Clinician perspectives on how situational context and augmented intelligence design features impact perceived usefulness of sepsis prediction scores embedded within a simulated electronic health record.

OBJECTIVE: Obtain clinicians' perspectives on early warning scores (EWS) use within context of clinical cases. MATERIAL AND METHODS: We developed cases mimicking sepsis situations. De-identified data, synthesized physician notes, and EWS representing deterioration risk were displayed in a simulated EHR for analysis. Twelve clinicians participated in semi-structured interviews to ascertain perspectives across four domains: (1) Familiarity with and understanding of artificial intelligence (AI), prediction models and risk scores; (2) Clinical reasoning processes; (3) Impression and response to EWS; and (4) Interface design. Transcripts were coded and analyzed using content and thematic analysis. RESULTS: Analysis revealed clinicians have experience but limited AI and prediction/risk modeling understanding. Case assessments were primarily based on clinical data. EWS went unmentioned during initial case analysis; although when prompted to comment on it, they discussed it in subsequent cases. Clinicians were unsure how to interpret or apply the EWS, and desired evidence on its derivation and validation. Design recommendations centered around EWS display in multi-patient lists for triage, and EWS trends within the patient record. Themes included a "Trust but Verify" approach to AI and early warning information, dichotomy that EWS is helpful for triage yet has disproportional signal-to-high noise ratio, and action driven by clinical judgment, not the EWS. CONCLUSIONS: Clinicians were unsure of how to apply EWS, acted on clinical data, desired score composition and validation information, and felt EWS was most useful when embedded in multi-patient views. Systems providing interactive visualization may facilitate EWS transparency and increase confidence in AI-generated information.

Efficacy of dietary supplements on mortality and clinical outcomes in adults with sepsis and septic shock: A systematic review and network meta-analysis.

AIM: The aim of this network meta-analysis (NMA) was to investigate the effects of different dietary supplements on the mortality and clinical status of adults with sepsis. METHODS: We searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials until February 2023. The inclusion criteria were: 1) randomized controlled trials (RCT)s; 2) adults suffering sepsis or septic shock; 3) evaluation of short- or long-mortality; and 4) publications between 1994 and 2023. The general information of studies and details of interventions were extracted. The primary outcome was short-term mortality (<90 days), and the secondary outcomes were long-term mortality (≥90 days), length of ICU and hospital stays, and duration of mechanical ventilation (MV). The risk of bias of RCTs was assessed using the Cochrane risk of bias tool 2 (ROB2). A random effect NMA was performed to rank the effect of each intervention using a frequentist approach. RESULTS: Finally, 56 RCTs with 5957 participants met the criteria. Approximately, one-third of RCTs were low risk of bias. NMA analysis revealed that there was no treatment more effective in short- or long-term mortality than control or other interventions, except for magnesium (RR: 0.33, 95% CI: 0.14, 0.79; GRADE = low) and vitamin C (RR: 0.81, 95% CI: 0.67, 0.99; low certainty evidence), which had beneficial effects on short-term mortality. Moreover, eicosapentaenoic acid, gamma-linolenic acid, and antioxidants (EPA + GLA + AOs) combination was the most effective, and magnesium, vitamin D and vitamin C were the other effective approaches in terms of duration of MV, and ICU length of stay. There was no beneficial dietary supplement for hospital stay in these patients. CONCLUSIONS: In septic patients, none of the dietary supplements had a substantial effect on mortality except for magnesium and vitamin C, which were linked to lower short-term mortality with low certainty of evidence. Further investigation into high-quality studies with the use of dietary supplements for sepsis should be highly discouraged.

Long-term efficacy of liposomal nanocarriers of preassembled glycocalyx in restoring cerebral endothelial glycocalyx in sepsis.

The endothelial glycocalyx (EG) undergoes early degradation in sepsis. Our recent work introduced a novel therapeutic approach involving liposomal nanocarriers of preassembled glycocalyx (LNPG) to restore EG in lipopolysaccharide (LPS)-induced sepsis model of mice. While short-term effects were promising, this study focuses on the long-term impact of LNPG on mouse cerebral microcirculation. Utilizing cranial window, we assessed the stability of vascular density (VD) and perfused boundary region (PBR), an index of EG thickness, over a five-day period in normal control mice. In septic groups (LPS, LPS + 1-dose LNPG, and LPS + 2-dose LNPG), the exposure of mice to LPS significantly reduced VD and increased PBR within 3 h. Without LNPG treatment, PBR returned to the normal control level by endogenous processes at 48 h, associated with the recovery of VD to the baseline level at 72 h. However, mice receiving LNPG treatment significantly reduced the increment of PBR at 3 h. The therapeutic effect of 1-dose LNPG persisted for 6 h while the 2-dose LNPG treatment further reduced PBR and significantly increased VD at 12 h compared to LPS group. This study provides valuable insights into the potential therapeutic benefits of LNPG in mitigating EG degradation in sepsis.

REPAIRS Delphi: A UK and Ireland Consensus Statement on the Management of Infected Arterial Pseudoaneurysms Secondary to Groin Injecting Drug Use.

OBJECTIVE: Consensus guidelines on the optimal management of infected arterial pseudoaneurysms secondary to groin injecting drug use are lacking. This pathology is a problem in the UK and globally, and operative management options remain contentious. This study was designed to establish consensus to promote better management of these patients, drawing on the expert experience of those in a location with a high prevalence of illicit drug use. METHODS: A three round modified Delphi was undertaken, systematically surveying consultant vascular surgeons in the UK and Ireland using an online platform. Seventy five vascular surgery units were invited to participate, with one consultant providing the unit consensus practice. Round one responses were thematically analysed to generate statements for round two. These statements were evaluated by participants using a five point Likert scale. Consensus was achieved at a threshold of 70% or more agreement or disagreement. Those statements not reaching consensus were assessed and modified for round three. The results of the Delphi process constituted the consensus statement. RESULTS: Round one received 64 (86%) responses, round two 59 (79%) responses, and round three 62 (83%) responses; 73 out of 75 (97%) units contributed. Round two comprised 150 statements and round three 24 statements. Ninety one statements achieved consensus agreement and 15 consensus disagreement. The Delphi statements covered sequential management of these patients from diagnosis and imaging, antibiotics and microbiology, surgical approach, wound management, follow up, and additional considerations. Pre-operative imaging achieved consensus agreement (97%), with computerised tomography angiogram being the modality of choice (97%). Ligation and debridement without arterial reconstruction was the preferred approach at initial surgical intervention (89%). Multidisciplinary management, ensuring holistic care and access to substance use services, also gained consensus agreement. CONCLUSION: This comprehensive consensus statement provides a strong insight into the standard of care for these patients.

Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications.

Sepsis, a prevalent critical condition in clinics, continues to be the leading cause of death from infections and a global healthcare issue. Among the organs susceptible to the harmful effects of sepsis, the lungs are notably the most frequently affected. Consequently, patients with sepsis are predisposed to developing acute lung injury (ALI), and in severe cases, acute respiratory distress syndrome (ARDS). Nevertheless, the precise mechanisms associated with the onset of ALI/ARDS remain elusive. In recent years, there has been a growing emphasis on the role of endothelial cells (ECs), a cell type integral to lung barrier function, and their interactions with various stromal cells in sepsis-induced ALI/ARDS. In this comprehensive review, we summarize the involvement of endothelial cells and their intricate interplay with immune cells and stromal cells, including pulmonary epithelial cells and fibroblasts, in the pathogenesis of sepsis-induced ALI/ARDS, with particular emphasis placed on discussing the several pivotal pathways implicated in this process. Furthermore, we discuss the potential therapeutic interventions for modulating the functions of endothelial cells, their interactions with immune cells and stromal cells, and relevant pathways associated with ALI/ARDS to present a potential therapeutic strategy for managing sepsis and sepsis-induced ALI/ARDS.

IL-1ß, the first piece to the puzzle of sepsis-related cognitive impairment?

Sepsis is a leading cause of death resulting from an uncontrolled inflammatory response to an infectious agent. Multiple organ injuries, including brain injuries, are common in sepsis. The underlying mechanism of sepsis-associated encephalopathy (SAE), which is associated with neuroinflammation, is not yet fully understood. Recent studies suggest that the release of interleukin-1ß (IL-1ß) following activation of microglial cells plays a crucial role in the development of long-lasting neuroinflammation after the initial sepsis episode. This review provides a comprehensive analysis of the recent literature on the molecular signaling pathways involved in microglial cell activation and interleukin-1ß release. It also explores the physiological and pathophysiological role of IL-1ß in cognitive function, with a particular focus on its contribution to long-lasting neuroinflammation after sepsis. The findings from this review may assist healthcare providers in developing novel interventions against SAE.

4-phenylbutyric acid improves sepsis-induced cardiac dysfunction by modulating amino acid metabolism and lipid metabolism via Comt/Ptgs2/Ppara.

INTRODUCTION: Cardiac dysfunction after sepsis the most common and severe sepsis-related organ failure. The severity of cardiac damage in sepsis patients was positively associated to mortality. It is important to look for drugs targeting sepsis-induced cardiac damage. Our previous studies found that 4-phenylbutyric acid (PBA) was beneficial to septic shock by improving cardiovascular function and survival, while the specific mechanism is unclear. OBJECTIVES: We aimed to explore the specific mechanism and PBA for protecting cardiac function in sepsis. METHODS: The cecal ligation and puncture-induced septic shock models were used to observe the therapeutic effects of PBA on myocardial contractility and the serum levels of cardiac troponin-T. The mechanisms of PBA against sepsis were explored by metabolomics and network pharmacology. RESULTS: The results showed that PBA alleviated the sepsis-induced cardiac damage. The metabolomics results showed that there were 28 metabolites involving in the therapeutic effects of PBA against sepsis. According to network pharmacology, 11 hub genes were found that were involved in lipid metabolism and amino acid transport following PBA treatment. The further integrated analysis focused on 7 key targets, including Comt, Slc6a4, Maoa, Ppara, Pparg, Ptgs2 and Trpv1, as well as their core metabolites and pathways. In an in vitro assay, PBA effectively inhibited sepsis-induced reductions in Comt, Ptgs2 and Ppara after sepsis. CONCLUSIONS: PBA protects sepsis-induced cardiac injury by targeting Comt/Ptgs2/Ppara, which regulates amino acid metabolism and lipid metabolism. The study reveals the complicated mechanisms of PBA against sepsis.

Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling.

Pien Tze Huang (PZH), a class I nationally protected traditional Chinese medicine (TCM), has been used to treat liver diseases such as hepatitis; however, the effect of PZH on the progression of sepsis is unknown. Here, we reported that PZH attenuated lipopolysaccharide (LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalling. Mechanistically, PZH stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation to induce the expression of A20, which could inhibit the activation of NF-κB and MAPK signalling. Knockdown of the bile acid (BA) receptor G protein-coupled bile acid receptor 1 (TGR5) in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction, as well as the LPS-induced inflammatory response, suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5. Consistently, deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20, the activation of NF-κB and MAPK signalling, and the production of proinflammatory cytokines, whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines. Overall, our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia.

BACKGROUND: Neonatal sepsis, a formidable threat to newborns, is a leading cause of neonatal mortality, with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning. Pneumonia, a prevalent sepsis presentation, poses a significant risk, especially during the neonatal phase when lung defenses are compromised. Accurate diagnosis of pneumonia is imperative for timely and effective interventions. Saliva, a minimally invasive diagnostic medium, holds great promise for evaluating infections, especially in infants. AIM: To investigate the potential of serum C-reactive protein (CRP), salivary CRP (sCRP), and mean platelet volume (MPV) as diagnostic markers for late-onset neonatal pneumonia (LONP). METHODS: Eighty full-term neonates were systematically examined, considering anthropometric measurements, clinical manifestations, radiology findings, and essential biomarkers, including serum CRP, sCRP, and MPV. RESULTS: The study reveals noteworthy distinctions in serum CRP levels, MPV, and the serum CRP/MPV ratio between neonates with LONP and healthy controls. MPV exhibited a robust discriminatory ability [area under the curve (AUC) = 0.87] with high sensitivity and specificity at a cutoff value of > 8.8. Correlations between serum CRP, sCRP, and MPV were also identified. Notably, sCRP demonstrated excellent predictive value for serum CRP levels (AUC = 0.89), underscoring its potential as a diagnostic tool. CONCLUSION: This study underscores the diagnostic promise of salivary and serum biomarkers, specifically MPV and CRP, in identifying and predicting LONP among neonates. These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.

P75NTR+CD64+ neutrophils promote sepsis-induced acute lung injury.

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

Predictive performance of NEWS and qSOFA in immunocompromised sepsis patients at the emergency department.

PURPOSE: Sepsis has a high incidence and a poor prognosis. Early recognition is important to facilitate timely initiation of adequate care. Sepsis screening tools, such as the (quick) Sequential Organ Failure Assessment ((q)SOFA) and National Early Warning Score (NEWS), could help recognize sepsis. These tools have been validated in a general immunocompetent population, while their performance in immunocompromised patients, who are particularly at risk of sepsis development, remains unknown. METHODS: This study is a post hoc analysis of a prospective observational study performed at the emergency department. Inclusion criteria were age ≥ 18 years with a suspected infection, while ≥ two qSOFA and/or SOFA criteria were used to classify patients as having suspected sepsis. The primary outcome was in-hospital mortality. RESULTS: 1516 patients, of which 40.5% used one or more immunosuppressives, were included. NEWS had a higher prognostic accuracy as compared to qSOFA for predicting poor outcome among immunocompromised sepsis patients. Of all tested immunosuppressives, high-dose glucocorticoid therapy was associated with a threefold increased risk of both in-hospital and 28-day mortality. CONCLUSION: In contrast to NEWS, qSOFA underestimates the risk of adverse outcome in patients using high-dose glucocorticoids. As a clinical consequence, to adequately assess the severity of illness among immunocompromised patients, health care professionals should best use the NEWS.

CD8+ T cells are necessary for improved sepsis survival induced by CD28 agonism in immunologically experienced mice.

Introduction: A hallmark of T cell dysregulation during sepsis is the downregulation of costimulatory molecules. CD28 is one of T cell costimulatory molecules significantly altered on memory T cells during sepsis. We recently showed that treatment with a αCD28 agonist in septic immunologically experienced mice led to improved survival. Therefore, here we aimed to identify the cell subset(s) necessary for the survival benefit observed in the context of CD28 agonism, and to further investigate the mechanism by which CD28 agonism improves sepsis survival in immunologically experienced mice. Methods: Mice received specific pathogen inoculation to generate memory T cell populations similar in frequency to that of adult humans. Once these infections were cleared and the T cell response had transitioned to the memory phase, animals were rendered septic via cecal ligation and puncture in the presence or absence of an agonistic anti-CD28 mAb. Results: Results demonstrated that CD8+ T cells, and not bulk CD4+ T cells or CD25+ regulatory T cells, were necessary for the survival benefit observed in CD28 agonist-treated septic immunologically experienced mice. Upon examination of these CD8+ T cells, we found that CD28 agonism in septic immunologically experienced mice was associated with an increase in Foxp3+ CD8+ T cells as compared to vehicle-treated controls. When CD8+ T cells were depleted in septic immunologically experienced mice in the setting of CD28 agonism, a significant increase in levels of inflammatory cytokines in the blood was observed. Discussion: Taken together, these results indicate that CD28 agonism in immunologically experienced mice effectively suppresses inflammation via a CD8+-dependent mechanism to decrease mortality during sepsis.

Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study.

OBJECTIVES: The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. DESIGN: Prospective randomized large-animal peritoneal septic shock experiment. SETTING: Laboratory investigation. SUBJECTS: Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 µg/kg/min (LATE, n = 8). INTERVENTIONS: Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. CONCLUSIONS: In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.

Applications of peptides in nanosystems for diagnosing and managing bacterial sepsis.

Sepsis represents a critical medical condition stemming from an imbalanced host immune response to infections, which is linked to a significant burden of disease. Despite substantial efforts in laboratory and clinical research, sepsis remains a prominent contributor to mortality worldwide. Nanotechnology presents innovative opportunities for the advancement of sepsis diagnosis and treatment. Due to their unique properties, including diversity, ease of synthesis, biocompatibility, high specificity, and excellent pharmacological efficacy, peptides hold great potential as part of nanotechnology approaches against sepsis. Herein, we present a comprehensive and up-to-date review of the applications of peptides in nanosystems for combating sepsis, with the potential to expedite diagnosis and enhance management outcomes. Firstly, sepsis pathophysiology, antisepsis drug targets, current modalities in management and diagnosis with their limitations, and the potential of peptides to advance the diagnosis and management of sepsis have been adequately addressed. The applications have been organized into diagnostic or managing applications, with the last one being further sub-organized into nano-delivered bioactive peptides with antimicrobial or anti-inflammatory activity, peptides as targeting moieties on the surface of nanosystems against sepsis, and peptides as nanocarriers for antisepsis agents. The studies have been grouped thematically and discussed, emphasizing the constructed nanosystem, physicochemical properties, and peptide-imparted enhancement in diagnostic and therapeutic efficacy. The strengths, limitations, and research gaps in each section have been elaborated. Finally, current challenges and potential future paths to enhance the use of peptides in nanosystems for combating sepsis have been deliberately spotlighted. This review reaffirms peptides' potential as promising biomaterials within nanotechnology strategies aimed at improving sepsis diagnosis and management.

MicroRNA-1258 suppresses oxidative stress and inflammation in septic acute lung injury through the Pknox1-regulated TGF-ß1/SMAD3 cascade.

AIM: The study was to clarify the mechanism of miR-1258 targeting Prep1 (pKnox1) to control Transforming Growth Factor ß1 (TGF-ß1)/SMAD3 pathway in septic Acute Lung Injury (ALI)-induced oxidative stress and inflammation. METHODS: BEAS-2B cells and C57BL/6 mice were used to make in vitro and in vivo septic ALI models, respectively. miR-1258 expression was checked by RT-qPCR. After transfection in the in vitro experimental model, inflammation, oxidative stress, viability, and apoptosis were observed through ELISA, MTT, and flow cytometry. RESULTS: In the in vivo model after miR-1258 overexpression treatment, inflammation, oxidative stress, and lung injury were further investigated. The targeting relationship between miR-1258 and Pknox1 was tested. Low miR-1258 was expressed in septic ALI patients, LPS-treated BEAS-2B cells, and mice. Upregulated miR-1258 prevented inflammation, oxidative stress, and apoptosis but enhanced the viability of LPS-treated BEAS-2B cells. The impact of upregulated miR-1258 on LPS-treated BEAS-2B cells was mitigated by inhibiting Pknox1 expression. MiR-1258 overexpression had the alleviating effects on inflammation, oxidative stress, and lung injury of LPS-injured mice through suppressing Pknox1 expression and TGF-ß1/SMAD3 cascade activation. CONCLUSIONS: The study concludes that miR-1258 suppresses oxidative stress and inflammation in septic ALI through the Pknox1-regulated TGF-ß1/SMAD3 cascade.

Determinants of puerperal sepsis among postpartum women at a tertiary care hospital in Ethiopia: an unmatched case-control study.

BACKGROUND: Puerperal sepsis, is a significant factor in maternal morbidity and mortality, especially in regions with lower income levels where maternal mortality rates are highest. However, it can be largely avoided if detected in time. Recognizing and dealing with the root causes early is essential in addressing this problem. Therefore, this study aimed to identify the determinants of puerperal sepsis among postpartum women at a tertiary care hospital in Ethiopia. METHODS: An institutional-based unmatched case-control study was conducted among 266 postpartum women (88 cases and 178 controls) from October 1, 2023 to November 30, 2023. For each case, two controls were chosen using a systematic random sampling approach. Data were collected using an interviewer-administered, structured questionnaire and medical record review. The collected data were entered into Epi Info version 7.2 and analyzed using SPSS version 27. Binary logistic regression analysis was used to model the association between puerperal sepsis and independent variables. variables that had a crude association in the bivariable analysis (p < 0.25) were entered and analyzed by a multivariable binary logistic regression model to identify statistically significant factors. In the final model, Adjusted odds ratios with their 95% confidence intervals were calculated to determine the strength of the association. Statistical significance was declared at p < 0.05. RESULT: Rural residence (AOR = 6.9; 95% CI:2.77-17.10), having no formal education (AOR = 3.8; 95% CI: 2.55, 10.76), cesarean section delivery (AOR: 5.1; 95% CI: 1.30, 11.00) and complication during pregnancy (AOR: 4.6, 95% CI: 1.96, 11.10) were independent determinants of puerperal sepsis. CONCLUSION: Place of residence, maternal education level, mode of delivery, and complication during pregnancy were determinants of puerperal sepsis. It is crucial to implement education and awareness initiatives aimed at mothers, ensure universal access to healthcare services, advocate for evidence-based delivery protocols, and conduct comprehensive antenatal screenings.

The Relationship Between Blood Culture, C-reactive Protein, and Neonatal Sepsis: A Cross-Sectional Study.

Background Sepsis is one of the most common causes of morbidity and mortality in newborns. Diagnosis of neonatal sepsis may be difficult because the clinical presentations are often nonspecific. Neonatal sepsis may have an early onset (zero to three days) or a late onset (four days or later). Onset is most rapid in premature neonates. In this study, we aimed to assess the correlation between positive cultures, high C-reactive protein (CRP) levels, and the diagnosis of neonatal sepsis. Methodology This descriptive, prospective, cross-sectional study was undertaken over four months starting from December 15, 2019, to April 15, 2020, in Atbara Teaching Hospital, Sudan. Data were collected from 71 patients. CRP levels were measured, and blood cultures were performed. Results High CRP level >10 mg/L was seen in patients having positive blood culture (55.3%), mainly in preterm babies (CRP >10 mg/dL (61.1%), positive culture (55.6%)) and very low birth weight babies (CRP >10 mg/dL (83.3%) and positive culture (67%)). Conclusions Our findings suggest that Klebsiella is an important cause of neonatal sepsis. CRP was positive in babies mainly with proven sepsis. There is a high correlation between CRP and blood culture in patients with neonatal sepsis which may give access to remodeling the prioritization of the management options in the clinical setting.

Evaluation of the efficacy of silymarin and dexmedetomidine on kidney and lung tissue in the treatment of sepsis in rats with cecal perforation.

Sepsis is a systemic inflammatory response syndrome that develops in the host against microorganisms. This response develops away from the primary infection site and results in end-organ damage. The present study aimed to investigate the protective and therapeutic effects on lung and kidney tissue of silymarin (S) and dexmedetomidine (DEX) applied 1 h before and after sepsis induced by the cecal ligation and puncture (CLP) method in rats. A total of 62 rats was randomly divided into eight groups: i) Control (n=6); ii) cecal perforation (CLP; n=8); iii) S + CLP (n=8; S + CLP; S administered 1 h before CPL); iv) CLP + S (n=8; S administered 1 h after CLP); v) DEX + CLP (n=8; D + CLP; DEX administered 1 h before CLP); vi) CLP + D (n=8; DEX administered 1 h after CLP); vii) SD + CLP (n=8; S and DEX administered 1 h before CLP) and viii) CLP + SD (n=8; S and DEX administered 1 h after CLP). After the cecum filled with stool, it was tied with 3/0 silk under the ileocecal valve and the anterior surface of the cecum was punctured twice with an 18-gauge needle. A total of 100 mg/kg silymarin and 100 µg/kg DEX were administered intraperitoneally to the treatment groups. Lung and kidney tissue samples were collected to evaluate biochemical and histopathological parameters. In the histopathological examination, all parameters indicating kidney injury; interstitial edema, peritubular capillary dilatation, vacuolization, ablation of tubular epithelium from the basement membrane, loss of brush border in the proximal tubule epithelium, cell swelling and nuclear defragmentation; were increased in the CLP compared with the control group. Silymarin administration increased kidney damage, including ablation of tubular epithelium from the basement membrane, compared with that in the CLP group. DEX significantly reduced kidney damage compared with the CLP and silymarin groups. The co-administration of DEX + silymarin decreased kidney damage, although it was not as effective as DEX-alone. To conclude, intraperitoneal DEX ameliorated injury in CLP rats. DEX + silymarin partially ameliorated injury but silymarin administration increased damage. As a result, silymarin has a negative effects with this dosage and DEX has a protective effect. In the present study, it was determined that using the two drugs together had a greater therapeutic effect than silymarin and no differences in the effects were not observed any when the application times of the agents were changed.

Clinical image of sepsis-associated encephalopathy midst E. coli urosepsis: Emergency department database study.

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, which, if untreated, leads to multi-organ failure. One of the severe possible complications is sepsis associated encephalopathy (SAE), a neurological dysfunction occurring secondary to a severe inflammatory response. It manifests as acute cognitive dysfunction and sudden-onset dysfunctions in mental state. Uropathogenic Escherichia coli is the most common pathogen causing bacteremia, responsible for 80% of uncomplicated outpatient urinary tract infections and 40% of nosocomial infections. The study aimed to assess the difference in the severity and the course of urosepsis caused by E. coli in patients with and without septic encephalopathy. Materials and methods: This study presents a retrospective analysis of the population of urosepsis patients admitted to the Emergency Department between September 2019 and June 2022. Inflammatory parameters, urinalysis and blood cultures were performed, along with a clinical evaluation of sepsis severity and encephalopathy. The patients were then stratified into SAE and non-SAE groups based on neurological manifestations and compared according to the collected data. Results: A total of 199 septic patients were included in the study. E. coli-induced urosepsis was diagnosed in 84 patients. In this group, SAE was diagnosed in 31 (36.9%) patients (33.3% in males, 40.5% females). Patients with SAE were found to be hypotensive (p < 0,005), with a higher respiratory rate (p < 0,017) resulting in a higher mortality rate (p = 0.002) compared to non-SAE septic patients. The APACHE II score was an independent risk factor associated with a higher mortality rate. Biochemical parameters between the groups did not show any statistical importance related to the severity of urosepsis. Conclusions: The severity of urosepsis and risk of SAE development increase according to the clinical condition and underlying comorbidities. Urosepsis patients with SAE are at a higher risk of death. Patients should undergo more careful screening for the presence of SAE on admission, and more intense monitoring and treatment should be provided for patients with SAE. This study indicates the need to develop projects aiming to further investigate neuroprotective interventions in sepsis.

Cardiac index and heart rate as prognostic indicators for mortality in septic shock: A retrospective cohort study from the MIMIC-IV database.

Background: Septic shock is a life-threatening condition that can lead to organ dysfunction and death. In the ICU, monitoring of cardiac index (CI) and heart rate (HR) is commonly used to guide management and predict outcomes in septic shock patients. However, there is a lack of research on the association between CI and HR and the risk of mortality in this patient population. Therefore, the aim of this study was to investigate the relationship between different levels of CI and HR and mortality in septic shock patients. Methods: Data analysis was obtained from the MIMIC-IV version 2.0 database. Sepsis and septic shock were primarily defined by sepsis-3, the third international consensus on sepsis and septic shock. CI was computed using cardiac output (CO) and body surface area (BSA). To evaluate the incidence of CI with respect to each endpoint (7-, 14-, 21-, and 28-day mortality), a restricted cubic spline curve function (RCS) was used. The optimal cutoff value for predicted mortality was determined using the Youden index. Analyses of KM curves, cox regression, and logistic regression were conducted separately to determine the relationship between various CI and HR and 28-day mortality. Results: This study included 1498 patients with septic shock. A U-shaped relationship between CI levels and risk of mortality in septic shock was found by RCS analysis (p < 0.001). CI levels within the intermediate range of 1.85-2.8 L/min/m2 were associated with a mortality hazard ratio (HR) < 1. In contrast, low CI (HR = 1.87 95% CI: 1.01-3.49) and high CI (HR = 1.93 95% CI: 1.26-2.97) had a significantly increased risk of mortality. The AUC for heart rate prediction of mortality by Youden index analysis was 0.70 95%CI:0.64-0.76 with a cut-off value of 93.63 bpm. According to the characteristics of HR and CI, patients were divided into six subgroups HR↓+CI intermediate group (n = 772), HR↓+CI↓ group (n = 126), HR↓+CI↑ group (n = 294), HR↑+CI intermediate group (n = 132), HR↑+CI↓ group (n = 24), and HR↑+CI↑ group (n = 150). The KM curves, COX regression, and logistic regression analysis showed that the survival rates the of HR↓+CI intermediate group, HR↓+CI↓ group, and HR↓+CI↑ were higher than the other groups. The risk factors of HR↑+CI intermediate group, HR↑+CI↓, and HR↑+CI↑ with ICU 28-day mortality were HR = 2.91 (95% CI: 1.39-5.97), HR = 3.67 (95% CI: 1.39-11.63), and HR = 5.77 (95% CI: 2.98-11.28), respectively. Conclusion: Our retrospective study shows that monitoring cardiac index and heart rate in patients with septic shock may help predict the organismal response and hemodynamic consequences, as well as the prognosis. Thus, healthcare providers should carefully monitor changes in these parameters in septic shock patients transferred to the ICU for treatment.