients with fever to classify as sepsis was 2.87 ng/mL, with a sensitivity of 79.5%, and a specificity of 79.8%. CONCLUSION: PCT has good diagnosis accuracy in advanced solid tumor patients with fever to classify as sepsis, however a higher cut-off compared to non-cancerous patients should be used.

Modeling lung endothelial dysfunction in sepsis-associated ARDS using a microphysiological system.

Endothelial dysfunction is a critical feature of acute respiratory distress syndrome (ARDS) associated with higher disease severity and worse outcomes. Preclinical in vivo models of sepsis and ARDS have failed to yield useful therapies in humans, perhaps due to interspecies differences in inflammatory responses and heterogeneity of human host responses. Use of microphysiological systems (MPS) to investigate lung endothelial function may shed light on underlying mechanisms and targeted treatments for ARDS. We assessed the response to plasma from critically ill sepsis patients in our lung endothelial MPS through measurement of endothelial permeability, expression of adhesion molecules, and inflammatory cytokine secretion. Sepsis plasma induced areas of endothelial cell (EC) contraction, loss of cellular coverage, and luminal defects. EC barrier function was significantly worse following incubation with sepsis plasma compared to healthy plasma. EC ICAM-1 expression, IL-6 and soluble ICAM-1 secretion increased significantly more after incubation with sepsis plasma compared with healthy plasma. Plasma from sepsis patients who developed ARDS further increased IL-6 and sICAM-1 compared to plasma from sepsis patients without ARDS and healthy plasma. Our results demonstrate the proof of concept that lung endothelial MPS can enable interrogation of specific mechanisms of endothelial dysfunction that promote ARDS in sepsis patients.

A Comparative Study of Community-acquired Acute Kidney Injury and Hospital-acquired Acute Kidney Injury from a Tertiary Care Hospital in North India.

BACKGROUND: In this observational study, clinical characteristics, etiologies, and outcomes of patients admitted to the hospital with community-acquired acute kidney injury (CAAKI) have been compared in contrast to those who hospital-acquired Acute Kidney Injury (HAAKI). METHODS: This was a prospective study of adults aged 18 years or above diagnosed with acute kidney injury (AKI) over a period of 17 months at a tertiary care hospital. RESULTS: 230 patients had AKI with the mean age of the study population being 45.33 ± 12.68 years. 178 (77.4%) patients were enrolled from medical unit, 25 (10.7%) from surgical unit, and 27 (11.7%) from obstetrical unit. The observed incidence of AKI was 15/1000 admissions. About 58.2% had CAAKI and 96 (43.7%) had HAAKI. Out of 230 patients, 170 (73.9%) patients were male and 60 (26.1%) were female. Sepsis was the most common (52.1%) etiology of AKI among the medical cases. Urosepsis, scrub typhus, and pneumonia were the most common causes of AKI. Sixty percent of AKI was Kidney Disease Improving Global Outcomes Stage 1 or 2 and 40% was in Stage 3. Oliguria was seen in 56.5%, hyperkalemia in 34.7%, fluid overload in 6.1%, and metabolic acidosis in 22.6%. The majority of patients had multiple organ involvement (52.1%) at the time of enrollment. About 116 (50.4%) had lung injury requiring mechanical ventilation and 95 (41.3%) were on inotropes. Mortality occurred in 19.5%. Anemia, the use of vasopressor drugs, and the need for intensive care support were independent predictive factors for mortality. CONCLUSION: AKI was common in hospitalized patients and leads to significant inhospital mortality. AKI is largely a CAAKI, and the lesser extent is due to HAAKI. Many causes are potentially preventable. Early fluid resuscitation, effective antibiotics, appropriate antidotes, and timely referral of established AKI patients to centers with dialysis facilities can improve AKI outcomes.

Résumé Contexte:Dans cette étude observationnelle, les caractéristiques cliniques, les étiologies et les résultats des patients admis à l'hôpital pour des affections aiguës d'origine communautaire. les lésions rénales (CAAKI) ont été comparées à celles qui ont contracté une lésion rénale aiguë à l'hôpital (HAAKI).Méthodes:Il s'agissait d'une étude prospective portant sur des adultes âgés de 18 ans ou plus ayant reçu un diagnostic d'insuffisance rénale aiguë (IRA) sur une période de 17 mois dans un hôpital de soins tertiaires.Résultats:230 patients avaient une IRA, l'âge moyen de la population étudiée étant de 45,33 ± 12,68 ans. 178 (77,4 %) patientes ont été recrutées dans l'unité médicale, 25 (10,7 %) dans l'unité chirurgicale et 27 (11,7 %) dans l'unité obstétricale. L'incidence observée de l'IRA était de 15/1 000 admissions. Environ 58,2 % avaient CAAKI et 96 (43,7 %) avaient HAAKI. Sur 230 patients, 170 (73,9 %) étaient des hommes et 60 (26,1 %) étaient des femmes. Le sepsis était l'étiologie d'IRA la plus courante (52,1 %) parmi les cas médicaux. L'urosepsie, le typhus des broussailles et la pneumonie étaient les causes les plus fréquentes d'AKI. Soixante pour cent des AKI étaient des maladies rénales améliorant les résultats globaux de stade 1 ou 2 et 40 % étaient au stade 3. Une oligurie a été observée dans 56,5 %, une hyperkaliémie dans 34,7 %, une surcharge hydrique dans 6,1 % et une acidose métabolique dans 22,6 %. La majorité des patients présentaient une atteinte de plusieurs organes (52,1 %) au moment de l'inscription. Environ 116 (50,4 %) souffraient de lésions pulmonaires nécessitant une ventilation mécanique et 95 (41,3 %) prenaient des inotropes. La mortalité est survenue dans 19,5%. L'anémie, l'utilisation de médicaments vasopresseurs et la nécessité d'un soutien en soins intensifs étaient des facteurs prédictifs indépendants de mortalité.Conclusion:L'IRA était fréquente chez les patients hospitalisés et entraîne une mortalité hospitalière significative. AKI est en grande partie un CAAKI, et dans une moindre mesure est dû au HAAKI. De nombreuses causes sont potentiellement évitables. Une réanimation liquidienne précoce, des antibiotiques efficaces, des antidotes appropriés et une orientation rapide des patients atteints d'IRA établis vers des centres dotés d'installations de dialyse peuvent améliorer les résultats de l'IRA.

[A multicenter clinical study of critically ill patients with sepsis complicated with acute kidney injury in Beijing: incidence, clinical characteristics and outcomes].

OBJECTIVE: To investigate the epidemiological characteristics and prognosis of critically ill patients with sepsis combined with acute kidney injury (AKI) in intensive care unit (ICU) in Beijing, and to analyze the risk factors associated with in-hospital mortality among these critically ill patients. METHODS: Data were collected from the Beijing AKI Trial (BAKIT) database, including 9 049 patients consecutively admitted to 30 ICUs in 28 tertiary hospitals in Beijing from March 1 to August 31, 2012. Patients were divided into non-AKI and non-sepsis group, AKI and non-sepsis group, non-AKI and sepsis group, AKI and sepsis group. Clinical data recorded included demographic characteristics, primary reasons for ICU admission, comorbidities, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II(APACHE II) within 24 hours of ICU admission, physiological and laboratory indexes, treatment in the ICU, AKI staging based on the Kidney Disease: Improving Global Outcomes (KDIGO), as well as the prognostic indicators including length of stay in ICU, length of stay in hospital, ICU and in-hospital mortality. The primary endpoint was discharge or in-hospital death. Multivariate Logistic regression analysis was used to investigate the risk factors for hospital death in ICU patients. Kaplan-Meier survival curve was drawn to analyze the cumulative survival of ICU patients during hospitalization. RESULTS: A total of 3 107 critically ill patients were ultimately enrolled, including 1 259 cases in the non-AKI and non-sepsis group, 931 cases in the AKI and non-sepsis group, 264 cases in the non-AKI and sepsis groups, and 653 cases in the AKI and sepsis group. Compared with the other three group, patients in the AKI and sepsis group were the oldest, had the lowest mean arterial pressure (MAP), and the highest APACHE II score, SOFA score, blood urea nitrogen (BUN), and serum creatinine (SCr) levels, and they also had the highest proportion of receiving mechanical ventilation, requiring vasopressor support, and undergoing renal replacement therapy (RRT), all P < 0.01. Of these 3 107 patients, 1 584 (51.0%) were diagnosed with AKI, and the incidence of AKI in patients with sepsis was significantly higher than in those without sepsis [71.2% (653/917) vs. 42.5% (931/2 190), P < 0.01]. The highest proportion of KDIGO 0 stage was observed in the non-sepsis group (57.5%), while the highest proportion of KDIGO 3 stage was observed in the sepsis group (32.2%). Within the same KDIGO stage, the mortality of patients with sepsis was significantly higher than that of non-sepsis patients (0 stage: 17.8% vs. 3.1%, 1 stage: 36.3% vs. 7.4%, 2 stage: 42.7% vs. 17.1%, 3 stage: 54.6% vs. 28.6%, AKI: 46.1% vs. 14.2%). The ICU mortality (38.7%) and in-hospital mortality (46.1%) in the AKI and sepsis group were significantly higher than those in the other three groups. Kaplan-Meier survival curves further showed that the cumulative survival rate of patients with AKI and sepsis during hospitalization was significantly lower than that of the other three groups (53.9% vs. 96.9%, 85.8%, 82.2%, Log-Rank: χ 2 = 379.901, P < 0.001). Subgroup analysis showed that among surviving patients, length of ICU stay and total length of hospital stay were significantly longer in the AKI and sepsis group than those in the other three groups (both P < 0.01). Multivariate regression analysis showed that age, APACHE II score and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, sepsis, and AKI combined with sepsis were independent risk factors for ICU mortality in patients (all P < 0.05). After adjusting for covariates, AKI, sepsis, and sepsis combined with AKI were significantly associated with higher ICU and in-hospital mortality, with the highest ICU mortality [adjusted odds ratio (OR) = 14.82, 95% confidence interval (95%CI) was 8.10-27.12; Hosmer-Lemeshow test: P = 0.816] and in-hospital mortality (adjusted OR = 7.40, 95%CI was 4.94-11.08; Hosmer-Lemeshow test: P = 0.708) observed in patients with sepsis combined with AKI. CONCLUSIONS: The incidence of AKI is high in sepsis patients, and those with both AKI and sepsis have a higher disease burden, more abnormalities in physiological and laboratory indicators, and significantly increased ICU and in-hospital mortality. Among surviving patients, the length of ICU stay and total length of hospital stay are also longer in the AKI and sepsis group. Age, APACHE II score and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, and sepsis are independent risk factors for in-hospital mortality in ICU patients.

[Protective effects and mechanisms of berberine hydrochloride on intestinal mucosal barrier injury in rats with sepsis].

OBJECTIVE: To investigate the protective effect of berberine hydrochloride on intestinal mucosal barrier damage in sepsis rats and its mechanism. METHODS: Forty-eight male SD rats were divided into a control group (Sham group, 6 cases), a sepsis model group (LPS group, 14 cases), a berberine hydrochloride intervention group (Ber group, 14 cases), and a Notch signaling pathway inhibition group (DAPT group, 14 cases) according to random number table method. The DAPT group was intraperitoneally injected with 5 mg/kg Notch signaling pathway inhibition DAPT 2 hours before modeling. The sepsis model was established by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS); Sham group was injected with an equal amount of saline (2 mL). The Ber group and DAPT group were treated with gavage of 50 mg/kg berberine hydrochloride 2 hours after modeling; Sham group and LPS group were treated with gavage of an equal amount of saline (2 mL). The temperature, weight, behavior and survival rate of rats were observed at 0, 6, 12 and 24 hours of modeling. After 24 hours of modeling, abdominal aortic blood was collected under anesthesia, and intestinal tissues were obtained after euthanasia. The pathological changes of ileum were observed under light microscope. The ultrastructure of ileum was observed under transmission electron microscope. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Real time-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of tight junction proteins (Occludin and Claudin1), Notch1 and their downstream target signals in the ileum tissue. RESULTS: After 24 hours of modeling, compared with the Sham group, the LPS group, Ber group, and DAPT group showed a decrease in weight and an increase in temperature. Among them, the LPS group showed the most significant changes, followed by the DAPT group, and the Ber group showed the least significant changes. The survival rates of the LPS group, Ber group, and DAPT group were all lower than those of the Sham group [42.9% (6/14), 57.1% (8/14), 57.1% (8/14) vs. 100% (6/6)], and six rats were taken from each group for subsequent testing. Macroscopic observation of the intestine showed that the LPS group had the most severe edema in the ileum tissue and abdominal bleeding, with significant improvement in the Ber group and followed by the DAPT group. Under the light microscope, the LPS group showed disordered arrangement of glandular tissue in the ileum mucosa, significantly reduced goblet cells, and extensive infiltration of inflammatory cells, which were significantly improved in the Ber group but less improved in the DAPT group. Under electron microscopy, the LPS group showed extensive shedding of ileal microvilli and severe damage to the tight junction complex structure of intestinal epithelial cells, which was significantly improved in the Ber group but less improved in the DAPT group. The levels of serum DAO, iFABP, TNF-α, IL-6 in the LPS group were significantly higher than those in the Sham group, while the above indicators in the Ber group were significantly lower than those in the LPS group [DAO (µg/L): 4.94±0.44 vs. 6.53±0.49, iFABP (ng/L): 709.67±176.97 vs. 1 417.71±431.44, TNF-α (ng/L): 74.70±8.15 vs. 110.36±3.51, IL-6 (ng/L): 77.34±9.80 vs. 101.65±6.92, all P < 0.01], while the above indicators in the DAPT group were significantly higher than those in the Ber group. The results of RT-PCR and Western blotting showed that the mRNA and protein expressions of Occludin, Claudin1, Notch1, and Hes1 in the ileum tissue of LPS group rats were decreased compared to the Sham group, which were significantly increased in the Ber group compared with the LPS group [mRNA expression: Occludin mRNA (2-ΔΔCt): 1.61±0.74 vs. 0.30±0.12, Claudin1 mRNA (2-ΔΔCt): 1.97±0.37 vs. 0.58±0.14, Notch1 mRNA (2-ΔΔCt): 1.29±0.29 vs. 0.36±0.10, Hes1 mRNA (2-ΔΔCt): 1.22±0.39 vs. 0.27±0.04; protein expression: Occludin/GAPDH: 1.17±0.14 vs. 0.74±0.04, Claudin1/GAPDH: 1.14±0.06 vs. 0.58±0.10, Notch1/GAPDH: 0.87±0.11 vs. 0.56±0.09, Hes1/GAPDH: 1.02±0.13 vs. 0.62±0.01; all P < 0.05], while those in the DAPT group were significantly lower than those in the Ber group. CONCLUSIONS: Early use of berberine hydrochloride can significantly improve intestinal mucosal barrier damage in sepsis rats, and its mechanism may be related to inhibiting inflammatory response and regulating the expression of intestinal mechanical barrier tight junction protein through Notch1 signal.

[Clinical characteristics and prognosis of acute gastrointestinal injury in patients with sepsis-associated acute respiratory distress syndrome].

OBJECTIVE: To observe the clinical characteristics and prognosis of patients with acute respiratory distress syndrome (ARDS) in sepsis combined with acute gastrointestinal injury (AGI) of different grades, and to further explore the risk factors associated with the poor prognosis of patients. METHODS: The clinical data of patients with septic ARDS admitted to the intensive care unit (ICU) of Tianjin First Central Hospital from March to October 2023 were collected. According to the 2012 European Association of Critical Care Medicine AGI definition and grading criteria, the patients were categorized into AGI grade 0- IV groups. The clinical characteristics and 28-day clinical outcomes of the patients were observed; the risk factors related to the prognosis of patients with septic ARDS combined with AGI were analyzed by using univariate and multivariate Logistic regression; and the receiver operator characteristic curve (ROC curve) and calibration curves were plotted to evaluate the predictive value of each risk factor on the prognosis of patients with septic ARDS combined with AGI. RESULTS: A total of 92 patients with septic ARDS were enrolled, including 7 patients in the AGI 0 group, 20 patients in the AGI I group, 38 patients in the AGI II group, 23 patients in the AGI III group, and 4 patients in the AGI IV group. The incidence of AGI was 92.39%. With the increase of AGI grade, the ARDS grade increased, and acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), intra-abdominal pressure (IAP), white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), lymphocyte percentage (LYM%), and 28-day mortality all showed a significant increasing trend, while the oxygenation index (PaO2/FiO2) showed a significant decreasing trend (all P < 0.05). Pearson correlation analysis showed that APACHE II score, SOFA score, and ARDS classification were positively correlated with patients' AGI grade (Pearson correlation index was 0.386, 0.473, and 0.372, respectively, all P < 0.001), and PaO2/FiO2 was negatively correlated with patients' AGI grade (Pearson correlation index was -0.425, P < 0.001). Among the patients with septic ARDS combined with AGI, there were 68 survivors and 17 deaths at 28 days. The differences in APACHE II score, SOFA score, ARDS grade, AGI grade, PaO2/FiO2, IAP, AGI 7-day worst value, length of ICU stay, and total length of hospital stay between the survival and death groups were statistically significant. Univariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.350, 95% confidence interval (95%CI) was 1.071-1.702, P = 0.011], PaO2/FiO2 (OR = 0.964, 95%CI was 0.933-0.996, P = 0.027) and AGI 7-day worst value (OR = 2.103, 95%CI was 1.194-3.702, P = 0.010) were the risk factors for 28-day mortality in patients with septic ARDS combined with AGI. Multivariate Logistic regression analysis showed that SOFA score (OR = 1.384, 95%CI was 1.153-1.661, P < 0.001), PaO2/FiO2 (OR = 0.983, 95%CI was 0.968-0.999, P = 0.035) and AGI 7-day worst value (OR = 1.992, 95%CI was 1.141-3.478, P = 0.015) were the independent risk factors for 28-day mortality in patients with septic ARDS combined with AGI. ROC curve analysis showed that SOFA score, PaO2/FiO2 and AGI 7-day worst value had predictive value for the 28-day prognosis of patients with septic ARDS combined with AGI. The area under the ROC curve (AUC) was 0.824 (95%CI was 0.697-0.950), 0.760 (95%CI was 0.642-0.877) and 0.721 (95%CI was 0.586-0.857), respectively, all P < 0.01; when the best cut-off values of the above metrics were 5.50 points, 163.45 mmHg (1 mmHg≈0.133 kPa), and 2.50 grade, the sensitivities were 94.1%, 94.1%, 31.9%, respectively, and the specificities were 80.9%, 67.6%, 88.2%, respectively. CONCLUSIONS: The incidence of AGI in patients with septic ARDS is about 90%, and the higher the AGI grade, the worse the prognosis of the patients. SOFA score, PaO2/FiO2 and AGI 7-day worst value have a certain predictive value for the prognosis of patients with septic ARDS combined with AGI, among which, the larger the SOFA score and AGI 7-day worst value, and the smaller the PaO2/FiO2, the higher the patients' mortality.

[Protective effect and mechanism of methylene blue on myocardial injury in rats with sepsis].

OBJECTIVE: To explore the protective effect of methylene blue (MB) on myocardial injury in sepsis and its possible signaling pathway. METHODS: A total of 32 female Wistar rats were randomly divided into sham operation group, sepsis model group, MB prevention group, and MB treatment group, with 8 rats in each group. The MB prevention group was injected with 15 mg/kg MB in the peritoneal cavity 6 hours before modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. The sepsis model was established by cecal ligation puncture (CLP); the sham operation group was only subjected to an exploratory incision without ligation or puncture of the caecum. The MB treatment group was injected with 15 mg/kg MB in the peritoneal cavity 0.5 hours after modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. Peripheral blood and myocardial tissue were collected from each group at 6 hours and 12 hours after modeling. Histological changes in the myocardial tissue were observed under the microscope; the levels of serum cardiac troponin I (cTnI), MB isoenzyme of creatine kinase (CK-MB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA); and the expressions of inducible nitric oxide synthase (iNOS), light chain 3 (LC3), and p62 in the myocardial tissue were detected by Western blotting. RESULTS: Under light microscopy, no obvious abnormalities were found in the myocardium of the sham operation group; the myocardium of the sepsis model group showed obvious inflammatory changes; the myocardium of the MB prevention group showed mild inflammatory changes at 6 hours after modeling, severe inflammatory changes at 12 hours but less severe than the sepsis model group; the myocardium of the MB treatment group showed more obvious inflammatory changes at 6 hours after modeling but less severe than the MB prevention group at 12 hours after modeling, and the inflammatory changes at 12 hours after modeling were alleviated but more severe than the 6 hours after modeling in MB prevention group. Compared with the sham operation group, the levels of cTnI, CK-MB, TNF-α and IL-6 in the MB prevention group at 6 hours and 12 hours after modeling were not significantly changed; compared with the sepsis model group, the cTnI, CK-MB, TNF-α and IL-6 levels in the MB treatment group at 6 hours and 12 hours after modeling were significantly lower [cTnI (ng/L): 175.03±12.26, 411.24±21.20 vs. 677.79±43.95 at 6 hours of modeling, 159.52±6.44, 412.46±32.94 vs. 687.61±55.09 at 12 hours of modeling; CK-MB (ng/L): 8.38±0.49, 16.87±1.41 vs. 24.87±1.74 at 6 hours of modeling, 7.94±0.30, 16.66±2.03 vs. 25.02±7.29 at 12 hours of modeling; TNF-α (ng/L): 26.98±3.31, 46.95±3.74 vs. 112.60±6.64 at 6 hours of modeling, 31.31±5.83, 90.97±5.14 vs. 149.30±4.67 at 12 hours of modeling; IL-6 (ng/L): 40.86±4.48, 128.90±3.14 vs. 248.90±12.76 at 6 hours of modeling, 80.13±7.94, 190.40±9.56 vs. 288.90±6.01 at 12 hours of modeling; all P < 0.05]. Western blotting showed that compared with the sham operation group, the protein expressions of iNOS, LC3, and p62 in the sepsis model group were significantly higher at 6 hours and 12 hours after modeling; compared with the sepsis model group, the protein expressions of iNOS, LC3, and p62 in the MB treatment group and MB prevention group were significantly lower at 6 hours and 12 hours after modeling (iNOS/GAPDH: 0.38±0.04, 0.60±0.04 vs. 0.77±0.04 at 6 hours of modeling; 0.38±0.02, 0.66±0.04 vs. 0.79±0.05 at 12 hours of modeling; LC3/GAPDH: 0.13±0.07, 0.42±0.07 vs. 1.05±0.16 at 6 hours of modeling; 0.08±0.02, 0.25±0.03 vs. 0.48±0.09 at 12 hours of modeling; p62/GAPDH: 0.17±0.05, 0.44±0.10 vs. 1.19±0.07 at 6 hours of modeling; 0.07±0.00, 0.28±0.08 vs. 0.69±0.02 at 12 hours of modeling; all P < 0.05). CONCLUSIONS: MB can reduce myocardial oxidative stress by inhibiting iNOS expression and mitochondrial autophagy in septic rats, thereby alleviating myocardial damage in sepsis, and has protective effect on myocardial damage in sepsis.

[Research progress in the mechanism of intestinal environmental disturbance on the occurrence and development of sepsis-associated liver injury].

Sepsis-associated liver injury (SALI) is a common complication of sepsis, which is characterized by systemic immune disorders induced by sepsis leading to liver damage. Currently, there are no effective treatments for SALI, which is related to its complex pathophysiological mechanisms. In recent years, the disorder of intestinal environment after sepsis has been considered as an important factor for SALI, but the specific molecular mechanism of the above process is still unclear. This article will review the pathological role and molecular mechanisms between intestinal environmental disturbance and SALI, aiming to analyze the potential research direction of SALI and identify potential therapeutic targets for its treatment.

Immune profiling of critically ill patients with acute kidney injury during the first week after various types of injuries: the REALAKI study.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and results in significant morbidity and mortality. The objective of the study was to explore the systemic immune response of intensive care unit patients presenting with AKI, especially the association between immune profiles and persistent AKI during the first week after admission following various types of injuries (sepsis, trauma, surgery, and burns). METHODS: REALAKI is an ancillary analysis of the REAnimation Low Immune Status Marker (REALISM) cohort study, in which 359 critically ill patients were enrolled in three different intensive care units. Patients with end-stage renal disease were excluded from the REALAKI study. Clinical samples and data were collected three times after admission: at day 1 or 2 (D1-2), day 3 or 4 (D3-4) and day 5, 6 or 7 (D5-7). Immune profiles were compared between patients presenting with or without AKI. Patients with AKI at both D1-2 and D5-7 were defined as persistent AKI. A multivariable logistic regression model was performed to determine the independent association between AKI and patients' immunological parameters. RESULTS: Three hundred and fifty-nine patients were included in this analysis. Among them, 137 (38%) were trauma patients, 103 (29%) post-surgery patients, 95 (26%) sepsis patients, and 24 (7%) were burn patients. One hundred and thirty-nine (39%) patients presented with AKI at D1-2 and 61 (20%) at D5-7. Overall, 94% presented with persistent AKI at D5-7. Patients with AKI presented with increased pro and anti-inflammatory cytokines and altered innate and adaptive immune responses. The modifications observed in the immune profiles tended to be more pronounced with increasing KDIGO stages. In the logistic regression model, a statistically significant association was observed at D1-2 between AKI and CD10lowCD16low immature neutrophils (OR 3.03 [1.7-5.5]-p < 0.001). At D5-7, increased interleukin-10 (IL-10) levels and reduced ex vivo TNF-α production after LPS stimulation were significantly associated with the presence of AKI (OR 1.38 [1.12-1.71]-p = 0.001 and 0.51 [0.27-0.91]-p = 0.03, respectively). Patients who recovered from AKI between D1-2 and D5-7 compared to patients with persistent AKI at D5-7, tended to correct these alterations. CONCLUSION: Following various types of severe injuries, early AKI is associated with the initial inflammatory response. Presence of AKI at the end of the first week after injury is associated with injury-induced immunosuppression.

Reversal of cerebral ischaemia and hypoxia and of sickness behaviour by megadose sodium ascorbate in ovine Gram-negative sepsis.

BACKGROUND: The mechanisms by which megadose sodium ascorbate improves clinical status in experimental sepsis is unclear. We determined its effects on cerebral perfusion, oxygenation, and temperature, and plasma levels of inflammatory biomarkers, nitrates, nitrites, and ascorbate in ovine Gram-negative sepsis. METHODS: Sepsis was induced by i.v. infusion of live Escherichia coli for 31 h in unanaesthetised Merino ewes instrumented with a combination sensor in the frontal cerebral cortex to measure tissue perfusion, oxygenation, and temperature. Fluid resuscitation at 23 h was followed by i.v. megadose sodium ascorbate (0.5 g kg-1 over 30 min+0.5 g kg-1 h-1 for 6.5 h) or vehicle (n=6 per group). Norepinephrine was titrated to restore mean arterial pressure (MAP) to 70-80 mm Hg. RESULTS: At 23 h of sepsis, MAP (mean [sem]: 85 [2] to 64 [2] mm Hg) and plasma ascorbate (27 [2] to 15 [1] µM) decreased (both P<0.001). Cerebral ischaemia (901 [58] to 396 [40] units), hypoxia (34 [1] to 19 [3] mm Hg), and hyperthermia (39.5 [0.1]°C to 40.8 [0.1]°C) (all P<0.001) developed, accompanied by malaise and lethargy. Sodium ascorbate restored cerebral perfusion (703 [121] units], oxygenation (30 [2] mm Hg), temperature (39.2 [0.1]°C) (all PTreatment<0.05), and the behavioural state to normal. Sodium ascorbate slightly reduced the sepsis-induced increase in interleukin-6, returned VEGF-A to normal (both PGroupxTime<0.01), and increased plasma ascorbate (20 000 [300] µM; PGroup<0.001). The effects of sodium ascorbate were not reproduced by equimolar sodium bicarbonate. CONCLUSIONS: Megadose sodium ascorbate rapidly reversed sepsis-induced cerebral ischaemia, hypoxia, hyperthermia, and sickness behaviour. These effects were not reproduced by an equimolar sodium load.

A secondary abdominal aorta-duodenal fistula accompanied with acquired Immune Deficiency Syndrome presented with recurrent sepsis: a case report.

BACKGROUND: Abdominal aorta-duodenal fistulas are rare abnormal communications between the abdominal aorta and duodenum. Secondary abdominal aorta-duodenal fistulas often result from endovascular surgery for aneurysms and can present as severe late complications. CASE PRESENTATION: A 50-year-old male patient underwent endovascular reconstruction for an infrarenal abdominal aortic pseudoaneurysm. Prior to the operation, he was diagnosed with Acquired Immune Deficiency Syndrome and Syphilis. Two years later, he was readmitted with lower extremity pain and fever. Blood cultures grew Enterococcus faecium, Salmonella, and Streptococcus anginosus. Sepsis was successfully treated with comprehensive anti-infective therapy. He was readmitted 6 months later, with blood cultures growing Enterococcus faecium and Escherichia coli. Although computed tomography did not show contrast agent leakage, we suspected an abdominal aorta-duodenal fistula. Esophagogastroduodenoscopy confirmed this suspicion. The patient underwent in situ abdominal aortic repair and received long-term antibiotic therapy. He remained symptom-free during a year and a half of follow-up. CONCLUSIONS: This case suggests that recurrent infections with non-typhoidal Salmonella and gut bacteria may be an initial clue to secondary abdominal aorta-duodenal fistula.