Prediction of postoperative infection in elderly using deep learning-based analysis: an observational cohort study.

Elderly patients are susceptible to postoperative infections with increased mortality. Analyzing with a deep learning model, the perioperative factors that could predict and/or contribute to postoperative infections may improve the outcome in elderly. This was an observational cohort study with 2014 elderly patients who had elective surgery from 28 hospitals in China from April to June 2014. We aimed to develop and validate deep learning-based predictive models for postoperative infections in the elderly. 1510 patients were randomly assigned to be training dataset for establishing deep learning-based models, and 504 patients were used to validate the effectiveness of these models. The conventional model predicted postoperative infections was 0.728 (95% CI 0.688-0.768) with the sensitivity of 66.2% (95% CI 58.2-73.6) and specificity of 66.8% (95% CI 64.6-68.9). The deep learning model including risk factors relevant to baseline clinical characteristics predicted postoperative infections was 0.641 (95% CI 0.545-0.737), and sensitivity and specificity were 34.2% (95% CI 19.6-51.4) and 88.8% (95% CI 85.6-91.6), respectively. Including risk factors relevant to baseline variables and surgery, the deep learning model predicted postoperative infections was 0.763 (95% CI 0.681-0.844) with the sensitivity of 63.2% (95% CI 46-78.2) and specificity of 80.5% (95% CI 76.6-84). Our feasibility study indicated that a deep learning model including risk factors for the prediction of postoperative infections can be achieved in elderly. Further study is needed to assess whether this model can be used to guide clinical practice to improve surgical outcomes in elderly.

Postoperative Complications Associated with Moderate Sedation in Endoscopic Procedures Among Patients with Cirrhosis.

BACKGROUND Moderate sedation for endoscopic intervention has become common and offers increased safety and comfort. Patients with cirrhosis are sicker and at increased risk for complications related to sedation. However, postoperative complications associated with moderate sedation and their risk factors have not been adequately studied in this population. MATERIAL AND METHODS This retrospective study included cirrhotic patients who underwent endoscopic procedures with moderate sedation and were admitted to the First Affiliated Hospital, Zhejiang University School of Medicine, between January 1, 2015, and December 31, 2019. A mixed-effects multivariate logistic regression model determined odds ratios between variables and complications, adjusting for potential confounders. The model was validated with 51 patients admitted from August 28, 2020, to October 12, 2020, at 3 hospitals. RESULTS Among 232 cirrhotic patients, complications were recorded for 40 patients (17.2%). These patients had a significantly longer hospital length of stay (P<0.05), and postprocedural complications (35/40; 87.5%) were the most common type of complication. Moderate sedation-associated postoperative complications were significantly associated with portal hypertension history (odds ratio [OR] 2.201; 95% confidence interval [CI] 0.903, 5.364) and the procedure being performed in the evening (OR 1.971; 95% CI 0.946, 4.106). The area under the receiver-operating characteristic curve was 0.627 (95% CI, 0.534 to 0.719, P=0.012) in the validated subgroup, and the predicted accordance rate was 70%. CONCLUSIONS Moderate sedation-associated postoperative complications were relatively high among cirrhotic patients undergoing endoscopic procedures. Complications were associated with sicker patients who underwent endoscopic procedures in the evening, suggesting the potential need for more intensive care of perioperative management in this population, including anesthesia monitoring.

Effects of Preoperative Oral Carbohydrate on Cirrhotic Patients under Endoscopic Therapy with Anesthesia: A Randomized Controlled Trial.

Preoperative fasting causes significant perioperative discomfort in patients. Preoperative oral carbohydrate (POC) is an important element of the enhanced recovery after surgery protocol, but its effect on cirrhotic patients who tend to have abnormal gastric emptying remains unclarified. We investigated the influence of POC on gastric emptying and preprocedural well-being in cirrhotic patients. A prospective, randomized, controlled study of cirrhotic patients with gastroesophageal varices scheduled for elective therapeutic endoscopy under intravenous anesthesia was conducted. We enrolled 180 patients and divided them into three groups: those not supplemented with carbohydrates for 8 h before therapeutic endoscopy (control group) and those administered a carbohydrate beverage 2 h (2 h group) and 4 h (4 h group) before endoscopy. The residual gastric volume was quantified before anesthesia, gastric emptying was evaluated using gastric ultrasonography, and preprocedural well-being was assessed using the visual analogue scale (VAS). Preanesthesia gastric sonography scores were similar among the three groups. No patient had residual gastric volume > 1.5 ml/kg in the control and 4 h groups, but six patients (11%) had a residual gastric volume of >1.5 ml/kg in the 2 h group, hence were at a risk of regurgitation and aspiration. Moreover, VAS scores for six parameters (thirst, hunger, mouth dryness, nausea, vomiting, and fatigue) in the 2 h group and three parameters (thirst, hunger, and mouth dryness) in the 4 h group were significantly lower than those in the control group, suggesting a beneficial effect on cirrhotic patients' well-being. Preoperative gastric peristaltic and operation scores, postoperative complications, length of hospital stay, and in-hospital expenses were not significantly different among the three groups. Our study indicated that avoiding preoperative fasting with oral carbohydrates administered 4 h before anesthesia can be achieved in cirrhotic patients. Further studies to assess whether POC can help improve postoperative outcomes in cirrhotic patients are needed.

ABT-263 enhanced bacterial phagocytosis of macrophages in aged mouse through Beclin-1-dependent autophagy.

BACKGROUND: Sepsis is a critical challenge for the older adults as the immune function is less responsive by aging. Although cell numbers seem preserved in the older adults, macrophages present age-related function decline, which including reduced chemokines, phagocytosis, and autophagy. ABT-263, an inhibitor of the anti-apoptotic protein Bcl-2, is reported had a senolytic effect which can selectively clear the senescent cells in vivo and rejuvenate the aged tissues. METHODS: We treated the aged (12-16 months) and young (4-6 months) C57BL/6 mouse with ABT-263, then gave the animals cecal slurry injection to induce sepsis to observe the effect of senolytic compound ABT-263 on the survival rate of sepsis. Additionally, we isolated peritoneal macrophages from the aged mouse to investigate the cell function and molecular mechanism. 3-methyladenine (3-MA), a phosphatidylinositol 3-kinases (PI3K) inhibitor, and rapamycin, an autophagy-enhancer, were used to block or mimic the autophagy, respectively. RT-PCR and Western Blot were used to detect autophagy related gene and protein changes in sepsis. EGFP-expressing E. coli was used as a marker to evaluate the phagocytic ability of macrophages. RESULTS: The results showed ABT-263 treatment improved the survival rate of sepsis in the aged mouse which related to autophagy, while blocking the autophagy can eliminate this effect. It is revealed that ABT-263 enhanced the phagocytic ability of the peritoneal macrophages by increasing the Trem-2 receptor. Additionally, ABT-263 blocked the binding of Bcl-2 to Beclin-1, thus induced Beclin-1-dependent autophagy. CONCLUSION: ABT-263 enhanced the macrophage function in aged mouse by increasing the Trem-2 receptors and inducing a beclin-1-dependent autophagy, consequently, protected the aged mouse from sepsis.

Confocal laser endomicroscopy under propofol-based sedation for early gastric cancer and pre-cancerous lesions is associated with better diagnostic accuracy: a retrospective cohort study in China.

BACKGROUND: Confocal laser endomicroscopy (CLE) has advantages in detecting gastric neoplastic lesions, meanwhile it requires strict patient cooperation. Sedation could improve patient cooperation and quality of endoscopy. However, sedation is still not very popular in some resource-limited countries and regions. The purpose of this study was to compare propofol-based sedated versus un-sedated CLE in the value of diagnosing early gastric cancer (EGC) and precancerous lesions. METHODS: A retrospective, cohort, single center study of 226 patients who underwent CLE between January 1, 2015 and December 31, 2017 was performed. Patients enrolled were allocated into the propofol-based sedated group (n = 126) and the un-sedated group (n = 100). The comparison of validity and reliability of CLE for identifying EGC and precancerous lesions between the two groups was performed through analyzing CLE diagnosis and pathological diagnosis. Reporting followed the STROBE guidelines. RESULTS: The area under receiver operating characteristic curve (AUROC) of diagnosing EGC in the sedated group was 0.97 (95 % CI: 0.95 to 0.99), which was higher than that in the un-sedated group (0.88 (95 % CI: 0.80 to 0.97), P = 0.0407). CLE with sedation performed better than without sedation in diagnosing intraepithelial neoplasia and intestinal metaplasia (P = 0.0008 and P = 0.0001, respectively). For patients considered as high-grade intraepithelial neoplasia or EGC by endoscopists, they would not get biopsy during CLE but receive endoscopic submucosal dissection (ESD) subsequently, and the misdiagnosis rate of CLE was 0 % in the sedated group and 27.59 % (95 % CI: 10.30-44.91 %) in the un-sedated group (P = 0.006). CONCLUSIONS: Propofol based sedation was associated with improved diagnostic value of CLE for detecting EGC as well as precancerous lesions (intraepithelial neoplasia OR intestinal metaplasia).

TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis.

Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of their high content of miR-106b-5p, which blocks Mitofusin 2 (Mfn2). In a mouse model of NAFLD-associated sepsis, TREM2 deficiency accelerated the initial progression of NAFLD and subsequent susceptibility to sepsis. Conversely, overexpression of TREM2 in liver macrophages improved hepatic energy supply and sepsis outcome. This study demonstrates that NAFLD is a risk factor for sepsis, providing a basis for precision treatment, and identifies hepatocyte-macrophage metabolic coordination and TREM2 as potential targets for future clinical trials.

Postoperative infectious complications in elderly patients after elective surgery in China: results of a 7-day cohort study from the International Surgical Outcomes Study.

AIM: Despite initiatives to increase elderly patients' access to surgical treatments, the prevalence and impact of postoperative infectious complications (PICs) in elderly patients in China are poorly described. The aim of our study was to describe PICs and associated mortality in elderly patients undertaking elective surgery in China. METHODS: We analyzed data about elderly patients from China during the International Surgical Outcomes Study (ISOS), a 7-day prospective cohort study of outcomes after elective surgery in in-patient adults. All elderly patients (age ≥60 years) from 28 hospitals in China included in the ISOS study were included in this study as well. A review of 2014 elderly patients who underwent elective surgery in April 2014 was conducted. RESULTS: Of 2014 elderly patients, 209 (10.4%) developed at least one postoperative complication. Infectious complications were most frequent, affecting 154 patients (7.6%); there was one death, or 0.6% 30-day mortality, which was a significantly higher rate than among patients without PICs (0%). The most frequent infectious complication was superficial surgical-site infection (3.3%). The length of hospital stay was longer in elderly patients with PICs than in those without PICs. Moreover, a total of 142 elderly patients (7.1%) were routinely sent to critical care after surgery, of whom 97 (68.3%) developed PICs. Compared to elderly patients admitted to a standard ward, those admitted to critical care immediately after surgery had a higher postoperative complication rate and critical care admission rate to treat complications. CONCLUSIONS: The present prospective, multicentre study found that 7.6% of elderly patients in China had PICs after elective surgery that could prolong hospital stay and increase 30-day mortality. The clinical effectiveness of admission to critical care after surgery on elderly patients is not identified. Initiatives to increase elderly patients' access to surgical interventions should also enhance safe perioperative care to reduce PICs in China.

Lung aeration and ventilation after general anesthesia in left lateral position: a prospective observational study using electrical impedance tomography.

BACKGROUND: Endoscopic submucosal dissection (ESD) under general anesthesia in left lateral position may lead to transient impairment of pulmonary function. We used electrical impedance tomography (EIT), an increasingly implied non-invasive instrument for bedside real-time monitoring regional changes in ventilation, to assess the changes of regional lung aeration and ventilation in patients undergoing ESD. METHODS: Twenty-two patients scheduled for elective ESD under mechanical ventilation in left lateral position were studied. We acquired 2-min EIT records at four time points: (M1) baseline, before induction of anesthesia, (M2) after the start of mechanical ventilation and before surgery, (M3) after surgery and before extubation, and (M4) after extubation and before leaving operation room, respectively. To quantify regional changes in lung ventilation, we calculated the ventilation proportion of left and right lung regions. Possible changes in lung aeration were detected by changes in end-expiratory lung impedance (EELI). Global inhomogeneity index (GI) was also analyzed. RESULTS: After tracheal intubation in the left lateral position, left lung showed a lower ventilation proportion (M1, 49.6% vs. M2, 36.2% P<0.05), a reduction in EELI {∆EELI -87 [-809; 253]} and a higher GI index value (M1, 0.29±0.09 vs. M2, 0.41±0.12, P<0.05), while right lung showed a higher ventilation proportion (M1, 50.4% vs. M2, 63.8%, P<0.05) and an increase in EELI {∆EELI 161 [-952; 1,905]}. During ESD operation, no changes in either regional ventilation distribution or GI index were observed. After extubation, the GI values in right and left lung were both returned to the level before anesthesia. CONCLUSIONS: In patients with left lateral position undergoing ESD, left lung was characterized by decreased ventilation and more inhomogeneity while right lung was opposite after intubation. ESD procedure with carbon dioxide insufflation did not lead to significant changes in either regional ventilation or homogeneity. And the change of lung inhomogeneity during ESD procedure is transient.

Improved Analgesic Effect of Paravertebral Blocks before and after Video-Assisted Thoracic Surgery: A Prospective, Double-Blinded, Randomized Controlled Trial.

Despite being less invasive, patients who underwent video-assisted thoracic surgery (VATS) suffered considerable postoperative pain. Paravertebral block (PVB) was proven to provide effective analgesia in patients with VATS; however, there is no difference in pain relief between preoperative PVB and postoperative PVB. This study was aimed to investigate the analgesic efficacy of combination of preoperative and postoperative PVB on the same patient undergoing VATS. In this prospective, double-blinded, randomized controlled trial, 44 patients undergoing VATS were enrolled, and they received patient-controlled intravenous analgesia (PCIA) with sufentanil plus preoperative PVB (Group A, n = 15) or postoperative PVB (Group B, n = 15), or combination of preoperative and postoperative PVB (Group C, n = 14). The primary outcome was sufentanil consumption and PCIA press times in the first 24 hours postoperatively. Also, data of postoperative use of PCIA and visual analogue scale (VAS) were collected. In the first 24 hours postoperatively, median sufentanil consumption in Group C was 0 (0-34.75) µg, which was much less than that in Group A (45.00 (33.00-47.00) µg, p=0.005) and Group B (36 (20.00-50.00) µg, p=0.023). Patients in Group C pressed less times of PCIA (0 (0-0) times) than patients in Group A (2 (1-6) times, p < 0.001) and Group B (2 (1-3) times, p=0.009). Kaplan-Meier analysis showed patients with combination of preoperative and postoperative PVB had a higher PCIA-free rate than patients with either technique alone (p=0.003). The VAS among the three groups was comparable postoperatively. The combination of both preoperative and postoperative PVB provides better analgesic efficacy during the early postoperative period and may be an alternative option for pain control after VATS. This trial is registered with ChiCTR1800017102.

Effects of preoperative oral carbohydrates on patients undergoing ESD surgery under general anesthesia: A randomized control study.

BACKGROUND: Preoperative oral carbohydrate (POC) has been recommended as an important element of the enhanced recovery after surgery (ERAS) protocol, but its effect on patients undergoing endoscopic submucosal dissection (ESD) remains unclear. Our study aims to investigate the effects of POC for ESD surgery, with particular focus on perioperative well-being and gastric peristalsis. METHODS: A prospective, randomized, and controlled study of patients undergoing ESD was conducted. Seventy-three patients were assigned to 2 groups: experiment (36 patients) and control (37 patients). The experiment group received oral carbohydrate solution 710 mL the night before and 355 mL 2 hours prior to operation. The control group fasted for 10 hours prior to operation. Gastric empty assessment, peristaltic score, and operation score were measured. In addition, visual analogue scale (VAS) scores for 6 parameters (thirst, hunger, mouth dryness, nausea, vomit, and weakness) of wellbeing were compared perioperatively. Preoperative basic conditions of patients, postoperative complications, and their clinical outcomes were also recorded. RESULTS: Before anesthesia induction, gastric sonography score was higher in experiment group, while sucked fluid by gastroscopy was similar between 2 groups. And no patient had regurgitation. Moreover, gastric peristaltic score and operation score before operation were both lower in experiment group. Importantly, VAS scores for 3 parameters (thirst, hunger, and mouth dryness) were significantly lower in experiment patients. In addition, clinical outcomes including first time exhaust, first time for drinking water, the usage of hemostasis, postoperative complication, lengths of hospital stay, and in-hospital expense were not significantly different between 2 groups. CONCLUSIONS: Oral administration of carbohydrates preoperatively instead of fasting improves the feelings of thirst, hunger, and mouth dryness in patients following ESD surgery without enhancing risk of regurgitation. And, avoiding preoperative fasting with POC can decrease the degree of gastric peristalsis that may facilitate the successful completion of ESD surgery.

Sphingosine-1-phosphate Receptor 2 Signaling Promotes Caspase-11-dependent Macrophage Pyroptosis and Worsens Escherichia coli Sepsis Outcome.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Pyroptosis, a type of proinflammatory programmed cell death, drives cytokine storm. Caspase-11-dependent macrophage pyroptosis contributes to mortality during sepsis. Sphingosine-1-phosphate receptor 2 (S1PR2) signaling can amplify interleukin-1ß secretion in endotoxin-induced inflammation. Here, we hypothesized that S1PR2 signaling increases caspase-11-dependent macrophage pyroptosis and worsens Gram-negative sepsis outcome. METHODS: A Gram-negative sepsis model was induced through intraperitoneal injection of Escherichia coli. Primary peritoneal macrophages isolated from wild-type, S1pr2-deficient (S1pr2), or nucleotide-binding oligomerization domain-like receptor protein-3-deficient mice were treated with E. coli. Caspase-11 activation, macrophage pyroptosis, and Ras homolog gene family, member A-guanosine triphosphate levels were assessed in those cells. Additionally, monocyte caspase-4 (an analog of caspase-11) expression and its correlation with S1PR2 expression were determined in patients with Gram-negative sepsis (n = 11). RESULTS: Genetic deficiency of S1PR2 significantly improved survival rate (2/10 [20%] in wild-type vs. 7/10 [70%] in S1pr2, P = 0.004) and decreased peritoneal macrophage pyroptosis (pyroptosis rate: 35 ± 3% in wild-type vs. 10 ± 3% in S1pr2, P < 0.001). Decreased caspase-11 activation in S1PR2 deficiency cells contributed to the reduced macrophage pyroptosis. In addition, RhoA inhibitor abrogated the amplified caspase-11 activation in wild-type or S1PR2-overexpressing cells. In patients with Gram-negative sepsis, caspase-4 increased significantly in monocytes compared to nonseptic controls and was positively correlated with S1PR2 (r = 0.636, P = 0.035). CONCLUSIONS: S1PR2 deficiency decreased macrophage pyroptosis and improved survival in E. coli sepsis. These beneficial effects were attributed to the decreased caspase-11 activation of S1PR2-deficient macrophages. S1PR2 and caspase-11 may be promising new targets for treatment of sepsis.

A multifactor model for predicting mortality in critically ill patients: A multicenter prospective cohort study.

PURPOSE: The objective of this study was to develop a model using a combination of routine clinical variables to predict mortality in critically ill patients. METHODS: A cohort of 500 patients recruited from eight university hospital intensive care units (ICUs) was used to develop a model via logistic regression analyses. Discrimination and calibration analyses were performed to assess the model. RESULTS: The model included the lactate level (odds ratio [OR]=1.11, 95% confidence interval [CI] 1.01 to 1.22, P=0.029), neutrophil-to-lymphocyte ratio (OR=1.03, 95% CI 1.01 to 1.04, P=0.002), acute physiology score (OR=1.11, 95% CI 1.06 to 1.15, P<0.001), Charlson comorbidity index (OR=1.36, 95% CI 1.15 to 1.60, P<0.001) and surgery type (OR: selective=Ref, no surgery=8.04, 95% CI 3.74 to 17.30, P<0.001, emergency=3.66, 95% CI 1.60 to 8.36, P=0.002). The model showed good discrimination (area under receiver operating characteristic curve: 0.84, 95% CI: 0.80 to 0.87) and calibration (Hosmer-Lemeshow test P=0.137) for predicting in-hospital mortality. CONCLUSION: The developed multifactor model can be used to effectively predict mortality in critically ill patients at ICU admission.

Adipose-derived mesenchymal stem cells modulate CD14++CD16+ expression on monocytes from sepsis patients in vitro via prostaglandin E2.

BACKGROUND: Mesenchymal stem cells (MSCs) have been shown to reduce sepsis-induced inflammation and improve survival in mouse models of sepsis. CD16+ monocytes are proinflammatory and abundant in inflammatory conditions such as sepsis. The primary objective in this exploratory study was to determine the effects of adipose-derived MSCs (ASCs) on three subsets of monocytes from sepsis patients in vitro and to delineate the underlying mechanism. METHODS: This is a prospective cohort study of patients admitted to the medical intensive care unit (ICU) at an academic medical center. The levels of CD14++CD16+, CD14+CD16++, and CD14++CD16- monocytes from 23 patients in the early phase of severe sepsis or septic shock as well as 25 healthy volunteers were determined via flow cytometry after coculture with or without ASCs. To determine the molecular mechanisms, the effects of exogenous prostaglandin E2 (PGE2) and the cyclooxygenase-2 (COX-2) inhibitor NS-398 on monocyte phenotypes and cytokine expression were also examined. RESULTS: Basal levels of CD14++CD16+ but not CD14+CD16++ monocytes were significantly elevated in severe sepsis and septic shock. A positive linear relationship existed between the levels of CD14++CD16+ monocytes and the Acute Physiology and Chronic Health Evaluation (APACHE) II score as well as Sequential Organ Failure Assessment (SOFA) score. Coculture of ASCs with monocytes from sepsis patients for 24 h significantly reduced CD14++CD16+ expression while increasing the CD14++CD16- phenotype. The coculture also significantly elevated PGE2, COX-2, and prostaglandin E2 receptor (EP)4 levels generated from monocytes. Functionally, ASCs reduced the tumor necrosis factor (TNF)-α and increased the interleukin (IL)-10 secretion in monocytes of septic patients. Furthermore, the effects of ASCs on the CD14++CD16+ phenotype and cytokine expression were mimicked by exogenous PGE2 and abolished by the COX-2 inhibitor NS-398. Additionally, ASCs also modified levels of monocyte phenotypes in a mouse model of sepsis. CONCLUSIONS: Levels of CD14++CD16+ monocytes positively correlate with disease severity scores in the early phase of severe sepsis and septic shock. ASCs switch monocytes of sepsis patients from CD14++CD16+ to CD14++CD16- in vitro and modulate the production of inflammatory cytokines. The immunomodulatory effect of ASCs on monocytes is PGE2-dependent. ASCs may exert their therapeutic effect on sepsis via altering monocyte phenotypes and functions.

Dexmedetomidine Versus Propofol Sedation Improves Sublingual Microcirculation After Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: To compare the effects of dexmedetomidine and propofol on sublingual microcirculation in patients after cardiac surgery. DESIGN: A prospective, randomized, single-blind study. SETTING: University hospital. PARTICIPANTS: Adult patients undergoing elective valve surgery with cardiopulmonary bypass. INTERVENTIONS: On arrival in the intensive care unit (ICU), patients were assigned randomly to receive either dexmedetomidine (0.2-1.5 µg/kg/h) or propofol (5-50 µg/kg/min) with open-label titration to a target Richmond Agitation-Sedation Scale of 0 to -3. MEASUREMENTS AND MAIN RESULTS: Sublingual microcirculation was recorded using sidestream dark-field imaging at ICU admission (baseline [T1]) and 4 hours (T2) and 24 hours after ICU admission (T3). At T2, median changes in perfused small-vessel density and the De Backer score from baseline were significantly greater in the dexmedetomidine group (n = 29) than in the propofol group (n = 32) (1.3 v 0 mm/mm2, p = 0.025; 0.9 v -0.1/mm, p = 0.005, respectively); median changes in small-vessel density and the proportion of perfused small vessels from baseline also tended to be higher in the dexmedetomidine group compared with the propofol group (1.0 v -0.1 mm/mm2, p = 0.050; 2.1% v 0.5%, p = 0.062, respectively). At T3, there still was a trend toward greater improvements in the small-vessel density, proportion of perfused small-vessels, perfused small-vessel density, and De Backer score from baseline in the dexmedetomidine group than in the propofol group. CONCLUSIONS: This trial demonstrated that dexmedetomidine sedation may be better able to improve microcirculation in cardiac surgery patients during the early postoperative period compared with propofol.

Mesenchymal Stem Cell-Educated Macrophages Ameliorate LPS-Induced Systemic Response.

Both bone marrow and adipose-derived mesenchymal stem cells (ASCs) have immunomodulatory effects. The goal of this study was to determine whether ASCs-educated macrophages could directly ameliorate LPS-induced systemic response in a mouse model. Mouse peritoneal macrophages were cocultured with ASCs in a Transwell system for 2 days to educate macrophages. Mice were divided into 5 groups: control, LPS, LPS + ASCs, LPS + untreated macrophages, and LPS + educated macrophages. Educated macrophages decreased lung inflammation, weight loss, pulmonary edema, and inflammatory cytokine response. In vitro, ASCs increased expression of M2 macrophages independent of direct cell-to-cell contact when macrophages were treated with LPS or serum from patients with acute respiratory distress syndrome (ARDS). When macrophages were cultured with serum from ARDS patients who were treated with ASCs or placebo in our previous clinical trial, there was no difference in M2 macrophage levels before and after ASCs treatment indicating a suboptimal response to the treatment protocol. ASCs also reduced the levels of LPS-induced proinflammatory cytokines in vitro which were mimicked by IL-10 and blocked by antibodies for IL-10 and IL-10 receptor supporting the notion that educated macrophages exert their anti-inflammatory effects via IL-10-dependent mechanisms.

Effects of Heart Bypass Surgery on Plasma Aß40 and Aß42 Levels in Infants and Young Children.

Accumulation of ß-amyloid (Aß) plaques is a pathological hallmark of Alzheimer disease. Aß levels in animals and adults were reported to be associated with postoperative cognitive dysfunction (POCD). Our goal was to determine the plasma levels of Aß in infants and young children after cardiac surgery with cardiopulmonary bypass (CPB).Forty-two infants and young children aged from 1 to 35 months undergoing cardiac surgery with general anesthetics were prospectively enrolled from January to June 2014 at a tertiary medical center. Perioperative plasma samples were obtained, and Aß42 and Aß40 levels were measured using ELISA. Other clinical characteristics of the patients were also recorded.Plasma levels of Aß42 and Aß40 decreased dramatically 2 hours after surgery and remained significantly lower 6 hours after operation. Baseline Aß42 level correlated significantly with surgical intensive care unit (SICU) length of stay (LOS) and was an independent predictor for SICU LOS on multivariate analysis.Cardiac surgery with CPB decreases plasma Aß levels. Plasma levels of Aß42 and Aß40 might be used as novel biomarkers for predicting outcomes in the patient population.

Sphingosine 1-phosphate Receptor 2 Signaling Suppresses Macrophage Phagocytosis and Impairs Host Defense against Sepsis.

BACKGROUND: Sepsis is characterized by an inappropriate systemic inflammatory response and bacteremia that promote multiorgan failure and mortality. Sphingosine 1-phosphate receptor 2 (S1PR2) modulates endotoxin-induced inflammation in endothelium. However, as a highly expressed S1P receptor in macrophages, its role in regulating macrophage response to bacterial infection remains unclear. METHODS: Cecal ligation and puncture or intratracheal instillation of Escherichia coli was induced in wild-type or S1pr2-deficient mice. The antibacterial ability of cell-specific S1PR2 was tested in bone marrow reconstitution mice or mice with macrophage-specific deletion. Signaling molecules responsible for S1PR2-mediated phagocytosis were also measured in the bone marrow-derived macrophages. In addition, S1PR2 expression levels and its correlation with severity of sepsis were determined in critically ill patients (n = 25). RESULTS: Both genetic deletion and pharmaceutical inhibition of S1PR2 significantly limited bacterial burden, reduced lung damage, and improved survival (genetic deletion, 0% in S1pr2 vs. 78.6% in S1pr2, P < 0.001; pharmaceutical inhibition, 9.1% in vehicle vs. 22.2% in S1PR2 antagonist, P < 0.05). This protection was attributed to the enhanced phagocytic function of S1PR2-deficient macrophages (mean fluorescent intensity, 2035.2 ± 202.1 vs. 407.8 ± 71.6, P < 0.001). Absence of S1PR2 in macrophage inhibits RhoA-dependent cell contraction and promotes IQGAP1-Rac1-dependent lamellipodial protrusion, whose signaling pathways depend on extracellular stimulators. In septic patients, increased S1PR2 levels in peripheral blood mononuclear cells were positively correlated with the severity of sepsis (r = 0.845, P < 0.001). CONCLUSIONS: This study implies that S1PR2, as a critical receptor in macrophage, impairs phagocytosis and antimicrobial defense in the pathogenesis of sepsis. Interventions targeting S1PR2 signaling may serve as promising therapeutic approaches for sepsis.

Incidence and risk factors of postoperative pulmonary complications in noncardiac Chinese patients: a multicenter observational study in university hospitals.

PURPOSE: To assess the incidence of postoperative pulmonary complications (PPCs) in Chinese inpatients, and to develop a brief predictive risk index. METHODS: Between August 6, 2012, and August 12, 2012, patients undergoing noncardiac operations in four university hospitals were enrolled. The cohort was divided into two subsamples, cohort 1 to develop a predictive risk index of PPCs and cohort 2 to validate it. RESULTS: 1673 patients were enrolled. PPCs were recorded for 163 patients (9.7%), of whom the hospital length of stay (LOS) was longer (P < 0.001). The mortality was 1.84% in patients with PPCs and 0.07% in those without. Logistic Regression modeling in cohort 1 identified nine independent risk factors, including smoking, respiratory infection in the last month, preoperative antibiotic use, preoperative saturation of peripheral oxygen, surgery site, blood lost, postoperative blood glucose, albumin, and ventilation. The model was validated within cohort 2 with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.86 to 0.94). CONCLUSIONS: PPCs are common in noncardiac surgical patients and are associated with prolonged LOS in China. The current study developed a risk index, which can be used to assess individual risk of PPCs and guide individualized perioperative respiratory care.

Defensins and sepsis.

Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1ß production and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins' effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis.