Background/Objectives: Sepsis, as a major cause of mortality worldwide, requires timely diagnosis and prompt treatment to improve patient outcomes. In this study, we evaluated sepsis management strategies and their impact on clinical outcomes in hospitalized patients. Methods: A retrospective study was conducted by analyzing clinical and treatment data from the electronic records of sepsis patients who had been admitted to tertiary care hospitals in eastern Saudi Arabia. Using systematic sampling, the details of eligible patients were obtained. Data were collected on patient demographics, vital signs, Sequential Organ Failure Assessment (SOFA) and laboratory parameters, treatment (antibiotic therapy, vasopressor use, or fluid resuscitation), and outcomes (survival in hospital). Statistical analyses were performed to assess the association between clinical and treatment strategies and patient outcomes. Results: A total of 234 sepsis cases were analyzed, of which 70.9% were survivors and 29.1% were non-survivors. Patients aged 60 years and above were the most affected. Statistically significant differences were observed across all of the measured vital sign variables and outcomes (p < 0.0001). Based on SOFA scores, 56.41% of patients were assessed as having a moderate risk. Through our comparison of clinical and laboratory parameters between survivors and non-survivors, significant differences were found in all of the measured variables (p < 0.0001). The odds of survival were significantly higher in those who received early administration of broad-spectrum antibiotics (OR = 4.9449, p = 0.0001), vasopressor therapy (OR = 1.9408, p = 0.0262), and fluid resuscitation OR = 11.035, p = 0.0001). Conclusions: The results of this study highlight the importance of early sepsis recognition, prompt antibiotic therapy, and standardized protocol adherence in improving patient outcomes and reducing mortality and morbidity.

Background: Sepsis is a major global health issue and the leading cause of death in critically ill patients, with rising incidence and associated healthcare costs. Early administration of antibiotic therapy is crucial, but increasing antibiotic resistance poses a threat. Beta-lactam antibiotics, commonly used as a first-line therapy option against sepsis, often demonstrate unpredictable concentrations due to pharmacokinetic and pharmacodynamic changes in critically ill patients. Acute kidney injury (AKI) affects a significant portion of septic patients, and continuous renal replacement therapy can further complicate treatment by reducing antibiotic levels and, consequently, increasing antibiotic resistance risk. Objectives: To develop pharmacokinetic/pharmacodynamic models for beta-lactam antibiotics in septic shock patients undergoing continuous renal replacement therapy (CRRT), with the goal of optimizing antibiotic dosing and then improving treatment outcomes. Methods: Septic shock Caucasian adult patients treated with beta-lactams and who have undergone major surgery in AKI failure that requires CRRT will be eligible with previous informed written consent. CRRT will be performed exclusively using Continuous Venovenous Hemodiafiltration (CVVHDF) modality. Antimicrobial determination analyses will be carried out with LC-MS/MS. Further calculation of pharmacokinetic parameters and determination of PK/PD breakpoints will be made using Monte Carlo simulation. Conclusions: The expected results from this study will lead to a better understanding of the pharmacokinetics of beta-lactam antibiotics in critically ill patients with AKI and septic shock undergoing CVVHDF, allowing for improved therapeutic strategies.

The obesity paradox has been widely studied recently; however, its impact on the long-term prognosis of sepsis and the protective mechanism of body mass have not yet been sufficiently revealed.

We retrospectively evaluated the association between obesity and 1-year survival after sepsis in a single university-affiliated hospital and examined the differential effects of muscle mass and adiposity.

Adult patients with sepsis or septic shock (n = 1492)were classified into obese (n = 300) and nonobese (n = 1192) groups. One-year mortality due to sepsis was lower in the obese than in the nonobese (52.0 % vs. 64.8 %; p < 0.001). In multivariate Cox analysis, one-year mortality due to sepsis was independently associated with body mass index (BMI) (hazard ratio 0.96). In the subgroup analysis, 705 were divided into four groups according to the psoas muscle index (PMI) and body fat percentage (BFP) to assess the differential impact of body fat and muscle mass on the one-year outcome of sepsis. One-year mortality was significantly different among the four groups (high BFP/low PMI, 60.6 %; high BFP/high PMI, 42.1 %; low BFP/high PMI, 34.8 %; low BFP/low PMI, 63.2 %; p = 0.002). The adjusted hazards ratio of one-year mortality of sepsis, which was normalized to the low BFP/high PMI group, were 1.2 (p = 0.585), 2.2 (p = 0.016), and 2.3 (p = 0.009) in groups of high BFP/high PMI, high BFP/low PMI, and low BFP/low PMI, respectively.

An obesity paradox has been observed in the long-term outcomes of patients with sepsis, and muscle mass may be more critical than fat mass as a protective mechanism against obesity.

A high BMI is linked to a more favorable long-term prognosis in sepsis, with muscle mass playing a more critical role than fat mass. A proactive nutritional and conditioning program may benefit patients anticipating major procedures and potential ICU admission. Such preparation could enhance their resilience and improve outcomes when facing critical illness, including sepsis.

Sepsis shock is caused by a systemic infection characterized by circulatory disorders and metabolic abnormalities. Microorganisms or their toxins enter the bloodstream, releasing inflammatory mediators and triggering systemic inflammatory reactions, leading to multiple organ dysfunction and even failure. To explore new treatment methods, we studied the improvement effect of sesamoside on the inflammatory response in septic shock. We performed in vitro experiments and animal models. We found that sesamoside reduced inflammatory cytokines such as TNF-α, IL-6, IL-1β, iNOS, and NO. Sesamoside inhibited the LPS-induced phosphorylation of ERK and JNK and downregulated the expression of NLRP3, reducing the systemic inflammatory response. In addition, sesamoside reduces multi-organ injuries in LPS-induced septic shock and restricts the nuclear localization of P65 to regulate the immune response, enhance immune function, and help restore cell metabolism and organ function. This study reveals the improved effect of sesamoside on inflammatory response in septic shock, providing new ideas and methods for treating septic shock. Future research will explore the mechanism of action of sesamoside and its clinical application value in the treatment of septic shock. Clinical trial number: Not applicable.

Introduction Recombinant human soluble thrombomodulin (rhsTM) is a therapeutic agent for sepsis-induced disseminated intravascular coagulation (DIC) and is reported to be associated with bleeding events. Although several studies on rhsTM have been reported, the safety and efficacy of rhsTM for sepsis-induced DIC after emergency laparotomy remain controversial. In this study, we aimed to investigate the efficacy, safety, and bleeding complications of rhsTM in patients with sepsis-induced DIC following emergency abdominal surgery. Methods In this retrospective observational study, we reviewed the data of patients who underwent emergency surgery for gastrointestinal necrosis and perforation and received rhsTM for sepsis-induced DIC at a single center between January 2014 and December 2023. We evaluated the incidence rate of bleeding complications associated with rhsTM treatment, clinical characteristics, and changes in Japanese Association for Acute Medicine (JAAM) DIC scores. Patients with DIC were identified as having the JAAM DIC diagnostic criteria (DIC score ≥4). Results We analyzed a total of 32 patients with sepsis-induced DIC. The APACHE II (Acute Physiology and Chronic Health Evaluation II) score at admission to the intensive care unit was 20. A total of 46.9% of the patients had poor renal function with CKD (chronic kidney disease), classified based on KDIGO (Kidney Disease: Improving Global Outcomes) stage 4 or higher, and 37.5% were on regular hemodialysis. A total of 59.4% of the patients received antithrombotic therapy. The JAAM DIC score was significantly ameliorated from the first day of rhsTM administration (5.3) to days 5-7 of rhsTM administration (3.3) (p < 0.0001). A total of 75% of the patients had a HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Use) score, an indicator of bleeding risk, of 3 or higher. The mortality rate in the whole cohort was 37.5%. Patients were also classified into the following groups: HAS-BLED score ≥3 (n = 24) and <3 (n = 8), and survivors (n = 20) and non-survivors (n = 12). No perioperative bleeding complications were observed. Conclusion rhsTM was not associated with an increased incidence of bleeding complications, even in patients with sepsis-induced DIC following emergency abdominal surgery and in critically ill patients with poor renal function or those receiving antithrombotic therapy. rhsTM is a safe and effective anticoagulant for the management of sepsis-induced DIC after emergency surgery and is clinically feasible.

Infections caused by antibiotic-resistant bacteria are increasingly frequent, burdening healthcare systems worldwide. As pathogens acquire resistance to all known antibiotics - i.e., become pan-resistant - treatment of the associated infections will become exceedingly difficult. We hypothesized that the emergence of pan-resistant bacterial pathogens will result in a sharp increase in human mortality.

We tested this hypothesis by modeling the impact of a single hypothetical pan-resistant Escherichia coli strain on sepsis deaths in the United States. We used long-term data on sepsis incidence, mortality rates, strain dynamics, and treatment outcomes to parameterize a set of models encompassing a range of plausible future scenarios. All models accounted for historical and projected temporal changes in population size and age distribution.

The models suggest that sepsis deaths could increase 18- to 46-fold within 5 years of the emergence of a single pan-resistant E. coli strain. This large and rapid change contrasts sharply with the current expectation of gradual change under continuing multidrug-resistance.

Failure to prevent the emergence of pan-resistance would have dire consequences for public health.

Glucocorticoids, vitamin C and thiamine have important biological effects in patients with sepsis and septic shock. Multiple studies have demonstrated the beneficial role of a combination therapy of vitamin C, hydrocortisone and thiamine in patients with sepsis and septic shock in terms of mortality reduction, and increase in the number of days free of ventilators and vasopressors.

Patients who had septic shock were assessed for eligibility after intensive care unit (ICU) admission. After randomization, the treatment group received a combination of vitamin C, thiamine and hydrocortisone for a duration of 96 hours (16 doses) and the control group received hydrocortisone for a duration till the patient was on vasopressors. The primary outcome assessed was ICU mortality, and the key secondary outcome was the duration free of vasopressor administration at the end of 7 days.

A total of 86 patients were included in the study. Seventy percent of patients in the control group and 58 percent in the intervention group died during ICU stay. None of the primary and secondary outcomes were statistically significant.

The use of a combination of vitamin C, hydrocortisone and thiamine has no added benefits over the use of hydrocortisone alone in patients with septic shock.

The results of this clinical trial shows that the use of a combination of vitamin C, hydrocortisone and thiamine in patients with septic shock is not useful and should not be a routine practice in critically ill septic patients.

Sharma S, Paneru HR, Shrestha GS, Shrestha PS, Acharya SP. Evaluation of the Effects of a Combination of Vitamin C, Thiamine and Hydrocortisone vs Hydrocortisone Alone on ICU Outcome in Patients with Septic Shock: A Randomized Controlled Trial. Indian J Crit Care Med 2024;28(12):1147-1152.

A dysregulated host response to infection resulting in life-threatening organ dysfunction defines the onset of sepsis. Unfortunately, sepsis is common, costly, and deadly. The Surviving Sepsis Campaign publishes regularly updated, evidence-informed, detection, and treatment guidelines culminating in time-sensitive care "bundles." The goal of these bundles is to expedite sepsis recognition because it is widely held that early treatment is life-saving. Hospitals are mandated to publicly report their bundle compliance, and this will soon be tied to hospital reimbursement. For these reasons, hospitals are creating sepsis emergency response teams which are a form of a rapid response team consisting of dedicated medical professionals who evaluate patients with suspected sepsis and initiate therapy when appropriate. Evidence to date support sepsis emergency response teams as a mechanism to improve bundle compliance, and potentially, patient outcome. Nevertheless, some elements of bundled sepsis care are controversial (e.g., intravenous fluid administration) as some argue that mandated treatment precludes personalized care. Herein, we briefly describe general sepsis emergency response team structure, review evidence supporting sepsis emergency response teams to improve bundle compliance and patient outcome and report our unique experience incorporating point of care ultrasound-to guide intravenous fluid-into a nursing-led sepsis team. We propose that our sepsis emergency response team approach allays concern that sepsis care is either bundled or personalized. Instead, incorporating point of care ultrasound into a nursing-led sepsis emergency response team increases bundle compliance and individualizes care.

Sepsis is a leading cause of maternal morbidity and mortality worldwide. Early recognition and treatment improve outcomes. Multiple sepsis diagnostic screening tools are available and may be used in clinical practice; however, early thorough bedside evaluation of the patient is fundamental. Obstetricians should be able to recognize sepsis and promptly initiate potentially life-saving treatments, such as fluid resuscitation, vasopressors, broad-spectrum antibiotics, and early source control. It is recommended that obstetrical care, including delivery timing, not be altered solely due to the diagnosis of sepsis.

Sepsis is a common admission diagnosis in the intensive care unit (ICU). The Sepsis-3 consensus associates sepsis diagnosis with acute organ dysfunction. In these patients troponin elevation is a well-established phenomenon, but its clinical significance is not settled, as no systematic review has addressed the prognostic significance of the increasingly prevalent high-sensitivity troponin assays in acute organ dysfunction setting. This study aims to clarify the association between early serum troponin levels in high-sensitivity assays with short-term mortality risk in septic patients with acute organ dysfunction.

We will systematically search PubMed, Scopus and Embase for original articles; additionally, a manual search will be carried out through relevant literature. Generally, studies will be deemed eligible for inclusion if they evaluate the association between high-sensitivity troponin in the first 24 hours of admission and ICU, 30-days, or In-hospital mortality; in patients with septic shock or sepsis related to acute organ dysfunction. Two reviewers will independently select studies and extract the data. A meta-analysis for mortality outcome will be performed for comparative data regarding two effect measures: Odd ratios and Standardized Mean differences.

This study will provide further evidence about the role of high-sensitivity troponin assays in predicting mortality in septic patients; potentially helping to guide further research and yielding valuable information for patient assessment. Conclusion about the certainty of evidence will be presented in a ´Summary of findings´ table.

PROSPERO registration: (CRD42024468883).

To evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion.

This study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization.

A total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days-6.0 days vs. median=5.0 days, IQR: 3.0 days-8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3-2.0 mmol/L vs. median=0.0 mmol/L, IQR: -0.2 to 0.8 mmol/L, respectively; P <0.001) and 24 h (median=1.4 mmol/L, IQR: 0.3-2.2 mmol/L vs. median=0.4 mmol/L, IQR: -0.4 to 1.6 mmol/L, respectively; P=0.001).

SFI plus standard therapy did not significantly decrease 28-day all-cause mortality for septic patients with hypoperfusion and TCM syndrome with Yang-Qi deficiency.Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR1800020435.

Background: Despite rapid advances in treatment, sepsis currently remains a major public health challenge worldwide. Over the past several years, there has been an increase in the clinical incidence of sepsis, as well as an increase in hospitalization rates, which bear the majority of the economic burden associated with sepsis. Sepsis is a public health burden due to the high fatality rates and accompanying morbidity. However, the sepsis-related mortality rates have fallen steadily over the years. One of the most common organs to fail in patients with sepsis is the kidney, and acute kidney injury (AKI) is associated with high mortality rates. This study's primary goal was to assess the impact of AKI on the evolution and outcome of hospitalization of patients with sepsis. Methods: Adults (≥18 years) hospitalized for sepsis in the United States between 2010 and 2019 were retrospectively analyzed using the nationally representative Nationwide Inpatient Sample database. Sepsis and AKI were defined using the codes of the International Classification of Diseases, Ninth Revision, Clinical Modification and the International Classification of Diseases, Tenth Revision, Clinical Modification. Results: Of the 4,258,360 outcomes, 3,946,048 met the inclusion criteria. The prevalence of AKI among sepsis inpatients increased from 39.10% in 2010 to 41% in 2019, but the impact of AKI on mortality declined over time, with in-hospital mortality from AKI among sepsis inpatients decreasing from 26.30% in 2010 to 16.30% in 2019. Hospitalizations linked to AKI were substantially more likely to involve infection sites such as the urinary tract, gastrointestinal tract, and endocarditis. Numerous pathogenic floras, including Escherichia coli , Staphylococcus aureus , Streptococcal , Enterococcus , and Pseudomonas , had greater rates among sepsis-related contacts with AKI. Furthermore, compared to hospitalization without comorbid AKI, the median total hospital charges and length of stay days for sepsis hospitalization with comorbid AKI were greater. Conclusion: With time, patients with sepsis have a higher frequency of AKI and a corresponding decline in mortality.

Sepsis is a life-threatening condition but predicting its development and progression remains a challenge.

This study aimed to assess the impact of infection site on sepsis development among emergency department (ED) patients.

Data were collected from a single-center ED between January 2016 and December 2019. Patient encounters with documented infections, as defined by the Systematized Nomenclature of Medicine-Clinical Terms for upper respiratory tract (URI), lower respiratory tract (LRI), urinary tract (UTI), or skin or soft-tissue infections were included. Primary outcome was the development of sepsis or septic shock, as defined by Sepsis-1/2 criteria. Secondary outcomes included hospital disposition and length of stay, blood and urine culture positivity, antibiotic administration, vasopressor use, in-hospital mortality, and 30-day mortality. Analysis of variance and various different logistic regression approaches were used for analysis with URI used as the reference variable.

LRI was most associated with sepsis (relative risk ratio [RRR] 5.63; 95% CI 5.07-6.24) and septic shock (RRR 21.2; 95% CI 17.99-24.98) development, as well as hospital admission rates (odds ratio [OR] 8.23; 95% CI 7.41-9.14), intensive care unit admission (OR 4.27; 95% CI 3.84-4.74), in-hospital mortality (OR 6.93; 95% CI 5.60-8.57), and 30-day mortality (OR 7.34; 95% CI 5.86-9.19). UTIs were also associated with sepsis and septic shock development, but to a lesser degree than LRI.

Primary infection sites including LRI and UTI were significantly associated with sepsis development, hospitalization, length of stay, and mortality among patients presenting with infections in the ED.

Adult rats exposed to hyperoxia (>95% O2) die from respiratory failure in 60-72 h. However, rats preconditioned with >95% O2 for 48 h followed by 24 h in room air acquire tolerance of hyperoxia (H-T), whereas rats preconditioned with 60% O2 for 7 days become more susceptible (H-S). Our objective was to evaluate lung tissue mitochondrial bioenergetics in H-T and H-S rats. Bioenergetics was assessed in mitochondria isolated from lung tissue of H-T, H-S, and control rats. Expressions of complexes involved in oxidative phosphorylation (OxPhos) were measured in lung tissue homogenate. Pulmonary endothelial filtration coefficient (Kf) and tissue mitochondrial membrane potential (Δψm) were evaluated in isolated perfused lungs (IPLs). Results show that ADP-induced state 3 OxPhos capacity (Vmax) decreased in H-S mitochondria but increased in H-T. Δψm repolarization time following ADP-stimulated depolarization increased in H-S mitochondria. Complex I expression decreased in H-T (38%) and H-S (43%) lung homogenate, whereas complex V expression increased (70%) in H-T lung homogenate. Δψm is unchanged in H-S and H-T lungs, but complex II has a larger contribution to Δψm in H-S than H-T lungs. Kf increased in H-S, but not in H-T lungs. For H-T, increased complex V expression and Vmax counter the effect of the decrease in complex I expression on Δψm. A larger complex II contribution to Δψm along with decreased Vmax and increased Kf could make H-S rats more hyperoxia susceptible. Results are clinically relevant since ventilation with ≥60% O2 is often required for extended periods in patients with acute respiratory distress syndrome (ARDS).NEW & NOTEWORTHY We assessed lung tissue mitochondrial bioenergetics in rats with tolerance (H-T) or susceptibility (H-S) to hyperoxia-induced ARDS. Results from studies in isolated mitochondria, tissue homogenate, and isolated perfused lungs show that mitochondrial bioenergetics are differentially altered in H-T and H-S lungs suggesting a potential role for mitochondrial bioenergetics in hyperoxia-induced ARDS. Results are clinically relevant since hyperoxia exposure is a primary therapy for patients with ARDS, and differential sensitivity to hyperoxia surely occurs in humans.

Biomarker dynamics in different time-courses might be the primary reason why a static measurement of a single biomarker cannot accurately predict sepsis outcomes. Therefore, we conducted this prospective hospital-based cohort study to simultaneously evaluate the performance of several conventional and novel biomarkers of sepsis in predicting sepsis-associated mortality on different days of illness among patients with suspected sepsis.

We evaluated the performance of 15 novel biomarkers including angiopoietin-2, pentraxin 3, sTREM-1, ICAM-1, VCAM-1, sCD14 and 163, E-selectin, P-selectin, TNF-alpha, interferon-gamma, CD64, IL-6, 8, and 10, along with few conventional markers for predicting sepsis-associated mortality. Patients were grouped into quartiles according to the number of days since symptom onset. Receiver operating characteristic curve (ROC) analysis was used to evaluate the biomarker performance.

From 2014 to 2017, 1483 patients were enrolled, of which 78% fulfilled the systemic inflammatory response syndrome criteria, 62% fulfilled the sepsis-3 criteria, 32% had septic shock, and 3.3% developed sepsis-associated mortality. IL-6, pentraxin 3, sCD163, and the blood gas profile demonstrated better performance in the early days of illness, both before and after adjusting for potential confounders (adjusted area under ROC curve [AUROC]:0.81-0.88). Notably, the Sequential Organ Failure Assessment (SOFA) score was relatively consistent throughout the course of illness (adjusted AUROC:0.70-0.91).

IL-6, pentraxin 3, sCD163, and the blood gas profile showed excellent predictive accuracy in the early days of illness. The SOFA score was consistently predictive of sepsis-associated mortality throughout the course of illness, with an acceptable performance.

Sepsis, a syndrome of organ dysfunction caused by an unregulated host response to infection. This study aimed to develop a novel sepsis diagnostic model of hematological parameters and evaluate its effectiveness in the early identification and prognosis of sepsis in emergency departments.

A retrospective study was conducted in Emergency Department. Cell population data parameters related to monocytes and neutrophils were obtained using the Mindary BC-6800 plus hematology analyzer. Receiver operating characteristic (ROC) curve analysis, logistic regression analysis was performed to assess the performance of the parameters and establish a diagnostic and prognostic model of sepsis, which was then verified with a validation cohort.

Mon_XW exhibited the best diagnostic performance (area under the ROC curve [AUC] = 0.848, 95% confidence interval [CI]: 0.810-0.885, p < 0.001), followed by Neu_Y and Neu_YW (AUC = 0.777 95% CI: 0.730-0.824, p < 0.001). Logistic regression analysis identified Mon_XW and Neu_Y as independent predictors, which were used to establish a diagnostic model named hematological parameter for sepsis (HPS). HPS demonstrated the best diagnostic performance with an AUC of 0.862 (95% CI: 0.826-0.898, p < 0.001), sensitivity of 70.0%, and specificity of 87.1%, compared to C-reactive protein (CRP) and procalcitonin (PCT). The validation cohort also found that the positive predictive value of HPS was 70.4% and the negative predictive value was 92.2%.

The developed HPS model showed promising diagnostic efficacy for sepsis in the emergency department, which outperformed CRP and PCT in terms of sensitivity and specificity. By enabling early identification and prognosis of sepsis, that contributes to reducing sepsis-related mortality.

Data to support the use of specific vasopressors in septic shock are limited. Since angiotensin II (AT2) was approved by the Food and Drug Administration in 2017, multiple mechanistically distinct vasopressors are available to treat septic shock, but minimal data exist regarding which patients are most likely to benefit from each agent. Renin and dipeptidyl peptidase 3 (DPP3) are components of the renin-angiotensin-aldosterone system which have been shown to outperform lactate in predicting sepsis prognosis, and preliminary data suggest they could prove useful as biomarkers to guide AT2 use in septic shock.

The DARK-Sepsis trial is an investigator-initiated industry-funded, open-label, single-center randomized controlled trial of the use of AT2 versus standard of care (SOC) vasopressor therapy in patients admitted to the intensive care unit (ICU) with vasodilatory shock requiring norepinephrine ≥ 0.1 mcg/kg/min. In both groups, a series of renin and DPP3 levels will be obtained over the first 24 h of treatment with AT2 or SOC. The primary study outcome will be the ability of these biomarkers to predict response to vasopressor therapy, as measured by change in total norepinephrine equivalent dose of vasopressors at 3 h post-drug initiation or the equivalent timepoint in the SOC arm. To determine if the ability to predict vasopressor response is specific to AT2 therapy, the primary analysis will be the ability of baseline renin and DPP3 levels to predict vasopressor response adjusted for treatment arm (AT2 versus control) and Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes will include rates of acute kidney injury, need for mechanical ventilation and kidney replacement therapy, lengths of stay in the ICU and hospital, ICU and hospital mortality, and rates of prespecified adverse events.

With an armamentarium of mechanistically distinct vasopressor agents now available, sub-phenotyping patients using biomarkers has the potential to improve septic shock outcomes by enabling treatment of the correct patient with the correct vasopressor at the correct time. However, this approach requires validation in a large definitive multicenter trial. The data generated through the DARK-Sepsis study will prove crucial to the optimal design and patient enrichment of such a pivotal trial.

ClinicalTrials.gov NCT05824767. Registered on April 24, 2023.

Previously healthy adults with community-onset sepsis were recently reported to have, counterintuitively, higher short-term mortality than those with comorbid conditions. However, the population-level generalizability of this finding and its applicability to all hospitalized septic patients are unclear.

We used a statewide dataset to identify hospitalizations aged ≥18 years with a diagnosis of sepsis in Texas during 2018-2019. Comorbidities were defined as those included in the Charlson Comorbidity Index and other prevalent conditions associated with mortality. Hierarchical models were used to estimate the association of comorbid state with short-term mortality (defined as in-hospital mortality or discharge to hospice), overall and in community-onset and hospital-onset sepsis.

Among 120,371 sepsis hospitalizations, 6611 (5.5%) were previously healthy and 105,455 (87.6%) had community-onset sepsis. Short-term mortality among the previously healthy and those with comorbidities was 11.7% vs 28.2% overall, 11.0% vs 25.2% in community-onset sepsis, and 22.0% vs 48.7% in hospital-onset sepsis, respectively. On adjusted analysis, being previously healthy remained associated with lower short-term mortality overall (adjusted odds ratio 0.62 [95% CI 0.57-0.69]), with findings consistent with the primary analysis in community-onset sepsis, hospital-onset sepsis.

Previously healthy septic patients had lower short-term mortality compared to those with comorbid conditions.

Objective: Compare changes in cholesterol and lipoprotein levels occurring in septic patients with and without acute respiratory distress syndrome (ARDS) and by survivorship. Methods: We reanalyzed data from prospective sepsis studies. Cholesterol and lipoprotein levels were analyzed using univariate testing to detect changes between septic patients with or without ARDS, and among ARDS survivors compared with nonsurvivors at enrollment (first 24 h of sepsis) and 48 to 72 h later. Results: 214 patients with sepsis were included of whom 48 had ARDS and 166 did not have ARDS. Cholesterol and lipoproteins among septic ARDS versus non-ARDS showed similar enrollment levels. However, 48 to 72 h after enrollment, change in median total cholesterol (48/72 h - enrollment) was significantly different between septic ARDS (-4, interquartile range [IQR] -23.5, 6.5, n = 35) and non-ARDS (0, -10.0, 17.5, P = 0.04; n = 106). When compared by ARDS survivorship, ARDS nonsurvivors (n = 14) had lower median total cholesterol levels (75.5, IQR 68.4, 93.5) compared with ARDS survivors (113.0, IQR 84.0, 126.8, P = 0.022), and lower median enrollment low-density lipoprotein cholesterol (LDL-C) levels (27, IQR 19.5-34.5) compared with ARDS survivors (43, IQR 27-67, P = 0.013; n = 33). Apolipoprotein A-I levels were also significantly lower in ARDS nonsurvivors (n = 14) (87.6, IQR 76.45-103.64) compared with ARDS survivors (130.0, IQR 73.25-165.47, P = 0.047; n = 33). At 48 to 72 h, for ARDS nonsurvivors, median levels of low-density lipoprotein cholesterol (9.0, IQR 4.3, 18.0; n = 10), LDL-C (17.0, IQR 5.0, 29.0; n = 9), and total cholesterol (59.0, 45.3, 81.5; n = 10) were significantly lower compared with ARDS survivors' (n = 25) levels of low-density lipoprotein cholesterol (20.0, IQR 12.0-39.0, P = 0.014), LDL-C (42.0, IQR 27.0-58.0, P = 0.019), and total cholesterol (105.0, IQR 91.0, 115.0, P = 0.003). Conclusions: Change in total cholesterol was different in septic ARDS versus non-ARDS. Total cholesterol, LDL-C, and apolipoprotein A-I levels were lower in ARDS nonsurvivors compared with survivors. Future studies of dysregulated cholesterol metabolism in septic ARDS patients are needed to understand biology and links to potential therapies.

Objective The objective of this study is to compare the outcomes of hospital mortality, the requirement of invasive ventilation, vasopressor requirement, duration of vasopressor requirement, and duration of intensive care unit (ICU) stay among the different causes of sepsis and to determine which cause of sepsis had the most severe outcomes. Methods A retrospective chart review was done in critically ill adult patients who were admitted with sepsis to the ICU from July 2017 until July 2019. Acute Physiology and Chronic Health Evaluation (APACHE) IV scores were calculated on patients admitted to ICU on day one of ICU admission. Each patient was then evaluated for outcomes of hospital mortality, need for invasive ventilation, requirement of vasopressors, duration of vasopressors, and duration of ICU stay. The outcomes were then compared between the different sources of sepsis to determine which source of sepsis had the highest severity. Results In total, 176 patients were included in the study. Ninety-three patients were admitted with respiratory sepsis, 26 patients were admitted with gastrointestinal sepsis, 31 patients were admitted with urosepsis, and 26 patients were admitted with other miscellaneous causes of sepsis. The hospital mortality was highest in the respiratory sepsis group at 32%, with a trend towards statistical significance with a P value of 0.057. ICU stay duration was highest in patients with respiratory sepsis at six days, with a statistically significant P value of < 0.001. The need for invasive ventilation was highest in patients with respiratory sepsis at 64%, with a statistically significant P value of < 0.001. The requirement of vasopressor support was highest in patients with respiratory sepsis at 47% and the duration of vasopressors was highest in both respiratory and gastrointestinal sepsis at three days, however, there was no statistical significance. Conclusion Among the different origins of sepsis, the patients with respiratory sepsis had the most severe outcomes, with the highest need for invasive ventilation and the highest ICU stay duration.

Comorbid conditions represent a major risk for severe illness among persons with COVID-19. Previously healthy people with COVID-19 can also develop severe illness, but are expected to have better outcomes than those with comorbid conditions. Nevertheless, recent data suggest that the former may have, counterintuitively, higher risk of death among those with non-COVID sepsis. However, the epidemiology and outcomes of previously healthy people among critically ill patients with COVID-19 are unknown. We used statewide data to identify intensive care unit (ICU) admissions aged ≥18 years in Texas with COVID-19 in 2020. Multilevel logistic regression was used to estimate the association of comorbid state with short-term mortality (defined as in-hospital mortality or discharge to hospice) overall and with higher illness severity among ICU admissions. Among 52,776 ICU admissions with COVID-19, 6373 (12.1%) were previously healthy. Short-term mortality among previously healthy ICU admissions and those with comorbidities was 16.9% versus 34.6%. On adjusted analyses, the odds of short-term mortality were lower among the previously healthy compared to those with comorbidities overall (adjusted odds ratio (aOR) 0.84 (95% CI: 0.73-0.98)), but did not differ among those with ≥3 organ dysfunctions (aOR 1.11 (95% CI: 0.84-1.46)) and the mechanically ventilated (aOR 0.87 (95% CI: 0.68-1.12)), while being higher among those with do-not-resuscitate status (aOR 1.40 (95% CI: 1.04-1.89)). Over one in eight ICU admissions with COVID-19 were previously healthy. Although being previously healthy was associated with lower risk of death compared to those with comorbidities overall, it had no prognostic advantage among the more severely ill.

Sepsis is a significant public health concern, particularly affecting individuals above 70 years in developed countries. This is a crucial fact due to the increasing aging population, their heightened vulnerability to sepsis, and the associated high mortality rates. However, the morbidity and long-term outcomes are even more notable. While many patients respond well to timely and appropriate interventions, it is imperative to enhance efforts in identifying, documenting, preventing, and treating sepsis. Managing sepsis in older patients poses greater challenges and necessitates a comprehensive understanding of predisposing factors and a heightened suspicion for diagnosing infections and assessing the risk of sudden deterioration into sepsis. Despite age often being considered an independent risk factor for mortality and morbidity, recent research emphasizes the pivotal roles of frailty, disease severity, and comorbid conditions in influencing health outcomes. In addition, it is important to inquire about the patient's preferences and establish a personalized treatment plan that considers their potential for recovery with quality of life and functional outcomes. This review provides a summary of the most crucial aspects to consider when dealing with an old critically ill patient with sepsis.

Sepsis is a life-threatening state that arises due to a hyperactive inflammatory response stimulated by infection and rarely other insults (e.g., non-infections tissue injury). Although changes in several proinflammatory cytokines and signals are documented in humans and small animal models, far less is known about responses within affected tissues of large animal models. We sought to understand the changes that occur during the initial stages of inflammation by administering intravenous lipopolysaccharide (LPS) to Yorkshire pigs and assessing transcriptomic alterations in the brain, kidney, and whole blood. Robust transcriptional alterations were found in the brain, with upregulated responses enriched in inflammatory pathways and downregulated responses enriched in tight junction and blood vessel functions. Comparison of the inflammatory response in the pig brain to a similar mouse model demonstrated some overlapping changes but also numerous differences, including oppositely dysregulated genes between species. Substantial changes also occurred in the kidneys following LPS with several enriched upregulated pathways (cytokines, lipids, unfolded protein response, etc.) and downregulated gene sets (tube morphogenesis, glomerulus development, GTPase signal transduction, etc.). We also found significant dysregulation of genes in whole blood that fell into several gene ontology categories (cytokines, cell cycle, neutrophil degranulation, etc.). We observed a strong correlation between the brain and kidney responses, with significantly shared upregulated pathways (cytokine signaling, cell death, VEGFA pathways) and downregulated pathways (vasculature and RAC1 GTPases). In summary, we have identified a core set of shared genes and pathways in a pig model of systemic inflammation.

COVID-19 has been associated with a higher incidence of acute myocardial infarction and related complications. We sought to assess the impact of COVID-19 diagnosis on hospitalizations with an index admission of AMI. The National inpatient sample 2020 was queried for hospitalizations with an index admission of AMI, further stratified for admissions with and without COVID-19. The 2 groups' mortality, procedure, and complication rates were compared using suitable statistical tests. Multivariate regression analysis was further performed to study the impact of COVID-19 on mortality as the primary outcome and length of stay and total hospital cost as secondary outcomes. A total of 555,540 admissions for AMI were identified, of which 5818 (1.04%) had concomitant COVID-19. Hospitalizations in the COVID-19 cohort of both groups had a lower procedure rate for coronary angiography. Thrombolysis use was higher in the STEMI patients with COVID-19. Most cardiac complications in AMI patients were higher when infected with SARS-CoV-2. Multivariate regression analysis revealed that COVID-19 led to higher odds of mortality and total length of stay in AMI hospitalizations. COVID-19 portends a worse prognosis in hospitalizations with AMI. These admissions have a significantly higher mortality rate and increased complications.

Few studies have reported on mortality beyond one year after sepsis. We aim to describe trends in short- and long-term mortality among patients admitted with sepsis, and to describe the association between clinical characteristics and mortality for improved monitoring, treatment and prognosis.

Patients ≥ 18 years admitted to all Norwegian hospitals (2008-2021) with a first sepsis episode were identified using Norwegian Patient Registry and International Classification of Diseases 10th Revision codes. Sepsis was classified as implicit (known infection site plus organ dysfunction), explicit (unknown infection site), or COVID-19-related sepsis. The outcome was all-cause mortality. We describe age-standardized 30-day, 90-day, 1-, 5- and 10-year mortality for each admission year and estimated the annual percentage change with 95% confidence interval (CI). The association between clinical characteristics and all-cause mortality is reported as hazard ratios (HRs) adjusted for age, sex and calendar year in Cox regression.

The study included 222,832 patients, of whom 127,059 (57.1%) had implicit, 92,928 (41.7%) had explicit, and 2,845 (1.3%) had COVID-19-related sepsis (data from 2020 and 2021). Trends in overall age-standardized 30-day, 90-day, 1- and 5-year mortality decreased by 0.29 (95% CI - 0.39 to - 0.19), 0.43 (95% CI - 0.56 to - 0.29), 0.61 (95% CI - 0.73 to - 0.49) and 0.66 (95% CI - 0.84 to - 0.48) percent per year, respectively. The decrease was observed for all infections sites but was largest among patients with respiratory tract infections. Implicit, explicit and COVID-19-related sepsis had largely similar overall mortality, with explicit sepsis having an adjusted HR of 0.980 (95% CI 0.969 to 0.991) and COVID-19-related sepsis an adjusted HR of 0.916 (95% CI 0.836 to 1.003) compared to implicit sepsis. Patients with respiratory tract infections have somewhat higher mortality than those with other infection sites. Number of comorbidities was positively associated with mortality, but mortality varied considerably between different comorbidities. Similarly, number of acute organ dysfunctions was strongly associated with mortality, whereas the risk varied for each type of organ dysfunction.

Overall mortality has declined over the past 14 years among patients with a first sepsis admission. Comorbidity, site of infection, and acute organ dysfunction are patient characteristics that are associated with mortality. This could inform health care workers and raise the awareness toward subgroups of patients that needs particular attention to improve long-term mortality.

Left ventricular assist devices are known to extend survival in patients with advanced heart failure; however, their association with intracranial hemorrhage is also well-known. We aimed to explore the risk trend and predictors of intracranial hemorrhage in patients with left ventricular assist devices.

We included patients aged 18 years or older with left ventricular assist devices hospitalized in the US from 2005 to 2014 using the National Inpatient Sample. We computed the survey-weighted percentages with intracranial hemorrhage across the 10-year study period and assessed whether the proportions changed over time. Predictors of intracranial hemorrhage were evaluated using multivariable logistic regression model.

Of 33,246 hospitalizations, 568 (1.7%) had intracranial hemorrhage. The number of left ventricular assist devices placements increased from 873 in 2005 to 5175 in 2014. However, the risk of intracranial hemorrhage remained largely unchanged (1.7% to 2.3%; linear trend, P = 0.604). The adjusted odds of intracranial hemorrhage were increased with the presence of one of the following variables: female sex (odds ratio [OR], 1.58; 95% CI, 1.03-2.43), history of ischemic stroke (OR, 3.13; 95% CI, 1.86-5.28), or Charlson Comorbidity Index score of 3 or more (OR, 77.40; 95% CI, 10.03-597.60).

Over the last decade, the risk of intracranial hemorrhage has remained relatively unchanged despite an increase in the use of left ventricular assist devices in patients with advanced heart failure. Women, higher Charlson Comorbidity Index scores, and history of ischemic stroke were associated with higher odds of intracranial hemorrhage in patients with left ventricular assist devices.

Maternal sepsis is a leading cause of maternal death in the United States. Approximately two-thirds of maternal deaths because of sepsis are related to delayed recognition or treatment. New early warning systems using a 2-step approach have been developed for the early recognition of sepsis in obstetrics; however, their performance has not been validated.

This study aimed to assess the performance of 3 primary screening tools introduced by the Society of Obstetric Medicine Australia and New Zealand and the California Maternal Quality Care Collaborative for use in the first step of their 2-step early warning systems. The obstetrically modified quick Sequential (sepsis-related) Organ Failure Assessment score tool, the obstetrically modified Systemic Inflammatory Response Syndrome tool, and the obstetrically modified Systemic Inflammatory Response Syndrome 1 tool were evaluated for the early detection of sepsis in patients with clinically diagnosed chorioamnionitis.

This was a retrospective cohort study using prospectively collected clinical data at a tertiary care center and an affiliated healthcare system. The electronic health records were searched to identify and verify cases with clinically diagnosed chorioamnionitis between November 2017 and September 2022. The flow sheet for every patient was reviewed to determine when criteria were met for any of the 3 tools. The performance of these tools was analyzed using their sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic curve for the identification of sepsis.

There were 545 cases that had the requisite data for inclusion in the analysis. Of note, 11 patients met the criteria for sepsis. Both the obstetrically modified Systemic Inflammatory Response Syndrome and obstetrically modified Systemic Inflammatory Response Syndrome 1 tools had overall similar test characteristics, which were notably different from the obstetrically modified quick Sequential Organ Failure Assessment tool. The screen-positive rate of the obstetrically modified quick Sequential Organ Failure Assessment tool (1.5%; 95% confidence interval, 0.6%-2.9%) was lower than that of the obstetrically modified Systemic Inflammatory Response Syndrome tool (60.0%; 95% confidence interval, 55.7%-64.1%) and the obstetrically modified Systemic Inflammatory Response Syndrome 1 tool (50.0%; 95% confidence interval, 45.8%-54.3%). The sensitivities of the obstetrically modified Systemic Inflammatory Response Syndrome tool (100.0%; 95% confidence interval, 71.5%-100.0%) and the obstetrically modified Systemic Inflammatory Response Syndrome 1 tool (100.0%; 95% confidence interval, 71.5%-100.0%) were higher than that of the obstetrically modified quick Sequential Organ Failure Assessment tool (18.0%; 95% confidence interval, 2.3%-51.8%). All 3 tools had high negative predictive values; however, their positive predictive values were poor.

This study demonstrated that all 3 tools had limitations in screening for sepsis among patients with a clinical diagnosis of chorioamnionitis. The obstetrically modified quick Sequential Organ Failure Assessment tool missed more than half of the sepsis cases and, thus, had poor performance as a primary screening tool for sepsis. Both the obstetrically modified Systemic Inflammatory Response Syndrome and obstetrically modified Systemic Inflammatory Response Syndrome 1 tools captured all sepsis cases; however, they tended to overdetect sepsis.

Teixeira et al. showed that patients admitted to the intensive care unit of a teaching hospital in a non-metropolitan region needed more support, had worse prognostic indices, and had a higher nursing workload in the first 24 hours of admission. In addition, worse outcomes, including mortality, need for dialysis, pressure injury, infection, prolonged mechanical ventilation, and prolonged hospital stay, were observed in the teaching hospital. Worse outcomes were more prevalent in the teaching hospital. Understanding the importance of teaching hospitals to implement well-established care protocols is critical.

To compare the clinical outcomes of patients admitted to the intensive care unit of teaching (HI) and nonteaching (without an academic affiliation; H2) hospitals.

In this prospective cohort study, adult patients hospitalized between August 2018 and July 2019, with a minimum length of stay of 24 hours in the intensive care unit, were included. Patients with no essential information in their medical records to evaluate the study outcomes were excluded. Resuslts: Overall, 219 patients participated in this study. The clinical and demographic characteristics of patients in H1 and H2 were similar. The most prevalent clinical outcomes were death, need for dialysis, pressure injury, length of hospital stay, mechanical ventilation >48 hours, and infection, all of which were more prevalent in the teaching hospital.

Worse outcomes were more prevalent in the teaching hospital. There was no difference between the institutions concerning the survival rate of patients as a function of length of hospital stay; however, a difference was observed in intensive care unit admissions.

Emergency sepsis is a common and serious infectious disease, and its prognosis is influenced by a number of factors.

To analyse the factors influencing the prognosis of patients with emergency sepsis in order to provide a basis for individualised patient treatment and care. By retrospectively analysing the clinical data collected, we conducted a comprehensive analysis of factors such as age, gender, underlying disease, etiology and site of infection, inflammatory indicators, multi-organ failure, cardiovascular function, therapeutic measures, immune status and severity of infection.

Data collection: Clinical data were collected from patients diagnosed with acute sepsis, including basic information, laboratory findings, medical history and treatment options. Variable selection: Variables associated with prognosis were selected, including age, gender, underlying disease, etiology and site of infection, inflammatory indicators, multi-organ failure, cardiovascular function, treatment measures, immune status and severity of infection. Data analysis: The data collected are analysed using appropriate statistical methods such as multiple regression analysis and survival analysis. The impact of each factor on prognosis was assessed according to prognostic indicators, such as survival, length of stay and complication rates.

Descriptive statistics: Descriptive statistics were performed on the data collected from the patients, including their basic characteristics and clinical presentation.

Type 2 diabetes mellitus were independent factors affecting the prognosis of patients with sepsis.

Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018-2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.

Maternal sepsis is a significant cause of maternal morbidity and mortality, and is a potentially preventable cause of maternal death. This Consult aims to summarize what is known about sepsis and provide guidance for the management of sepsis during pregnancy and the postpartum period. Most studies cited are from the nonpregnant population, but where available, pregnancy data are included. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend that clinicians consider the diagnosis of sepsis in pregnant or postpartum patients with otherwise unexplained end-organ damage in the presence of a suspected or confirmed infectious process, regardless of the presence of fever (GRADE 1C); (2) we recommend that sepsis and septic shock in pregnancy be considered medical emergencies and that treatment and resuscitation begin immediately (Best Practice); (3) we recommend that hospitals and health systems use a performance improvement program for sepsis in pregnancy with sepsis screening tools and metrics (GRADE 1B); (4) we recommend that institutions develop their own procedures and protocols for the detection of maternal sepsis, avoiding the use of a single screening tool alone (GRADE 1B); (5) we recommend obtaining tests to evaluate for infectious and noninfectious causes of life-threatening organ dysfunction in pregnant and postpartum patients with possible sepsis (Best Practice); (6) we recommend that an evaluation for infectious causes in pregnant or postpartum patients in whom sepsis is suspected or identified includes appropriate microbiologic cultures, including blood, before starting antimicrobial therapy, as long as there are no substantial delays in timely administration of antibiotics (Best Practice); (7) we recommend obtaining a serum lactate level in pregnant or postpartum patients in whom sepsis is suspected or identified (GRADE 1B); (8) in pregnant or postpartum patients with septic shock or a high likelihood of sepsis, we recommend administration of empiric broad-spectrum antimicrobial therapy, ideally within 1 hour of recognition (GRADE 1C); (9) after a diagnosis of sepsis in pregnancy is made, we recommend rapid identification or exclusion of an anatomic source of infection and emergency source control when indicated (Best Practice); (10) we recommend early intravenous administration (within the first 3 hours) of 1 to 2 L of balanced crystalloid solutions in sepsis complicated by hypotension or suspected organ hypoperfusion (GRADE 1C); (11) we recommend the use of a balanced crystalloid solution as a first-line fluid for resuscitation in pregnant and postpartum patients with sepsis or septic shock (GRADE 1B); (12) we recommend against the use of starches or gelatin for resuscitation in pregnant and postpartum patients with sepsis or septic shock (GRADE 1A); (13) we recommend ongoing, detailed evaluation of the patient's response to fluid resuscitation guided by dynamic measures of preload (GRADE 1B); (14) we recommend the use of norepinephrine as the first-line vasopressor during pregnancy and the postpartum period with septic shock (GRADE 1C); (15) we suggest using intravenous corticosteroids in pregnant or postpartum patients with septic shock who continue to require vasopressor therapy (GRADE 2B); (16) because of an increased risk of venous thromboembolism in sepsis and septic shock, we recommend the use of pharmacologic venous thromboembolism prophylaxis in pregnant and postpartum patients in septic shock (GRADE 1B); (17) we suggest initiating insulin therapy at a glucose level >180 mg/dL in critically ill pregnant patients with sepsis (GRADE 2C); (18) if a uterine source for sepsis is suspected or confirmed, we recommend prompt delivery or evacuation of uterine contents to achieve source control, regardless of gestational age (GRADE 1C); and (19) because of an increased risk of physical, cognitive, and emotional problems in survivors of sepsis and septic shock, we recommend ongoing comprehensive support for pregnant and postpartum sepsis survivors and their families (Best Practice).

To estimate temporal trends in incidence rate (IR) and case fatality during a 14-year period from 2008 to 2021, and to assess possible shifts in these trends during the COVID-19 pandemic.

All Norwegian hospitals 2008-2021.

317 705 patients ≥18 year with a sepsis International Classification of Diseases 10th revision code retrieved from The Norwegian Patient Registry.

Annual age-standardised IRs with 95% CIs. Poisson regression was used to estimate changes in IRs across time, and logistic regression was used to estimate ORs for in-hospital death.

Among 12 619 803 adult hospitalisations, a total of 317 705 (2.5%) hospitalisations in 222 832 (70.0%) unique patients met the sepsis criteria. The overall age-standardised IR of a first sepsis admission was 246/100 000 (95% CI 245 to 247), whereas the age-standardised IR of all sepsis admissions was 352/100 000 (95% CI 351 to 354). In the period 2009-2019, the annual IR for a first sepsis episode was stable (IR ratio (IRR) per year, 0.999; 95% CI 0.994 to 1.004), whereas for recurrent sepsis the IR increased (annual IRR, 1.048; 95% CI 1.037 to 1.059). During the COVID-19 pandemic, the IRR for a first sepsis was 0.877 (95% CI 0.829 to 0.927) in 2020 and 0.929 (95% CI 0.870 to 0.992) in 2021, and for all sepsis it was 0.870 (95% CI 0.810 to 0.935) in 2020 and 0.908 (95% CI 0.840 to 0.980) in 2021, compared with the previous 11-year period. Case fatality among first sepsis admissions declined in the period 2009-2019 (annual OR 0.954 (95% CI 0.950 to 0.958)), whereas case fatality increased during the COVID-19 pandemic in 2020 (OR 1.061 (95% CI 1.001 to 1.124) and in 2021 (OR 1.164 (95% CI 1.098 to 1.233)).

The overall IR of sepsis increased from 2009 to 2019, due to an increasing IR of recurrent sepsis, and indicates that sepsis awareness with updated guidelines and education must continue.

Serum lactate is a potentially valuable biomarker for risk assessment for patients with sepsis, as hyperlactatemia is associated with elevated short-term mortality risks. However, the associations between hyperlactatemia and long-term clinical outcomes in sepsis survivors remain unknown. The objective of this study was to investigate whether hyperlactatemia at the time of hospitalisation for sepsis was associated with worse long-term clinical outcomes in sepsis survivors.

In total, of 4983 sepsis survivors aged ≥ 20 years were enrolled in this study between January 1, 2012, and December 31, 2018. They were divided into low (≤18 mg/dL; n = 2698) and high (>18 mg/dL; n = 2285) lactate groups. The high lactate group was then matched 1:1 by propensity-score method to the low lactate group. The outcomes of interest were all-cause mortality, major adverse cardiac events (MACEs), ischaemic stroke, myocardial infarction, hospitalisation for heart failure, and end-stage renal disease.

After propensity score matching, the high lactate group had greater risks of all-cause mortality (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.41-1.67), MACEs (HR 1.53, 95% CI 1.29-1.81), ischaemic stroke (HR 1.47, 95% CI 1.19-1.81), myocardial infarction (HR 1.52, 95% CI 1.17-1.99), and end-stage renal disease (HR 1.42, 95% CI 1.16-1.72). Subgroup analyses stratified by baseline renal function revealed almost similarity across groups.

We found that hyperlactatemia is associated with long-term risks of mortality and MACEs in sepsis survivors. Physicians may consider more aggressive and prompter management of sepsis in patients who present with hyperlactatemia to improve long-term prognoses.

Introduction: Although there is evidence describing the immunomodulatory effects of macrolide antibiotics, there is little literature exploring the clinical effects these properties may have and their impact on measurable outcomes. Objective: The purpose of this study was to determine if empiric antimicrobial regimens containing azithromycin shorten time to shock resolution. Methods: A retrospective study was performed in adults with septic shock admitted to intensive care units (ICUs) of 3 university-affiliated, urban teaching hospitals between June 2012 and June 2016. Eligible patients with septic shock required treatment with norepinephrine as the first-line vasopressor for a minimum of 4 hours and received at least 48 hours of antimicrobial treatment from the time of shock onset. Propensity scores were utilized to match patients who received azithromycin to those who did not. Results: A total of 3116 patients met initial inclusion criteria. After propensity score matching, 258 patients were included, with 124 and 134 patients in the azithromycin and control groups, respectively. Median shock duration was similar in patients treated with or without azithromycin (45.6 hr vs 59.7 hr, P = .44). In-hospital mortality was also similar (37.9% vs 38.1%, P = .979). There were no significant differences in mechanical ventilation duration, ICU length of stay (LOS), or hospital LOS. Conclusions: In patients admitted to the ICU with septic shock, empiric azithromycin did not have a significant effect on shock duration, mechanical ventilation duration, ICU LOS, hospital LOS, or in-hospital mortality.

This is a study of lipid metabolic gene expression patterns to discover precision medicine for sepsis.

Sepsis patients experience poor outcomes including chronic critical illness (CCI) or early death (within 14 d). We investigated lipid metabolic gene expression differences by outcome to discover therapeutic targets.

Secondary analysis of samples from prospectively enrolled sepsis patients (first 24 hr) and a zebrafish endotoxemia model for drug discovery. Patients were enrolled from the emergency department or ICU at an urban teaching hospital. Enrollment samples from sepsis patients were analyzed. Clinical data and cholesterol levels were recorded. Leukocytes were processed for RNA sequencing and reverse transcriptase polymerase chain reaction. A lipopolysaccharide zebrafish endotoxemia model was used for confirmation of human transcriptomic findings and drug discovery.

The derivation cohort included 96 patients and controls (12 early death, 13 CCI, 51 rapid recovery, and 20 controls) and the validation cohort had 52 patients (6 early death, 8 CCI, and 38 rapid recovery).

The cholesterol metabolism gene 7-dehydrocholesterol reductase (DHCR7) was significantly up-regulated in both derivation and validation cohorts in poor outcome sepsis compared with rapid recovery patients and in 90-day nonsurvivors (validation only) and validated using RT-qPCR analysis. Our zebrafish sepsis model showed up-regulation of dhcr7 and several of the same lipid genes up-regulated in poor outcome human sepsis (dhcr24, sqlea, cyp51, msmo1, and ldlra) compared with controls. We then tested six lipid-based drugs in the zebrafish endotoxemia model. Of these, only the Dhcr7 inhibitor AY9944 completely rescued zebrafish from lipopolysaccharide death in a model with 100% lethality.

DHCR7, an important cholesterol metabolism gene, was up-regulated in poor outcome sepsis patients warranting external validation. This pathway may serve as a potential therapeutic target to improve sepsis outcomes.

Despite recent advances in the clinical management and understanding of sepsis and septic shock, these complex clinical syndromes continue to have high mortality rates. The effect of sex on these diseases' mortality, clinical presentation and morbidity remains controversial. This study aimed to investigate the association of sex with mortality and organ dysfunction in patients with sepsis and septic shock.

Prospectively enrolled patients with clinically defined sepsis and septic shock in three intensive care units at University Medical Center Göttingen, Germany, were investigated. The primary outcomes were 28- and 90-day mortality, while the secondary endpoints included the evaluation of organ dysfunction as measured by clinical scores and laboratory parameters.

A total of 737 septic patients were enrolled, including 373 in septic shock, 484 males, and 253 females. No significant differences in 28- and 90-day mortality were observed in the cohort. However, men with sepsis had significantly higher SOFA scores, SOFA respiratory and renal subscores, bilirubin and creatinine values, and lower weight-adapted urine outputs, indicating higher organ dysfunction compared to women.

Our findings revealed notable differences in organ dysfunction between male and female patients, with males exhibiting more pronounced dysfunction across multiple clinical indicators. These results highlight the potential influence of sex on sepsis disease severity and suggest the need for tailored approaches in sepsis management according to patient sex.

Early diagnosis of sepsis is essential for a favorable disease outcome. The aim of this study was to evaluate the association of initial and subsequent presepsin concentrations with sepsis outcomes.

One hundred sepsis patients were enrolled in the study from two different university centers. Four times during study, concentrations of presepsin, procalcitonin (PCT), and C-reactive protein (CRP) were measured, and Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) score were calculated. Patients were grouped into survivors and nonsurvivors. A sandwich ELISA kit was used to measure presepsin concentrations. To test the changes in biomarkers concentrations and SOFA score and APACHE II score during the disease course and to estimate the differences between outcome groups, generalized linear mixed effects model was used. Receiver operating characteristic curve analysis was performed to determine the prognostic value of presepsin concentrations.

Initial values of presepsin, SOFA score, and APACHE II score were significantly higher in nonsurvivors compared to survivors. Concentrations of PCT and CRP did not differ significantly between outcome groups. ROC curve analyses show a greater predictive ability of initial presepsin concentrations for predicting mortality compared to subsequent measurements of presepsin concentrations.

Presepsin has a good ability to predict mortality. Initial presepsin concentrations better reflects poor disease outcome compared to presepsin concentrations 24 and 72 hours after admission.

Sepsis, defined as an increase of 2 points or more in the sequential organ failure assessment score, is a life-threatening organ dysfunction caused by the dysregulated host response to infection. Volume-conductivity-scatter (VCS) parameters of cell counters which are known as cell population data (CPD) have been suggested to be beneficial in diagnosing sepsis. We aimed to evaluate the diagnostic value of CPD parameters in sepsis in comparison to nonsystemic infection cases (NSI) and non-infectious acute and chronic inflammatory conditions.

We prospectively included four groups of patients" data: sepsis (n = 66), localized infection (pneumonia, n = 59), chronic inflammation (rheumatoid arthritis, n = 92) and noninfectious inflammation (coronary artery bypass graft operation, n = 56) groups, according to their clinical status and laboratory results. Samples for cell counting and serum markers were collected on the same day of culture collection. VCS parameters were measured by Unicel DxH800 Coulter Cellular Analyzer (Beckman Coulter, USA).

Mean neutrophil volume (MN-V-NE), was highest in the sepsis group [155(149-168)] compared to the localized infection [148(140-158)], chronic inflammation [144.5(142-149)] and noninfectious inflammation [149(145.2-153.7)] (P = 0.001, P < 0.001, P < 0.001, respectively). Neutrophil volume SD (SD-V-NE) was higher in the sepsis [21(18.8-23.7)], significantly differentiating sepsis from other groups. The area under curves of procalcitonin and hs-C-reactive protein were 0.846 and 0.837, respectively, in the receiver-operating characteristic curves (ROC) . CPD combinations, (SD-V NE + SD-V LY + SD-V MO), (SD-V NE + SD-V MO), and (MN-V NE + SD-V NE + SD-C LY + SD-V MO) had greater AUC values than procalcitonin's.

VCS parameters might be promising for differentiating sepsis and non-sepsis cases. Additionally, obtaining these data routinely makes their prospects promising without any additional cost and time.

Shock is one of the most common severe syndromes requiring emergency treatment. Acute myocardial infarction guidelines, the surviving sepsis campaign, and low blood volume resuscitation guidelines indicate the prioritization of early identification of shock. APACHE II (Acute Physiology and Chronic Health Evaluation II), SOFA (Sequential Organ Failure Assessment), and MEWS (Modified Early Warning System) scores are used to predict mortality in ICU (intensive care unit) patients. However, similar to APACHE II, SOFA cannot be used for rapid assessment. Hence the need for a new scoring system that is simple, faster, and efficacious in predicting and preventing mortality among shock patients. The present study was conducted to evaluate a new MEWS scoring system for early identification and estimate mortality risk in patients with shock.

A total of 170 patients with shock meeting the inclusion criteria who presented to the ICU of Ramaiah Hospitals from November 2019 to August 2021 were included in the study. Baseline variables, laboratory parameters, APACHE II score, SOFA score, MEWS score, and new MEWS score were compared between the two groups. Patients were followed up till mortality or discharge from ICU.

Among the 170 patients included in the study septic shock (69.4%) was the most common type of shock followed by cardiogenic (7.64%) and hypovolemic shock (7.64%). The requirement of inotropic support and mechanical ventilation was associated with significantly higher mortality (55.6% and 52.6% respectively). The AUROC (area under the curve) for SOFA in predicting mortality was 0.738 (p<0.001). The AUROC for APACHE II score in predicting mortality was 0.758 (p<0.001). The AUROC for MEWS score in predicting mortality was 0.655 (p=0.0002). The AUROC for the new MEWS score in predicting mortality was 0.684 which is more than that of the conventional MEWS score (p <0.001).

New MEWS score is better than the MEWS score in predicting mortality. The new MEWS score is a simple, entirely clinical, inexpensive scoring system that can be done within a short time as a patient contact in an emergency. Hence, the new MEWS score can help in the quick identification of patients who are at high risk for developing shock and can be used as a better predictor of mortality.

Systemic lupus erythematosus (SLE) is associated with higher risks of sepsis and sepsis-related mortality compared to the general population. However, the prognostic impact of SLE in sepsis is uncertain. We used statewide data to identify hospitalizations aged ≥18 years in Texas with sepsis, with and without SLE during 2014-2017. Multilevel logistic regression with propensity adjustment (primary model), propensity score matching, and multivariable logistic regression without propensity adjustment were used to estimate the association of SLE with short-term mortality (defined as in-hospital mortality or discharge to hospice) among sepsis hospitalizations. Among 283,025 sepsis hospitalizations, 2933 (1.0%) had SLE. Compared to sepsis hospitalizations without SLE, those with SLE were younger (aged ≥65 years, 25.0% vs 57.0%) and had higher burden of comorbidities (mean Deyo comorbidity index 3.0 vs 2.6). Short-term mortality of sepsis hospitalizations with and without SLE was 22.9% vs 31.3%. SLE remained associated with lower short-term mortality on the secondary models, but not on the primary one (adjusted odds ratio: 0.905; 95% confidence interval: 0.817-1.001). When in-hospital mortality was used as secondary outcome, SLE was associated with mortality only on propensity score matching. The increased sepsis-related mortality in SLE is driven by higher risk of sepsis, but not by higher case fatality among septic patients. SLE may be associated with lower risk of mortality among septic patients, but further studies are needed due to heterogeneity of the prognostic associations across models.