Human defensin-inspired discovery of peptidomimetic antibiotics.

SignificanceWe report the development of peptidomimetic antibiotics derived from a natural antimicrobial peptide, human α-defensin 5. By engaging multiple bacterial targets, the lead compound is efficacious in vitro and in vivo against bacteria with highly inducible antibiotic resistance, promising a useful therapeutic agent for the treatment of infections caused by antibiotic-resistant bacteria.

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.

Tracheostomy timing and clinical outcomes in ventilated COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: The association of tracheostomy timing and clinical outcomes in ventilated COVID-19 patients remains controversial. We performed a meta-analysis to evaluate the impact of early tracheostomy compared to late tracheostomy on COVID-19 patients' outcomes. METHODS: We searched Medline, Embase, Cochrane, and Scopus database, along with medRxiv, bioRxiv, and Research Square, from December 1, 2019, to August 24, 2021. Early tracheostomy was defined as a tracheostomy conducted 14 days or less after initiation of invasive mechanical ventilation (IMV). Late tracheostomy was any time thereafter. Duration of IMV, duration of ICU stay, and overall mortality were the primary outcomes of the meta-analysis. Pooled odds ratios (OR) or the mean differences (MD) with 95%CIs were calculated using a random-effects model. RESULTS: Fourteen studies with a cumulative 2371 tracheostomized COVID-19 patients were included in this review. Early tracheostomy was associated with significant reductions in duration of IMV (2098 patients; MD - 9.08 days, 95% CI - 10.91 to - 7.26 days, p < 0.01) and duration of ICU stay (1224 patients; MD - 9.41 days, 95% CI - 12.36 to - 6.46 days, p < 0.01). Mortality was reported for 2343 patients and was comparable between groups (OR 1.09, 95% CI 0.79-1.51, p = 0.59). CONCLUSIONS: The results of this meta-analysis suggest that, compared with late tracheostomy, early tracheostomy in COVID-19 patients was associated with shorter duration of IMV and ICU stay without modifying the mortality rate. These findings may have important implications to improve ICU availability during the COVID-19 pandemic. Trial registration The protocol was registered at INPLASY (INPLASY202180088).

Global research trends in perioperative care for the elderly: a bibliometric and visualized study.

PURPOSE: Aged surgical patients are at a relatively higher risk of morbidity and mortality than younger surgical patients. The present study aimed to investigate the trends and research status of perioperative care for the elderly in the anesthesiology field. METHODS: We screened manuscripts published between May 31, 1991, and May 31, 2020, from the Web of Science Core Collection (WoSCC). A clustered network was derived from all references cited in all of the included manuscripts. The top authors, journals, institutions, countries, keywords, co-cited articles, and trends were identified through bibliometric analysis and visualization using CiteSpace 5.8.R3 and VOSviewer 1.6.15. RESULTS: We included a total of 1860 manuscripts published between 1991 and 2020. The number of publications on perioperative care for the elderly sharply increased from 2014 onwards. The United States of America and the University of California, San Francisco were the leading publication country (24.8%, 461/1860) and institution (2.6%, 48/1860), respectively. High-frequency keywords in cluster analysis included the type of anesthesia, postoperative pain management, postoperative cognitive dysfunction, and postoperative delirium, indicating postoperative cognitive dysfunction and postoperative delirium remain the focus areas for research in perioperative care for the elderly. Organ function protection was the new research focus according to the burst detection analysis of top keywords. CONCLUSIONS: The number of studies on perioperative care for the elderly has increased apparently worldwide. Postoperative cognitive dysfunction and postoperative delirium remain primary research focus areas. Organ function protection appears to be the second most highly researched topic in the perioperative care for the 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.

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).

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.

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.

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.

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.

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.

Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot study.

BACKGROUND: Recent studies have demonstrated that mesenchymal stem cells (MSCs) modulate the immune response and reduce lung injury in animal models. Currently, no clinical studies of the effects of MSCs in acute respiratory distress syndrome (ARDS) exist. The objectives of this study were first to examine the possible adverse events after systemic administration of allogeneic adipose-derived MSCs in ARDS patients and second to determine potential efficacy of MSCs on ARDS. METHODS: Twelve adult patients meeting the Berlin definition of acute respiratory distress syndrome with a PaO2/FiO2 ratio of < 200 were randomized to receive allogeneic adipose-derived MSCs or placebo in a 1:1 fashion. Patients received one intravenous dose of 1 × 106 cells/kg of body weight or saline. Possible side effects were monitored after treatment. Acute lung injury biomarkers, including IL-6, IL-8 and surfactant protein D (SP-D), were examined to determine the effects of MSCs on lung injury and inflammation. RESULTS: There were no infusion toxicities or serious adverse events related to MSCs administration and there were no significant differences in the overall number of adverse events between the two groups. Length of hospital stay, ventilator-free days and ICU-free days at day 28 after treatment were similar. There were no changes in biomarkers examined in the placebo group. In the MSCs group, serum SP-D levels at day 5 were significantly lower than those at day 0 (p = 0.027) while the changes in IL-8 levels were not significant. The IL-6 levels at day 5 showed a trend towards lower levels as compared with day 0, but this trend was not statistically significant (p = 0.06). CONCLUSIONS: Administration of allogeneic adipose-derived MSCs appears to be safe and feasible in the treatment of ARDS. However, the clinical effect with the doses of MSCs used is weak, and further optimization of this strategy will probably be required to reach the goal of reduced alveolar epithelial injury in ARDS. TRIAL REGISTRATION: Clinical trials.gov, NCT01902082.

Triggering receptor expressed on myeloid cells-2 protects against polymicrobial sepsis by enhancing bacterial clearance.

RATIONALE: Triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor primarily expressed on macrophages and monocyte-derived cells. TREM-2 not only functions as a regulator of inflammatory response, but also serves as a phagocytic receptor for bacteria. However, the role of TREM-2 in sepsis remains unknown. OBJECTIVES: To investigate whether TREM-2 plays a role in sepsis. METHODS: The manner of expression of TREM-2 was evaluated in patients with sepsis and in polymicrobial septic mouse model induced by the cecum ligation and puncture approach. Recombinant mouse TREM-2 was used to block the effect of TREM-2. Bone marrow-derived myeloid cells (BMMCs) that overexpress TREM-2 were administrated into septic mice at various times after cecum ligation and puncture. MEASUREMENTS AND MAIN RESULTS: The expression levels of TREM-2 were up-regulated in patients with sepsis and septic mice. The kinetics of TREM-2 expression in polymicrobial sepsis was comparable with that of bacteria burden in peritoneal lavage fluid. Blocking the effect of TREM-2 resulted in markedly increased mortality and bacterial burden in polymicrobial sepsis. Administration of TREM-2-overexpressing BMMCs significantly reduced the mortality, even when it was administered 4 hours after the initiation of sepsis. However, injection of TREM-2-overexpressing BMMCs into LPS-challenged endotoxemia mice did not improve the survival rate. The protective effect of TREM-2 in polymicrobial sepsis was not associated with its antiinflammatory properties, but it enhanced bacterial clearance in vivo. Furthermore, administration of TREM-2-overexpressing BMMCs improved the organ injury. CONCLUSIONS: TREM-2 plays an important role in the host defense response to sepsis by enhancing bacterial clearance.

The role of plasma gelsolin in cardiopulmonary bypass induced acute lung injury in infants and young children: a pilot study.

BACKGROUND: Acute lung injury (ALI) induced by cardiopulmonary bypass (CPB, CPB-ALI) is a common and serious complication after cardiac surgery. And infants and young children are more prone to CPB-ALI. The purpose of this study was to investigate the perioperative changes of plasma gelsolin (pGSN) in patients below 3 years of age with cardiac surgeries and CPB, and determine whether pGSN are associated with the occurrence and severity of CPB-ALI. METHODS: Seventy-seven consecutive patients ≤3 years of age with congenital heart diseases (CHD) performed on open heart surgery with CPB were finally enrolled, and assigned to ALI and non-ALI groups according to the American-European Consensus Criteria. Plasma concentrations of gelsolin and total protein were measured at following 8 time points: before CPB (a), after CPB (b), 2 hours after CPB (c), 6 hours after CPB (d), 12 hours after CPB (e), 24 hours after CPB (f), 48 hours after CPB (g) and 72 hours after CPB (h). RESULTS: Twenty-seven (35.1%) patients developed CPB-ALI in the study, including eleven (14.3%) patients with ARDS. The earliest significant drop of pGSN and normalized pGSN (pGSNN) of ALI group both occurred at 6 hours after CPB (p = 0.04 and p < 0.01), which was much earlier than those of non-ALI group (48 hours, p = 0.03 and 24 hours, p < 0.01); PGSN of ALI group before CPB and 6 hours after CPB were both significantly lower than those of non-ALI group (p < 0.01); PGSNN of ALI group before CPB and 6 hours after CPB were both significantly lower than those of non-ALI group (p < 0.01, p = 0.04); PGSN before CPB was the only independent risk factor predicting the occurrence of CPB-ALI (OR, 1.023; 95% CI, 1.007-1.039; p < 0.01) with an AUC of 0.753 (95% CI, 0.626-0.880); The optimal cutoff value of pGSN before CPB was 264.2 mg/L, with a sensitivity of 58.3% and a specificity 94.7%. And lower pGSN before CPB was significantly associated with the severity of CS-AKI (r = -0.45, p < 0.01). CONCLUSIONS: Patients developing CPB-ALI had lower plasma gelsolin reservoir and a much more amount and rapid consumption of plasma gelsolin early after operation. PGSN before CPB was an early and sensitive predictor of CPB-ALI in infants and young children undergoing cardiac surgery, and was negatively correlated with the severity of CPB-ALI.

Establishment of Difficult Caudal Epidural Blockade Prediction Model.

Background: We aimed to develop a predictive difficult caudal epidural blockade (pDCEB) model when ultrasound was not available and verified the role of ultrasound in difficult caudal epidural blockade (CEB). Methods: From October 2018 to March 2019, this study consisted of three phases. First, we prospectively enrolled 202 patients scheduled to undergo caudal epidural anesthesia and assessed risk factors by binary logistic regression to develop the predictive scoring system. Second, we enrolled 87 patients to validate it. The receiver operating characteristic (ROC) curve was used to evaluate the performance of the prediction model. Youden-index was used to determine the cut-off value. Third, we enrolled 68 patients with a high risk of difficult CEB (pDCEB score ≥3) and randomized them into ultrasound and landmark groups to verify the role of ultrasound. Result: The rate of difficult CEB was 14.98% overall 289 patients. We found a correlation between unclear palpation of the sacral hiatus (OR 9.688) and cornua (OR 4.725), the number of the sacral hiatus by palpation ≥1 (OR 4.451), and history of difficult CEB (OR 39.282) with a higher possibility of difficult CEB. The area under the receiver operating characteristic curve of the pDCEB model involving the aforementioned factors was 0.889 (95% CI, 0.827-0.952) in the development cohort and 0.862 (95% CI, 0.747-0.977) in the validation cohort. For patients with a pDCEB score ≥3, a preprocedure ultrasound scan could reduce the incidence of difficult CEB (55.56% in the Landmark group vs. 9.38% in the ultrasound group, p < 0.001). Conclusion: This novel pDCEB score, which takes into account palpation of the sacral hiatus/cornua, number of the sacral hiatus by palpation ≥1, and history of difficult CEB, showed a good predictive ability of difficult CEB. The findings suggested that performing an ultrasound scan is essential for patients with a pDCEB score ≥3. Trial registration: No: ChiCTR1800018871, Site URL: https://www.chictr.org.cn/edit.aspx?pid=31875&htm=4; Principal investigator: Jialian Zhao, Date of registration: 2018.10.14.

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.

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.

[Knowledge graph characteristics of sepsis research based on scientometric study].

OBJECTIVE: To illustrate a relatively complete knowledge system (e.g., research outputs, current hotspots, and future trends) in the sepsis field and to help scholars grasp the scientific research direction or clinical focus of treatment. METHODS: The relevant literatures of sepsis during the time from 1985 to 2019 in Web of Science database were collected. Sepsis-related research contents were generated using softwares (CiteSpace 5.6.R2 and VOSviewer 1.6.13), which using data mining, information processing and knowledge map methods, to analyze the historical evolution and predict the development trend. RESULTS: A total of 8 189 papers on sepsis were published. The volume of publications were increasing yearly from 1985 to 2019, and reached the top list of 1 276 in 2019. For research contents of sepsis, it has formed the basic characteristics of sepsis which focusing on epidemiological studies and animal experiments. Through cluster analysis, the researches mainly focused on six aspects: septic rat, necrotizingenterocolitis, sepsis-associated encephalopathy, acute kidney injury (AKI), gut-derived sepsis, and inflammatory mediator. And it presented the literature characteristics that related to the injury or dysfunction of intestines, brain, liver, kidney or other organs, but the heart and lung researches were more marginal. Additionally, based on the top key words with the strongest citation bursts, it reflected that the development trend of the continuous attention hotspots with "endotoxin" or "endotoxin shock", the significant attention hotspots with "inflammation", "immunity" and "multiple organ dysfunction syndrome" (MODS), and the novel burst attention hotspots with sepsis management including "diagnosis" and "chemotherapy". CONCLUSIONS: Through the hotspots and trends visualization of sepsis, the current researches are prefer to animal experiments, epidemiology, or other basic scientific aspects. Meanwhile, the researches are mostly focusing on inflammatory reaction, immune function or organ dysfunctions. Integrating the knowledge maps of hotspots and trends, based on researches of epidemiology, diagnosis, risk factors, pathogenesis, or treatment, we predict that the future scientific topics will concentrating on childhood sepsis, organ injury mechanism or intervention relating to MODS, and integrated management of sepsis by combining traditional Chinese medicine and Western medicine.

Knowledge of and Compliance with Surviving Sepsis Campaign Guidelines among Anesthesiologists: A Nationwide Survey in China.

We aimed to describe anesthesiologists' knowledge of and compliance with the Surviving Sepsis Campaign (SSC) guidelines in the perioperative management of patients with sepsis in China. We designed a questionnaire-based, cross-sectional survey. We sent out online questionnaires during 2019 to evaluate whether anesthesiologists in China were familiar with and applied SSC guidelines in perioperative management. We also compared anesthesiologists' knowledge of and compliance with the guidelines among different levels of hospital. In this study, we obtained 971 responses from anesthesiology departments across China. The survey responses showed that 39.0% of anesthesiologists rated their knowledge of the SSC guidelines as being "very familiar" or at least "somewhat familiar." In total, 68.9% of respondents chose "Initial fluid resuscitation followed by frequent hemodynamic reassessment" as their therapy strategy for patients with septic shock; 62.0% of anesthesiologists chose lactate as a marker of initial resuscitation in clinical practice, and 39.1% thought bundle therapy needed to be started within 1 hour of sepsis diagnosis. A total of 37.1% and 27.1% of respondents chose hydroxyethyl starches and gelatins, respectively, as the preferred fluids for septic shock. As the first choice of vasopressors in patients with sepsis, 727 (74.9%) anesthesiologists chose the correct answer (norepinephrine). Anesthesiologists from tertiary hospitals (class A) had greater familiarity and compliance with the SSC guidelines than those from other hospitals (P < 0.001). In summary, anesthesiologists in China have some knowledge of the SSC guidelines and tend to practice in keeping with these guidelines. However, for some items, anesthesiologists are not up to date with the latest version of the SSC guidelines. The popularity of these guidelines is not homogenous among different levels of hospital. Anesthesiologists must strengthen their knowledge of the SSC guidelines and update their practice in a regular and timely manner, especially in other tertiary and primary hospitals.