Criteria For Sepsis Research Articles

Phoenix criteria for sepsis: are these enough to guide a clinician?

In conclusion, Phoenix criteria are a step in the right direction to define life-threatening organ dysfunction in sepsis, but clinicians need to be mindful that diagnosis/treatment of less severe sepsis should not be delayed if these criteria are not met. Therefore, local early detection and management tools for sepsis should be followed. • There has always been a quest for a definition for pediatric sepsis. There are limitations to the previous pediatric sepsis criteria which were published in 2005 by the International Pediatric Sepsis Consensus Conference (IPSCC). IPSCC defines sepsis as a suspected or confirmed infection in the presence of systemic inflammatory response syndrome (SIRS). These new Phoenix Pediatric Sepsis (PPS) criteria for sepsis and septic shock are intended to identify children with life-threatening organ dysfunction due to infection, and the score was developed based on a very large pediatric dataset. • Though the intention of Phoenix criteria is to help identify children with life threatening organ dysfunction, unfortunately the crietria will miss signs of early sepis. In this manuscript, we point out some of the drawbacks of these criteria which need to be borne in mind while applying these criteria.

Characteristics, clinical care, and outcomes of sepsis among patients boarding in the emergency department.

Patients who first meet clinical criteria for sepsis while boarding in the emergency department (ED) may not receive optimal sepsis care. Assess the association between ED boarding status and sepsis quality of care and outcomes. We conducted a retrospective cohort study of adult patients admitted to a large academic hospital from July 2021 to October 2023 who had clinical features consistent with sepsis present while physically in the ED. We compared outcomes for patients who experienced time zero (T-0; the time clinical features of sepsis were first present) while boarding in the ED (physically in the ED but admitted to a different service) to those experiencing T-0 while still under the care of the ED provider team. We used logistic regression to estimate the association between ED boarding status at T-0 and compliance with the US Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock: Management Bundle (SEP-1) core measure, individual bundle element compliance, and hospital mortality adjusting for prespecified covariates. In a subgroup analysis among patients who had not already received antibiotics before T-0, we conducted a Cox proportional hazards model to estimate the association between boarding status on time-to-antibiotics. Among 4795 patients meeting a clinical definition of sepsis in the ED, 422 (8.8%) experienced T-0 as ED boarders. These patients were similar in age, sex, and comorbidities compared with patients experiencing T-0 while still under ED care. Fewer patients with T-0 as an ED boarder received SEP-1 compliant care (25% vs. 38%, p < .001), including a lower proportion of fluid resuscitation (15% vs. 26%, p = .004) and lactate assessment (62% vs. 94%, p < .001). Overall, more patients in the ED boarder group received antibiotics within 3 hours, but one-third of patients had already received antibiotics prior to T-0. Among patients who had not already received antibiotics prior to T-0, experiencing T-0 as an ED boarder was associated with a decreased likelihood of receiving antibiotics (hazard ratio [HR]: 0.67 [95% confidence interval [CI], 0.54-0.84]) and longer time to antibiotics from T-0 (142 min vs. 100 min, p = .007). Sepsis patients experiencing T-0 as a boarder in the ED have a lower likelihood of receiving SEP-1 compliant care compared to patients who experience T-0 while still under ED care.

Effect of heart rate control with ivabradine on hemodynamic in patients with sepsis: study protocol for a prospective, multicenter, randomized controlled trial

IntroductionSepsis, a life-threatening syndrome, is often accompanied by tachycardia in spite of hypovolemia and hypotension have been corrected. Recently, relevant studies have shown that sustained tachycardia in sepsis was related to high mortality, and appropriate control of heart rate (HR) could improve prognosis. Ivabradine reduces HR directly without a negative inotropic effect through inhibition of the If ionic current, which is different from the traditional rate control drug (beta-blockers).Methods and analysisThis is a prospective, multicenter, randomized, open label study designed to investigate the effect of heart rate control with ivabradine on hemodynamic in patients with sepsis. Our study will enroll 172 patients with sepsis as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria with sinus rate of 95 bpm or higher despite a hemodynamic optimization. Patients will be randomly assigned to standard treatment group (GS) or ivabradine group (GI, standard treatment for sepsis plus enteral ivabradine). Patients in GI will receive ivabradine to maintain HR between 70 and 94 bpm. The primary outcome is the difference of a reduction in HR below 95 bpm and the effect of ivabradine on hemodynamics between GI and GS group within the first 96 h after randomization. The secondary outcomes include organ function measures, the difference in SOFA score, incidence of adverse events, need for organ support, length of ICU stay, and 28-day overall mortality.DiscussionThere are limited studies on ivabradine to control heart rate in patients with sepsis. Our study aims to evaluate whether direct sinus node inhibition can improve hemodynamics, as well as its impact on organ function and prognosis in patients with sepsis, so as to provide evidence for the safe usage in clinical practice.Trial registrationClinicalTrials.gov NCT05882708. Registered on May 11, 2023, https://clinicaltrials.gov/ct2/show/NCT05882708.

Procalcitonin-Guided Management and Duration of Antibiotic Therapy in Critically Ill Cancer Patients With Sepsis (Pro-Can Study): A Randomized Controlled Trial.

To evaluate the effect of procalcitonin-guided management on the duration of antibiotic therapy in critically ill cancer patients with sepsis. Randomized, controlled, single-blinded trial. A comprehensive multidisciplinary cancer hospital in Jordan. Adults with cancer treated in the ICU who were started on antibiotics for suspected infection, met the SEPSIS-3 criteria, and were expected to stay in the ICU greater than or equal to 48 hours. Patients were randomized to the procalcitonin-guided or standard care (SC) arms. All patients had procalcitonin measured daily, up to 5 days or until ICU discharge or death. For the procalcitonin arm, a procalcitonin-guided algorithm was provided to guide antibiotic management, but clinicians were allowed to override the algorithm, if clinically indicated. In the SC arm, ICU clinicians were blinded to the procalcitonin levels. Primary outcome was time to antibiotic cessation. We also evaluated the number of antibiotic-free days at 28 days, hospital discharge, or death, whichever came first, and antibiotic defined daily doses (DDDs). We enrolled 77 patients in the procalcitonin arm and 76 in the SC arm. Mean age was 58 ± 14 (sd) years, 67% were males, 74% had solid tumors, and 13% were neutropenic. Median (interquartile range [IQR]) Sequential Organ Failure Assessment scores were 7 (6-10) and 7 (5-9) and procalcitonin concentrations (ng/mL) at baseline were 3.4 (0.8-16) and 3.4 (0.5-26), in the procalcitonin and SC arms, respectively. There was no difference in the median (IQR) time to antibiotic cessation in the procalcitonin and SC arms, 8 (4-11) and 8 (5-13), respectively (p = 0.463). Median (IQR) number of antibiotic-free days were 20 (17-24) and 20 (16-23), (p = 0.484) and total DDDs were 1541.4 and 2050.4 in the procalcitonin and SC arms, respectively. In critically ill cancer patients with sepsis, procalcitonin-guided management did not reduce the duration of antibiotic treatment.

Community-acquired sepsis in the medical intensive care unit – an experience from a lower-middle-income country

Objective: To determine microbiological pathogens and in-hospital mortality in patients admitted with community-acquired sepsis to the intensive care unit in a tertiary-care setting in a low- and middle-income country. Methods: The retrospective, observational study was conducted at the medical intensive care unit of a large tertiary care hospital in Karachi, and comprised data from January 1 to December 31, 2019, and comprised data of patients with community-acquired sepsis who were assessed using the Sepsis-3 criteria. Data was compared between survivors and non-survivors, and independent factors associated with escalation to a higher level of care were identified. Data was analysed using SPSS 23. Results: Of the 135 patients with mean age 49.8±18.0 years, 91(67.4%) were males and 44(32.6%) were females. The most common primary site of infection was the respiratory tract 63(46.7%). In-hospital mortality was noted in 52(38.5%) cases, while there were 83(61.5%) survivors. Serum levels of lactate and bicarbonate as well as urine output, fungal pathogens, septic shock and sequential organ failure were significantly associated with mortality (p&lt;0.05). Conclusions: Clinical and microbiological spectrum of community-acquired sepsis in a low- and middle-income country was found to be different from other regions of the world. Clinicians should keep these differences in mind while managing these critically ill patients. Key Words: Sepsis, Septic shock, Critical care, Drug resistance, Fungi.

Burns, Sepsis and Procalcitonin

The basis of the pathogenesis of burn disease is a systemic inflammatory response syndrome with episodes of bacteremia and the development of sepsis. An analysis of the literature showed that the existing clinical diagnostic scales for sepsis do not allow a confident diagnosis. The interest in changes in the concentration of procalcitonin in the blood serum is justified by the fact that this prohormone is one of the proinflammatory mediators, the concentration of which quickly increases during local and systemic bacterial and fungal infections. It seems important to consider the possibilities of various scales for determining the criteria for sepsis, analyze the values of procalcitonin and its monitoring for more effective diagnosis and procalcitonin-controlled antibiotic therapy in patients with burns.CONCLUSION. The problem of clinical diagnosis of sepsis in patients with burns has not yet been solved. Procalcitonin is an effective biomarker of bacterial infection, and its monitoring reflects the dynamics of the burn disease, predicts the outcome, indicates the effectiveness of antibiotic therapy and allows for its correction.

Infections Deaths in Acute Lymphoblastic Leukemia More Frequent in High Risk Leukemia

Abstract Background Acute lymphoblastic leukemia (ALL) in children currently has more than 90% survival in higher resource countries. However, in less resource countries, the survival rates are lower and infections are frequent causes. Risks for infections and poor outcomes vary during the chemotherapy phases. There is a paucity of data concerning the frequencies of the chemotherapy phase where the event is more probable. Our primary objective is to describe infections frequencies and outcomes of infection in children and also to look for association with risk factors. Methods Patients (Pts) were treated according to ALLIC-BFM-2010 protocol, a simpler branch of the BFM-AEIOP protocol and accrued prospectively. The main question is comparing outcomes of two randomizations using higher dose chemotherapy based on the leukemia risk. The risk severity was based on levels of measurable residual disease (&amp;lt;0.1, 0.1-10, &amp;gt;10 %,) and categorized in high (HR), intermediate (IR), and low (LR) risks. In SR Pts with B-cell-precursor ALL two doses of daunorubicin were prescribed in induction compared with four doses in all others. In consolidation, high-dose methotrexate was administered at 5g/m2 for SR/IR T-cell ALL and at 2g/m2 for SR/IR B-precursor-ALL. Consolidation for HR pts consisted of three intensive polychemotherapy blocks. Only T-ALL and HR pts age &amp;gt; 1 year received prophylactic cranial radiotherapy (12 Gy). Therapeutic cranial radiotherapy was reserved for pts with initial CNS. We performed a descriptive analysis, comparison of frequencies and proportions using Fisher test/Ji2. For time to event proportion we used Cox Analysis. Results 2232 de novo ALL pts were analyzed. Median age 5y (IQR 3-10), 56.3% were males. 2.1% had Down Syndrome; 24% categorized as HR, 56% as IR, and 20% as LR. The Immunophenotype analysis mostly B lineage (88.8%) and less T lineage (11.2%). The majority (96.7%) of pts achieved complete remission. Estimated mean time of survival was 8.8 years (ES 0.099, CI 95% 8.38-8.77) and the overall survival rate was 74 % (0.01). Trial wide, 518 (23.2%) pts died, 59 (2.6%) pts had criteria for clinical sepsis and 459 (20%) for not related sepsis causes. According to phase of the protocol, in less than one month from diagnosis, 21 events (35.6%) were observed; from 2-3 months 9 events (15.3%), from 4-6 months 6 events, (10.2%) and afterwards 23 events (39%) (p-value 0.000). No difference was found on T vs B immunophenotype, sex, age or Down syndrome. (P-value NS). However significant differences were found on risk groups 26/538 pts (4.8%) died on HR, 24/1248 (1.9%) in IR and 9/433 (2.1%) on standard risk (p-value 0.009). There was an association between the rates of sepsis and death on pts randomized to I and II protocols (p-value 0.007 and P-value 0.007). Conclusion In this large cohort of pts, we could demonstrate association between sepsis and mortality in those high-risk groups and in those pts randomized to higher chemotherapy doses. These results will allow to establish strategies to prevent infections or maximize medical interventions preventing poor infectious outcomes in high-risk groups.

Presepsin Does Not Predict Risk of Death in Sepsis Patients Admitted to the Intensive Care Unit: A Prospective Single-Center Study.

Background: Sepsis is defined as life-threatening organ dysfunction caused by an abnormal host response to infection. The study aimed to evaluate the utility of presepsin (P-SEP) in predicting the risk of death in patients with sepsis at the time of intensive care unit (ICU) admission. Methods: Adult patients were included in the study if they met SEPSIS-3 criteria at ICU admission. Demographic and clinical data were collected. The following inflammatory parameters were determined: C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and presepsin (P-SEP). Material was collected for microbiological testing depending on the suspected source of infection. The primary endpoint was patient death before ICU discharge. The secondary endpoint was a positive microbiological test result. Results: Eighty-six patients were included in the study. Thirty patients (35%) died before discharge from the ICU. There was no difference in P-SEP, CRP, PCT, and IL-6 values between patients who survived and those who died (p > 0.05 for all). P-SEP, CRP, PCT, and IL-6 were determined at ICU admission and did not accurately predict the risk of death in ROC curve analysis (p > 0.05 for all). Confirmation of the location of the focus of bacterial infection by microbiological testing was obtained in 43 (49%) patients. P-SEP, PCT, CRP, and IL-6 were significantly higher in patients with positive microbiological findings. Conclusions: In patients with suspected sepsis admitted to the Intensive Care Unit, presepsin does not accurately predict the risk of in-hospital death, but it can predict a positive microbiological culture.

Damage-associated molecular patterns in bacteraemic infection, including a comparative analysis with bacterial DNA, a pathogen-associated molecular pattern

Damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) are key triggers of inflammation in sepsis. However, they have rarely been studied simultaneously. Thus, in the present study of patients with bacteraemic infection, we aimed to study how DAMP dynamics are linked to disease severity and outcome and to compare diagnostic and prognostic properties of a DAMP and a previously analysed PAMP (16S rDNA). In a prospective study of adult patients hospitalized with culture-proven community-onset bacteraemic infection, caused by Streptococcus pneumonia (n = 30), Staphylococcus aureus (n = 27), or Escherichia coli (n = 26), dynamics of a PAMP, i.e. 16S rDNA, have previously been presented. For the present study, blood samples obtained on hospital days 1–2 (when blood culture was positive), 3–4, 7 ± 1, 14 ± 2, and 28 ± 4 were analysed for four different DAMPs, i.e., nuclear DNA (nDNA), mitochondrial DNA (mtDNA), heat shock protein 90 alpha (HSP90α), and extracellular high mobility group box 1 (HMGB1). Sepsis was defined according to the Sepsis-3 criteria. The study outcomes were sepsis at admission and negative outcome, defined as intensive care unit (ICU) admission and/or death within 60 days. Of 83 study patients, sepsis was noted in 41 patients (49%) and a negative outcome was noted in 17 patients (20%). nDNA had areas under the receiver operating characteristic (ROC) curves of 0.78 for sepsis and 0.76 for negative outcome, which were higher than those of the other DAMPs and additional biomarkers (CRP, IL-6, IL-8, and IL-10). The nDNA and positive 16S rDNA results on day 1–2 were correlated with each other (r = 0.68, p < 0.001). Multivariate analyses showed that high day 1–2 concentrations of both nDNA and 16S rDNA were independently associated with sepsis. In addition, high day 1–2 concentration of nDNA was independently associated with negative outcomes. While 16S rDNA dissipated from the circulation within days, nDNA concentrations remained elevated throughout the follow-up period in patients with negative outcome. In conclusion, nDNA outperformed the other DAMPs regarding sepsis detection and outcome prediction. Both nDNA (a DAMP) and 16S rDNA (a PAMP) were independently linked to sepsis; nDNA was also associated with negative outcomes and persisted elevated in such cases. This highlights nDNA as an interesting marker within sepsis pathogenesis and as a promising clinical biomarker, warranting further studies.

A-249 Monocyte distribution width (MDW) as a reliable diagnostic biomarker for sepsis in HIV-infected patients

Abstract Background Sepsis is the main cause of death in patients with acquired immunodeficiency syndrome (AIDS) and early diagnosis of sepsis in AIDS remains a significant challenge. Monocyte distribution width (MDW), as a new type of sepsis auxiliary diagnostic marker, has attracted widespread attention in the research and exploration of its clinical application. This study aims to evaluate the diagnostic efficacy of MDW in the occurrence of sepsis in HIV-infected patients and to construct a new clinical diagnostic model in combination MDW with other indicators. Methods A prospective cohort study was conducted at Shanghai Public Health Center with a total of 602 patients enrolled between December 2022 and August 2023. Sepsis-3 criteria were employed as the diagnostic standard for sepsis. MDW was measured at admission, using the hematology analyzer DxH900 (Beckman Coulter Inc.). Comprehensive clinical data, including complete blood counts and biochemical profiles, were collected. Enrolled participants received a follow-up about their survivals on day 30 and day 90. Five machine learning models were evaluated and compared to select the best performing model. Results The diagnostic performance of MDW for sepsis yielded an AUC of 0.818. With a cut-off value of 25.26, the sensitivity and specificity reached 0.822 and 0.754 respectively. The best performing variable among all five ML algorithms was Random Forest model. The top three variables with the highest importance ranking were platelet, albumin, and hemoglobin. Incorporating MDW and the top three laboratory indicators into a random forest model, the AUC value improved to 0.931. With a cut-off value of 0.5, the sensitivity was 1.00 while the specificity was 0.732. Conclusions MDW was an auxiliary diagnostic biomarker for sepsis in HIV-infected patients with reliable sensitivity and specificity. In combination MDW with other common laboratory biomarkers, a diagnostic model can be established to further improve the diagnostic efficiency of sepsis.

Divergent autoantibody and cytokine levels in COVID-19 sepsis patients influence survival.

Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID-19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID-19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung-associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel. We observed significantly increased levels of autoantibodies in 59% of the COVID-19-Sepsis group compared to 48% of the Sepsis group. Significant differences were identified between the groups for the levels of autoantibodies against gATPase. The cytokine levels of interferon (IFN)-λ1 and IP-10 were higher in the COVID-19-Sepsis groupcompared to the Sepsis group. Additional correlations between autoantibodies, cytokines and 30-day survival could be demonstrated, suggesting varied underlying pathological mechanisms. Elevated levels of cytokines and autoantibodies may serve as prognostic indicators for the survival probability of sepsis patients, highlighting the intricate relationship between immune responses and patient outcomes in the context of both sepsis and COVID-19.

The Role of Monocyte Distribution Width in the Early Prediction of Sepsis in Patients Undergoing Cardiovascular Surgery: A Cross-Sectional Study.

Background and Objectives: This is the first study to examine the role of monocyte distribution width (MDW) in predicting sepsis after cardiovascular surgery. Methods: This study included 43 consecutive patients who had undergone cardiovascular surgery between July 2021 and July 2022. All patients were examined at the following three time points (TPs): preoperative period (TP1), postoperative at 24 h (TP2), and discharge (TP3). SOFA score, leukocyte count, neutrophil-to-lymphocyte ratio (NLR), MDW, C-reactive protein (CRP), and procalcitonin (PCT) levels were tested at each TPs. The Sepsis-3 criteria were used to diagnose patients with sepsis. Results: The mean values of all variables (leukocyte count, NLR, MDW, CRP, and PCT levels) were significantly higher at TP2 and TP3 than at TP1 (p < 0.05). All these values were significantly higher at TP2 than at TP3 (p < 0.05). Patients with sepsis had significantly higher mean values for leukocyte count, NLR, MDW, CRP, and PCT levels than those without sepsis (p < 0.05). There was a significant correlation between MDW and inflammatory markers (CRP, PCT, and NLR) during the three time periods (p < 0.05). According to the ROC analysis, the optimal MDW cutoff value with the highest sensitivity and specificity for predicting sepsis in the postoperative period was 20.5. Conclusions: Our findings indicate that elevated MDW levels may be a valuable predictor of sepsis in patients following cardiovascular surgery.

Blood immune profiles reveal a CXCR3/CCR5 axis of dysregulation in early sepsis

Abstract We report on a pilot study exploring whether blood immune signatures can reveal early specific indicator profiles for patients meeting sepsis criteria upon hospital admission. We analysed samples of sepsis-suspected patients (N=20) and age-spanning healthy controls (N=12), using flow cytometry-based assays. We measured inflammatory markers from plasma fractions, and immunophenotyped freshly isolated unfixed PBMCs for leukocytes subsets representation and expression of activation markers, including chemokine receptors. We found that beside IL-6 and sCD14, CXCR3 ligands (CXCL9 and CXCL10) separated sepsis-suspected patients from healthy controls. The abundance of CD4+ T cells was significantly reduced in patients, while they displayed substantial losses of CCR5-expressing monocytes and CXCR3/CCR5 double positive T cells. Post-hoc subgrouping of patients according to their sepsis diagnosis on discharge, identified CXCR3/CCR5 double expression on T cells as a separating characteristic for confirmed cases. This work suggests a potential novel axis of dysregulation affecting CXCR3 and CCR5 in early sepsis.

Validation and comparison of triage-based screening strategies for sepsis

ObjectiveThis study sought to externally validate and compare proposed methods for stratifying sepsis risk at emergency department (ED) triage. MethodsThis nested case/control study enrolled ED patients from four hospitals in Utah and evaluated the performance of previously-published sepsis risk scores amenable to use at ED triage based on their area under the precision-recall curve (AUPRC, which balances positive predictive value and sensitivity) and area under the receiver operator characteristic curve (AUROC, which balances sensitivity and specificity). Score performance for predicting whether patients met Sepsis-3 criteria in the ED was compared to patients' assigned ED triage score (Canadian Triage Acuity Score [CTAS]) with adjustment for multiple comparisons. ResultsAmong 2000 case/control patients, 981 met Sepsis-3 criteria on final adjudication. The best performing sepsis risk scores were the Predict Sepsis version #3 (AUPRC 0.183, 95 % CI 0.148–0.256; AUROC 0.859, 95 % CI 0.843–0.875) and Borelli scores (AUPRC 0.127, 95 % CI 0.107–0.160, AUROC 0.845, 95 % CI 0.829–0.862), which significantly outperformed CTAS (AUPRC 0.038, 95 % CI 0.035–0.042, AUROC 0.650, 95 % CI 0.628–0.671, p < 0.001 for all AUPRC and AUROC comparisons). The Predict Sepsis and Borelli scores exhibited sensitivity of 0.670 and 0.678 and specificity of 0.902 and 0.834, respectively, at their recommended cutoff values and outperformed Systemic Inflammatory Response Syndrome (SIRS) criteria (AUPRC 0.083, 95 % CI 0.070–0.102, p = 0.052 and p = 0.078, respectively; AUROC 0.775, 95 % CI 0.756–0.795, p < 0.001 for both scores). ConclusionsThe Predict Sepsis and Borelli scores exhibited improved performance including increased specificity and positive predictive values for sepsis identification at ED triage compared to CTAS and SIRS criteria.

Implementing an obstetric sepsis bundle in a large academic hospital system

For the purposes of this review, obstetric sepsis refers to sepsis (from all causes, including non-obstetric such as pneumonia) in pregnant or postpartum patients, which was previously described as maternal sepsis. Obstetric sepsis poses a significant threat to pregnant, birthing, and postpartum individuals, contributing prominently to maternal mortality and morbidity despite being largely preventable1. In response to identified gaps in sepsis management, particularly the lack of specific protocols tailored to obstetric populations, New York-Presbyterian undertook a system-wide initiative to implement a comprehensive sepsis bundle. This initiative included the development of new criteria for identifying sepsis in obstetric patients, the creation of electronic medical record (EMR) alerts aligned with obstetric-specific indicators, and the establishment of a structured sepsis management algorithm.The project involved collaboration across eight hospital campuses within the New York-Presbyterian system, aiming to standardize and improve the early recognition and treatment of sepsis in maternal care. Key components included rigorous data analysis to select appropriate sepsis criteria, simulation-based training to familiarize clinical teams with the new algorithm, and continuous refinement of alert systems to mitigate alarm fatigue and enhance responsiveness.Post-implementation evaluation revealed a significant reduction in preventable morbidity related to sepsis, accompanied by the identification of additional gaps in fever and chorioamnionitis management. These findings prompted the development of new clinical guidelines to further enhance patient safety. Challenges encountered included adapting sepsis criteria to balance sensitivity and specificity, as well as integrating trauma-informed care principles into clinical practice.This project underscores the effectiveness of tailored quality improvement efforts in maternal health, emphasizing the critical role of proactive interventions in enhancing patient outcomes and safety within obstetric settings. Ongoing efforts focus on monitoring process metrics through a dedicated sepsis dashboard and advancing education on trauma-informed care principles, highlighting the continued commitment to sustained improvement in maternal health outcomes.

Outpatient use of antibiotics in uncomplicated diverticulitis decreases hospital admissions.

Recently, antibiotics use in uncomplicated acute diverticulitis (AD) has been controversial in Europe. The American Gastroenterological Association (AGA) in their 2015 guidelines recommend their selective use. Our study highlights their role in outpatient management. We queried the Diamond Network through TriNetX-Research Network including 92 healthcare organizations. We included large intestine diverticulitis without perforation, abscess or bleeding. Exclusion criteria included any of sepsis criteria, CRP > 15 mg/L, immunodeficiency or HIV, coronary artery disease, chronic kidney disease, history of Crohn's disease or ulcerative colitis, heart failure, hypertension, diabetes or any of the following in the 3 months before study date; clostridium difficile (C. diff) infection, diverticulitis or antibiotics. Patients with AD were divided into two cohorts; patients on antibiotics, and patients not on antibiotics. Cohorts were compared after propensity-score matching (PSM). 214,277 patients met inclusion criteria. 58.9% received antibiotics, and 41% did not. After PSM, both cohorts had 84,320. Rate of hospital admission was lower in the antibiotic group (3.3% vs 4.2%, p < .001). There was a statistical difference between ICU admission (0.1% vs 0.15%, p < .01) and the rate of bowel perforation, peritonitis, abscess formation or bleeding (1.3% vs 1.4%, p = .044). There was no difference in mortality (0.1% vs 0.1%, p = .11), C. diff (0.1% vs 0.1%, p = .9), colectomies (0.2% vs 0.2%, p = .33), or Acute Kidney Injury (AKI) (0.1% vs 0.1%, p = .28). Outpatient use of antibiotics in patients with uncomplicated AD is associated with lower rates of hospital admissions and complications without changing mortality rate or surgical intervention.

Diagnosis and Management of Neonatal Bacterial Sepsis: Current Challenges and Future Perspectives.

Sepsis remains the second cause of death among neonates after the pathological consequences of extreme prematurity. In this review we summarized knowledge about pathogens causing early-onset sepsis (EOS) and late-onset sepsis (LOS), the role of perinatal risk factors in determining the EOS risk, and the tools used to reduce unnecessary antibiotics. New molecular assays could improve the accuracy of standard blood cultures, providing the opportunity for a quick and sensitive tool. Different sepsis criteria and biomarkers are available to date, but further research is needed to guide the use of antibiotics according to these tools. Beyond the historical antibiotic regimens in EOS and LOS episodes, antibiotics should be based on the local flora and promptly modulated if specific pathogens are identified. The possibility of an antibiotic lock therapy for central venous catheters should be further investigated. In the near future, artificial intelligence could help us to personalize treatments and reduce the increasing trend of multidrug-resistant bacteria.

U-shaped correlation of lymphocyte count with all-cause hospital mortality in sepsis and septic shock patients: a MIMIC-IV and eICU-CRD database study

BackgroundIn sepsis, the relationship between lymphocyte counts and patient outcomes is complex. Lymphocytopenia and lymphocytosis significantly influence survival, illustrating the dual functionality of lymphocytes in responding to infections. This study investigates this complex interaction, focusing on how variations in lymphocyte counts correlate with all-cause hospital mortality among sepsis patients.MethodsThis retrospective cohort study analyzed data from two extensive critical care databases: the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV 2.0) from Beth Israel Deaconess Medical Center, Boston, Massachusetts, and the eICU Collaborative Research Database (eICU-CRD), which was Multi-center database from over 200 hospitals across the United States conducted by Philips eICU Research Institute. We included adult patients aged 18 years and older who met the Sepsis-3 criteria, characterized by documented or suspected infection and a Sequential Organ Failure Assessment (SOFA) score of 2 or higher. Sepsis patients were categorized into quartiles based on lymphocyte counts. The primary outcome was all-cause mortality in the hospital, with 90 and 60-day all-cause mortality as the secondary outcomes. Univariable and multivariable Cox proportional hazard regressions were utilized to assess lymphocyte counts' impact on hospital mortality. An adjusted restricted cubic spline (RCS) analysis was performed to elucidate this relationship further. Subgroup analyses were also conducted to explore the association across various comorbidity groups among sepsis and septic shock patients.ResultsOur study included 37,054 patients, with an observed in-hospital mortality rate of 16.6%. Univariable and multivariable Cox proportional hazard regression models showed that lymphocyte counts were independently associated with in-hospital mortality (HR = 1.04, P < 0.01; HR = 1.06, P < 0.01). RCS regression analysis revealed a U-shaped relationship between lymphocyte levels and hospital mortality risk in sepsis and septic shock patients (P for overall < 0.001, P for nonliner < 0.01; P for overall = 0.002, P for nonliner = 0.014). Subgroup analyses revealed that elevated lymphocyte counts correlated with increased hospital mortality among sepsis patients with liver disease and requiring renal replacement therapy (P for overall = 0.021, P for nonliner = 0.158; P for overall = 0.025, P for nonliner = 0.759). These findings suggest that lymphocytes may have enhanced prognostic value in specific subsets of critically ill sepsis patients.ConclusionOur findings demonstrate that lymphocyte counts are a significant independent predictor of hospital mortality in sepsis and septic shock patients. We observed a U-shaped association between lymphocyte levels and mortality risk, indicating that high and low counts are linked to increased mortality. This result highlights the complex role of lymphocytes in sepsis outcomes and suggests the need for further investigation into the underlying mechanisms and potential therapeutic approaches. Integrating lymphocyte count assessment into risk stratification algorithms and clinical decision support tools could enhance the early identification of high-risk sepsis patients.

Bacterial sepsis causes more dramatic pathogenetic changes in the Th1 pathway than does viral (COVID-19) sepsis: a prospective observational study of whole blood transcriptomes

ObjectivesThis study aimed to comprehensively compare host responses of patients with bacterial sepsis and those with viral (COVID-19) sepsis by analyzing messenger RNA (mRNA) and microRNA (miRNA) profiles to shed light on their distinct pathophysiological mechanisms.DesignProspective observational study.SettingWhole blood RNA sequencing was used to analyze mRNA and miRNA profiles of patients diagnosed as having bacterial sepsis or viral (COVID-19) sepsis at the Department of Trauma and Emergency Medicine, Osaka University Graduate School of Medicine.PatientsTwenty-two bacterial sepsis patients, 35 viral (COVID-19) sepsis patients, and 15 healthy subjects admitted to the department were included. We diagnosed bacterial sepsis patients according to the sepsis-3 criterion that the Sequential Organ Failure Assessment score must increase to 2 points or more among patients with suspected infections. Viral (COVID-19) sepsis patients were diagnosed using SARS-CoV-2 RT-PCR testing, and presence of pneumonia was assessed through chest computed tomography scans.InterventionsNone.Measurements and main resultsFor RNA sequencing, 14,500 mRNAs, 1121 miRNAs, and 2556 miRNA-targeted mRNAs were available for analysis in the bacterial sepsis patients. Numbers of genes showing upregulated: downregulated gene expression (false discovery rate < 0.05, |log2 fold change| > 1.5) were 256:2887 for mRNA, 53:5 for miRNA, and 49:2507 for miRNA-targeted mRNA. Similarly, in viral (COVID-19) sepsis patients, 14,500 mRNAs, 1121 miRNAs, and 327 miRNA-targeted mRNAs were analyzed, with numbers of genes exhibiting upregulated: downregulated gene expression of 672:1147 for mRNA, 3:4 for miRNA, and 165:162 for miRNA-targeted mRNA. This analysis revealed significant differences in the numbers of upregulated and downregulated genes expressed and pathways between the bacterial sepsis and viral (COVID-19) sepsis patients. Bacterial sepsis patients showed activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathway and concurrent suppression of Th1 signaling.ConclusionOur study illuminated distinct molecular variances between bacterial sepsis and viral (COVID-19) sepsis. Bacterial sepsis patients had a greater number of upregulated and downregulated genes and pathways compared to viral (COVID-19) sepsis patients. Especially, bacterial sepsis caused more dramatic pathogenetic changes in the Th1 pathway than did viral (COVID-19) sepsis.

Efficacy and safety of dynamic arterial elastance for weaning vasopressor support in septic shock patients: a randomised controlled trial protocol

IntroductionThe dynamic arterial elastance (EaDyn), calculated as pulse pressure variation divided by stroke volume variation, has been studied as a predictor of vasopressor weaning. However, its potential as a haemodynamic...