A decrease in integrin α5ß1/FAK is associated with increased apoptosis of aortic smooth muscle cells in acute type a aortic dissection.

BACKGROUND: Acute type A aortic dissection (AAAD) is a devastating disease. Human aortic smooth muscle cells (HASMCs) exhibit decreased proliferation and increased apoptosis, and integrin α5ß1 and FAK are important proangiogenic factors involved in regulating angiogenesis. The aim of this study was to investigate the role of integrin α5ß1 and FAK in patients with AAAD and the potential underlying mechanisms. METHODS: Aortic tissue samples were obtained from 8 patients with AAAD and 4 organ donors at Zhongshan Hospital of Fudan University. The level of apoptosis in the aortic tissues was assessed by immunohistochemical (IHC) staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays. The expression of integrin α5ß1 and FAK was determined. Integrin α5ß1 was found to be significantly expressed in HASMCs, and its interaction with FAK was assessed via coimmunoprecipitation (Co-IP) analysis. Proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assays and flow cytometry after integrin α5ß1 deficiency. RESULTS: The levels of integrin α5ß1 and FAK were both significantly decreased in patients with AAAD. Downregulating the expression of integrin α5ß1-FAK strongly increased apoptosis and decreased proliferation in HASMCs, indicating that integrin α5ß1-FAK might play an important role in the development of AAAD. CONCLUSIONS: Downregulation of integrin α5ß1-FAK is associated with increased apoptosis and decreased proliferation in aortic smooth muscle cells and may be a potential therapeutic strategy for AAAD.

Machine learning prediction model of major adverse outcomes after pediatric congenital heart surgery: a retrospective cohort study.

BACKGROUND: Major adverse postoperative outcomes (APOs) can greatly affect mortality, hospital stay, care management and planning, and quality of life. This study aimed to evaluate the performance of five machine learning (ML) algorithms for predicting four major APOs after pediatric congenital heart surgery and their clinically meaningful model interpretations. METHODS: Between August 2014 and December 2021, 23 000 consecutive pediatric patients receiving congenital heart surgery were enrolled. Based on the split date of 1 January 2019, the authors selected 13 927 participants for the training cohort, and 9073 participants for the testing cohort. Four predefined major APOs including low cardiac output syndrome (LCOS), pneumonia, renal failure, and deep venous thrombosis (DVT) were investigated. Thirty-nine clinical and laboratory features were inputted in five ML models: light gradient boosting machine (LightGBM), logistic regression (LR), support vector machine, random forest, and CatBoost. The performance and interpretations of ML models were evaluated using the area under the receiver operating characteristic curve (AUC) and Shapley Additive Explanations (SHAP). RESULTS: In the training cohort, CatBoost algorithms outperformed others with the mean AUCs of 0.908 for LCOS and 0.957 for renal failure, while LightGBM and LR achieved the best mean AUCs of 0.886 for pneumonia and 0.942 for DVT, respectively. In the testing cohort, the best-performing ML model for each major APOs with the following mean AUCs: LCOS (LightGBM), 0.893 (95% CI: 0.884-0.895); pneumonia (LR), 0.929 (95% CI: 0.926-0.931); renal failure (LightGBM), 0.963 (95% CI: 0.947-0.979), and DVT (LightGBM), 0.970 (95% CI: 0.953-0.982). The performance of ML models using only clinical variables was slightly lower than those using combined data, with the mean AUCs of 0.873 for LCOS, 0.894 for pneumonia, 0.953 for renal failure, and 0.933 for DVT. The SHAP showed that mechanical ventilation time was the most important contributor of four major APOs. CONCLUSIONS: In pediatric congenital heart surgery, the established ML model can accurately predict the risk of four major APOs, providing reliable interpretations for high-risk contributor identification and informed clinical decisions-making.

Development and external validation of a novel model for predicting new clinically important atrial fibrillation after thoracoscopic anatomical lung cancer surgery: a multicenter retrospective cohort study.

BACKGROUND: New clinically important postoperative atrial fibrillation (POAF) is the most common arrhythmia after thoracoscopic anatomical lung cancer surgery and is associated with increased morbidity and mortality. The full spectrum of predictors remains unclear, and effective assessment tools are lacking. This study aimed to develop and externally validate a novel model for predicting new clinically important POAF. METHODS: This retrospective study included 14 074 consecutive patients who received thoracoscopic anatomical lung cancer surgery from January 2016 to December 2018 in Shanghai Chest Hospital. Based on the split date of 1 January 2018, we selected 8717 participants for the training cohort and 5357 participants for the testing cohort. For external validation, we pooled 2941 consecutive patients who received this surgical treatment from July 2016 to July 2021 in Shanghai Ruijin Hospital. Independent predictors were used to develop a model and internally validated using a bootstrap-resampling approach. The area under the receiver operating characteristic curves (AUROCs) and Brier score were performed to assess the model discrimination and calibration. The decision curve analysis (DCA) was used to evaluate clinical validity and net benefit. New clinically important POAF was defined as a new-onset of POAF that causes symptoms or requires treatment. RESULTS: Multivariate analysis suggested that age, hypertension, preoperative treatment, clinical tumor stage, intraoperative arrhythmia and transfusion, and operative time were independent predictors of new clinically important POAF. These seven candidate predictors were used to develop a nomogram, which showed a concordance statistic (C-statistic) value of 0.740 and good calibration (Brier score; 0.025). Internal validation revealed similarly good discrimination (C-statistic, 0.736; 95% CI: 0.705-0.768) and calibration. The decision curve analysis showed positive net benefits with the threshold risk range of 0-100%. C-statistic value and Brier score were 0.717 and 0.028 in the testing cohort, and 0.768 and 0.012 in the external validation cohort, respectively. CONCLUSIONS: This study identified seven predictors of new clinically important POAF, among which preoperative treatment, intraoperative arrhythmia, and operative time were rarely reported. The established and externally validated model has good performance and clinical usefulness, which may promote the application of prevention and treatment in high-risk patients, and reduce the development and related adverse outcomes of this event.

Derivation of a HEAR Pathway for Emergency Department Chest Pain Patients to Safely Avoid a Second Troponin Test.

The study aims to develop a decision pathway based on HEAR score and 0 h high-sensitivity cardiac troponin T (hs-cTnT) to safely avoid a second troponin test for suspected non-ST elevation myocardial infarction (NSTEMI) in emergency departments. A HEAR score consists of history, electrocardiogram, age, and risk factors. A HEAR pathway is established using a Bayesian approach based on a predefined safety threshold of NSTEMI prevalence in the rule-out group. In total, 7131 patients were retrospectively enrolled, 582 (8.2%) with index visit NSTEMI and 940 (13.2%) with 180-day major adverse cardiovascular events (MACE). For patients with a low-risk HEAR score (0 to 2) and low 0 h hs-cTnT (<14 ng/L), the HEAR pathway recommends early discharge without further testing. After the HEAR pathway had been applied to rule out NSTEMI, the negative predictive value of index visit NSTEMI was 100.0% (95% CI, 99.8% to 100.0%) and false-negative rate of 180-day MACE was 0.40% (95% CI, 0.18% to 0.87%). Compared with the 0 h hs-cTnT < limit of detection (LoD) strategy (<5 ng/L), the HEAR pathway could correctly reclassify 1298 patients without MACE as low risk and lead to a 18.2% decrease (95% CI, 17.4-19.1%) in the need for a second troponin test. The HEAR pathway may lead to a substantial and safe reduction in repeated troponin test for emergency department patients with suspected NSTEMI.

PECSS: Pulmonary Embolism Comprehensive Screening Score to safely rule out pulmonary embolism among suspected patients presenting to emergency department.

BACKGROUND: Pulmonary embolism is a severe cardiovascular disease and can be life-threatening if left untreated. However, the detection rate of pulmonary embolism using existing pretest probability scores remained relatively low and clinical rule out often relied on excessive use of computed tomographic pulmonary angiography. METHODS: We retrospectively collected data from pulmonary embolism suspected patients in Zhongshan Hospital from July 2018 to October 2022. Pulmonary embolism diagnosis and severity grades were confirmed by computed tomographic pulmonary angiography. Patients were randomly divided into derivation and validation set. To construct the Pulmonary Embolism Comprehensive Screening Score (PECSS), we first screened for candidate clinical predictors using univariate logistic regression models. These predictors were then included in a searching algorithm with indicators of Wells score, where a series of points were assigned to each predictor. Optimal D-Dimer cutoff values were investigated and incorporated with PECSS to rule out pulmonary embolism. RESULTS: In addition to Wells score, PECSS identified seven clinical predictors (anhelation, abnormal blood pressure, in critical condition when admitted, age > 65 years and high levels of pro-BNP, CRP and UA,) strongly associated with pulmonary embolism. Patients can be safely ruled out of pulmonary embolism if PECSS ≤ 4, or if 4 < PECSS ≤ 6 and D-Dimer ≤ 2.5 mg/L. Comparing with Wells approach, PECSS achieved lower failure rates across all pulmonary embolism severity grades. These findings were validated in the held-out validation set. CONCLUSIONS: Compared to Wells score, PECSS approaches achieved lower failure rates and better compromise between sensitivity and specificity. Calculation of PECSS is easy and all predictors are readily available upon emergency department admission, making it widely applicable in clinical settings. TRAIL REGISTRATION: The study was retrospectively registered (No. CJ0647) and approved by Human Genetic Resources in China in April 2022. Ethical approval was received from the Medical Ethics Committee of Zhongshan Hospital (NO.B2021-839R).

A novel nomogram for predicting the decision to delayed extubation after thoracoscopic lung cancer surgery.

OBJECTIVE: Delayed extubation was commonly associated with increased adverse outcomes. This study aimed to explore the incidence and predictors and to construct a nomogram for delayed extubation after thoracoscopic lung cancer surgery. METHODS: We reviewed medical records of 8716 consecutive patients undergoing this surgical treatment from January 2016 to December 2017. Using potential predictors to develop a nomogram and using a bootstrap-resampling approach to conduct internal validation. For external validation, we additionally pooled 3676 consecutive patients who underwent this procedure between January 2018 and June 2018. Extubation performed outside the operating room was defined as delayed extubation. RESULTS: The rate of delayed extubation was 1.60%. Multivariate analysis identified age, BMI, FEV1/FVC, lymph nodes calcification, thoracic paravertebral blockade (TPVB) usage, intraoperative transfusion, operative time and operation later than 6 p.m. as independent predictors for delayed extubation. Using these eight candidates to develop a nomogram, with a concordance statistic (C-statistic) value of 0.798 and good calibration. After internal validation, similarly good calibration and discrimination (C-statistic, 0.789; 95%CI, 0.748 to 0.830) were observed. The decision curve analysis (DCA) indicated the positive net benefit with the threshold risk range of 0 to 30%. Goodness-of-fit test and discrimination in the external validation were 0.113 and 0.785, respectively. CONCLUSION: The proposed nomogram can reliably identify patients at high risk for the decision to delayed extubation after thoracoscopic lung cancer surgery. Optimizing four modifiable factors including BMI, FEV1/FVC, TPVB usage, and operation later than 6 p.m. may reduce the risk of delayed extubation.Key Messages:This study identified eight independent predictors for delayed extubation, among which lymph node calcification and anaesthesia type were not commonly reported.Using these eight candidates to develop a nomogram, we could reliably identify high-risk patients for the decision to delayed extubation.Optimizing four modifiable factors, including BMI, FEV1/FVC, TPVB usage, and operation later than 6 p.m. may reduce the risk of delayed extubation.

Progesterone alleviates esketamine-induced hypomyelination via PI3K/Akt signaling pathway in the developing rat brain.

The neurodevelopmental toxicity of anesthetics has been confirmed repeatedly, and esketamine is now widely used in pediatric surgeries. Oligodendrocyte precursor cells (OPCs) evolved into mature oligodendrocytes (OLs) and formed myeline sheath during the early brain development. In this study, we investigated whether esketamine exposure interrupted development of OPCs and induced hypomyelination in rats. Further we explored the roles of PI3K/Akt phosphorylation in OPCs development and myelination. Sprague Dawley rats with different ages (postnatal day (P) 1, 3, 7 and 12) were exposed to 40mg/kg esketamine. Progesterone treatment was given (16 mg/kg per day for 3 days) 24 h after esketamine exposure via the intraperitoneal route. Corpus callosum tissues were collected at P8 or P14 for western blot and immunofluorescence analyses. Esketamine exposure at P7 and P12 significantly reduced myelin basic protein (MBP) expression and CC1+ OLs number in corpus callosum. Esketamine exposure at P7 not only aggravated the mature OLs apoptosis, also decreased the OPCs proliferation and differentiation, which was related with dephosphorylation of PI3K/Akt. Progesterone was able to promote OPCs differentiation and ameliorate esketamine-induced hypomyelination by enhancing PI3K/Akt phosphorylation. Stage-dependent abnormality of OPCs/OLs after esketamine leads to the esketamine-induced hypomyelination. Esketamine interrupted OPCs evolution via PI3K/Akt signaling pathway, which can be ameliorated by progesterone.

Continuous Relationship of Operative Duration with Risk of Adverse Perioperative Outcomes and Early Discharge Undergoing Thoracoscopic Lung Cancer Surgery.

Background: For thoracoscopic lung cancer surgery, the continuous relationship and the trigger point of operative duration with a risk of adverse perioperative outcomes (APOs) and early discharge remain unknown. Methods: This study enrolled 12,392 patients who underwent this surgical treatment. Five groups were stratified by operative duration: <60 min, 60−120 min, 120−180 min, 180−240 min, and ≥240 min. APOs included intraoperative hypoxemia, delayed extubation, postoperative pulmonary complications (PPCs), prolonged air leakage (PAL), postoperative atrial fibrillation (POAF), and transfusion. A restricted cubic spline (RCS) plot was used to characterize the continuous relationship of operative duration with the risk of APOs and early discharge. Results: The risks of the aforementioned APOs increased with each additional hour after the first hour. A J-shaped association with APOs was observed, with a higher risk in those with prolonged operative duration compared with those with shorter values. However, the probability of early discharge decreased from 0.465 to 0.350, 0.217, and 0.227 for each additional hour of operative duration compared with counterparts (<60 min), showing an inverse J-shaped association. The 90 min procedure appears to be a tipping point for a sharp increase in APOs and a significant reduction in early discharge. Conclusions: Our findings have important and meaningful implications for risk predictions and clinical interventions, and early rehabilitation, for APOs.

Albumin alleviated esketamine-induced neuronal apoptosis of rat retina through downregulation of Zn2+-dependent matrix metalloproteinase 9 during the early development.

AIMS: Esketamine upregulates Zn2+-dependent matrix metalloproteinase 9 (MMP9) and increases the neuronal apoptosis in retinal ganglion cell layer during the early development. We aimed to test whether albumin can alleviate esketamine-induced apoptosis through downregulating Zn2+-dependent MMP9. METHODS: We investigate the role of Zn2+ in esketamine-induced neuronal apoptosis by immunofluorescence. MMP9 protein expression and enzyme activity were investigated by zymography in situ., western blot and immunofluorescence. Whole-mount retinas from P7 Sprague-Dawley rats were used. RESULTS: We demonstrated that esketamine exposure increased Zn2+ in the retinal GCL during the early development. Zn2+-dependent MMP9 expression and enzyme activity up-regulated, which eventually aggravated apoptosis. Albumin effectively down-regulated MMP9 expression and activity via binding of free zinc, ultimately protected neurons from apoptosis. Meanwhile albumin treatment promoted activated microglia into multi-nucleated macrophagocytes and decreased the inflammation. CONCLUSION: Albumin alleviates esketamine-induced neuronal apoptosis through decreasing Zn2+ accumulation in GCL and downregulating Zn2+-dependent MMP9.

Role of CD8+ T cell exhaustion in the progression and prognosis of acute respiratory distress syndrome induced by sepsis: a prospective observational study.

BACKGROUND: CD8+ T cells are important for protective immunity against intracellular pathogens. Excessive amounts of antigen and/or inflammatory signals often lead to the gradual deterioration of CD8+ T cell function, a state called "exhaustion". However, the association between CD8+ T cell exhaustion and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how CD8+ T cells and inhibitory receptors were related to the clinical prognosis of ARDS. METHODS: A prospective observational study in an emergency department enrolled patients who were diagnosed with sepsis-associated ARDS according to the sepsis-3 criteria and Berlin definition. Peripheral blood samples were collected within 24 h post recruitment. CD8+ T cell count, proliferation ratio, cytokine secretion, and the expression of coinhibitory receptors were assayed. RESULTS: Sixty-two patients with ARDS met the inclusion criteria. CD8+ T cell counts and proliferation rates were dramatically decreased in non-surviving ARDS patients. Increasing programmed cell death 1 (PD-1) expression on the CD8+ T cell surface was seen in patients with worse organ function, while an increasing level of T cell immunoglobulin mucin-3 (Tim-3) was associated with a longer duration of the shock. Kaplan-Meier analysis showed that low CD8+ T cell percentages and increased inhibitory molecule expression were significantly associated with a worse survival rate. CONCLUSIONS: CD8+ T cells and coinhibitory receptors are promising independent prognostic markers of sepsis-induced ARDS, and increased CD8+ T cell exhaustion is significantly correlated with poor prognosis.

A novel nomogram for predicting respiratory adverse events during transport after interventional cardiac catheterization in children.

Objective: The rate and predictors of respiratory adverse events (RAEs) during transport discharged from operating room after interventional cardiac catheterization in children remain unclear. This study aimed to investigate the incidence and predictors, and to construct a nomogram for predicting RAEs during transport in this pediatric surgical treatment. Methods: This prospective cohort study enrolled 290 consecutive pediatric patients who underwent ventricular septal defects (VSD), atrial septal defects (ASD), and patent ductus arteriosus (PDA) between February 2019 and December 2020. Independent predictors were used to develop a nomogram, and a bootstrap resampling approach was used to conduct internal validation. Composite RAEs were defined as the occurrence of at least 1 complication regarding laryngospasm, bronchospasm, apnea, severe cough, airway secretions, airway obstruction, and oxygen desaturation. Results: The rate of RAEs during transport was 23.1% (67 out of 290). Multivariate analysis identified age (vs. ≤3 years, adjusted odds ratio (aOR) = 0.507, 95% confidence interval (CI), 0.268-0.958, P = 0.036), preoperative upper respiratory tract infections (URI, aOR = 2.335, 95% CI, 1.223-4.460, P = 0.01), type of surgery (vs. VSD, for ASD, aOR = 2.856, 95% CI, 1.272-6.411, P = 0.011; for PDA, aOR = 5.518, 95% CI, 2.425-12.553, P < 0.001), morphine equivalent (vs. ≤0.153 mg/kg, aOR = 2.904, 95% CI, 1.371-6.150, P = 0.005), atropine usage (aOR = 0.463, 95% CI, 0.244-0.879, P = 0.019), and RAEs during extubation to transport (aOR = 5.004, 95% CI, 2.633-9.511, P < 0.001) as independent predictors of RAEs during transport. These six candidate predictors were used to develop a nomogram, which showed a C-statistic value of 0.809 and good calibration (P = 0.844). Internal validation revealed similarly good discrimination (C-statistic, 0.782; 95% CI, 0.726-0.837) and calibration. Decision curve analysis (DCA) also demonstrated the clinical usefulness of the nomogram. Conclusion: The high rate of RAEs during transport reminds us of the need for more medical care and attention. The proposed nomogram can reliably identify pediatric patients at high risk of RAEs during transport and guide clinicians to make proper transport plans. Our findings have important and meaningful implications for RAEs risk prediction, clinical intervention and healthcare quality control.

High-dose vitamin C on sepsis: Protocol of a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study.

Background: Sepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis. Methods and design: Here, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events. Conclusion: The findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis. Clinical trial registration: [http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633].

Influence of the Driving Pressure on Mortality in ARDS Patients with or without Abdominal Obesity: A Retrospective Cohort Study.

Objective: This study sets out to explore if the relationship between the driving pressure and hospital mortality in ARDS patients is influenced by body mass index (BMI) level or the presence of abdominal obesity. Methods: Data were extracted from an online database named "Multiparameter Intelligent Monitoring in Intensive Care III." A total of 1556 patients were included and divided into four subgroups based on both BMI level (BMI ≥30 kg/m2 or BMI ＜30 kg/m2) and abdominal assessment. Driving pressure [i.e., the difference between plateau pressure and positive end-expiratory pressure (PEEP)] within 24 h of invasive mechanical ventilation was compared between survivors and nonsurvivors during hospitalization in each group. A logistic regression model was used for hospital mortality. Results: There were 1556 patients with mild-to-severe ARDS, 666 (42.80%) nonobese patients with nonabdominal obesity, 259 (16.65%) nonobese patients with abdominal obesity, 97 (6.23%) obese patients with nonabdominal obesity, and 534 (34.32%) obese patients with abdominal obesity. Driving pressure in nonobese patients with nonabdominal obesity was significantly lower in survivors (12.77 ± 4.53 cm H2O) than in nonsurvivors (14.26 ± 5.52 cm H2O, p < 0.01). On the contrary, in the other three groups, driving pressure was not significantly different between survivors and nonsurvivors. After a logistic multivariable regression analysis, in nonobese (BMI<30 kg/m2) patients with nonabdominal obesity, the driving pressure was independently associated with increased hospital mortality (OR: 1.04, 95% CI 1.00-1.09, p < 0.05) but not in the other three subgroups. Conclusion: Driving pressure is associated with increase in hospital mortality only in nonobese (BMI <30 kg/m2) patients with nonabdominal obesity.

Gpr174 Knockout Alleviates DSS-Induced Colitis via Regulating the Immune Function of Dendritic Cells.

Background: Dysfunction of the immune system would disturb the intestinal homeostasis and lead to inflammatory bowel disease (IBD). Dendritic cells (DCs) help maintain intestinal homeostasis and immediately respond to pathogens or injuries once the mucosa barriers are destroyed during IBD. G protein-coupled receptors(GPR)174 is an essential regulator of immunity that is widely expressed in most immune cells, including DCs. However, the role of GPR174 in regulating the immune function of DC in colitis has not been investigated. Methods: Dextran sodium sulfate (DSS) was administered to establish the mice colitis model. Data of weight, length of colon, disease activity index (DAI), and macroscopic scores were collected. The flow cytometry was used to detect the infiltrations of T cells and DCs, the mean fluorescence intensity (MFI) of CD80, CD86, CD40, and major histocompatibility complex-II (MHC-II). And T cells proliferataion was measured by carboxyfluorescein diacetate succinimidyl ester (CFSE). The expression of cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-γ (IFN-γ), interleukin -4 (IL-4)) and GPR174 mRNA were measured by Elisa, quantitative polymerase chain reaction (qPCR), and immunofluorescence. RNA of bone-marrow-derived dendritic cells (BMDCs) was extracted for sequencing. Adoptive transfer of BMDCs was administrated intravenously. Results: Gpr174-/- mice exposed to 3% DSS showed significant alleviation characterized by reduced loss of weight, more minor colon damage, and better DAI and macroscopic scores. The expression of pro-inflammatory cytokines (TNF-α, IL-6) decreased, while anti-inflammatory cytokine (IL-10) increased compared with WT mice. In vitro, Gpr174-/- BMDCs showed less maturity, with a declined expression of MHC-II, CD80, CD86 and reduced TNF-α, higher IL-10 after LPS stimulation. Gpr174-/- BMDCs were less capable of activating OT-II naïve CD4+ T cells than WT BMDCs and induced more Th0 cells to differentiate into Treg while less into Th1. Furthermore, the transcriptome sequencing analysis exhibited that Gpr174 participated in TNF-α (NF-κB) signaling, leukocyte transendothelial migration, and Th1/Th2 cell differentiation pathways. Adoptive transfer of Gpr174-/- BMDCs to WT mice ameliorated DSS-induced colitis. Conclusion: Our study indicated that GPR174 was involved in the pathogenesis of IBD by regulating the maturation of the dendritic cells to maintain immune homeostasis. TNF-α (NF-κB) signaling pathway, leukocyte transendothelial migration, and Th1/Th2 cell differentiation pathways may be the target pathway.

Single Cell Raman Spectroscopy Deuterium Isotope Probing for Rapid Antimicrobial Susceptibility Test of Elizabethkingia spp.

Nosocomial infection by multi-drug resistance Elizabethkingia spp. is an emerging concern with severe clinical consequences, particularly in immunocompromised individuals and infants. Efficient control of this infection requires quick and reliable methods to determine the appropriate drugs for treatment. In this study, a total of 31 Elizabethkingia spp., including two standard strains (ATCC 13253 and FMS-007) and 29 clinical isolates obtained from hospitals in China were subjected to single cell Raman spectroscopy analysis coupled with deuterium probing (single cell Raman-DIP). The results demonstrated that single cell Raman-DIP could determine antimicrobial susceptibility of Elizabethkingia spp. in 4 h, only one third of the time required by standard broth microdilution method. The method could be integrated into current clinical protocol for sepsis and halve the report time. The study also confirmed that minocycline and levofloxacin are the first-line antimicrobials for Elizabethkingia spp. infection.

Obesity Does Not Increase Perioperative Outcomes in Older Patients Undergoing Thoracoscopic Anatomic Lung Cancer Surgery.

Objectives: To investigate the relationship between obesity status and perioperative outcomes in elderly patients undergoing thoracoscopic anatomic lung cancer surgery. Methods: From January 2016 to December 2018, we performed a monocentric retrospective cohort study among 4164 consecutive patients aged 65 years or older who underwent thoracoscopic anatomic lung cancer surgery at Shanghai Chest Hospital. Two groups were stratified by body mass index (BMI): nonobese (BMI<28kg/m2) and obese status (BMI≥28kg/m2). Using a 1:1 propensity score matching (PSM) analysis to compare perioperative outcomes between two groups. Results: 4035 older patients were eventually enrolled, with a mean age of 69.8 years (range: 65-87), and 305 patients were eligible for obese status, with a mean BMI of 29.8 ± 1.7kg/m2. Compared with nonobese patients, obese patients were more likely to have higher rates of intraoperative hypoxemia (1.2% vs 3.9%, P=0.001) and new-onset arrhythmia (2.3% vs 4.3%, P=0.034). The difference in intraoperative transfusion and conversion rates and postoperative outcomes regarding pulmonary complications, new-onset arrhythmia, transfusion, length of hospital stay, 30-day readmission and hospitalization costs between two groups were not significant (P>0.05). After a 1:1 PSM analysis, the difference in both intraoperative and postoperative complications among two groups were not significant (P>0.05). In subgroup analysis, patients with BMI≥30kg/m2 had a similar incidence of perioperative complications compared to patients with BMI between 28 and 30 kg/m2 (P>0.05). Conclusions: Our research data support evidence for "obesity paradox" and also contribute the growing body of evidence that obesity in older patients should not exclude candidates for thoracoscopic anatomic lung cancer surgery.

The pathogens of secondary infection in septic patients share a similar genotype to those that predominate in the gut.

BACKGROUND: Secondary nosocomial infections, which are commonly caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and vancomycin-resistant Enterococcus faecium (VRE), often develop in septic patients. This study aimed to identify the origin of secondary systemic pathogens and reveal the underlying mechanism of infection. METHODS: In this prospective, observational case-control study, a total of 34 septic patients, 33 non-septic intensive care unit (ICU) patients and 10 healthy individuals serving as controls were enrolled. Three hundred and twelve fecal samples were collected and subjected to 16S rRNA gene amplicon sequencing. Metagenome sequencing was performed to identify the homology between dominant CRKP or VRE in the intestine and pathogens isolated from secondary infectious sites. C57/BL mice were established as pseudo germ-free animal model by pretreatment with broad-spectrum antibiotics for two weeks. RESULTS: The abundance and diversity of the gut microbiota in septic patients was drastically decreased one week after ICU admission, potentially leading to the enrichment of antibiotic-resistant bacteria, such as CRKP. Furthermore, secondary bloodstream and abdominal infections caused by CRKP or VRE in septic patients occurred after intestinal colonization with the predominant bacterial species. Genomic analysis showed that bacteria isolated from secondary infection had high homology with the corresponding predominant intestinal opportunistic pathogens. In addition, animal model experiments validated the hypothesis that the administration of antibiotics caused the enrichment of CRKP and VRE among the intestinal microbiota, increasing the likelihood of permeation of other tissues and potentially causing subsequent systemic infection in pseudo germ-free mice. CONCLUSION: Our study indicated that the pathogens causing secondary infection in septic patients might originate from the intestinal colonization of pathogens following broad-spectrum antibiotic treatment.

Impact of body mass index on perioperative and oncological outcomes in elderly patients undergoing minimally invasive McKeown esophagectomy for esophageal squamous cell carcinoma.

BACKGROUND: The association between elevated body mass index (BMI) and perioperative and oncological outcomes among elderly patients undergoing minimally invasive McKeown esophagectomy (MIE) remains unclear. METHODS: We performed a single-center retrospective analysis of 526 consecutive patients aged 65 years or older who underwent MIE for esophageal squamous cell carcinoma (SCC) between January 2016 and December 2019. Two groups were stratified by BMI: normal (18.5 ≤ BMI < 24 kg/m2 ) and elevated groups (BMI ≥ 24 kg/m2 ). A 1:1 propensity score matching (PSM) analysis was used to compare perioperative and oncological outcomes between the two groups. RESULTS: A total of 480 elderly patients were eventually enrolled, with a mean age of 70.2 years (range: 65-87), and 185 patients were eligible for elevated BMI, with a mean BMI of 26.3 ± 1.9 kg/m2 . Compared with the normal BMI group, the elevated BMI group had prolonged operation time (261.7 ± 57.2 vs. 278.9 ± 62.7 mins, p = 0.002) and increased incidence of intraoperative hypoxemia (12.2% vs. 21.6%, p = 0.006). The differences in intraoperative estimated blood loss, transfusion, new-onset arrhythmia, and conversion rates and postoperative outcomes regarding pulmonary and surgical complications, intensive care unit and 30-day readmissions, the length of hospital stay, and oncological outcomes regarding R0 dissection, and the number of dissected lymph nodes between two groups were comparable. After a 1:1 PSM analysis, there was no significant difference in both perioperative and oncological outcomes between two groups. CONCLUSIONS: Among elderly patients undergoing MIE for esophageal SCC, there was insufficient evidence to demonstrate that elevated BMI could increase perioperative and oncological adverse outcomes.

The effects of paravertebral blockade usage on pulmonary complications, atrial fibrillation and length of hospital stay following thoracoscopic lung cancer surgery.

STUDY OBJECTIVE: Although combined thoracic paravertebral blockade (TPVB)-general anesthesia (GA) could improve pain control compared to GA alone after thoracoscopic lung cancer surgery, it has not been established whether this improvement in pain control could reduce associated adverse outcomes. Thus, this study aimed to explore the association between TPVB usage and adverse outcomes after thoracoscopic lung cancer surgery. DESIGN: Retrospective cohort study from a prospective database. SETTING: A high-volume thoracic center in China. PATIENTS: 13966 consecutive patients who received thoracoscopic lung cancer surgery from January 2016 to December 2018 in Shanghai Chest Hospital were enrolled. MEASUREMENTS: With a 1:1 propensity score matching (PSM) analysis, adverse outcomes between GA alone and GA-TPVB were investigated. Multivariate and multiple linear regression analysis were used to identify factors and calculate odds radio (OR) for adverse outcomes. RESULTS: The rate of TPVB usage was 14.8% (2070 out of 13,966). TPVB combined with GA was associated with lower rates of postoperative pulmonary complications (PPCs) (30.4% vs 33.5%, P = 0.005) and postoperative atrial fibrillation (POAF) (2.1% vs 2.9%, P = 0.041), and shorter length of hospital stay (LOS) (Median [IQR]; 5[4-5] vs 5[4-6]) days, P < 0.001) compared to GA alone. After a 1:1 PSM analysis, we investigated adverse outcomes in 2640 (1320 pairs) patients with or without TPVB usage, and this association remained existed, namely, the rates of PPCs (29.8% vs 34.2%, P = 0.014) and POAF (2.2% vs 3.6%, P = 0.028) were lower and LOS was shorter (5[4-5] vs 5[4-6] days, P < 0.001) in the GA-TPVB group. In multivariate analysis, the combination of GA plus TPVB was independent predictor for PPCs (OR = 0.879, 95%CI, 0.793-0.974, P = 0.014) and POAF (OR = 0.714, 95%CI, 0.516-0.988, P = 0.042), respectively. However, in multiple linear analysis, lower rates of PPCs and POAF associated with TPVB usage, rather than TPVB usage, were responsible for the reduced LOS. CONCLUSIONS: The usage of TPVB may be a feasible and adjustable approach to reduce the rates of PPCs and POAF and associated LOS in thoracoscopic lung cancer surgery.

Artificial intelligence computed tomography helps evaluate the severity of COVID-19 patients: A retrospective study.

BACKGROUND: Computed tomography (CT) is a noninvasive imaging approach to assist the early diagnosis of pneumonia. However, coronavirus disease 2019 (COVID-19) shares similar imaging features with other types of pneumonia, which makes differential diagnosis problematic. Artificial intelligence (AI) has been proven successful in the medical imaging field, which has helped disease identification. However, whether AI can be used to identify the severity of COVID-19 is still underdetermined. METHODS: Data were extracted from 140 patients with confirmed COVID-19. The severity of COVID-19 patients (severe vs. non-severe) was defined at admission, according to American Thoracic Society (ATS) guidelines for community-acquired pneumonia (CAP). The AI-CT rating system constructed by Hangzhou YITU Healthcare Technology Co., Ltd. was used as the analysis tool to analyze chest CT images. RESULTS: A total of 117 diagnosed cases were enrolled, with 40 severe cases and 77 non-severe cases. Severe patients had more dyspnea symptoms on admission (12 vs. 3), higher acute physiology and chronic health evaluation (APACHE) II (9 vs. 4) and sequential organ failure assessment (SOFA) (3 vs. 1) scores, as well as higher CT semiquantitative rating scores (4 vs. 1) and AI-CT rating scores than non-severe patients (P<0.001). The AI-CT score was more predictive of the severity of COVID-19 (AUC=0.929), and ground-glass opacity (GGO) was more predictive of further intubation and mechanical ventilation (AUC=0.836). Furthermore, the CT semiquantitative score was linearly associated with the AI-CT rating system (Adj R 2=75.5%, P<0.001). CONCLUSIONS: AI technology could be used to evaluate disease severity in COVID-19 patients. Although it could not be considered an independent factor, there was no doubt that GGOs displayed more predictive value for further mechanical ventilation.