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.

Protective role of IL-17-producing γδ T cells in a laser-induced choroidal neovascularization mouse model.

BACKGROUND: Vision loss in patients with wet/exudative age-related macular degeneration (AMD) is associated with choroidal neovascularization (CNV), and AMD is the leading cause of irreversible vision impairment in older adults. Interleukin-17A (IL-17A) is a component of the microenvironment associated with some autoimmune diseases. Previous studies have indicated that wet AMD patients have elevated serum IL-17A levels. However, the effect of IL-17A on AMD progression needs to be better understood. We aimed to investigate the role of IL-17A in a laser-induced CNV mouse model. METHODS: We established a laser-induced CNV mouse model in wild-type (WT) and IL-17A-deficient mice and then evaluated the disease severity of these mice by using fluorescence angiography. We performed enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS) to analyze the levels of IL-17A and to investigate the immune cell populations in the eyes of WT and IL-17A-deficient mice. We used ARPE-19 cells to clarify the effect of IL-17A under oxidative stress. RESULTS: In the laser-induced CNV model, the CNV lesions were larger in IL-17A-deficient mice than in WT mice. The numbers of γδ T cells, CD3+CD4+RORγt+ T cells, Treg cells, and neutrophils were decreased and the number of macrophages was increased in the eyes of IL-17A-deficient mice compared with WT mice. In WT mice, IL-17A-producing γδ T-cell numbers increased in a time-dependent manner from day 7 to 28 after laser injury. IL-6 levels increased and IL-10, IL-24, IL-17F, and GM-CSF levels decreased in the eyes of IL-17A-deficient mice after laser injury. In vitro, IL-17A inhibited apoptosis and induced the expression of the antioxidant protein HO-1 in ARPE-19 cells under oxidative stress conditions. IL-17A facilitated the repair of oxidative stress-induced barrier dysfunction in ARPE-19 cells. CONCLUSIONS: Our findings provide new insight into the protective effect of IL-17A in a laser-induced CNV model and reveal a novel regulatory role of IL-17A-producing γδ T cells in the ocular microenvironment in wet AMD.

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.

Predictive Efficacy of the Perfusion Index for Hypotension following Spinal Anesthesia in Parturient Undergoing Elective Cesarean Section: A Systematic Review and Meta-Analysis.

This meta-analysis assessed the predictive efficacy of perfusion index for hypotension following spinal anesthesia (SA) in parturients undergoing elective cesarean section (CS). Electronic databases, including Google Scholar, EMBASE, Cochrane Library, and MEDLINE, were searched from inception to June 2023. The primary outcome was the diagnostic accuracy of the perfusion index in predicting the probability of perioperative hypotension following SA. The review included 12 studies involving 2009 patients, published between 2017 and 2023. The pooled sensitivity and specificity were 0.81 (95% confidence interval (CI) = 0.72-0.87) and 0.75 (95% CI = 0.67-0.82), respectively. Additionally, the pooled area under the curve (AUC) was calculated as 0.84 (95% CI = 0.81-0.87), suggesting a moderate to good accuracy of the diagnostic test. Using Fagan's nomogram plot, the positive likelihood ratio (LR) and negative LR were found to be 3 and 0.26, respectively. The results demonstrated that the perfusion index exhibited an acceptable level of accuracy in predicting perioperative hypotension after spinal anesthesia in parturients undergoing elective CS. These findings highlight the potential value of incorporating a perfusion index as a useful tool for clinicians to integrate into routine clinical practice, which necessitates further large-scale studies for verification.

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.

Association of labor epidural analgesia exposure with long-term risk of autism spectrum disorder in offspring: A meta-analysis of observational studies.

LAY ABSTRACT: A previous meta-analysis has demonstrated a superior analgesic efficacy of epidural analgesia (e.g. labor epidural analgesia) in comparison with non-epidural approaches. The widely accepted safety of labor epidural analgesia also endorses its current popularity in obstetric practice. However, the results of a recent large-scale longitudinal study that demonstrated a significant increase in risk of autism spectrum disorder in offspring from mothers with labor epidural analgesia exposure have raised some concerns over the safety of its use. The current meta-analysis aimed at examining the strength of evidence regarding this issue based on updated clinical data. Through systematically reviewing seven eligible observational studies involving 4,021,406 children from electronic databases, our results showed a slight but statistically significant increase in risk of autism spectrum disorder in children with exposure to labor epidural analgesia compared with those without. The finding was consistent in subgroup analysis focusing on siblings and children delivered vaginally. Nevertheless, despite the tendency of an increased risk of autism spectrum disorder in children exposed to labor epidural analgesia <4 h, this effect was not observed in those exposed to labor epidural analgesia >8 h (data from two studies). In conclusion, the level of evidence linking labor epidural analgesia to autism spectrum disorder development in offspring was very low based on the latest data because of the small effect size and the finding of a lack of cumulative dose-response effect in the current analysis. Further studies are warranted to provide an insight into this issue.

Association of scalp block with intraoperative hemodynamic profiles and postoperative pain outcomes at 24-48 hours following craniotomy: An updated systematic review and meta-analysis of randomized controlled studies.

BACKGROUND: Despite the demonstrated analgesic efficacy of scalp block (SB) during the immediate postoperative period, the impact of SB on pain outcomes at postoperative 24 and 48 h in adults receiving craniotomy remains unclear. METHODS: The databases of Medline, Embase, and Cochrane Central Register were searched from inception to January 2022 for available randomized controlled trials (RCTs). The primary outcome was the severity of pain at postoperative 24 and 48 h, while the secondary outcomes included morphine consumption, hemodynamic profiles after surgical incision and in the postanesthesia care unit (PACU), and risk of postoperative nausea/vomiting (PONV). RESULTS: Meta-analysis of 12 studies revealed a lower pain score [MD = -0.83, p = 0.03, 375 patients, certainty of evidence (COE): low] and morphine consumption (MD = -9.21 mg, p = 0.03, 246 patients, COE: low) at postoperative 24 h, while there were no differences in these pain outcomes at postoperative 48 h (COE: low). The use of SB significantly decreased intraoperative heart rate (MD = -10.9 beats/min, p < 0.0001, 189 patients, COE: moderate) and mean blood pressure (MD = -13.02 mmHg, p < 0.00001, 189 patients, COE: moderate) after surgical incision, but these hemodynamic profiles were comparable in both groups in the PACU setting. There was also no difference in the risk of PONV between the two groups (RR = 0.78, p = 0.2, 299 patients, COE: high). CONCLUSION: This meta-analysis demonstrated that scalp block not only provided hemodynamic stability immediately after surgical incision but was also associated with a lower pain score and morphine consumption at postoperative 24 h. Further studies are needed for elucidation of its findings.

Interferon Family Cytokines in Obesity and Insulin Sensitivity.

Obesity and its associated complications are global public health concerns. Metabolic disturbances and immune dysregulation cause adipose tissue stress and dysfunction in obese individuals. Immune cell accumulation in the adipose microenvironment is the main cause of insulin resistance and metabolic dysfunction. Infiltrated immune cells, adipocytes, and stromal cells are all involved in the production of proinflammatory cytokines and chemokines in adipose tissues and affect systemic homeostasis. Interferons (IFNs) are a large family of pleiotropic cytokines that play a pivotal role in host antiviral defenses. IFNs are critical immune modulators in response to pathogens, dead cells, and several inflammation-mediated diseases. Several studies have indicated that IFNs are involved in the pathogenesis of obesity. In this review, we discuss the roles of IFN family cytokines in the development of obesity-induced inflammation and insulin resistance.

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.

Emerging Roles of Type-I Interferons in Neuroinflammation, Neurological Diseases, and Long-Haul COVID.

Interferons (IFNs) are pleiotropic cytokines originally identified for their antiviral activity. IFN-α and IFN-ß are both type I IFNs that have been used to treat neurological diseases such as multiple sclerosis. Microglia, astrocytes, as well as neurons in the central and peripheral nervous systems, including spinal cord neurons and dorsal root ganglion neurons, express type I IFN receptors (IFNARs). Type I IFNs play an active role in regulating cognition, aging, depression, and neurodegenerative diseases. Notably, by suppressing neuronal activity and synaptic transmission, IFN-α and IFN-ß produced potent analgesia. In this article, we discuss the role of type I IFNs in cognition, neurodegenerative diseases, and pain with a focus on neuroinflammation and neuro-glial interactions and their effects on cognition, neurodegenerative diseases, and pain. The role of type I IFNs in long-haul COVID-associated neurological disorders is also discussed. Insights into type I IFN signaling in neurons and non-neuronal cells will improve our treatments of neurological disorders in various disease conditions.

General anesthesia but not conscious sedation improves functional outcome in patients receiving endovascular thrombectomy for acute ischemic stroke: A meta-analysis of randomized clinical trials and trial sequence analysis.

Background: This study aimed at comparing the difference in prognostic outcomes between patients receiving general anesthesia (GA) and conscious sedation (CS) for endovascular thrombectomy after acute ischemic stroke. Methods: Databases from Medline, Embase, Google scholar, and Cochrane library were searched for randomized controlled studies (RCTs) comparing patients undergoing GA and CS for endovascular thrombectomy following anterior circulation ischemic stroke. The primary outcome was frequency of 90-day good functional outcome [defined as modified Rankin Scale score of ≤ 2], while secondary outcomes included successful recanalization rate (SRR) [i.e., modified thrombolysis in cerebral infarction = 2b or 3], mortality risk, symptomatic intracranial hemorrhage (ICH), procedure-related complications, hypotension, pneumonia, neurological outcome at post-procedure 24-48 h, and puncture-to-recanalization time. Results: Six RCTs including 883 patients published between 2016 and 2022 were included. Merged results revealed a higher SRR [risk ratio (RR) = 1.11, 95% CI: 1.03-1.2, p = 0.007; I 2 = 29%] and favorable neurological outcomes at 3-months (RR = 1.2, 95% CI: 1.01-1.41, p = 0.04; I 2 = 8%) in the GA group compared to CS group, without difference in the risk of mortality (RR = 0.88), symptomatic ICH (RR = 0.91), procedure-related complications (RR = 1.05), and pneumonia (RR = 1.9) as well as post-procedure neurological outcome (MD = -0.21) and successful recanalization time (MD = 3.33 min). However, GA was associated with a higher risk of hypotension compared with that of CS. Conclusion: Patients with acute anterior circulation ischemic stroke receiving GA were associated with a higher successful recanalization rate as well as a better 3-month neurological outcome compared to the use of CS. Further investigations are warranted to verify our findings. Systematic review registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022342483, identifier: CRD42022342483.

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.

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.

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.