The dynamic change of serum S100B levels from day 1 to day 3 is more associated with sepsis-associated encephalopathy.

We investigated the role of dynamic changes of serum levels S100B protein in brain injury and poor outcome of sepsis. This is a prospective cohort study designed to include 104 adult patients with sepsis who are admitted to ICU from Jan 2015 to Aug 2016. Sepsis was defined as sepsis 3.0. Patients with a GCS score of <15, or at least one positive CAM-ICU score were thought to have brain dysfunction. 59 patients were diagnosed with SAE and the rest 45 patients were diagnosed with non-SAE. Serum S100B was measured on day 1 and 3 after ICU admission. Primary outcomes included brain dysfunction and 28-day/180-day mortality. The SAE group showed a significantly higher APACHE II score, SOFA scores, length of ICU stay, 28-day and 180-day mortality, serum S100B levels on day 1 and day 3. S100B levels on day 1 of 0.226 µg/L were diagnostic for SAE with 80.0% specificity and 66.1% sensitivity, and the area under (AUC) the curve was 0.728, S100B levels on day 3 of 0.144 µg/L were diagnostic for SAE with 84.44% specificity and 69.49% sensitivity, and the AUC was 0.819. In addition, the AUC for S100B on day 3 for predicting 180-day mortality was larger than for S100B on day 1 (0.731 vs. 0.611). Multiple logistic regression analysis showed that S100B3 (p = 0.001) but not S100B1 (p = 0.927) were independently correlated with SAE. Kaplan-Meier survival analysis showed that patients with S100B levels higher than 0.144 µg/L had a lower probability of survival at day 180. There were more patients with encephalopathy and a higher 28-day or 180-day mortality in the ΔS100B + group than in the ΔS100B- group. Multiple logistic regression analysis showed that SAE and IL-6 on day 3 were independently correlated with S100B dynamic increase. These findings suggest that elevated serum S100B levels on day 3 and the dynamic changes of serum S100B levels from day three to one were more associated with brain dysfunction and mortality than that on day 1 in patients with sepsis.

Serum glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 for diagnosis of sepsis-associated encephalopathy and outcome prognostication.

PURPOSE: We investigated the role of serum Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase-L1 (UCH-L1) in diagnosis of sepsis-associated encephalopathy(SAE), predicting prognosis and long-term quality of life with patients of sepsis. MATERIALS AND METHODS: This is a prospective single center study entailed 105 patients whosuffered from sepsis from Jan 2015 to Aug 2016. Serum concentrations of GFAP and UCH-L1 for diagnosis of SAE and predicting prognosis and long-term quality of life with patients of sepsis were analyzed. RESULTS: The serum concentrations of GFAP and UCH-L1 were higher in SAE group than in no-SAE group (p < .001). GFAP and UCH-L1 produced an AUC of 0.824 and 0.812 respectively for diagnosis of SAE with optimal cut-off values 0.532 ng/ml and 7.72 ng/ml respectively. The optimal cut-off values of GFAP and UCH-L1 to distinguish patients with survivors from non-survivors were 0.536 ng/ml and 8.06 ng/ml with an area under the curve of 0.773 and 0.746. Patients with a higher GFAP levels had worse long-term usual activities and patients with a higher UCH-L1 levels had more long-term pain (P = .026). CONCLUSIONS: Serum concentrations GFAP and UCH-L1 early elevated and associated with sepsis-associated encephalopathy, poor prognosis and quality of life.

Characterization of Sepsis and Sepsis-Associated Encephalopathy.

BACKGROUND: Sepsis and sepsis-associated encephalopathy (SAE) are common intensive care unit (ICU) diseases; the morbidity and mortality are high. The present study analyzed the sensitivity of different diagnostic criteria of sepsis 1.0 and 3.0, epidemiological characteristics of sepsis and SAE, and explored its risk factors for death, short-term, and long-term prognosis. METHODS: The retrospective study included patients in ICU from January 2015 to June 2016. After excluding 58 patients, 175 were assigned to either an SAE or a non-SAE group (patients with sepsis but no encephalopathy). The sensitivity of the diagnostic criteria was compared between sepsis 1.0 and 3.0, respectively. Between-group differences in baseline data, Acute Physiology and Chronic Health Evaluation II score (APACHE II score), Sequential Organ Failure Assessment score (SOFA score), etiological data, biochemical indicators, and 28-day and 180-day mortality rates were analyzed. Survival outcomes and long-term prognosis were observed, and risk factors for death were analyzed through 180-day follow-up. RESULTS: The sensitivity did not differ significantly between the diagnostic criteria of sepsis 1.0 and 3.0 (P = .286). The 42.3% incidence of SAE presented a significantly high APACHE II and SOFA scores as well as 28-day mortality and 180-day mortality (all P < .001). The incidence of death was 37.1%. The multivariate stepwise regression analysis demonstrated that the risk of death in SAE group was significantly higher than the non-SAE group (P < .001). Sepsis-associated encephalopathy is a risk factor for sepsis-related death (relative risk [RR] = 2.868; 95% confidence interval: 1.730-4.754; P < .001). Although males showed a significantly high rate of 28-day and 180-day mortality (P = .035 and .045), it was not an independent risk factor for sepsis-related death (P = .072). The long-term prognosis of patients with sepsis was poor with decreased quality of life. No significant difference was observed in prognosis between the SAE and non-SAE groups (P > .05). CONCLUSION: Both diagnostic criteria cause misdiagnosis, and the sensitivity did not differ significantly. The incidence of SAE was high, and 28-day and 180-day mortality rates were significantly higher than those without SAE. Sepsis-associated encephalopathy is a risk factor for poor outcome. The overall long-term prognosis of patients with sepsis was poor, and the quality of life decreased.

Common Carotid Artery Sonography Versus Transthoracic Echocardiography for Cardiac Output Measurements in Intensive Care Unit Patients.

OBJECTIVES: This study was designed to test the effectiveness of common carotid artery sonography in comparison with transthoracic echocardiography (TTE) for cardiac output measurements to provide an easier alternative for cardiac output monitoring in the intensive care unit. METHODS: This study included 148 patients who had common carotid artery Doppler examinations and TTE performed within 8 hours of each other, and the cardiac output measurement results were compared with each other. RESULTS: The mean age of the participants ± SD was 56.8 ± 16.2 years, with male patients composing 54.7% of the cohort. There was no significant difference in carotid and TTE cardiac output between different sexes, age groups, patients with and without mechanical ventilation, and primary indication groups. The overall intraclass correlation coefficient between the carotid and TTE cardiac output was 0.537. In patients with septic shock, multiple trauma, and respiratory failure, the intraclass correlation coefficients between TTE and carotid cardiac output were 0.241, 0.061, and 0.095, respectively. CONCLUSIONS: Carotid cardiac output shows moderate agreement with TTE cardiac output; thus, its use may be considered as an alternative for estimating cardiac output in emergencies and when TTE cardiac output is unobtainable. However, in patients with septic shock, multiple trauma, and respiratory failure, the use of carotid cardiac output is not recommended.

Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats.

BACKGROUND: Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality. Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI, and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization. The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI. METHODS: Septic rat models were established by cecal ligation and puncture (CLP). Rats were divided into the sham group, the CLP group, and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group. Nicotinamide adenine dinucleotide (NAD+), cADPR, CD38, and intracellular Ca2+ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor (TNF)-µ, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities were measured. RESULTS: NAD+, cADPR, CD38, and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca2+ levels (P = 0.007), attenuated lung histological injury (P = 0.023), reduced TNF-µ and MDA levels (P < 0.001 and P = 0.002, respectively) and recovered SOD activity (P = 0.031) in the lungs of septic rats. CONCLUSIONS: The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI.

Blocking NAD(+)/CD38/cADPR/Ca(2+) pathway in sepsis prevents organ damage.

BACKGROUND: Although the nicotinamide adenine dinucleotide (NAD(+))/CD38/cyclic ADP ribose (cADPR)/Ca(2+) signaling pathway has been shown to regulate intracellular calcium homeostasis and functions in multiple inflammatory processes, its role in sepsis remains unknown. The aim of this study was to determine whether the NAD(+)/CD38/cADPR/Ca(2+) signaling pathway is activated during sepsis and whether an inhibitor of this pathway, 8-Br-cADPR, protects the organs from sepsis-induced damage. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP) or sham laparotomies. NAD(+), cADPR, CD38, and intracellular Ca(2+) levels were measured in the hearts, livers, and kidneys of septic rats at 0, 6, 12, 24, and 48 h after CLP surgery. Rats were also divided into sham, CLP, and CLP+8-Br-cADPR groups, and the hearts, livers, and kidneys were hematoxylin-eosin-stained and assayed for malondialdehyde and superoxide dismutase activities. RESULTS: NAD(+), cADPR, CD38, and intracellular Ca(2+) levels increased in the hearts, livers, and kidneys of septic rats as early as 6-24 h after CLP surgery. Treatment with 8-Br-cADPR inhibited sepsis-induced intracellular Ca(2+) mobilization, attenuated tissue injury, reduced malondialdehyde levels, and increased superoxide dismutase activity in septic rats. CONCLUSIONS: The NAD(+)/CD38/cADPR/Ca(2+) signaling pathway was activated during sepsis in the CLP rat model. Blocking this pathway with 8-Br-cADPR protected hearts, livers, and kidneys from sepsis-induced damage.