The impact of perioperative ketamine or esketamine on the subjective quality of recovery after surgery: a meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to evaluate the impact of ketamine/esketamine on postoperative subjective quality of recovery (QoR). METHODS: MEDLINE, Embase, Cochrane library, and Google Scholar were searched for randomised controlled trials (RCTs) that examined the impacts of perioperative ketamine/esketamine use and postoperative QoR. The primary outcome was subjective QoR (QoR-9, QoR-15, QoR-40) on postoperative day (POD) 1-3, whereas the secondary outcomes included pain severity, anxiety scores, depression scores, risk of adverse events (i.e. nausea, vomiting, dizziness, drowsiness), and length of stay. RESULTS: The analysis included 18 RCTs (1554 participants; ketamine: seven trials, esketamine: 11 trials), of which 15 were conducted in China. Ketamine/esketamine improved the QoR scores on PODs 1 and 2 compared with the control (standardised mean difference [SMD]: 0.63, P<0.0001 for POD 1; SMD: 0.56, P=0.04 for POD 2), without beneficial effect on POD 3. Subgroup analyses revealed significant differences in QoR scores on POD 1 by regimen (SMD: esketamine 1.14, ketamine 0.01) and country (SMD: China 0.82, other countries -0.21). The emotional domain of QoR was improved from PODs 1 to 3, whereas the other domains were only improved on POD 1. Lower postoperative anxiety (SMD: -0.48, P=0.003) and depression (SMD: -0.72, P=0.001) scores were also observed with ketamine/esketamine use. Furthermore, pain severity was reduced on PODs 1 and 2, with no difference in the risk of adverse events or length of stay. CONCLUSIONS: This meta-analysis demonstrated that ketamine/esketamine use in the perioperative period is associated with improved early subjective QoR, pain severity, and psychological symptoms without an increase in the likelihood of adverse events. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023477580).

Systemic immune-inflammation index for predicting postoperative atrial fibrillation following cardiac surgery: a meta-analysis.

Background: Postoperative atrial fibrillation (POAF) is a frequent complication that may increase morbidity and mortality risk following cardiac surgery. The systemic immune-inflammation index (SII) is an emerging biomarker that provides an integrated measure of inflammation by incorporating neutrophil, lymphocyte, and platelet counts. Recent studies have reported associations between elevated SII and increased POAF risk; however, significant heterogeneity exists regarding its predictive efficacy. This meta-analysis aimed to assess SII's diagnostic efficacy for predicting POAF risk. Methods: To synthesize existing evidence on the ability of perioperative SII for predicting POAF in patients undergoing cardiac surgery, a systematic review and meta-analysis was conducted. In August 2023, a comprehensive literature search was performed to identify relevant studies reporting SII cutoff values with corresponding sensitivity and specificity. The primary aim was to evaluate SII's diagnostic utility for predicting POAF, whereas secondary outcomes included the pooled incidence of POAF and the relationship between the SII and POAF. Results: Eight studies published between 2021 and 2023 with 3,245 patients were included. Six studies involved coronary artery bypass grafting (CABG) surgery; one encompassed various cardiac procedures, and another focused solely on mitral valve surgery. The pooled incidence of POAF was 23.6% [95% confidence interval (CI), 18.7%-29.2%]. Elevated SII significantly increased the odds of POAF by 3.24-fold (odds ratio, 3.24; 95% CI, 1.6-6.55; p = 0.001). SII's pooled sensitivity and specificity for predicting POAF were 0.80 (95% CI, 0.68-0.89) and 0.53 (95% CI, 0.23-0.8), respectively. The SII had moderate predictive accuracy based on a hierarchical summary receiver operating characteristic (HSROC) area under the curve of 0.78 (95% CI, 0.74-0.81). Subgroup analyses, whether focusing on CABG alone or CABG with cardiopulmonary bypass (CPB), both indicated an area under the HSROC curve of 0.78 (95% CI, 0.74-0.81). Conclusion: Elevated SII is significantly correlated with an increased POAF risk following cardiac surgery, highlighting its utility as a predictive biomarker. Considering its moderate diagnostic accuracy, further research is essential for clarifying SII's clinical effectiveness, either as an independent predictor or combined with other risk factors, for stratifying patients at high POAF risk. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023456128].

Efficacy of electroacupuncture in improving postoperative ileus in patients receiving colorectal surgery: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to evaluate the efficacy and safety of electroacupuncture (EA) in improving postoperative ileus after colorectal surgery. METHODS: Electronic databases (e.g. Medline) were screened to identify randomized controlled trials that focused on the association between EA and postoperative ileus. Time to first flatus served as the primary outcome, while the secondary outcomes included time required for the recovery of other gastrointestinal functions (e.g. bowel sound recovery), time to tolerability of liquid/solid food, postoperative pain scores, risk of overall complications, and hospital length of stay. RESULTS: Our meta-analysis focusing on 16 studies with a total of 1562 patients demonstrated positive associations of EA with shorter times to the first flatus [mean difference (MD): -10.1 h, P <0.00001, n =1562], first defecation (MD: -11.77 h, P <0.00001, n =1231), bowel sound recovery (MD: -10.76 h, P <0.00001, n =670), tolerability of liquid (MD: -16.44 h, P =0.0002, n =243), and solid food (MD: -17.21 h, P =0.005, n =582) than those who received standard care. The use of EA was also correlated with a lower risk of overall complications (risk ratio:0.71, P =0.04, n =1011), shorter hospital length of stay (MD: -1.22 days, P =0.0001, n =988), and a lower pain score on postoperative days two (standardized MD: -0.87, P =0.009, n =665) and three (standardized MD: -0.45, P <0.00001, n =795), without a difference in time to first ambulation. CONCLUSION: Our findings showed an association between EA and enhanced gastrointestinal functional recovery and reduced pain severity following colorectal surgery, highlighting the potential benefits of incorporating EA into perioperative care to enhance recovery outcomes in this setting.

Association between the neutrophil-to-lymphocyte ratio and cognitive impairment: a meta-analysis of observational studies.

Background: Systemic inflammation is one of the underlying mechanisms of cognitive impairment. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a systemic inflammation indicator. This meta-analysis aimed to evaluate the association between high NLR and cognitive impairment (CI) risk. Method: A comprehensive systematic search was conducted to identify eligible studies published until May 30, 2023. The reference group comprised patients with the lowest NLR level, whereas the exposure group comprised those with the highest NLR level. The main outcome was to examine the relationship between NLR and CI risk. The secondary outcome included the association between patient characteristics or comorbidities and CI risk. Results: This meta-analysis included 11 studies published between 2018 and 2023, involving 10,357 patients. Patients with CI had a higher NLR than those without (mean difference=0.35, 95% confidence interval [CI]: 0.26-0.44, p < 00001, I2 = 86%). Consistently, pooled results revealed an association between high NLR and CI risk (odds ratio [OR]=2.53, 95% CI:1.67-3.82, p<0.0001, I2 = 84%). Furthermore, aging (mean difference =4.31 years, 95% CI:2.83-5.8, p < 0.00001, I2 = 92%), diabetes (OR=1.59, 95% CI:1.35-1.88, p < 0.00001, I2 = 66%), and hypertension (OR=1.36, 95% CI:1.19-1.57, p < 0.00001, I2 = 0%) were significant risk factors for CI. However, no significant associations were observed between CI and male gender (OR = 0.84, 95% CI:0.64-1.11, p = 0.22, I2 = 81%), body mass index (mean = -0.32 kg/m2, 95% CI: -0.82, 0.18, p = 0.2, I2 = 82%), alcohol consumption (OR = 1.11, 95% CI:0.95-1.3, p = 1.35, I2 = 0%), and smoking (OR = 0.99, 95% CI:0.87-1.13, p = 0.86, I2 = 0%). Meta-regression found that diabetes and hypertension, but not age, significantly moderated the association between NLR and CI. Conclusion: This meta-analysis showed a significant association between high NLR and increased CI risk. Moreover, meta-regression identified diabetes and hypertension, but not age, as significant moderating factors in the relationship between NLR and CI. To validate and strengthen these findings, further large-scale studies are required. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023430384, identifier CRD42023430384.

The efficacy of Perfusion Index for identifying failed nerve block in patients receiving upper extremity surgery: a meta-analysis.

INTRODUCTION: Nerve block success is commonly assessed through a variety of techniques, including testing sensations for temperature over the relevant dermatomes and evaluating pain response (e.g., pin-prick). This meta-analysis aimed to investigate the diagnostic efficacy of Perfusion Index (PI) in identifying failed nerve blocks in patients undergoing upper extremity surgery. EVIDENCE ACQUISITION: A literature search was conducted using four databases, including Medline (OVID), Google Scholar, EMBASE (OVID), and the Cochrane Database of Systematic Reviews, to identify relevant studies from the inception of the databases until June 2023. The main purpose of this study was to evaluate the diagnostic accuracy of PI values and PI ratios in identifying failed nerve blocks. EVIDENCE SYNTHESIS: Nine studies (published from 2006 to 2022) involving 533 participants (age ranged from 31.8 to 52 years) were included. The failure rate of nerve blocks ranged from 0% to 18.9%. Pooled results demonstrated promising diagnostic accuracy when using PI values as a predictor of failed nerve block (sensitivity, 77%; specificity, 88.1%; diagnostic odds ratio [DOR], 30.585). Additionally, the analysis of PI ratios as a diagnostic measure showed even higher diagnostic efficacy than using PI values alone, with a sensitivity of 82.9%, specificity of 93.1%, and DOR of 74.543. CONCLUSIONS: Our meta-analysis confirmed that the PI values and ratios are promising objective predictors of nerve block failure. The simplicity of these techniques supports their feasibility for routine clinical practice. Further studies focusing on different patient populations, such as pregnant women or the elderly, are needed to validate and expand upon our findings.

Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma.

BACKGROUND: Dihydropyrimidinase-like 3 (DPYSL3) is a cytosolic phosphoprotein expressed in the nervous system and is crucial for neurogenesis. A previous study showed that increased DPYSL3 expression promotes tumour aggressiveness in pancreatic ductal adenocarcinoma, gastric cancer, and colon cancer. However, the role of DPYSL3 in affecting the biological behaviour of urothelial carcinoma (UC) is not yet understood. METHODS: A UC transcriptomic dataset from the Gene Expression Omnibus and the Urothelial Bladder Cancer (BLCA) dataset from The Cancer Genome Atlas were used for the in silico study. We collected 340 upper urinary tract urothelial carcinoma (UTUC) and 295 urinary bladder urothelial carcinoma (UBUC) samples for the immunohistochemical study. Fresh tumour tissue from 50 patients was used to examine the DPYSL3 mRNA level. In addition, urothelial cell lines with and without DPYSL3 knockdown were used for the functional study. RESULTS: The in silico study revealed that DPYSL3 correlated with advanced tumour stage and metastasis development while functioning primarily in the nucleobase-containing compound metabolic process (GO:0006139). DPYSL3 mRNA expression is significantly upregulated in advanced UC. Furthermore, overexpression of the DPYSL3 protein is significantly associated with the aggressive behaviour of UTUC and UBUC. DPYSL3 expression independently predicts disease-specific survival (DSS) and metastatic-free survival (MFS) in patients with UC. In non-muscle-invasive UBUC, DPYSL3 expression predicts local recurrence-free survival. UC cell lines with DPYSL3 knockdown exhibited decreased proliferation, migration, invasion, and human umbilical vein endothelial cells (HUVECs) tube formation but increased apoptosis and G1 arrest. Gene ontology enrichment analysis revealed that the enriched processes related to DPYSL3 overexpression in UC were tissue morphogenesis, cell mesenchyme migration, smooth muscle regulation, metabolic processes, and RNA processing. In vivo study revealed DPYSL3 knockdown in UC tumours significantly suppressed the growth of tumours and decreased MYC and GLUT1 protein expression. CONCLUSIONS: DPYSL3 promotes the aggressiveness of UC cells by changing their biological behaviours and is likely associated with cytoskeletal and metabolic process modifications. Furthermore, DPYSL3 protein overexpression in UC was associated with aggressive clinicopathological characteristics and independently predicted poor clinical outcomes. Therefore, DPYSL3 can be used as a novel therapeutic target for UC.

Low expression of ZSCAN4 predicts unfavorable outcome in urothelial carcinoma of upper urinary tract and urinary bladder.

BACKGROUND: With the advance in genome-wide analyses, genetic alternations have been found to play an important role in carcinogenesis and aggressiveness of UC. Through bioinformatic analysis of gene expression profiles of urinary bladder urothelial carcinoma (UBUC) from publicly available GEO dataset (GSE31684), Zinc finger and SCAN domain containing 4 (ZSCAN4) was identified as a significant downregulated gene in muscle-invasive bladder cancer when compared with non-muscle-invasive bladder cancer. METHODS: The expression of ZSCAN4 was evaluated by immunohistochemistry in 340 upper urinary tract urothelial carcinomas (UTUCs) and 295 UBUCs. The expression profiles of ZSCAN4 and potential signaling pathways were analyzed bioinformatically. RESULTS: In UTUC, low expression of ZSCAN4 was significantly associated with advanced primary pT stage (P = 0.011), increased nodal metastasis (P = 0.002) and increased vascular invasion (P = 0.019). In UBUC, low expression of ZSCAN4 was significantly correlated with advanced primary pT stage (P < 0.001), increased nodal metastasis (P = 0.001), high histological grade (P = 0.003) and increased vascular invasion (P = 0.003). In survival analysis, low expression of ZSCAN4 acted as an independent negative prognostic factor for disease-specific survival and metastasis-free survival both in UTUC and UBUC. Gene ontology analysis showed that ZSCAN4 mRNA and its co-downregulated genes are associated with the mitotic cell cycle. CONCLUSIONS: Low expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.

Impact of prior bariatric surgery on risk and severity of COVID-19 infection: A meta-analysis of observational studies.

BACKGROUND: The association of prior bariatric surgery (BS) with infection rate and prognosis of coronavirus disease 2019 (COVID-19) remains unclear. We conducted a meta-analysis of observational studies to address this issue. METHODS: We searched databases including MEDLINE, Embase, and CENTRAL from inception to May, 2022. The primary outcome was risk of mortality, while secondary outcomes included risk of hospital/intensive care unit (ICU) admission, mechanical ventilation, acute kidney injury (AKI), and infection rate. RESULTS: Eleven studies involving 151,475 patients were analyzed. Meta-analysis showed lower risks of mortality [odd ratio (OR)= 0.42, 95% CI: 0.27-0.65, p < 0.001, I2 = 67%; nine studies; 151,113 patients, certainty of evidence (COE):moderate], hospital admission (OR=0.56, 95% CI: 0.36-0.85, p = 0.007, I2 =74.6%; seven studies; 17,810 patients; COE:low), ICU admission (OR=0.5, 95% CI: 0.37-0.67, p < 0.001, I2 =0%; six studies; 17,496 patients, COE:moderate), mechanical ventilation (OR=0.52, 95% CI: 0.37-0.72, p < 0.001, I2 =57.1%; seven studies; 137,992 patients, COE:moderate) in patients with prior BS (BS group) than those with obesity without surgical treatment (non-BS group). There was no difference in risk of AKI (OR=0.74, 95% CI: 0.41-1.32, p = 0.304, I2 =83.6%; four studies; 129,562 patients, COE: very low) and infection rate (OR=1.05, 95% CI: 0.89-1.22, p = 0.572, I2 =0%; four studies; 12,633 patients, COE:low) between the two groups. Subgroup analysis from matched cohort studies demonstrated associations of prior BS with lower risks of mortality, ICU admission, mechanical ventilation, and AKI. CONCLUSION: Our results showed a correlation between prior BS and less severe COVID-19, which warrants further investigations to verify.

Upregulation of Cartilage Oligomeric Matrix Protein Predicts Poor Prognosis in Urothelial Carcinoma.

Purpose: Cartilage oligomeric matrix protein (COMP) is known as a large pentameric glycoprotein, which interacts with various extracellular matrix proteins in tissues. COMP has been reported to play a role in multiple connective tissue disorders. Recently, elevated COMP levels have been found to be associated with increased tumor size, metastases, faster recurrence of cancer, and overall poorer survival in several cancers. However, the clinical importance of COMP in urothelial carcinoma remains unclear. We investigated the association between COMP expression and clinical outcomes in urothelial carcinoma. Patients and Methods: In this retrospective study, we collected urothelial carcinoma (UC) tissue from 340 upper urinary tract UC (UTUC) patients and 295 urinary bladder UC (UBUC) patients. Pearson's chi-square test, Kaplan-Meier analysis, and the multivariate Cox proportional hazards model was used to examine the relationship between COMP expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MFS) and disease-specific survival (DSS). Results: A total of 295 UBUC patients and 340 UTUC patients were recruited. The COMP mRNA level was significantly higher among invasive tumors (pT2-pT4) than in noninvasive tumors (pTa-T1) in UBUC groups (P < 0.01). COMP overexpression was associated with advanced T stage, nodal metastases, vascular invasion, perineural invasion, high histological grade, and high mitotic rate in both UBUC and UTUC cohorts. COMP overexpression was predictive of shorter DSS (hazard ratio [HR] in UBUC, 3.986, P < 0.001; in UTUC, 2.283, P = 0.027] and MFS (HR in UBUC, 6.813, P < 0.001; in UTUC, 4.070, P < 0.001). Kaplan-Meier analysis demonstrated high COMP expression associated with poor DSS and MFS in UTUC and UBUC groups (all P < 0.0001). Conclusion: COMP overexpression was linked to poor clinical prognosis and poor pathological features in UC. These results suggest COMP as a biomarker for UC.

Impact of combined epidural anaesthesia/analgesia on postoperative cognitive impairment in patients receiving general anaesthesia: a meta-analysis of randomised controlled studies.

BACKGROUND: To investigate the efficacy of combined epidural anaesthesia/analgesia (EAA) against postoperative delirium/cognitive dysfunction (POD/POCD) in adults after major non-cardiac surgery under general anaesthesia (GA). METHODS: The databases of PubMed, Google Scholar, Embase and Cochrane Central Register were searched from inception to November 2021 for available randomised controlled trials (RCTs) that assessed the impact of EAA on risk of POD/POCD. The primary outcome was risk of POD/POCD, while the secondary outcomes comprised postoperative pain score, length of hospital stay (LOS), risk of complications, and postoperative nausea/vomiting (PONV). RESULTS: Meta-analysis of eight studies with a total of 2376 patients (EAA group: 1189 patients; non-EAA group: 1187 patients) revealed no difference in risk of POD/POCD between the EAA and the non-EAA groups [Risk ratio (RR): 0.68; 95% CI: 0.41 to 1.13, p = 0.14, I2 = 73%], but the certainty of evidence was very low. Nevertheless, the EAA group had lower pain score at postoperative 24 h [mean difference (MD): -1.49, 95% CI: -2.38 to -0.61; I2 = 98%; five RCTs; n = 476] and risk of PONV (RR = 0.73, 95% CI: 0.57 to 0.93, p = 0.01, I2 = 0%; three RCTs, 1876 patients) than those in the non-EAA group. Our results showed no significant impact of EAA on the pain score at postoperative 36-72 h, LOS, and risk of complications. CONCLUSION: This meta-analysis demonstrated that EAA had no significant impact on the incidence of POD/POCD in patients following non-cardiac surgery.

High MT2A Expression Predicts Worse Prognosis in Patients with Urothelial Carcinoma.

Introduction: Dysregulation of metal ion homeostasis is associated with urothelial carcinogenesis. From a published urinary bladder urothelial carcinoma (UBUC) transcriptome, we identified metallothionein 2A (MT2A) as the most significantly upregulated gene implicated in cancer progression among metal ion binding-related genes. Therefore, we analyzed the association between MT2A expression and clinical significance in our well-characterized cohort of patients with upper tract urothelial carcinoma (UTUC) and UBUC. Methods: We retrospectively reviewed the clinicopathological characteristics of 295 and 340 patients with UBUC and UTUC, respectively. MT2A expression was assessed using real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. We further correlated MT2A expression with clinicopathological factors, disease-specific survival (DSS) and metastasis-free survival (MFS) using the Pearson's χ2 test, Kaplan-Meier analysis, and multivariate Cox proportional hazards model. Results: High MT2A expression was significantly associated with aggressive pathological features including high tumor stage, lymph node metastasis, high tumor grade, vascular invasion, and perineural invasion. In the Kaplan-Meier analysis, high MT2A expression was significantly correlated with poor DSS (p < 0.0001) and MFS (p < 0.0001); in the multivariate analysis, it was an independent predictor of CSS (p < 0.001) and MFS (p = 0.001). Gene coexpression analysis demonstrated that MT2A overexpression promotes UC progression through complement activation. Conclusion: High MT2A expression correlated with aggressive UC features and was an independent predictor of cancer metastasis and patient survival, suggesting its role in risk stratification and decision-making in patients with UTUC and UBUC.

High Stromal SFRP2 Expression in Urothelial Carcinoma Confers an Unfavorable Prognosis.

Background: Urothelial carcinoma (UC) patients often bear clinical and genetic heterogeneity, which may differ in management and prognosis. Especially, patients with advanced/metastatic UC generally have a poor prognosis and survive for only few months. The Wnt/ß-catenin signaling is found to be highly activated in several cancers, including UC. However, accumulated evidence has shown discordance between the Wnt/ß-catenin signaling and UC carcinogenesis. Accordingly, we aim to get a better understanding of the molecular characterization of UC, focusing on the Wnt signaling, which may add value to guiding management more precisely. Patients and Methods: Clinical data and pathological features were retrospectively surveyed. The correlations of secreted Frizzled-related protein 2 (SFRP2) immunoexpression with clinicopathological features were analyzed by Pearson's chi-square test. The Kaplan-Meier method with a log-rank test was employed to plot survival curves. All significant features from the univariate analysis were incorporated into the Cox regression model for multivariate analysis. Results: Following data mining on a transcriptome dataset (GSE31684), we identified that 8 transcripts in relation to the Wnt signaling pathway (GO: 0016055) were significantly upregulated in advanced/metastatic bladder tumors. Among these transcripts, the SFRP2 level showed the most significant upregulation. Additionally, as SFRP2 is a putative Wnt inhibitor and may be expressed by stroma, we were interested in examining the immunoexpression and clinical relevance of stromal and tumoral SFRP2 in our urothelial carcinoma cohorts containing 295 urinary bladder UC (UBUC) and 340 upper urinary tract UC (UTUC) patients. We observed that high SFRP2 expression in stroma but not in tumors is significantly linked to aggressive UC features, including high tumor stage and histological grade, positive nodal metastasis, the presence of vascular and perineural invasion, and high mitotic activity in UBUC and UTUC. Moreover, high stromal SFRP2 expression significantly and independently predicted worse clinical outcomes in UBUC and UTUC. Utilizing bioinformatic analysis, we further noticed that stromal SFRP2 may link epithelial-mesenchymal transition (EMT) to UC progression. Conclusion: Collectively, these results imply that stromal SFRP2 may exert oncogenic function beyond its Wnt antagonistic ability, and stromal SFRP2 expression can provide prognostic and therapeutic implications for UC patients.

Angiogenesis Driven by the CEBPD-hsa-miR-429-VEGFA Signaling Axis Promotes Urothelial Carcinoma Progression.

BACKGROUND AND PURPOSE: This research aimed to excavate the alternative mechanism of CEBPD on tumor growth and explore the biological significance of the CEBPD/hsa-miR-429/VEGFA axis on angiogenesis in urothelial carcinoma (UC). METHODS: Quantitative RT-PCR, immunoblotting assay and tube formation examined the effect of hsa-miR-429 mimic or/and inhibitor on VEGFA expression and angiogenesis in CEBPD-overexpressing UC-derived cells. The association between CEBPD, hsa-miR-429, VEGFA and microvascular density (MVD) and clinical outcome were evaluated in 296 patients with UBUC and 340 patients with UTUC, respectively. RESULTS: The increase in the transcript and protein of VEGFA as well as HUVECs tube formation was diminished upon the treatment of hsa-miR-429 mimic in CEBPD-overexpressing BFTC909 and TCCSUP. Nevertheless, the inhibited regulation of hsa-miR-429 mimic on the expression of VEGFA and ability of HUVECs tube formation was rescued by the combined incubation with hsa-miR-429 inhibitor in these two UC-derived cell lines. Furthermore, the clinical correlations showed that the higher level of VEGFA or MVD has a positive correlation with the expression of CEBPD and a negative relation to hsa-miR-429 and leads to tumor aggressiveness with worse disease-specific, metastasis-free survival in UBUC and UTUC cohorts. CONCLUSIONS: We decipher the oncogenic mechanism of CEBPD on angiogenesis through the hsa-miR-429 inhibition to stabilize the expression of VEGFA in UC. The novel research unveiled the modulation of the CEBPD/hsa-miR-429/VEGFA axis on the progression of UC and could be accessible to theranostic biomarkers.

Efficacy of high flow nasal oxygenation against hypoxemia in sedated patients receiving gastrointestinal endoscopic procedures: A systematic review and meta-analysis.

STUDY OBJECTIVE: To evaluate the impact of high flow nasal oxygenation (HFNO) on the risk of hypoxemia during gastrointestinal endoscopic procedures (GEPs) under sedation. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Gastrointestinal endoscopy. INTERVENTION: HFNO. PATIENTS: Adults patients undergoing GEPs under sedation. MEASUREMENTS: The primary outcome was risk of hypoxemia, while the secondary outcomes included risks of severe hypoxemia, hypercapnia, need for jaw thrust or other airway interventions, and procedural interruption as well as procedure time, minimum SpO2, and level of carbon dioxide (CO2). Analyses based on age, gender, flow rate, risk status of patients were performed to investigate subgroup effects. RESULTS: Medline, Google scholar, Cochrane Library, and EMBASE databases were searched from inception to July 2021. Seven randomized controlled trials (RCTs) involving 2998 patients published from 2019 to 2021 were included. All GEPs were performed under propofol sedation. Pooled results revealed significantly lower risks of hypoxemia [relative risk (RR) = 0.31, 95% CI:0.13-0.75; 2998 patients], severe hypoxemia (RR = 0.38, 95% CI:0.2-0.74; 2766 patients), other airway interventions (RR = 0.34, 95% CI:0.22-0.52; 2736 patients), procedural interruption (RR = 0.12, 95% CI:0.02-0.64, 451 patients) and a lower CO2 level [standard mean difference (MD) = -0.21, 95% CI: -0.4 to -0.03; 458 patients] in HFNO group compared to control group. Subgroup analysis focusing on risk of hypoxemia showed no significant subgroup effects, indicating consistent benefits of HFNO in different clinical settings. There were no difference in minimum SpO2 (p = 0.06; 262 patients), risk of hypercapnia (p = 0.09; 393 patients), need for jaw thrust (p = 0.28; 2256 patients), and procedure time (p = 0.41, 1004 patients) between the two groups. CONCLUSION: Our results demonstrated the efficacy of high flow nasal oxygenation for reducing the risk of hypoxemia in patients receiving elective gastrointestinal endoscopic procedures under sedation. Further studies are warranted to verify its cost-effectiveness in the gastrointestinal endoscopy setting.

Impact of Intraoperative Ketamine on Postoperative Analgesic Requirement Following Bariatric Surgery: a Meta-analysis of Randomized Controlled Trials.

This meta-analysis aimed at exploring the impact of intravenous ketamine on pain relief and analgesic consumption in patients undergoing bariatric surgery (BS). Literature searches identified nine eligible trials with 458 participants. Forest plot revealed a significantly lower pain score [mean difference (MD) = - 1.06, p = 0.005; 390 patients) and morphine consumption (MD = - 3.85 mg, p = 0.01; 212 patients) immediately after BS in patients with intravenous ketamine than in those without. In contrast, pooled analysis showed comparable pain score (p = 0.28), morphine consumption (p = 0.45) within 24 h, and risk of postoperative nausea/vomiting (p = 0.67) between the two groups. In conclusion, the meta-analysis demonstrated improvements in pain outcomes immediately after surgery through perioperative intravenous ketamine administration despite the absence of analgesic benefit in the late postoperative period and a positive impact on postoperative nausea/vomiting.

Overexpression of Pyruvate Dehydrogenase Kinase-3 Predicts Poor Prognosis in Urothelial Carcinoma.

BACKGROUND: The mitochondrial pyruvate dehydrogenase complex (PDC) link glycolysis to the tricarboxylic acid cycle by decarboxylating pyruvate to acetyl coenzyme A irreversibly. Cancer cells are characterized by a shift in cellular metabolism from mitochondrial respiration to glycolysis. PDC activity inhibition mediated by phosphorylation via pyruvate dehydrogenase kinase (PDK) has been linked to cancer. However, the clinical significance of PDKs in urothelial cancer prognosis is not clear. We investigated the role and prognostic value of PDK3 expression in patients with upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC). PATIENTS AND METHODS: We retrospectively analyzed clinical data and pathological features. Formalin-fixed urothelial carcinoma (UC) tissues were collected and embedded in paraffin. The correlation of PDK3 expression with clinical characteristics, pathological findings and patient outcomes, including metastasis-free survival (MFS) and disease-specific survival (DSS) were analyzed by Pearson's chi-square test, Kaplan-Meier analysis, and the multivariate Cox proportional hazards model. RESULTS: Data from 295 patients with UBUC and 340 patients with UTUC were evaluated. High PDK3 expression significantly correlated with several pathologic variables such as high T stage, lymph node metastases, high tumor grade, vascular invasion, and high mitotic rate (all P < 0.001). High PDK3 expression was associated with poor disease-specific survival (DSS) (P < 0.0001) and metastatic free survival (MFS) (P < 0.0001) in a Kaplan-Meier analysis. Additionally, multivariate analysis demonstrated increased PDK3 expression is a significant predictive risk factor for DSS [hazard ratio (HR) in UBUC, 2.79, P = 0.009; in UTUC, 2.561, P = 0.03] and MFS (HR in UBUC, 1.907, P = 0.024; in UTUC, 1.793, P = 0.044). The gene co-expression analysis showed abundant PDK3 co-upregulated genes were involved in the processes of DNA replication and repair through the Gene Ontology classification system. CONCLUSION: High PDK3 expression has been linked to negative pathologic characteristics and poor oncological outcomes, suggesting that it could be used as a predictive biomarker for UC. PDK3 mRNA levels and its co-upregulated genes were strongly associated with DNA replication and repair. These results suggest that PDK3 may play a key role in tumor proliferation and development.

Association between perioperative intravenous lidocaine and subjective quality of recovery: A meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: To evaluate the impact of perioperative intravenous lidocaine on the quality of recovery (QoR) following surgery. DESIGN: Meta-analysis of randomized controlled trials (RCTs). SETTING: Postoperative care. INTERVENTION: Intravenous lidocaine during perioperative period. PATIENTS: Adults undergoing surgery under general anesthesia. MEASUREMENTS: The primary outcome was postoperative QoR measured with QoR-40 questionnaire, while the secondary outcomes included five individual dimensions (i.e., emotional, state, physical comfort, psychological support, physical independence, and pain) of QoR-40, intraoperative opioid consumption, and risk of chronic postsurgical pain (CPSP). MAIN RESULTS: Medline, Cochrane Library, Google scholar, and EMBASE databases were searched from inception to June 2021. Fourteen RCTs involving 1148 patients in total undergoing elective surgery published from 2012 to 2021 were included. QoR-40 scores were evaluated at postoperative 24 h (12 trials), 72 h (one trial), and Day 5 (one trial), respectively. Pooled results revealed significantly higher global [mean difference (MD) = 9.65, 95% confidence interval (CI): 6.33 to 12.97; I2 = 97%; 13 RCTs; n = 1085] and individual dimension QoR-40 scores in the lidocaine group than those in placebo group. Subgroup analysis demonstrated no significant impact of the type of surgery, age, gender, surgical time, anesthetic technique, lidocaine dosage, and time of assessment on global QoR-40 scores. The use of intravenous lidocaine was associated with a significant reduction in intraoperative remifentanil consumption compared with that in the placebo group (standardized MD = -0.91, 95%CI: -1.32 to -0.51; I2 = 86%; 10 RCTs; n = 799). There was no difference in risk of CPSP between the two groups [relative risk (RR) = 0.65, 95%CI: 0.33 to 1.25; I2 = 58%; 4 RCTs; n = 309]. CONCLUSION: Our results verified the efficacy of intravenous lidocaine for enhancing postoperative quality of recovery by using a validated subjective tool and reducing intraoperative remifentanil consumption in patients receiving elective surgery under general anesthesia. Further studies are warranted to verify its efficacy in the acute care setting.

Increased TNF-α Initiates Cytoplasmic Vacuolization in Whole Blood Coculture with Dengue Virus.

During the acute febrile phase of dengue virus (DENV) infection, viremia can cause severe systemic immune responses accompanied by hematologic disorders. This study investigated the potential induction and mechanism of the cytopathic effects of DENV on peripheral blood cells ex vivo. At one day postinfection, there was viral nonstructural protein NS1 but no further virus replication measured in the whole blood culture. Notably, DENV exposure caused significant vacuolization in monocytic phagocytes. With a minor change in the complete blood cell count, except for a minor increase in neutrophils and a significant decrease in monocytes, the immune profiling assay identified several changes, particularly a significant reduction in CD14-positive monocytes as well as CD11c-positive dendritic cells. Abnormal production of TNF-α was highly associated with the induction of vacuolization. Manipulating TNF-α expression resulted in cytopathogenic effects. These results demonstrate the potential hematological damage caused by ex vivo DENV-induced TNF-α.

Antiviral Efficacy of the Anesthetic Propofol against Dengue Virus Infection and Cellular Inflammation.

Propofol, 2,6-diisopropylphenol, is a short-acting intravenous sedative agent used in adults and children. Current studies show its various antimicrobial as well as anti-inflammatory effects. Dengue virus (DENV) is an emerging infectious pathogen transmitted by mosquitoes that causes mild dengue fever and progressive severe dengue diseases. In the absence of safe vaccines and antiviral agents, adjuvant treatments and supportive care are generally administered. This study investigated the antiviral effects of propofol against DENV infection and cellular inflammation by using an in vitro cell model. Treatment with propofol significantly inhibited DENV release 24 h postinfection in BHK-21 cells. Furthermore, it also blocked viral protein expression independent of the translational blockade. Propofol neither caused inhibitory effects on endosomal acidification nor prevented dsRNA replication. Either the proinflammatory TNF-α or the antiviral STAT1 signaling was reduced by propofol treatment. These results provide evidence to show the potential antiviral effects of the sedative propofol against DENV infection and cellular inflammation.

Cataract surgery-related complications in patients with end-stage renal disease- a nationwide population-based study in Taiwan.

This nationwide retrospective case-control study was aimed at elucidating the risk from cataract surgery in end-stage renal disease (ESRD) patients. Cataract surgery patients were identified using the diagnostic and procedural codes for International Classification of Diseases, 9th Revision, Clinical Modification from Taiwan's National Health Insurance Research Database. ESRD patients were selected as cases, while propensity scores for age, sex, comorbidities and year-of-surgery-matched patients without chronic kidney disease constituted the controls. Patients who had undergone eye surgery within 3 years before cataract surgery were excluded. The main outcome measures were target cataract surgery-related complications within 3 months after surgery. A total of 352 cases and 1,760 controls were analysed. Patients with ESRD had a 5.06-fold (95% CI: 2.36-10.87; p < 0.001) risk of vitreous haemorrhage and a 2.74-fold (95% CI: 1.20-6.27; p = 0.017) risk of re-operation for dropped nucleus or vitreous complications. Non-diabetic ESRD patients had a 3.49-fold (95% CI: 1.36-8.91; p = 0.009) risk of corneal oedema. In conclusion, ESRD patients have a higher risk of vitreous haemorrhage, re-operation for dropped nucleus or vitreous complications and corneal oedema (non-diabetic patients) after cataract surgery. Pre-surgery corneal examination, surgery procedure and medication adjustment, closer and longer post-surgery follow-up may lower the risk and improve the visual outcome.