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]

Acute kidney injury in nonagenarians: clinical characteristics and mortality / Injúria renal aguda em nonagenários: características clínicas e mortalidade

Abstract Introduction: Nonagenarians constitute a rising percentage of inpatients, with acute kidney injury (AKI) being frequent in this population. Thus, it is important to analyze the clinical characteristics of this demographic and their impact on mortality. Methods: Retrospective study of nonagenarian patients with AKI at a tertiary hospital between 2013 and 2022. Only the latest hospital admission was considered, and patients with incomplete data were excluded. A logistic regression analysis was conducted to define risk factors for mortality. A p-value < 0.05 was considered statistically significant. Results: A total of 150 patients were included, with a median age of 93.0 years (91.2-95.0), and males accounting for 42.7% of the sample. Sepsis was the most common cause of AKI (53.3%), followed by dehydration/hypovolemia (17.7%), and heart failure (17.7%). ICU admission occurred in 39.3% of patients, mechanical ventilation in 14.7%, vasopressors use in 22.7% and renal replacement therapy (RRT) in 6.7%. Death occurred in 56.7% of patients. Dehydration/hypovolemia as an etiology of AKI was associated with a lower risk of mortality (OR 0.18; 95% CI 0.04-0.77, p = 0.020). KDIGO stage 3 (OR 3.15; 95% CI 1.17-8.47, p = 0.023), ICU admission (OR 12.27; 95% CI 3.03-49.74, p < 0.001), and oliguria (OR 5.77; 95% CI 1.98-16.85, p = 0.001) were associated with mortality. Conclusion: AKI nonagenarians had a high mortality rate, with AKI KDIGO stage 3, oliguria, and ICU admission being associated with death.

Resumo Introdução: Nonagenários constituem um percentual de pacientes internados em ascensão, sendo a injúria renal aguda (IRA) frequente nesses pacientes. Sendo assim, é importante analisar as características clínicas dessa população e seu impacto na mortalidade. Métodos: Estudo retrospectivo de pacientes nonagenários com IRA entre 2013 e 2022 em um hospital terciário. Apenas o último internamento foi considerado e pacientes com dados incompletos foram excluídos. Uma análise por regressão logística foi realizada para definir fatores de risco para mortalidade. Um valor de p < 0,05 foi considerado significativo. Resultados: Foram incluídos 150 pacientes com mediana de idade 93,0 anos (91,2-95,0) e sexo masculino em 42,7%. Sepse foi a causa mais comum de IRA (53,3%), seguida de desidratação/hipovolemia (17,7%) e insuficiência cardíaca (17,7%). Admissão na UTI ocorreu em 39,3% dos pacientes, ventilação mecânica em 14,7%, uso de vasopressores em 22,7% e realização de terapia renal substitutiva (TRS) em 6,7%. Óbito ocorreu em 56,7% dos pacientes. Desidratação/hipovolemia como etiologia da IRA foi associado a menor risco de mortalidade (OR 0,18; IC 95% 0,04-0,77, p = 0,020). Estágio KDIGO 3 (OR 3,15; IC 95% 1,17-8,47, p = 0,023), admissão na UTI (OR 12,27; IC 95% 3,03-49,74, p < 0,001) e oligúria (OR 5,77; IC 95% 1,98-16,85, p = 0,001) foram associados à mortalidade. Conclusão: Nonagenários com IRA apresentaram alta mortalidade e IRA KDIGO 3, oligúria e admissão na UTI foram associadas ao óbito.

Necrotising fasciitis of the upper limb: a review of the literature.

Necrotising fasciitis is an uncommon life-threatening surgical emergency. While most commonly seen in the lower limb it can also affect the upper limb. This article reviews and summarises the current literature on necrotising fasciitis in the upper limb, covering common predisposing factors, clinical presentations, scoring systems, common organism types and the timing of surgical treatment. The key to managing this condition continues to be early clinical diagnosis and aggressive surgical debridement to attempt to reduce the morbidity and mortality of this condition.

Lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells is inhibited by microRNA-494-3p via targeting lipoprotein-associated phospholipase A2.

BACKGROUND: Gram-negative bacterial lipopolysaccharide (LPS) is a major component of inflammation and plays a key role in the pathogenesis of sepsis. According to our previous study, the expression of lipoprotein-associated phospholipase A2 (Lp-PLA2) is significantly upregulated in septic patients and is positively correlated with the severity of this disease. Herein, we investigated the potential roles of Lp-PLA2-targeting microRNAs (miRNAs) in LPS-induced inflammation in murine mononuclear macrophages (RAW264.7 cells). METHODS: In LPS-stimulated RAW264.7 cells, Lp-PLA2 was confirmed to be expressed during the inflammatory response. The function of microRNA-494-3p (miR-494-3p) in the LPS-induced inflammatory response of RAW264.7 cells was determined by the transfection of a miR-494-3p mimic or inhibitor in vitro. RESULTS: Compared to the control, LPS induced a significant increase in the Lp-PLA2 level, which was accompanied by the release of inflammatory mediators. The bioinformatics and qRT‒PCR results indicated that the miR-494-3p level was associated with Lp-PLA2 expression in the LPS-induced inflammatory response of RAW264.7 cells. Dual-luciferase reporter assay results confirmed that the 3'-UTR of Lp-PLA2 was a functional target of microRNA-494-3p. During the LPS-induced inflammatory response of RAW264.7 cells, targeting Lp-PLA2 and transfecting miR-494-3p mimics significantly upregulated the expression of miR-494-3p, leading to a reduction in the release of inflammatory factors and conferring a protective effect on LPS-stimulated RAW264.7 cells. CONCLUSION: By targeting Lp-PLA2, miR-494-3p suppresses Lp-PLA2 secretion, thereby alleviating LPS-induced inflammation, which indicates that miR-494-3p may be a potential target for sepsis treatment.

Metabolomic Approach to Identify the Potential Metabolites from Alpinia malaccensis for Treating SARS-CoV-2 Infection.

The advent of the new coronavirus, leading to the SARS-CoV-2 pandemic, has presented a substantial worldwide health hazard since its inception in the latter part of 2019. The severity of the current pandemic is exacerbated by the occurrence of re-infection or co-infection with SARS-CoV-2. Hence, comprehending the molecular process underlying the pathophysiology of sepsis and discerning possible molecular targets for therapeutic intervention holds significant importance. For the first time, 31 metabolites were tentatively identified by GC-MS analysis from Alpinia malaccensis. On the other hand, five phenolic compounds were identified and quantified from the plant in HPLC-DAD analysis, including (-) epicatechin, rutin hydrate, rosmarinic acid, quercetin, and kaempferol. Nine GC-MS and five HPLC-identified metabolites had shown interactions with 45 and 30 COVID-19-associated human proteins, respectively. Among the proteins, PARP1, FN1, PRKCA, EGFR, ALDH2, AKR1C3, AHR, and IKBKB have been found as potential therapeutic targets to mitigate SARS-CoV-2 infection. KEGG pathway analysis also showed a strong association of FN1, EGFR, and IKBKB genes with SARS-CoV-2 viral replication and cytokine overexpression due to viral infection. Protein-protein interaction (PPI) analysis also showed that TP53, MMP9, FN1, EGFR, and NOS2 proteins are highly related to the genes involved in COVID-19 comorbidity. These proteins showed interaction with the plant phytoconstituents as well. As the study offers a robust network-based procedure for identifying biomolecules relevant to COVID-19 disease, A. malaccensis could be a good source of effective therapeutic agents against COVID-19 and related viral diseases.

Social determinants of health and sepsis: a case-control study.

PURPOSE: We aimed to identify whether social determinants of health (SDoH) are associated with the development of sepsis and assess the differences between individuals living within systematically disadvantaged neighbourhoods compared with those living outside these neighbourhoods. METHODS: We conducted a single-centre case-control study including 300 randomly selected adult patients (100 patients with sepsis and 200 patients without sepsis) admitted to the emergency department of a large academic tertiary care hospital in Hamilton, ON, Canada. We collected data on demographics and a limited set of SDoH variables, including neighbourhood household income, smoking history, social support, and history of alcohol disorder. We analyzed study data using multivariate logistic regression models. RESULTS: The study included 100 patients with sepsis with a median [interquartile range (IQR)] age of 75 [58-84] yr and 200 patients without sepsis with a median [IQR] age of 72 [60-83] yr. Factors significantly associated with sepsis included arrival by ambulance, absence of a family physician, higher Hamilton Early Warning Score, and a recorded history of dyslipidemia. Important SDoH variables, such as individual or household income and race, were not available in the medical chart. In patients with SDoH available in their medical records, no SDoH was significantly associated with sepsis. Nevertheless, compared with their proportion of the Hamilton population, the rate of sepsis cases and sepsis deaths was approximately two times higher among patients living in systematically disadvantaged neighbourhoods. CONCLUSIONS: This study revealed the lack of available SDoH data in electronic health records. Despite no association between the SDoH variables available and sepsis, we found a higher rate of sepsis cases and sepsis deaths among individuals living in systematically disadvantaged neighbourhoods. Including SDoH in electronic health records is crucial to study their effect on the risk of sepsis and to provide equitable care.

RéSUMé: OBJECTIF: Nous avons cherché à déterminer si les déterminants sociaux de la santé (DSS) étaient associés à l'apparition de sepsis et à évaluer les différences entre les personnes vivant dans des quartiers systématiquement défavorisés et celles vivant à l'extérieur de ces quartiers. MéTHODE: Nous avons mené une étude cas témoins monocentrique portant sur 300 patient·es adultes sélectionné·es au hasard (100 personnes atteintes de sepsis et 200 témoins sans sepsis) admis·es au service des urgences d'un grand hôpital universitaire de soins tertiaires à Hamilton, ON, Canada. Nous avons recueilli des données démographiques et un ensemble limité de variables de DSS, y compris le revenu des ménages du quartier, les antécédents de tabagisme, le soutien social et les antécédents de troubles liés à l'alcool. Nous avons analysé les données de l'étude à l'aide de modèles de régression logistique multivariés. RéSULTATS: L'étude a inclus 100 patient·es atteint·es de sepsis avec un âge médian [écart interquartile (ÉIQ)] de 75 [58-84] ans et 200 patient·es sans sepsis avec un âge médian [ÉIQ] de 72 [60-83] ans. Les facteurs significativement associés au sepsis comprenaient l'arrivée en ambulance, l'absence de médecin de famille, un score Hamilton Early Warning Score plus élevé et des antécédents enregistrés de dyslipidémie. D'importantes variables de DSS, telles que le revenu individuel et du ménage et la race, n'étaient pas disponibles dans le dossier médical. Chez les personnes dont les DSS étaient disponibles dans leur dossier médical, aucun DSS n'était significativement associé au sepsis. Néanmoins, comparativement à leur proportion dans la population de Hamilton, le taux de cas de sepsis et de décès dus au sepsis était environ deux fois plus élevé chez les personnes vivant dans des quartiers systématiquement défavorisés. CONCLUSION: Cette étude a révélé le manque de données disponibles sur les DSS dans les dossiers de santé électroniques. Bien qu'il n'y ait pas d'association entre les variables disponibles et le sepsis, nous avons constaté un taux plus élevé de cas de sepsis et de décès dus à la septicémie chez les personnes vivant dans des quartiers systématiquement défavorisés. L'inclusion des DSS dans les dossiers de santé électroniques est cruciale pour étudier leur effet sur le risque de sepsis et pour dispenser des soins équitables.

Pulmonary arterial hypertension in systemic sclerosis: a national inpatient analysis.

OBJECTIVES: We aim to study the prevalence and epidemiology of pulmonary arterial hypertension in SS, and the impact of PAH on SSc hospitalizations in the United States population. METHODS: We utilized the National Inpatient Sample (NIS) from 2016-2019 to obtain adult hospitalizations with the primary/secondary diagnosis of SSc and coexistent PAH (SSc-PAH). Epidemiological variables, mortality rates, and secondary outcomes were studied including pulmonary embolism, atrial flutter, atrial and ventricular fibrillation, pneumonia, sepsis, cardiac arrest and cardiac & renal failure, and ventilator requirement. Healthcare burden was estimated from total hospital charges (THC) and length of stay (LOS). Statistical analysis was performed on STATA 16.1, using linear and logistic regression analyses. RESULTS: Out of 126,685 adult systemic sclerosis hospitalizations, 16.89% had PAH (SSc-PAH). The SSc-PAH group had significantly more females (85.4 % vs. 83.8%) and higher mean age (64.85±13.29 vs. 62.56±14.51). More African Americans were in this group than in the control group (19.5% vs. 14.6, p-value<0.001) while Whites (61.3% vs. 65.6%, p<0.001) and Asians (18.0 % vs. 2.8%, p<0.001) were less common. Charlson comorbidity index was higher for the SSc-PAH population (3.42 vs. 2.94, p-value<0.001). SSc-PAH group had a higher adjusted odds ratio (aOR) for mortality (aOR: 1.39, p<0.001), increased LOS (6.64 vs. 6.0 days, p<0.001) increased THC ($83,813 vs. $71,016, p <0.001). For the SSc-PAH group, there were also significantly higher odds of cardiac failure (aOR 3.13), ventilator requirement (aOR 2.15), cardiac arrest (aOR 1.39), kidney failure (aOR 1.63), pulmonary embolism (aOR 1.84), atrial flutter (aOR 1.86) atrial fibrillation (aOR1.56) and pneumonia (aOR 1.22). No significant difference in ventricular fibrillation, sepsis, or respiratory failure was noted. CONCLUSION: Pulmonary arterial hypertension in SSc is associated with worse outcomes in terms of mortality and morbidity, and higher healthcare burden compared to SSc without PAH. Also, PAH disproportionately affects White, African American & Asian populations. There remains a pressing need to continue efforts for early diagnosis and management of PAH in SSc patients.

Gender and Racial Differences in the Provision of Palliative Care Services Among Critically ill Necrotizing Fasciitis and Septic Shock Geriatric Patients: Analysis of a Nationwide Database in the United States.

Introduction: Necrotizing fasciitis (NF) and sepsis shock (SS) are both severe and life-threatening conditions requiring specialized care, including palliative care (PC), to optimize comfort. However, data on the utilization of PC in this population, including racial and gender differences, are limited. Methods: We used the National Inpatient Sample (NIS) database from 2016 to 2020 to extract data on patients with NF and SS as well as PC utilization. Chi-squared tests and multivariate linear regression models were utilized to analyze relationships between categorical and continuous variables, respectively. Multivariable logistic regression was used to determine adjusted odds ratios (aORs) and 95% confidence intervals (CI) for various outcomes among various gender and racial groups. Mann-Kendall trend test was used to assess mortality trends over time. Results: Among the 11,260 patients with NF and SS, 2,645 received PC whereas 8,615 did not. Female patients had significantly higher odds of receiving PC versus males (aOR: 1.42, 95% CI 1.27-1.58). No significant racial differences in PC utilization were observed. Patients receiving PC had higher odds of in-hospital mortality (aOR: 1.18, 95% CI 1.03-1.35). No significant trend in in-hospital deaths was observed over the study period. PC was associated with significantly shorter length-of-stay and lower costs. Conclusion: Our study provides comprehensive insights, and identifies gender differences in PC utilization in NF and SS patients. Further research must aim to refine delivery strategies and address potential differences in PC.

Sex Differences of Neutrophil Extracellular Traps on Lipopolysaccharide-Stimulated Human Neutrophils.

Objective: Sex differences exist in sepsis, but the commitment of neutrophils to these differences remains unclear. Neutrophil extracellular traps (NETs) function to remove pathogens, yet excessive NETs release can contribute to organ damage. This study explores effects of the gender hormones on endotoxin-induced NETs using neutrophils from both male and female sources. Methods: Blood samples were collected from healthy volunteers. Isolated neutrophils were seeded in collagen-coated cell culture plates, and NETs were induced by lipopolysaccharide (LPS) treatment. After 15 minutes of LPS treatment, 17ß-estradiol (0.03-272.4 ng/mL), testosterone enanthate (0.01-10 ng/mL), dimethyl sulfoxide, or ethanol (vehicle control) was added to the plates. These were incubated for three hours at 37°C with 5% CO2. Neutrophil extracellular traps formation was assessed using immunofluorescence staining. Results: Lipopolysaccharide-induced NETs formation was significantly greater in females than in males. In male-derived neutrophils, 17ß-estradiol at above the blood concentrations significantly suppressed LPS-induced NETs. No effect was seen while using testosterone enanthate to NETs at any concentration. In female-derived neutrophils, 17ß-estradiol, which was near to the highest concentration of non-pregnant women's blood, tended to increase NETs. Testosterone enanthate, which was near to female blood concentration, significantly promoted NETs. Conclusions: Sex differences existed in LPS-induced NETs of human neutrophil. In males, high concentrations of 17ß-estradiol administration may have a suppressive effect on excessive NETs during infection. In females, endogenous gender hormones may promote NETs during infection. Sex differences in neutrophils may need to be considered in organ damage owing to NETs excess such as sepsis.

Physiologically based pharmacokinetic modelling of cefoperazone in paediatrics.

AIMS: Cefoperazone is commonly used off-label in the treatment of bacterial meningitis and sepsis in children, and the pharmacokinetic (PK) data are limited in this vulnerable population. The goal of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict pediatric cefoperazone exposure for rational dosing recommendations. METHODS: A cefoperazone PBPK model for adults was first constructed using Simcyp V22 simulator. Subsequently, the model was extended to children based on the built in age-dependent physiological parameters, while the drug characteristics remained unchanged. The verified pediatric PBPK model was then utilized to assess the rationality of the common dosing regimens for children at different age groups. RESULTS: Cefoperazone PBPK model included elimination via biliary excretion, glomerular filtration, and organic anion transporter 3 (OAT3)-mediated tubular secretion. 95.2% of the observed mean concentrations and 100% of the area under the plasma drug concentration-time curve (AUC) and peak concentration (Cmax) in adults were within a twofold range of model mean predictions. Good predictive accuracy was also observed in children, including neonates. 50 mg/kg q12h cefoperazone demonstrated effective target attainment in virtual term neonates (<1 month) when the MIC was ≤1 mg/L, adhering to the stringent PK/PD target of 75% fT > MIC. 37.5 mg/kg q12h cefoperazone achieved the common 50% fT > MIC target for an MIC ≤ 0. 25 mg/L in virtual pediatric patients ranging from 1 month to 18 years of age. CONCLUSIONS: A pediatric PBPK model was developed for cefoperazone, and it could serve as the basis for deriving rational dosing regimens in children.

Decreased susceptibility to viscosin in Streptococcus pneumoniae.

Growing numbers of infections caused by antibiotic-resistant Streptococcus pneumoniae strains are a major concern for healthcare systems that will require new antibiotics for treatment as well as preventative measures that reduce the number of infections. Lipopeptides are antimicrobial molecules, of which some are used as antibiotics, including the last resort antibiotics daptomycin and polymyxins. Here we have studied the antimicrobial effect of the cyclic lipopeptide viscosin on S. pneumoniae growth and morphology. Most lipopeptides function as surfactants that create pores in membrane layers, which is regarded as their main antimicrobial activity. We show that viscosin can inhibit growth of S. pneumoniae without disintegration of the cytoplasmic membrane. Instead, the cells developed abnormal shapes and misplaced new division sites. The cell wall of these bacteria appeared less dense in electron microscopy images, suggesting that viscosin interfered with normal cell wall synthesis. Corroborating this observation, a luciferase reporter assay was used to show that the two-component systems LiaFSR and CiaRH, which are known to be activated upon cell wall stress, were strongly induced by viscosin. Furthermore, a mutant displaying 1.8-fold decreased susceptibility to viscosin was generated by sequential exposure to increasing concentrations of the lipopeptide. The mutant suffered from significant fitness loss and had mutations in genes involved in fatty acid synthesis, teichoic acid synthesis, and cell wall synthesis as well as transcription and translation. How these mutations might be linked to decreased viscosin susceptibility is discussed.IMPORTANCEStreptococcus pneumoniae is a leading cause of bacterial pneumonia, sepsis, and meningitis in children, and the incidence of infections caused by antibiotic-resistant strains is increasing. Development of new antibiotics is therefore necessary to treat these types of infections in the future. Here, we have studied the activity of the antimicrobial lipopeptide viscosin on S. pneumoniae and show that in addition to having the typical membrane destabilizing activity of lipopeptides, viscosin inhibits pneumococcal growth by obstructing normal cell wall synthesis. This suggests a more specific mode of action than just the surfactant activity. Furthermore, we show that S. pneumoniae does not easily acquire resistance to viscosin, which makes it a promising molecule to explore further, for example, by synthesizing less toxic derivates that can be tested for therapeutic potential.

The Impact of Multi-Institution Datasets on the Generalizability of Machine Learning Prediction Models in the ICU.

OBJECTIVES: To evaluate the transferability of deep learning (DL) models for the early detection of adverse events to previously unseen hospitals. DESIGN: Retrospective observational cohort study utilizing harmonized intensive care data from four public datasets. SETTING: ICUs across Europe and the United States. PATIENTS: Adult patients admitted to the ICU for at least 6 hours who had good data quality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using carefully harmonized data from a total of 334,812 ICU stays, we systematically assessed the transferability of DL models for three common adverse events: death, acute kidney injury (AKI), and sepsis. We tested whether using more than one data source and/or algorithmically optimizing for generalizability during training improves model performance at new hospitals. We found that models achieved high area under the receiver operating characteristic (AUROC) for mortality (0.838-0.869), AKI (0.823-0.866), and sepsis (0.749-0.824) at the training hospital. As expected, AUROC dropped when models were applied at other hospitals, sometimes by as much as -0.200. Using more than one dataset for training mitigated the performance drop, with multicenter models performing roughly on par with the best single-center model. Dedicated methods promoting generalizability did not noticeably improve performance in our experiments. CONCLUSIONS: Our results emphasize the importance of diverse training data for DL-based risk prediction. They suggest that as data from more hospitals become available for training, models may become increasingly generalizable. Even so, good performance at a new hospital still depended on the inclusion of compatible hospitals during training.

The timing of death in burn patients.

Aim: When treating burn patients, some patients die in the chronic phase, even if they overcome the acute phase of the burn. To elucidate the timing of death and its underlying causes among burn patients. Methods: Patients evaluated were admitted to our burn center between January 2015, and December 2019. Patient information, time, and cause of death were retrospectively collected from their medical records. Results: Among 342 admitted patients, 49 died. The time of death was as follows: within 24 h (n = 9), within 3 days (n = 7), within 1 week (n = 5), within 2 weeks (n = 4), within 3 weeks (n = 3), within 30 days (n = 6), within 60 days (n = 5), and after 60 days (n = 9). The causes of death within 3 days were hypoxic encephalopathy, extensive burns (>80%), severe heat stroke, and acute coronary syndrome. The causes of death after 3 days were sepsis, pneumonia, intestinal ischemia, pancreatitis, and worsening of chronic diseases. The mortality rate was similar for patients ≥65 years of age and those with a burn area of ≥20%, with both groups showing a particularly poor prognosis. Conclusions: The timing of death in hospitalized burn patients showed a bimodal distribution as approximately 40% of patients who survived the resuscitation period died after 30 days. Elderly patients were at particularly high risk for mortality. In burn care, treatment planning should consider not only the short-term but also the long-term prognosis.

Experimental models of high-risk bowel anastomosis in rats: A systematic review.

BACKGROUND: Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity, that negatively affect the patients' quality of life. Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation. Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features. Despite the advances in experimental protocols and techniques, designing a high-quality study is still challenging for the investigators as there is a plethora of different models used. AIM: To review current state of the art for experimental protocols in high-risk anastomosis in rats. METHODS: This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. To identify eligible studies, a comprehensive literature search was performed in the electronic databases PubMed (MEDLINE) and Scopus, covering the period from conception until 18 October 2023. RESULTS: From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis. Methods of assessing anastomotic healing were extracted and were individually appraised. CONCLUSION: Anastomotic healing studies have evolved over the last decades, but the findings are yet to be translated into human studies. There is a need for high-quality, well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.

Exploring the relationship between life course adiposity and sepsis: insights from a two-sample Mendelian randomization analysis.

Objectives: The relationship between adiposity and sepsis has received increasing attention. This study aims to explore the causal relationship between life course adiposity and the sepsis incidence. Methods: Mendelian randomization (MR) method was employed in this study. Instrumental variants were obtained from genome-wide association studies for life course adiposity, including birth weight, childhood body mass index (BMI), childhood obesity, adult BMI, waist circumference, visceral adiposity, and body fat percentage. A meta-analysis of genome-wide association studies for sepsis including 10,154 cases and 454,764 controls was used in this study. MR analyses were performed using inverse variance weighted, MR Egger regression, weighted median, weighted mode, and simple mode. Instrumental variables were identified as significant single nucleotide polymorphisms at the genome-wide significance level (P < 5×10-8). The sensitivity analysis was conducted to assess the reliability of the MR estimates. Results: Analysis using the MR analysis of inverse variance weighted method revealed that genetic predisposition to increased childhood BMI (OR = 1.29, P = 0.003), childhood obesity (OR = 1.07, P = 0.034), adult BMI (OR = 1.38, P < 0.001), adult waist circumference (OR = 1.01, P = 0.028), and adult visceral adiposity (OR = 1.53, P < 0.001) predicted a higher risk of sepsis. Sensitivity analysis did not identify any bias in the MR results. Conclusion: The results demonstrated that adiposity in childhood and adults had causal effects on sepsis incidence. However, more well-designed studies are still needed to validate their association.

A Preclinical Model of Sepsis-Induced Myopathy with Disuse in Mice.

Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop muscle weakness and atrophy, increasing the incidence of hospital readmissions and mortality. However, the available preclinical models of sepsis do not address skeletal muscle disuse, a key component for the development of sepsis-induced myopathy. Our objective in this protocol is to provide a step-by-step guideline for a mouse model that reproduces the clinical setting experienced by a bedridden septic patient. Male C57Bl/6 mice were used to develop this model. Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Four days post-CLP, mice were subjected to hindlimb suspension (HLS) for seven days. Results were compared with sham-matched surgeries and/or animals with normal ambulation (NA). Muscles were dissected for in vitro muscle mechanics and morphological assessments. The model results in marked muscle atrophy and weakness, a similar phenotype observed in septic patients. The model represents a platform for testing potential therapeutic strategies for the mitigation of sepsis-induced myopathy.

KLF13 Attenuates Lipopolysaccharide-Induced Alveolar Epithelial Cell Damage by Regulating Mitochondrial Quality Control via Binding PGC-1α.

Sepsis is a clinically life-threatening syndrome, and acute lung injury is the earliest and most serious complication. We aimed to assess the role of kruppel-like factor 13 (KLF13) in lipopolysaccharide (LPS)-induced human alveolar type II epithelial cell damage and to reveal the possible mechanism related to peroxisome proliferator-activated receptor-γ co-activator 1-α (PGC-1α). In LPS-treated A549 cells with or without KLF13 overexpression or PGC-1α knockdown, cell viability was measured by a cell counting kit-8 assay. Enzyme-linked immunosorbent assay kits detected the levels of inflammatory factors, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining measured cell apoptosis. Besides, mitochondrial reactive oxygen species (MitoSOX) and mitochondrial membrane potential were detected using MitoSOX red- and JC-1 staining. Expression of proteins related to mitochondrial quality control (MQC) was evaluated by western blot. Co-immunoprecipitation (Co-IP) assay was used to analyze the interaction between KLF13 and PGC-1α. Results indicated that KLF13 was highly expressed in LPS-treated A549 cells. KLF13 upregulation elevated the viability and reduced the levels of inflammatory factors in A549 cells exposed to LPS. Moreover, KLF13 gain-of-function inhibited LPS-induced apoptosis of A549 cells, accompanied by upregulated BCL2 expression and downregulated Bax and cleaved caspase3 expression. Furthermore, MQC was improved by KLF13 overexpression, as evidenced by decreased MitoSOX, JC-1 monomers and increased JC-1 aggregates, coupled with the changes of proteins related to MQC. In addition, Co-IP assay confirmed the interaction between KLF13 and PGC-1α. PGC-1α deficiency restored the impacts of KLF13 upregulation on the inflammation, apoptosis, and MQC in LPS-treated A549 cells. In conclusion, KLF13 attenuated LPS-induced alveolar epithelial cell inflammation and apoptosis by regulating MQC via binding PGC-1α.

Micheliolide ameliorates lipopolysaccharide-induced acute kidney injury through suppression of NLRP3 activation by promoting mitophagy via Nrf2/PINK1/Parkin axis.

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) represents a frequent complication of in critically ill patients. The objective of this study is to illuminate the potential protective activity of Micheliolide (MCL) and its behind mechanism against SA-AKI. METHODS: The protective potential of MCL on SA-AKI was investigated in lipopolysaccharide (LPS) treated HK2 cells and SA-AKI mice model. The mitochondrial damage was determined by detection of reactive oxygen species and membrane potential. The Nrf2 silencing was achieved by transfection of Nrf2-shRNA in HK2 cells, and Nrf2 inhibitor, ML385 was employed in SA-AKI mice. The mechanism of MCL against SA-AKI was evaluated through detecting hallmarks related to inflammation, mitophagy and Nrf2 pathway via western blotting, immunohistochemistry, and enzyme linked immunosorbent assay. RESULTS: MCL enhanced viability, suppressed apoptosis, decreased inflammatory cytokine levels and improved mitochondrial damage in LPS-treated HK2 cells, and ameliorated renal injury in SA-AKI mice. Moreover, MCL could reduce the activation of NLRP3 inflammasome via enhancing mitophagy. Additionally, Nrf2 deficiency reduced the suppression effect of MCL on NLRP3 inflammasome activation and blocked the facilitation effect of MCL on mitophagy in LPS-treated HK2 cells, the consistent is true for ML385 treatment in SA-AKI mice. CONCLUSIONS: MCL might target Nrf2 and further reduce the NLRP3 inflammasome activation via enhancing mitophagy, which alleviated SA-AKI.

Dysregulation of Host-Pathogen Interactions in Sepsis: Host-Related Factors.

Sepsis stands as a prominent contributor to sickness and death on a global scale. The most current consensus definition characterizes sepsis as a life-threatening organ dysfunction stemming from an imbalanced host response to infection. This definition does not capture the intricate array of immune processes at play in sepsis, marked by simultaneous states of heightened inflammation and immune suppression. This overview delves into the immune-related processes of sepsis, elaborating about mechanisms involved in hyperinflammation and immune suppression. Moreover, we discuss stratification of patients with sepsis based on their immune profiles and how this could impact future sepsis management.

Early Diagnosis of Sepsis: The Role of Biomarkers and Rapid Microbiological Tests.

Sepsis is a medical emergency resulting from a dysregulated response to an infection, causing preventable deaths and a high burden of morbidity. Protocolized and accurate interventions in sepsis are time-critical. Therefore, earlier recognition of cases allows for preventive interventions, early treatment, and improved outcomes. Clinical diagnosis of sepsis by clinical scores cannot be considered an early diagnosis, given that underlying molecular pathophysiological mechanisms have been activated in the preceding hour or days. There is a lack of a widely available tool enhancing preclinical diagnosis of sepsis. Sophisticated technologies for sepsis prediction have several limitations, including high costs. Novel technologies for fast molecular and microbiological diagnosis are focusing on bedside point-of-care combined testing to reach most settings where sepsis represents a challenge.