Microbiological characteristics of bloodstream infections in a reference hospital in northeastern Brazil / Características microbiológicas de infecções da corrente sanguínea em hospital de referência no nordeste do Brasil

Abstract Routine blood culture is used for the detection of bloodstream infections by aerobic and anaerobic bacteria and by common pathogenic yeasts. A retrospective study was conducted in a public hospital in Maceió-AL, by collecting data of all medical records with positive blood cultures. Out of the 2,107 blood cultures performed, 17% were positive with Staphylococcus coagulase negative (51.14%), followed by Staphylococcus aureus (11.21%) and Klebsiella pneumoniae (6.32%). Gram-positive bacteria predominated among positive blood cultures, highlighting the group of Staphylococcus coagulase-negative. While Gram-negative bacteria had a higher number of species among positive blood cultures.

Resumo A cultura sanguínea de rotina é usada para a detecção de infecções na corrente sanguínea por bactérias aeróbias e anaeróbias e por leveduras patogênicas comuns. Estudo retrospectivo realizado em hospital público de Maceió-AL, por meio da coleta de dados de todos os prontuários com culturas sanguíneas positivas. Das 2.107 culturas sanguíneas realizadas, 17% foram positivas com Staphylococcus coagulase negativo (51,14%), seguido por Staphylococcus aureus (11,21%) e Klebsiella pneumoniae (6,32%). As bactérias Gram-positiva predominaram entre as culturas de sangue positivas, destacando-se o grupo das Staphylococcus coagulase-negativo. Enquanto as bactérias Gram-negativas apresentaram um número maior de espécies entre as culturas de sangue positivas.

Investigating Secretion Systems and Effectors on Galleria mellonella.

Infection experiments with Galleria mellonella enable the measurement of virulence that is mediated by secretion systems and their effector proteins in vivo. G. mellonella has an innate immune system and shares similarities with the complex host environment of mammals. Unlike other invertebrate model systems, experiments can be performed at mammalian body temperature. Here, we describe the systemic infection of G. mellonella with Pseudomonas aeruginosa with and without functional secretion systems. A Kaplan-Meier curve is constructed showing the percent survival of animals over time.

Simultaneous detection of C-reactive protein and lipopolysaccharide based on a dual-channel electrochemical biosensor for rapid Gram-typing of bacterial sepsis.

Sepsis is a life-threatening multi-organ failure syndrome, with bacterial infections being the most common cause. Rapid Gram-typing is imperative to assist in antibiotic intervention. C-reactive protein (CRP) and lipopolysaccharide (LPS) are effective biomarkers for discerning the Gram type of bacteria but differ by several orders of magnitude in clinical detection, thereby impeding their simultaneous detection. And two independent methods are time-consuming and laborious. In this study, a dual-channel electrochemical biosensor was developed for simultaneous detection of LPS and CRP. Under optimal conditions, linear ranges of LPS (0.5-1000 pg/mL) and CRP (0.1-20 µg/mL) were obtained in line with the clinical evaluation scopes. In simulated sample tests, Gram-positive, Gram-negative, and healthy plasma samples were clearly distinguished by the developed biosensors, and these results were consistent with that of enzyme-linked immunosorbent assay (ELISA). In addition, the results of the plasma samples tested by the electrochemical biosensor matched those derived from blood cultures in the laboratory. Collectively, the electrochemical biosensor was expected to provide the scientific basis for the rapid Gram-typing and point-of-care detection of bacterial sepsis.

From genes to systems: The role of food supplementation in the regulation of sepsis-induced inflammation.

Systemic inflammation includes a widespread immune response to a harmful stimulus that results in extensive systemic damage. One common example of systemic inflammation is sepsis, which is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Under the pro-inflammatory environment of sepsis, oxidative stress contributes to tissue damage due to dysfunctional microcirculation that progressively causes the failure of multiple organs that ultimately triggers death. To address the underlying inflammatory condition in critically ill patients, progress has been made to assess the beneficial effects of dietary supplements, which include polyphenols, amino acids, fatty acids, vitamins, and minerals that are recognized for their immuno-modulating, anticoagulating, and analgesic properties. Therefore, we aimed to review and discuss the contribution of food-derived supplementation in the regulation of inflammation from gene expression to physiological responses and summarize the precedented potential of current therapeutic approaches during systemic inflammation.

Identification of PIK3R5 as a hub in septic myocardial injury and the cardioprotective effects of Psoralidin.

BACKGROUND: Myocardial injury is a severe complication of sepsis, resulting in substantial morbidity and mortality. Psoralidin (PSO), derived from the seeds of Psoralea corylifolia L., has garnered considerable attention due to its potent pharmacological effects, including anti-inflammatory and antibacterial effects. PURPOSE: Our previous work conducted affirmed that PSO has a protective effect on sepsis and septic myocardial injury, however the specific molecular mechanisms need further clarification. STUDY DESIGN: This objective of this study was to use three analytic modalities and bioinformatics methods to identify potential targets, followed by experimental verification. METHODS: A series of experiments methods (including echocardiography, HE, western blot, qPCR, RNA-seq, network pharmacology) were used to evaluate the effects of PSO against sepsis and septic myocardial injury in cecal ligation and puncture (CLP)-injured BALB/c mice and lipopolysaccharide (LPS)-injured HL-1 cardiomyocytes. RESULTS: Firstly, a group of sepsis-related genes were identified by integrating database surveys, RNA-seq analysis, and weighted gene co-expression network analysis (WCGNA). Subsequently, the pharmacological targets of PSO were predicted. Furthermore, the identification of phosphoinositide 3- kinase regulatory subunit 5 (PIK3R5) as a crucial hub gene was accomplished via protein-protein interaction network and molecular docking approach. In vivo experiments showed that PSO treatment alleviated septic myocardial injury, as evidenced by improved cardiac function indicators and inflammation response. Similar results were obtained in vitro experiments. Importantly, the expression of PI3KR5 was decreased in the myocardium and cardiomyocytes, and the effect was reversed by PSO treatment. CONCLUSION: This study systematically revealed the key targets of PSO in the treatment of septic myocardial injury. These findings offer valuable insights into disease-drug targets, which have certain clinical significance to exploring disease biomarkers and potential therapeutic targets for septic patients.

RNA-seq revealed the anti-pyroptotic effect of suramin by suppressing NLRP3/caspase-1/GSDMD pathway in LPS-induced MH-S alveolar macrophages.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), acting as one common sepsis-associated organ injury, induces uncontrolled and self-amplifies pulmonary inflammation. Given the lack of clinically effective approaches, the mortality rate of it still remains high. Suramin(SUR), as an antiparasitic drug initially, was found to ameliorate sepsis associated ALI in our previous work. However, the underlying mechanism of its protective effects has not been clarified. Pyroptosis, categorized as an inflammatory form of programmed cell death, could aggravate lung inflammatory responses via inducing alveolar macrophages (AM) pyroptosis. METHODS: MH-S AM cell line was stimulated with or without lipopolysaccharide (LPS) or suramin, and the differential expression genes (DEGs) were excavated using RNA sequencing (RNA-seq). To identify the regulatory roles of these genes, pyroptosis-related genes (PRGs), GO/KEGG and GSEA analysis were conducted. We also performed WB, qRTPCR and ELISA to validate the RNA-seq results and further expound the protective effect of suramin. RESULTS: 624 DEGs were identified between control (CON) and lipopolysaccharide (LPS) groups, and enrichment analysis of these genes revealed significantly enriched pathways that related to immune system and signal transduction. Meanwhile, 500 DEGs were identified in LPS/SUR+LPS group. In addition to the pathways mentioned above, IL-17 pathway and C-type lectin receptor signaling pathway were also enriched. All 6 pathways were connected with pyroptosis. Concurrently, the "DESeq2" R package was used to identify differentially expressed PRGs. Nod1, Nod2, interleukin (IL)-1b, IL-6, tumor necrosis factor (TNF), NLRP3 were upregulated under LPS stimulation. Then, in SUR+LPS group, Nod2, IL-6, IL-1b, NLRP3 were downregulated. The validation results of WB, qRT-PCR, and ELISA showed: the protein and mRNA expression levels of NLRP3, caspase-1, GSDMD and the concentrations of IL-1b, IL-18 were decreased when treated with suramin and LPS. CONCLUSION: Suramin could inhibit NLRP3/caspase-1/GSDMD canonical pyroptosis pathway in LPS-induced MH-S alveolar macrophages.

Catalpol rescues LPS-induced cognitive impairment via inhibition of NF-Κb-regulated neuroinflammation and up-regulation of TrkB-mediated BDNF secretion in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Septic-associated encephalopathy (SAE) is a key manifestation of sepsis. Nevertheless, specific treatment for SAE is still lacking. Catalpol is an active component derived from Rehmanniae Radix, and has been demonstrated to be a potential neuroprotective agent. However, its effect on SAE still needs to be fully explored. AIM: To address the benefits of catalpol on post-sepsis cognitive deterioration and related mechanisms. MATERIALS AND METHODS: Novel object recognition test, temporal order task, histopathology, and immunochemistry were applied to address the benefits of catalpol on LPS-triggered post-sepsis cognitive decline in mice. Xuebijing injection (10 ml/kg) has been utilized as a positive control in the above animal studies. After treatment, the catalpol content in the hippocampus was determined using LC-MS/MS. Finally, the mechanisms of catalpol were further assessed in BV2 and PC12 cells in vitro using Western blot, RT-PCR, flow cytometry, molecular docking tests, thermal shift assay, transmission electron microscopy, and immunofluorescence analysis. RESULTS: Behavior tests showed that catalpol therapy could lessen the cognitive impairment induced by LPS damage. HE, Nissl, immunofluorescence, transmission electron microscopy, and Golgi staining further reflected that catalpol treatment could restore lymphocyte infiltration, blood-brain barrier (BBB) degradation, and the decreasing complexity of dendritic trees. According to LC-MS/MS analysis, catalpol had a 136 ng/mg concentration in the hippocampus. In vitro investigation showed that catalpol could inhibit microglia M1 polarization via blocking NF-κB phosphorylation, translocation and then reducing inflammatory cytokine release in BV2 microglia cells. Brain-derived neurotrophic factor (BDNF) release up-regulation and TrkB pathway activation were observed in the catalpol treatment group in vivo and in vitro. The effect of catalpol on enhancing BDNF expression was inhibited by the specific inhibitor of TrkB (GNF-5837) in PC12 cells. Further molecular docking tests showed that catalpol formed weak hydrophobic bonds with TrkB. Besides, thermal shift assay also reflected that catalpol incubation caused a considerable change in the melting temperature of the TrkB. CONCLUSION: Catalpol alleviates LPS-triggered post-sepsis cognitive impairment by reversing neuroinflammation via blocking the NF-κB pathway, up-regulating neurotrophic factors via the activation of TrkB pathway, and preserving BBB integrity.

Helenine blocks NLRP3 activation by disrupting the NEK7-NLRP3 interaction and ameliorates inflammatory diseases.

BACKGROUND: The involvement of NLRP3 inflammasome is associated with the progress of numerous inflammatory conditions. However, there is currently no single compound used in the clinic. Search for the inhibitor of NLRP3 inflammasome from natural products is an attractive direction. The compound Helenin (Hel), which is obtained from Inula helenium L., is reported to have anti-inflammatory activities. However, the underlying molecular mechanisms and specific inflammatory signal pathway remains not well understood. PURPOSE: This research aims to determine the impacts of Hel on NLRP3 inflammasome and the underlying mechanism involved, meanwhile also assessing its potential as a therapeutic intervention for inflammatory diseases mediated by NLRP3 overactivation. METHODS: Pretreated with Hel in BMDMs (bone marrow-derived macrophages), then stimulated with NLRP3 triggers and measured the expression of active caspase-1 and interleukin 1ß (IL-1ß). Determination of intracellular K+ and Ca2+, ASC oligomerization and mitochondrial reactive oxygen species (mtROS) production were employed to explore the preliminary mechanism of Hel on NLRP3 activation. Subsequently, Co-immunoprecipitation was used to investigate protein-protein interaction and reduction of covalent bonds of Hel was to explore the binding mode between drugs and proteins. Finally, in vivo experiments, we utilized mouse lethal sepsis and monosodium urate(MSU)-induced peritonitis models to evaluate the effectiveness of Hel in inhibiting inflammatory diseases. RESULTS: The findings revealed that Hel exhibited a specific blocking effect on NLRP3, with no impact on the assembly of NLRC4 and AIM2 inflammasome. Through the analysis of mechanisms targeting key upstream factors in NLRP3 activation, Hel inhibited NLRP3-dependent ASC oligomerization but did not regulating inflammasome priming, K+ efflux, Ca2+ influx, or mitochondrial damage and mtROS. Moreover, Hel effectively interrupted the binding of NEK7-NLRP3, which was dependent on the active double C=C of the α,ß-unsaturated carbonyl units in Hel. In mouse models, Hel showed promising therapeutic effects in the treatment of NLRP3 overactivation-associated diseases, including the lethal sepsis and acute systemic inflammation induced by lipopolysaccharide (LPS) and peritonitis induced by MSU. CONCLUSION: Our results indicate that Hel dependent α,ß-unsaturated carbonyl units interrupt the formation of the NLRP3-NEK7 interaction, thereby blocks the inflammasome assemblage and activation. These fundings would suggest that Hel is a promising inhibitor for treating diseases driven by NLRP3 overactivation.

Gut-derived 4-hydroxyphenylacetic acid attenuates sepsis-induced acute kidney injury by upregulating ARC to inhibit necroptosis.

BACKGROUND: Studies have found that the plasma content of gut-derived 4-hydroxyphenylacetic acid (4-HPA) was significantly increased in septic patients. However, the mechanism of 4-HPA elevation during sepsis and its relationship with sepsis-induced acute kidney injury (SAKI) remain unclear. METHODS: Cecal ligation and puncture (CLP) was performed in C57BL/6 mice to establish the SAKI animal model. Human renal tubular epithelial (HK-2) cells stimulated with lipopolysaccharide were used to establish the SAKI cell model. The widely targeted metabolomics was applied to analyze the renal metabolite changes after CLP. Proteomics was used to explore potential target proteins regulated by 4-HPA. The blood sample of clinical sepsis patients was collected to examine the 4-HPA content. RESULTS: We found that renal gut-derived 4-HPA levels were significantly increased after CLP. The high permeability of intestinal barrier after sepsis contributed to the dramatic increase of renal 4-HPA. Intriguingly, we demonstrated that exogenous 4-HPA administration could further significantly reduce CLP-induced increases in serum creatinine, urea nitrogen, and cystatin C, inhibit renal pathological damage and apoptosis, and improve the survival of mice. Mechanistically, 4-HPA inhibited necroptosis in renal tubular epithelial cells by upregulating the protein expression of apoptosis repressor with caspase recruitment domain (ARC) and enhancing the interaction between ARC and receptor-interacting protein kinase 1 (RIPK1). CONCLUSIONS: The increase of gut-derived 4-HPA in the kidney after sepsis could play a protective effect in SAKI by upregulating ARC to inhibit necroptosis.

Accuracy of International Classification of Disease Coding Methods to Estimate Sepsis Epidemiology: A Scoping Review.

PURPOSE: To provide an overview of various sepsis International Classification of Diseases (ICD) coding methods and their diagnostic accuracy. METHODS: We undertook a systematic scoping review between 1991 and 2020 (search terms: sepsis, coding, and epidemiology) to include studies reporting the accuracy of a sepsis ICD coding method. Studies were grouped by ICD coding method, number of diagnostic accuracy parameters, ICD version, reference standard, design, country, setting, type of dataset and sepsis definition. ICD coding methods were categorised as explicit or implicit, with the explicit methods further divided into wide and narrow groups. Descriptive statistics were used to present data. RESULTS: We analysed 17 studies, of which 16 (94.1%) used retrospective medical chart review as the reference standard for clinical sepsis, and eight (47.1%) used hospital administrative data to identify sepsis. There were 53 assessments of various ICD coding methods, with 32 (60.4%) of them being explicit and 21 (39.6%) implicit methods. The coding methods had a median sensitivity of <75% but a median specificity of >85%. However, a wide variation was noted in the diagnostic accuracy parameters of all ICD coding methods. Most of the studies showed high methodological quality. CONCLUSION: None of the current ICD coding methods is optimal for identifying sepsis.

Polygonum cuspidatum Sieb. et Zucc. Extracts improve sepsis-associated acute kidney injury by inhibiting NF-κB-mediated inflammation and pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum) is a herbaceous perennial plant in the Polygonaceae family that produces biofunctional stilbenes and quinones. The dried rhizome and root of P. cuspidatum in traditional oriental medicine have been used for ameliorating inflammatory illnesses, diabetes, gout, cancer, and other ailments. AIM OF THE STUDY: This work aimed to investigate the protective effects of P. cuspidatum extracts (PCE) on sepsis-associated acute kidney injury (SA-AKI) and its underlying mechanism. MATERIALS AND METHODS: The potential mechanisms by which PCE improved SA-AKI were preliminarily predicted by network pharmacology. The dry powders of PCE were obtained using the freeze-drying method. A mouse model of SA-AKI was established by intraperitoneal injection of lipopolysaccharide (LPS). The protective effects of PCE on SA-AKI in vivo were studied using pathological and biochemical methods. LPS-stimulated HK-2 cells were prepared for in vitro evaluation. The qPCR and immunoblotting assays were performed to confirm the mechanism involved. RESULTS: The network pharmacology results indicate that emodin (Emo) and polydatin (PD) are potential active components of P. cuspidatum ameliorating SA-AKI. The experimental results showed that PCE improved renal function indices (creatinine, urea nitrogen, and urinary protein) in SA-AKI mice. Mechanistically, PCE mitigated oxidative stress, regulated the expression levels of pyroptosis-related proteins, and repressed the production of inflammatory cytokines by inactivating nuclear factor-kappa B (NF-κB) signaling in vivo. Similar results were observed in LPS-stimulated HK-2 cells in the presence of Emo or PD. CONCLUSIONS: Our results demonstrated that PCE and active ingredients (Emo and PD) in PCE ameliorated SA-AKI by suppressing oxidative stress, inflammation, and pyroptosis.

Accelerating Detection and Intervention for Sepsis in Skilled Nursing Facilities Using a Sepsis Pathway.

BACKGROUND: Early detection of sepsis decreases mortality in hospitals, but recognition of sepsis is often delayed in skilled nursing facilities (SNFs). LOCAL PROBLEM: A local SNF in the northeastern United States sought to use a standardized sepsis pathway to prevent hospital readmissions due to sepsis. METHODS: A pre-/postimplementation design was used for this project. Outcome measures included sepsis detection and treatment, length of stay in the SNF, sepsis-related hospital transfer rate, mortality rate, and predictors of clinical outcomes. INTERVENTIONS: A SNF sepsis pathway was developed based on current sepsis detection tools. The pathway incorporated a sepsis screening tool and a sepsis bundle. Implementation of the pathway involved education of nurses and certified nursing assistants on the pathway. RESULTS: A total of 178 patients were included in data analysis (81 preimplementation and 97 implementation). Sepsis recognition increased from 56% to 86% ( P < .001), and sepsis-related hospital transfers decreased from 68% to 44% ( P = .07). Laboratory testing for lactate, white blood cell count, and blood cultures increased, and sepsis intervention rates significantly improved ( P < .001). CONCLUSIONS: Implementing a modified SNF sepsis pathway accelerated identification of sepsis and improved clinical outcomes.

Electrochemical analysis of total phospholipids in human serum for severe sepsis diagnosis.

Electrochemical analysis of total phospholipids was performed for the diagnosis of sepsis. The influence of electrode materials on the analysis of the chromogenic substrate was analyzed using Au, graphite, and pyrolyzed carbon electrodes. The total phospholipid analysis based on electrochemical analysis with pyrolyzed carbon was used for diagnosis of sepsis using sera from healthy volunteers, systemic inflammatory response syndrome (SIRS), and severe sepsis patients. The analysis results using the optical measurement and the electrochemical analysis were compared for the serum samples from sepsis patients and healthy controls. Additionally, the interference of human serum on the optical measurement and electrochemical analysis was estimated by signal-to-noise (S/N) calculation. The assay results of the levels of other biomarkers for sepsis (C-reactive protein and procalcitonin) and the total phospholipid levels obtained using the optical measurement and electrochemical analysis methods were statistically similar. Finally, the mortality of patients, indicated by the results of the total phospholipid assay performed using the electrochemical analysis of the patient samples collected daily (1, 3, and 7 day(s) after admission to hospital), was compared with the patient mortality assessed via conventional severity indexes, such as the SOFA and APACHE Ⅱ scores. The 28-day survival rate was estimated by Kaplan-Meier survival analysis based on the total phospholipid level of patient samples that were obtained after 1, 3, and 7 day(s) from hospital admission.

Chitosan modified graphene field-effect transistor biosensor for ultrasensitive procalcitonin detection.

Sepsis is a systemic inflammatory response caused by a bacterial infection that often leading to tissue damage, organ failure and death. Procalcitonin (PCT), as a peptide precursor to hormones, is the main biomarker to identification of the sepsis. In this study, a chitosan modified graphene field transistor (CTS-GFET) was established and first time used for PCT ultra-sensitive detection. CTS was functionalized on the GFET channel surface to immobilized anti-PCT by glutaraldehyde. This biosensor exhibited the detection limit as low as 0.82 ag/mL in PBS, which exhibited 3 times enhancement compared with GFET biosensors. The enhancement mechanisms of CTS-GFET were studied by electrical theoretical model. In addition, the CTS-GFET biosensor was successfully applied to quantify the concentration of the PCT in human serum samples, indicating the potential use in clinical application.

An ultra-sensitive electrochemical biosensor for the detection of procalcitonin in sepsis patients' serum, using a Cu-BHT-based thin film.

Procalcitonin (PCT) is a polypeptide produced by the parafollicular cells of the thyroid gland and serves as a vital marker for the diagnosis and treatment of sepsis and other infectious diseases, as well as multiple organ failure, due to its high expression levels in affected patients. This article reports on a highly sensitive electrochemical biosensor based on MOF composite materials, based on Cu-BHT, for detecting PCT levels. The surface of the glassy carbon electrode may have better charge transfer resistance owing to the nano-composite material made of Cu-BHT, chitosan, and AuNPs. At the same time, the anti-PCT antibody may also be covalently bonded to the composite material and measure PCT concentration using electrochemical impedance spectroscopy (EIS). The results of the investigation demonstrate that the sensor's response has excellent linear conjunction with the logarithm of PCT concentration under optimum circumstances. The detection limit (LOD) is 14.579 × 10-9 µg/mL, and the linear range of detection is 10-7 µg/mL to 10-1 µg/mL. Simultaneously, we successfully applied this method to detect serum PCT before and after treatment in different sepsis patients and compared it with chemiluminescence immunoassay. The findings indicate that the proposed method holds promising potential for timely diagnosis and treatment of sepsis patients.

Effect of Norepinephrine on Peripheral Perfusion Index and Its Association With the Prognosis of Patients With Sepsis.

Background: To evaluate whether the use of norepinephrine during the management of patients with sepsis affects the perfusion index (PI) and patient outcomes. Methods: We retrospectively studied patients with septic shock between January 2014 and December 2018 who had undergone Pulse index Continuous Cardiac Output-Plus cardiac output monitoring and received norepinephrine during the management. We collected data regarding basic clinical characteristics. Hemodynamic parameters, including lactate, PI, and norepinephrine dose at T0 and 24 h after Pulse index Continuous Cardiac Output catheterization (T24) were obtained. Results: The PI of the nonsurvivor group (n = 44) was significantly lower than that of the survivor group (n = 144) at T24, and the lactate level of the nonsurvivor group was significantly higher than that of the survivor group. The multiple logistic regression analysis suggested that the norepinephrine dose and PI were the most independent risk and protective factors, respectively, for intensive care unit mortality. The area under the curve for a poor prognosis was 0.847 (95% confidence interval, 0.782-0.912). The optimal cutoff value of the PI at T24 to predict intensive care unit mortality was 0.6, with a sensitivity of 77.1% and a specificity of 80%. Based on this optimal cutoff value, we divided patients into groups with PI ≥ 0.6 (n = 125) and PI < 0.6 (n = 59). The lactate level of the PI < 0.6 group was higher than that of the PI ≥ 0.6 group at T24. The PI < 0.6 group showed a significantly higher sublingual dose of norepinephrine indicators than the PI ≥ 0.6 group. The PI showed a strong negative correlation with norepinephrine dose (r = -0.344, P < .001) and lactate (r = -0.291, P < .001). Conclusions: A higher PI is a protective factor, and a higher dose of norepinephrine is a risk factor for the prognosis of critically ill patients with septic shock. A lower PI was associated with a higher dose of norepinephrine.

Validation of NEWS2, SIRS, and qSOFA in Postoperative Cardiac Patients: A Retrospective Cohort Study.

INTRODUCTION: The 'quick Sepsis Related Organ Failure Assessment' (qSOFA), 'Systemic Inflammatory Response Syndrome' (SIRS), and 'National Early Warning Score' 2 (NEWS2) scores are yet to be comparatively validated in ward-based cardiac surgical patients despite widespread routine use in clinical practice. We sought to assess the predictive validity of NEWS, SIRS, and qSOFA in identifying postoperative, ward-level cardiac surgical patients at risk of poor short-term mortality. METHODS: All adult patients who underwent cardiac surgery at a single tertiary center between November 2014 and October 2017 were identified. Data for bedside observations, hematological results, and microbiology requests were obtained from electronic health records. Survival data were acquired from a national registry. The primary outcome was the discriminatory ability, measured by the area under the receiver operating characteristic (AUROC), of each score for in-hospital mortality. RESULTS: One thousand five hundred forty three (male n = 1101, 71%) patients were included. Overall in-hospital mortality was 2.4%. There was no significant difference in discriminatory ability of NEWS (AUROC 0.5060), SIRS (AUROC 0.4874), and qSOFA (AUROC 0.5139) for in-hospital mortality (P = 0.881). Sensitivity for this outcome was ubiquitously low (13.51-40.54%). CONCLUSIONS: Current illness-severity scores show a low discriminatory ability for in-hospital mortality in ward-based cardiac surgical patients. Caution should be used in the application of these prognostic screening tools for early detection of poor outcomes in this population.

Invasive Streptococcus agalactiae (group B streptococcus) infection with toxic shock-like syndrome: A report of a fatal non-pregnant case and a review of the literature.

Streptococcus agalactiae (group B streptococcus; GBS) is a Gram-positive coccus. It has emerged as a cause of significant infections in non-pregnant adults, particularly neonates and individuals aged 65 years or older, which can lead to fatal outcomes. Streptococcal toxic shock-like syndrome (STSS) is an acute illness, which is mainly caused by exotoxin-producing strains of Streptococcus pyogenes and may result in death. In this report, we present a fatal non-pregnant case of STSS induced by GBS in a 45-year-old healthy female. The patient presented with fever, polyarthralgia, myalgia, and skin erythema. Matrix Assisted Laser Desorption/Ionization‒Time of Flight Mass Spectrometry (MALDI-TOF-MS) and PCR identified GBS in colonies from her blood and urine cultures, and she was diagnosed with septicemia and STSS. On the sixth day of her illness, she died from acute respiratory distress syndrome and multiple organ dysfunction syndrome. Whole-genome sequencing revealed the presence of several virulence genes in the genome of the GBS strain detected in the blood cultures, which may have contributed to the development of STSS and the patient's death.

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.

Dementia, stroke, age, use of medical devices and antipsychotic drugs may increase the risk of nosocomial infections among elderly patients hospitalized at Neurology Clinics.

Healthcare-acquired infections (HCAI) represent a major health problem worldwide. Stroke and dementia are considered risk factors for HCAI. Preliminary data suggest that use of antipsychotic drugs also increase the risk for HCAI. Here, we performed a retrospective study aimed at investigating the major risk and protective factors for HCAI in a cohort of elderly subjects hospitalized at an Italian tertiary Neurology Clinics. We included all patients with age ≥ 65 years hospitalized at Neurology Clinics of National Institute on Ageing, Ancona, Italy from 1st January 2018 to 31st December 2021. For each patient, the following data were collected: age, sex, use of medical devices, comorbidities, use of antipsychotic medications, development of HCAI. We included 1543 patients (41.4% males; median age 85 years [80-89]). According to multivariable analysis, age, stroke, duration of urinary catheter placement (for all p < 0.001) and midline placement (p = 0.035) resulted to be risk factors for HCAI, Diabetes resulted to be a protective factor for pneumonia (p = 0.041), while dementia and nasogastric tube were risks factor for this condition (p = 0.022 and p < 0.001, respectively). Urinary catheter was a risk factor for urinary tract infections (p < 0.001). Duration of placement of vascular catheters and use of antipsychotic drugs resulted to significantly increase the risk for bloodstream infections. Stroke, age and use of medical devices were confirmed to be risk factors for HCAI. Antipsychotic drugs resulted to increase risk for bloodstream infections. Further prospective studies will be needed to confirm these findings.