Dysfunction In Septic Patients Research Articles

A review of current landscape and definition of septic cardiomyopathy

Abstract Background Septic cardiomyopathy (SCM) is a reversible myocardial dysfunction that is increasingly recognised in critically-ill septic patients. SCM and sepsis cause significant morbidity and mortality. However, the lack of consensus on the diagnostic criteria for SCM makes it difficult to understand how sepsis can impact cardiac function. Purpose To review the current literature regarding SCM and compare the various proposed diagnostic criteria and imaging parameters utilised. Method This literature review comprised of a three-part research method: patient population, imaging modality, and outcomes. Our patient population included critically ill patients diagnosed with sepsis or septic shock. We analysed all cardiac imaging modalities, including TTE, TOE, CT, and CMR. Our outcome was mortality or any related terms. We conducted a comprehensive search of PubMed, EMBASE, and SCOPUS and manually searched for past reviews on the subject. We excluded conference abstracts, review articles, and duplicates using Covidence. Only English-language, adult-audience articles were considered, and the last search update was in November 2022. Result This study analysed 77 papers on SCM, of which 55 were prospective and 18 were retrospective (figure 1). The majority of research was conducted in the ICU, and 61 studies used TTE as the primary imaging modality for assessing SCM. Approximately 44% of the studies evaluated cardiac dysfunction in septic patients using systolic function as the primary metric. About half of the research lacked a clear definition of SCM, and 49% did not provide a definitive LVEF cut-off point (figure 2). 78% of the studies determined the reversibility period to be between 7 and 10 days. The majority of studies required that SCM be diagnosed within 24 hours. However, 66% of the studies did not include any type of imaging follow-up for septic patients with cardiac dysfunction. Conclusion The heterogeneity inherent among these studies points toward the lack of standardisation in measurements and use of various parameters to assesses cardiac dysfunction in septic patients. There is a need for a new definition of SCM that may be better suited to describing the spectrum of cardiac dysfunction in patients with severe sepsis. Further work is required to establish a consensus definition of SCM and a standardised diagnostic approach.Figure 1Figure 2

The association between higher cardiac troponin levels and the development of left ventricular diastolic dysfunction in septic patients with diabetes mellitus.

This study was designed to retrospectively analyze the relationship between the levels of cardiac troponin T (cTnT) and cardiac troponin I (cTnI) and the development of left ventricular diastolic dysfunction (LVDD) in septic patients with diabetes mellitus. Furthermore, the predictive value of cTnT and cTnI in the LVDDdevelopment in those patients was investigated. The clinical information of 159 septic patients with diabetes mellitus treated in the intensive care unit of Affiliated Hospital of Chengde Medical University from June 2016 to January 2023 were retrospectively analyzed. These patients were separated into LVDD group (LVFP > 15mmHg) and non-LVDD group (LVFP ≤ 15mmHg) based on left ventricular filling pressure (LVFP). The differences in clinical data, echocardiographic parameters, as well as cTnT and cTnI levels between the LVDD and non-LVDD groups were compared. The relationship between the cTnT and cTnI levels and the echocardiographic parameters was studied using Pearson correlation analysis. Logistic regression analysis wasconducted to explore the factors that influenced the LVDDdevelopment in septic patients with diabetes. Receiver operator characteristic (ROC) curves were created to evaluate the predictive value of cTnT and cTnI levels for the LVDD developmentin septic patients with diabetes. Totally 159 septic patients with diabetes were included in this study, with 97 patients in the LVDD group and 62 in the non-LVDD group. Compared with the non-LVDD group, patients in the LVDD group had much lower left ventricular (LV) early diastolic peak inflow velocity (E), LV advanced diastolic peak inflow velocity (A), E/A, and early diastolic mitral annular velocity (Em) while significantly higher E/Em. The LVDD group showed much higher levels of cTnI and cTnT than the non-LVDD group (P < 0.05). Significant positive correlation between log10cTnI level and E/Em ratio (r = 0.425, P < 0.001)was revealed by the Pearson correlation analysis. Multivariate analysis showed that E/A, E/Em, cTnI and cTnT were independent risk factorsfor the LVDD developmentin septic patients with diabetes (P < 0.05). As for ROC curve results, the area under the curve (AUC) of cTnT to predict the development of LVDD in septic patients with diabetes was 0.849 (95% CI 0.788-0.910, P < 0.001); the AUC of cTnI was 0.742 (95% CI 0.666-0.817, P < 0.001). Both cTnT and cTnI are independent risk factors and have predictive value for the LVDD development in septic patients with diabetes mellitus.

Emodin protects lipopolysaccharide-induced myocardial injury and mitochondrial dysfunction via PI3K/AKT signaling pathway based on Network Pharmacology

Sepsis combined with myocardial injury is an important cause of septic shock and multiple organ failure. Cardiac dysfunction is a significant manifestation of sepsis and it is associated with the prognosis of the disease. It is assumed that damage to myocardial mitochondrial function is one of the main causes of cardiac dysfunction in septic patients, and the repair of myocardial mitochondrial function may alleviate cardiac dysfunction in septic patients. Emodin has been discovered to serve a variety of pharmacological effects, including anti-tumor, anti-inflammatory, antioxidant, and anti-apoptotic properties. In this study, we investigated the potential protective effect of Emodin on sepsis and revealed the underlying mechanisms using a network pharmacology approach coupled with experimental validation. The model of myocardial injury induced by LPS was established and divided into three groups: the control group, the lipopolysaccharide (LPS) group, and the LPS+Emodin group. The apoptosis rate, reactive oxygen species (ROS), mitochondrial permeability transition pore(MPTP), and mitochondrial membrane potential (MMP) were determined in LPS-induced sepsis Cardiacmyocytes treated with different concentrations of Emodin. In addition, the degree of myocardial mitochondrial damage was evaluated by electron microscopy. Signal pathway-related proteins were determined by Western blotting in vitro. And then, network pharmacology screening revealed TP53, CASP3, ILB, MYC, TNF, PTGS2, and PPARG as the critical overlapping targets in a PPI network, and GO and KEGG analyses revealed the top 10 enriched biological processes and signaling pathways associated with the therapeutic effects of emodin on sepsis. The results show the PI3K-AKT pathway is mainly involved in the emodin-sepsis myocardial injury network. Meanwhile, Emodin has been demonstrated to protect the myocardium from LPS-induced myocardial injury in vitro, and moderate doses of Emodin showed the most prominent effect. Emodin alleviates mitochondrial damage by reducing apoptosis and inhibiting oxidative stress and ameliorates protecting LPS-induced myocardial injury and mitochondrial dysfunction through the PI3K-AKT pathway. This provides a feasible strategy for preventing and treating myocardial injury and mitochondrial dysfunction in sepsis. This study was supported by the Science and Technology Bureau of Zhengjiang (Grant No.SH2022068 and SH2022042). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The predictive value of left ventricular global longitudinal strain in normotensive critically ill septic patients.

Evaluation of left ventricular systolic function using speckle tracking echocardiography is more sensitive than conventional echocardiographic measurement in detecting subtle left ventricular dysfunction in septic patients. Our purpose was to investigate the predictive significance of left ventricular global longitudinal strain in normotensive septic intensive care patients. This observational, prospective cohort study included septic normotensive adults admitted to the intensive care unit between June 1, 2021, and August 31, 2021. Left ventricular systolic function was measured using speckle-tracking echocardiography within 24 hours of admission. One hundred fifty-two patients were enrolled. The intensive care unit mortality rate was 27%. Left ventricular global longitudinal strain was less negative, which indicated worse left ventricular function in non-survivors than survivors (median [interquartile range], -15.2 [-17.2 - -12.5] versus -17.3 [-18.8 - -15.5]; p < 0.001). The optimal cutoff value for left ventricular global longitudinal strain was -17% in predicting intensive care unit mortality (area under the curve, 0.728). Patients with left ventricular global longitudinal strain > -17% (less negative than -17%, which indicated worse left ventricular function) showed a significantly higher mortality rate (39.2% versus 13.7%; p < 0.001). According to multivariate analysis, left ventricular global longitudinal strain was an independent predictor of intensive care unit mortality [OR (95%CI), 1.326 (1.038 - 1.693); p = 0.024], along with invasive mechanical ventilation and Glasgow coma scale, APACHE II, and SOFA risk scores. Impaired left ventricular global longitudinal strain is associated with mortality and provided predictive data in normotensive septic intensive care patients.

Quantification of diaphragmatic dynamic dysfunction in septic patients by bedside ultrasound

Although diaphragmatic dysfunction is an important indicator of severity of illness and poor prognosis in ICU patients, there is no convenient and practical method to monitor diaphragmatic function. This study was designed to analyze diaphragmatic dynamic dysfunction by bedside ultrasound in septic patients and provide quantitative evidence to assess diaphragm function systematically. This prospective observational study was conducted from October 2019 to January 2021 in the Department of Respiratory and Critical Care Medicine. 74 patients suffered from sepsis were recruited and divided into two groups, sepsis group 1 (2 ≤ SOFA ≤ 5, n = 41) and sepsis group 2 (SOFA > 5, n = 33). 107 healthy volunteers were randomly recruited as the control group. In all participants, the diaphragmatic thickness and excursion were measured directly and the dynamic parameters including thickening fraction (TF), EQB/EDB, Contractile velocity, and area under diaphragmatic movement curve (AUDMC) were calculated by bedside ultrasound during quiet breathing (QB) and deep breathing (DB). Each parameter among three groups was analyzed separately by covariance analysis, which was adjusted by age, sex, body mass index, MAP, hypertension, and diabetes. First, contractile dysfunction occurred before diaphragmatic atrophy both in sepsis group 1 and sepsis group 2. Second, compared with the control group, the dynamic parameters showed significant decrease in sepsis group 1 and more obvious change in sepsis group 2, including TF, EQB/EDB. Third, the maximum contractile velocity decreased in sepsis group 1, reflecting the damage of intrinsic contraction efficiency accurately. Finally, per breathing AUDMC in two septic groups were lower than those in control group. However, per minute AUDMC was compensated by increasing respiratory rate in sepsis group 1, whereas it failed to be compensated which indicated gradual failure of diaphragm in sepsis group 2. Diaphragmatic ultrasound can be used to quantitatively evaluate the severity of sepsis patients whose contractile dysfunction occurred before diaphragmatic atrophy. As dynamic parameters, TF and EQB/EDB are early indicator associated with diaphragmatic injury. Furthermore, maximum contractile velocity can reflect intrinsic contraction efficiency accurately. AUDMC can evaluate diaphragmatic breathing effort and endurance to overcome resistance loads effectively.

Correlation between Immature Platetet Fraction Value and SOFA Score in Sepsis Patient

Sepsis is a medical emergency that describes systemic inflammation reaction to infectious process that can lead to organ dysfunction and death. Sequential Organ Failure Assesment (SOFA) score is used to assess severity of organ dysfunction in septic patients. Immature platelet fraction (IPF) value can be used to evaluate thrombopoiesis. Research shows IPF can provide information regarding inflammatory activity and disease prognosis. A high IPF value in septic patient indicates the formation and recruitment of immature platelets that are triggered by infection. The aim of this study was to determine correlation between IPF value and SOFA score in sepsis patients. This was an analytical study with a cross-sectional design in 28 patients with sepsis who met the inclusion and exclusion criteria and conducted IPF tests at Central Laboratory of Dr M. Djamil Padang Hospital. The study was conducted from February 2020 to March 2021. Value of IPF was performed using automated hematology analyzer with flow cytometry method and SOFA scores are assessed by clinicians and obtained from medical records. Data were analyzed by Pearson correlation test, significant if p &lt;0.05. Median value of IPF in patients with sepsis was 4.8 (1.4-15.7) %. Median of SOFA score in patients with sepsis was 5,5 (2-12). Correlation test showed a strong positive correlation between IPF values and SOFA score with r= 0.684 and p &lt;0.05. There was a strong positive correlation between IPF values and SOFA score in sepsis.

Diaphragm function in patients with sepsis and septic shock: A longitudinal ultrasound study

BackgroundPrevious literature on the determinants of diaphragm dysfunction in septic patients is limited. The goal of this study is to assess diaphragm dysfunction in terms of its prevalence and its potential associated factors in septic intensive care unit (ICU) patients. MethodsThis prospective and observational study was conducted between June 2015 and July 2019. Ultrasound measures of diaphragm thickness were performed daily on septic patients. The primary outcome was the prevalence of diaphragm dysfunction at baseline and during the ICU stay. The secondary outcome was the diaphragm thickness. Possible associated factors were prospectively recorded. ResultsFifty patients were enrolled in the study. The prevalence of diaphragm dysfunction was 58%. No diaphragm atrophy was found during the ICU stay. Diaphragm dysfunction was associated with the alteration of consciousness, intra-abdominal sepsis, hypnotics and opioids, and mechanical ventilation. Administration of hypnotics, opioids, and steroids was associated with a decreased diaphragm thickening fraction. Diaphragm dysfunction had no impact on patient outcomes. ConclusionsOur data reveal a high prevalence of diaphragm dysfunction in septic patients at the onset of sepsis. Administration of hypnotics, opioids, and steroids was associated with the alteration of diaphragm function as well as intra-abdominal sepsis.

MiR-501-5p alleviates cardiac dysfunction in septic patients through targeting NR4A3 to prevent its binding with Bcl-2

ABSTRACT Sepsis-induced myocardial dysfunction is a common complication in septic patients. To date, a limited number of biomarkers that could predict cardiomyocyte apoptosis have been explored. In this study, we successfully established a cecal ligation and puncture (CLP)-induced septic model, and it was found that miR-501-5p expression was down-regulated in peripheral blood samples of septic patients with cardiac dysfunction, lipopolysaccharide (LPS)-induced cardiomyocytes, and the myocardium and peripheral blood in the septic model. Moreover, it was revealed that miR-501-5p overexpression could increase left ventricular diastolic pressure (LVDP), fractional shortening (FS), ejection fraction (EF), and maximum rate of the rise of left ventricular pressure (+dp/dt) in vivo, while it decreased the levels of myocardial injury-related indicators. In addition, LPS induction accelerated apoptosis and elevated the inflammation in HL-1 and HCM cells, which could be reversed by miR-501-5p overexpression. Mechanistically, we considered nuclear receptor subfamily 4 group A member 3 (NR4A3) as the target of miR-501-5p, and it was found that miR-501-5p prevented the binding between NR4A3 and Bcl-2. It was found that miR-501-5p exerted an inhibitory effect on cardiomyocyte apoptosis and inflammation in a NR4A3-dependent manner. Overall, our results may provide evidence for consideration of miR-501-5p in the therapy of sepsis.

The Characteristics of Mortality Predictor Scoring for Sepsis Patients in Haji Adam Malik Hospital

Introduction: Sepsis is a leading cause of death in the Intensive Care Unit (ICU) in developed countries and its incidence is increasing. Many scoring systems are used to assess the severity of disease in patients admitted to the ICU. SOFA score to assess the degree of organ dysfunction in septic patients. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system is most often used for patients admitted to the ICU. CCI scoring system to assess the effect of comorbid disease in critically ill patients on mortality. The study aimed to describe the characteristics of the use of scoring to predict patients’ mortality admitted to Haji Adam Malik Hospital. Methods: This is an observational study with a cross-sectional design. A total of 299 study subjects met the inclusion criteria and exclusion criteria, three types of scoring, namely SOFA score, APACHE II score, and CCI score were used to assess the prognosis of septic patients. Data analysis was performed using SPSS. P-value &lt;0.05 was considered statistically significant. Results: A total of 252 people (84.3%) of sepsis patients died. The mean age of the septic patients who died was 54.25 years. The SOFA score ranged from 0-24, the median SOFA score in deceased sepsis patients was 5.0. The APACHE II score ranged from 0-71, the median APACHE II score in deceased sepsis patients was 23.0. The CCI score ranged from 0-37, the median CCI score in deceased sepsis patients was 5.0. Conclusion: Higher scores are associated with an increased probability of death in septic patients. Keywords: Sepsis; mortality predictor; SOFA score; APACHE II score, CCI score.

Immune checkpoint molecule TIGIT manipulates T cell dysfunction in septic patients

Sepsis is a dysregulated host response to infection. T cell dysfunction results in the failure to eradicate pathogens and the increased susceptibility to nosocomial infections and mortality during sepsis. Although PD-1 has shown to be a promising target to interfere with T cells dysfunction, the role of other coinhibitory receptors in sepsis remains largely elusive. Here we demonstrated that the immune checkpoint molecule TIGIT on lymphocytes and the critical role of TIGIT in regulating T cell responses in sepsis. Fifty septic patients and seventeen healthy donors were prospectively enrolled. The expression patterns of TIGIT and other molecules on lymphocytes were quantitated by flow cytometry. Ex vivo functional assays were also conducted. Results show that TIGIT expression on T cells was significantly upregulated in sepsis and septic shock patients relative to healthy donors. Elevated frequencies of TIGIT+ T cells correlated with aggravated inflammatory response and organ injuries. Of note, TIGIT expression on CD8+ T cells showed a competitive capability to predict ICU mortality in sepsis. TIGIT+ T cells expressed higher levels of PD-1, lower levels of CD226, and released fewer cytokines. Strikingly, ex vivo blockade of TIGIT using anti-TIGIT antibody restored the frequencies of cytokine-producing T cells from septic patients. These data illustrate that TIGIT on T cells is being used not only as a clinical predictor of poor prognosis but also as a potential target of novel immunotherapeutic intervention during sepsis.

What's New in Shock, July 2021?

What's New in Shock, July 2021?

Serum microtubule-associated protein light chain 3 type II levels correlate with aggravation and multi-organ dysfunction in septic patients.

Serum microtubule-associated protein light chain 3 type II levels correlate with aggravation and multi-organ dysfunction in septic patients.

The predictive value of central venous-arterial CO2 difference/arterial-central venous O2 difference ratio for progressive organ dysfunction in patients with septic shock after resuscitation

Objective: To study the predictive value of central venous-arterial CO2 difference (Pv-aCO2)/arterial-central venous O2 difference (Ca-vO2) ratio for progressive organ dysfunction in patients with septic shock after resuscitation. Methods: Septic shock patients receiving resuscitation in ICU were retrospectively enrolled from July 2018 to June 2019 at the First Affiliated Hospital Anhui Medical University. Hemodynamic and laboratory data were collected. Single and multivariate logistic regression model was constructed to explore the independent risk factors of progressive organ dysfunction. The predictive value of hemodynamic parameters to progression of organ dysfunction was determined using receiver operating characteristic (ROC)curve analysis. Results: A total of 99 patients were enrolled with 25 patients (25.25%) progressing to organ dysfunction. The norepinephrine dose [0.61 (0.27,1.42) μg·kg-1·min-1 vs. 0.91 (0.47,2.87) μg·kg-1·min-1], blood lactic acid [2.93 (1.77,5.88) mmol/L vs. 6.15 (2.56,8.59) mmol/L], Pv-aCO2 [5.00 (3.98,7.85) mmHg(1 mmHg=0.133 kPa) vs. 7.00 (5.00,8.35) mmHg] and Pv-aCO2/Ca-vO2 [1.36(1.17,1.69) vs. 2.23 (1.83,2.78)] in patients with progressive organ dysfunction were significantly higher than those in patients without(P<0.05). Multivariate logistic regression analysis suggested that Pv-aCO2/Ca-vO2 (OR=20.48,95%CI 5.25-79.93,P<0.001) was independent risk factors for predicting organ dysfunction. The cutoff value of Pv-aCO2/Ca-vO2 was equal or more than 1.77 with a sensitivity of 80.00% and a specificity of 79.73%. Compared with those with Pv-aCO2/Ca-vO2<1.77, patients with Pv-aCO2/Ca-vO2≥1.77 had a greater probability of progressive organ dysfunction (47.37% vs. 8.20%, P<0.001). Conclusion: The progression of organ dysfunction in septic patients after resuscitation is associated with poor prognosis. Pv-aCO2/Ca-vO2 is a good indicator to evaluate oxygen metabolism and predict the progression of organ dysfunction.

Therapeutic Rationale for Endotoxin Removal with Polymyxin B Immobilized Fiber Column (PMX) for Septic Shock.

Endotoxin removal therapy with polymyxin B immobilized fiber column (PMX) has been clinically applied for sepsis and septic shock patients since 1994. The effectiveness and usefulness of this therapy have been demonstrated for more than a quarter of a century. However, a documented survival benefit has not yet been demonstrable in a large, multicenter, randomized and controlled trial. Following the findings derived from a large sepsis clinical trial with PMX in North America, a new trial is ongoing to determine if PMX has a long-term survival benefit when administered to septic patients. Another approach to support a survival benefit from intervention with PMX is to utilize a detailed analysis available from a large clinical data base. The endotoxin adsorption capacity of PMX columns in vitro and the effectiveness of PMX columns can be further demonstrable in animal models. The capability of PMX and details of its mechanism of action to intervene in the sepsis cascade and impede organ dysfunction in septic patients is not fully understood. The surface antigen expression in monocytes and neutrophils are improved after PMX therapy. Immunomodulatory effects as a result of endotoxin removal and/or other mechanisms of action have been suggested. These effects and other potential immune effects may explain some of the improved effects upon organ dysfunction of sepsis and septic shock patients. Endotoxemia may be involved in the pathophysiology of other diseases than sepsis. A rapid diagnostic method to detect and target endotoxemia could allow us to practice precision medicine and expand the clinical indications of endotoxin removal therapy.

Serum Mitochondrial Quality Control Related Biomarker Levels are Associated with Organ Dysfunction in Septic Patients.

To investigate the feasibility and the value of using mitochondrial quality control (MQC)-related proteins as biomarkers in septic patients. The enrolled subjects were divided into four groups: healthy control group (n = 30), intensive care unit (ICU) control group (n = 62), septic nonshock group (n = 40), and septic shock group (n = 94). Serum levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), fission protein 1 (Fis1), mitofusin2 (Mfn2), and Parkin were measured by enzyme-linked immunosorbent assay at the time of enrollment for all groups. Clinical parameters and laboratory test results were also collected. The levels of MQC-related biomarkers between any two of the four groups were significantly different (P < 0.001 for all). The serum levels of PGC-1α, Mfn2, and Parkin were lowest in healthy individuals; the levels were dramatically higher in the ICU control group compared with the others, and they decreased progressively from the septic nonshock group to the septic shock group. However, the pattern for Fis1 was inverse; the more severe the condition was, the higher the level of Fis1. Moreover, there was moderate correlation between MQC-related biomarkers and the SOFA score (PGC-1α, r = -0.662; Fis1, r = 0.609; Mfn2, r = -0.677; Parkin, r = 0.-0.674, P < 0.001 for all). The serum levels of PGC-1α, Fis1, Mfn2, and Parkin were significantly correlated with organ dysfunction and reflected the disease progression and severity. The dynamic surveillance of these four biomarkers could be beneficial to predict outcome and guide treatment.

ASSOCIATION OF NEUTROPHIL-LYMPHOCYTE RATIO AND ACUTE KIDNEY INJURY IN SEPTIC PATIENTS IN THE ICU

SESSION TITLE: Advances in Critical Care Practice SESSION TYPE: Original Investigations PRESENTED ON: October 18-21, 2020 PURPOSE: Acute Kidney injury (AKI) is a common complication among patients with sepsis and conveys increased morbidity and mortality. Neutrophil-lymphocyte ratio (NLR) is a marker of inflammation and has been described to reflect severity of the infectious processes. We investigated the association between admission NLR and the development of AKI in septic patients admitted to the Intensive Care Unit (ICU). METHODS: Patients directly admitted to the ICU from the Emergency Department with a diagnosis of severe sepsis and septic shock between 2012-2014 at a large tertiary care center were included. Baseline demographics and laboratory values were collected retrospectively. The first absolute neutrophil and lymphocyte count of the hospital admission was used to calculate the NLR. Patients were classified into groups based on the degree of NLR elevation. The severe NLR group was defined as NLR greater than 18. The primary outcome was the development of AKI during ICU stay. Multivariate logistic regression was performed to determine predictors of AKI. RESULTS: A total of 125 patients were included in the study. There was a predominance of males (62%) and African Americans (53%). Mean (± SD) age was 54 ± 13 years and overall hospital mortality was 45%. 85 patients (68%) developed AKI during ICU stay. The median NLR in the AKI group was significantly higher than the non-AKI group: 14.14 (IQR 7.30-30.13) vs 8.64 (IQR 3.76-16.8) , p=0.012. The severe NLR group had a median NLR of 32.6 (IQR 24.5-45.7) and included a total of 46 patients (37%). In the univariate analysis, the severe NLR group was significantly associated with longer ICU stay (4 days in the severe NLR group vs 2 days in the non-severe NLR group, p=0.038) and development of AKI (p=0.023). On multivariate analysis, development of AKI was independently associated with severe NLR [adjusted Odds Ratio (OR)= 2.75, 95% Confidence Interval [CI] (1.03-7.39); p=0.044], creatinine level at admission (OR= 1.74, 95% CI 1.13-2.68, p=0.012) and Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR= 1.10, 95% CI 1.03-1.16, p=0.002). Chloride levels at 24 hours from admission was insignificant predictor of AKI in the model (OR= 1.05, 95% CI 0.97-1.13, p=0.229). CONCLUSIONS: Severe elevation of NLR was significantly associated with longer ICU stay and was independently associated with development of AKI in patients with severe sepsis and septic shock even after adjustment for SOFA scores. NLR is a simple laboratory parameter that can be easily obtained to predict kidney dysfunction in septic patients. CLINICAL IMPLICATIONS: AKI in the ICU is independently associated with adverse outcomes. Predictors of AKI may be helpful for early detection of patients at risk of kidney dysfunction and guide management for prevention of the same. DISCLOSURES: No relevant relationships by Afsana Asharaf, source=Web Response No relevant relationships by Rabab Nasim, source=Web Response No relevant relationships by Avantika Nathani, source=Web Response No relevant relationships by Prince Ntiamoah, source=Web Response No relevant relationships by VICTOR PRADO, source=Web Response No relevant relationships by Christian Trujillo, source=Web Response No relevant relationships by Connor Wakefield, source=Web Response

Myocardial Depression in Sepsis: Beneficial Adaptation or Sequelae that Requires Treatment?

Myocardial depression is a common yet reversible phenomenon that occurs in patients in septic shock. Initially, it was unclear whether this provided an adaptive survival benefit, as early studies showed decreased mortality in septic patients with myocardial depression. However, subsequent larger studies have debunked this myth. Given that no benefit exists, cardiac dysfunction in septic patients may be monitored via echocardiography and may be treated with inotropic agents. Beta-blockers provide a novel avenue of treatment as they aid in reducing adrenergic overstimulation and cytokine production, which may drive the pathogenesis of septic shock. This review chronicles how the understanding of myocardial depression in sepsis has evolved and how it should be clinically managed.

Notch signaling pathway regulates T cell dysfunction in septic patients

Sepsis disrupts innate and adaptive immune response, and immune disorders may also impact clinical course of sepsis. Notch signaling pathway plays a vital role in T cell modulation and differentiation. The aim of current study was to investigate the immunoregulatory function of Notch signaling pathway to T cells in patients with sepsis and septic shock. Twenty-seven sepsis patients, twenty-five septic shock patients, and twenty-one normal controls (NCs) were enrolled. Notch receptors mRNA levels were semi-quantified by real-time PCR. The absolute numbers of CD3+, CD4+, and CD8+ T cells were measured by flow cytometry. Key transcriptional factors of CD4+ T cells, cytotoxic molecules in CD8+ T cells, and cytotoxicity of CD8+ T cells were investigated. The regulatory activities of Notch signaling inhibition by γ-secretase inhibitor (GSI) on purified CD4+ and CD8+ T cells from sepsis and septic shock patients were also assessed. Notch1 mRNA relative level was significantly elevated in sepsis and septic shock patients when compared with NCs. CD4+ and CD8+ T cells were dysfunctional in sepsis and septic shock, which presented as decreased cell accounts, down-regulation of Th1/Th17 transcriptional factors and cytotoxic molecules (perforin, granzyme B, and FasL), and reduced cytotoxicity of CD8+ T cells. Notch signaling inhibition by GSI increased Th1 and Th17 differentiation of CD4+ T cells. Moreover, GSI stimulation not only promoted perforin, granzyme B, and FasL mRNA expression in CD8+ T cells, but also elevated CD8+ T cell-induced target cell death and IFN-γ/TNF-α production in sepsis and septic shock. The current data suggest that Notch signaling pathway contributes to T cell dysfunction and limited immune response in sepsis.

Anti-NMDA Receptor Autoantibody Is an Independent Predictor of Hospital Mortality but Not Brain Dysfunction in Septic Patients.

The presence of autoantibodies against neuronal cell surface or synaptic proteins and their relationship to autoimmune encephalitis have recently been characterized. These autoantibodies have been also reported in other pathologic conditions; however, their role during sepsis is not known. This study detected the presence of autoantibodies against neuronal cell surface or synaptic proteins in the serum of septic patients and determined their relationship to the occurrence of brain dysfunction and mortality. This prospective, observational cohort study was performed in four Brazilian intensive care units (ICUs). Sixty patients with community-acquired severe sepsis or septic shock admitted to the ICU were included. Blood samples were collected from patients within 24 h of ICU admission. Antibodies to six neuronal proteins were assessed, including glutamate receptors (types NMDA, AMPA1, and AMPA2); voltage-gated potassium channel complex (VGKC) proteins, leucine-rich glioma-inactivated protein 1 (LGI1), and contactin-associated protein-2 (Caspr2), as well as the GABAB1 receptor. There was no independent association between any of the measured autoantibodies and the occurrence of brain dysfunction (delirium or coma). However, there was an independent and significant relationship between anti-NMDAR fluorescence intensity and hospital mortality. In conclusion, anti-NMDAR was independently associated with hospital mortality but none of the measured antibodies were associated with brain dysfunction in septic patients.

The role of speckle tracking echocardiography for prognostication in patients with severe sepsis or septic shock

Ng et al. [1] reported the results of a very interesting study on sepsis-induced myocardial dysfunction. The authors elegantly matched patients with septic shock (90-day mortality of 41.9 %) with a control group of patients with sepsis (90-day mortality of 0 %) using a relatively novel and more sophisticated echocardiographic approach for the diagnosis of myocardial dysfunction in septic patients—speckle tracking echocardiography. With this approach, systolic dysfunction was assessed by means of global longitudinal strain (GLS) and showed a greater degree of myocardial dysfunction in patients with septic shock compared with controls (GLS −14.5 versus −18.3 %, respectively). On the other hand, left ventricular ejection fraction (LVEF) was similar among groups, again confirming that LVEF does not seem appropriate for evaluating myocardial dysfunction in such a population. This finding is in agreement with recent evidence suggesting no correlation between LVEF and mortality in patients with severe sepsis or septic shock, while an association between diastolic dysfunction and mortality has been suggested [2].