Efficacy of perioperatively application of ketamine on postoperative depressive symptoms in adult patients: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Whether ketamine used in the perioperative period reduces the risk of postoperative depressive symptoms remains uncertain. We conducted this systematic review and meta-analysis to evaluate the clinical efficacy of ketamine in adult surgical patients. METHODS: Two investigators independently systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Web of Science, and PsycINFO databases using a combination of relevant Medical Subject Headings terms and free-text keywords from database inception through May 24, 2023. RESULTS: 29 studies encompassing 5327 patients were included. The pooled analysis demonstrated that the ketamine group had no significantly reduced incidence of postoperative depressive mood compared with the control group, with trial sequential analysis (TSA) inconclusive. However, postoperative depression scale scores were significantly decreased in the ketamine group. LIMITATIONS: Most randomized controlled trials of surgical patients have included depression scale scores as the primary outcome. The incidence of postoperative depressive has been assessed as a secondary outcome or has not been assessed. In addition, non-uniform assessment scales have introduced greater heterogeneity. More rigorous methods and higher-quality evidence for further research are needed to better understand the effects of ketamine on perioperative depression in surgical anesthesia. CONCLUSIONS: Current evidence suggests that ketamine cannot significantly decrease the incidence of postoperative depressive mood in adult surgical patients. However, ketamine can reduce postoperative depression scores. PROSPERO registration: CRD42023431566.

4D DIA-PRM proteomic study identifying modulated pathways and biomarkers associated with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a highly disabling condition that negatively affects the quality of life of millions of women worldwide. However, the underlying mechanisms associated with the development and progression of the disease remain poorly understood. Here, an untargeted four-dimensional data-independent acquisition (4D DIA)-based proteomics approach was applied to vaginal wall tissue samples from POP (n = 19) and control (n = 8) patients to identify potential diagnostic biomarker(s) for POP and examine the molecular mechanisms underlying the disease. Of the 5713 tissue proteins that were detected, 1957 proteins were significantly changed in POP patients. Further bioinformatics analysis revealed that multiple biological processes including protein digestion & absorption, retrograde endocannabinoid signaling, tyrosine metabolism, and nucleotide metabolism were significantly enriched and associated with the pathogenesis of POP. Interestingly, 16 of these differentially expressed proteins associated with four pathways were also identified by targeted parallel reaction monitoring (PRM) proteomics analysis on the same 27 tissue samples. Changes in 94 % (15/16) of these proteins were consistent with the 4D DIA data. Furthermore, most proteins displayed good diagnostic accuracy with high area under the curve (AUC) values (AUC＞0.8). Specifically, five proteins including ELN, COL6A2, ENTPD1, AOC3, and COX7A2 distinguished between POP and control patients with very high accuracy (AUC ≥ 0.95) in both 4D DIA and PRM analyses, and may therefore be potential diagnostic biomarkers for POP. In summary, the present study not only provided several potential biomarker(s) for effective POP diagnosis, but extended our knowledge of the key regulatory pathways associated with the disease.

Influence of low-dose esketamine on postoperative depressive symptoms in patients with breast cancer (EASE): study protocol for a randomised controlled trial.

INTRODUCTION: Depressive symptoms have surfaced as the principal mental health concern among patients with breast cancer, with surgical interventions potentially exacerbating these symptoms and adversely influencing clinical outcomes. This study protocol is designed to investigate the efficacy of low-dose esketamine administered perioperatively on depressive symptoms in patients with breast cancer. It also aims to illuminate the potential neurobiological underpinnings of this effect. METHODS AND ANALYSIS: This research represents a single-centre, prospective, randomised, double-blind, placebo-controlled study. The trial anticipates enrolling 108 female patients exhibiting mild-to-severe depressive symptoms who are slated for radical mastectomy. Through stratified randomisation, eligible patients will be systematically assigned to either the esketamine group (0.25 mg/kg) or placebo group (0.9% saline) in a 1:1 ratio. The primary outcome is the response rate at the third postoperative day. Secondary outcomes encompass the remission rate, depression-related scores, depression severity and safety-related endpoints. Tertiary (exploratory) outcomes involve alterations in brain-derived neurotrophic factor and resting-state functional brain connectivity. ETHICS AND DISSEMINATION: The Clinical Trial Ethics Committee at The First Affiliated Hospital of Anhui Medical University has conferred ethical approvals for this trial (approval number: PJ2023-05-25). Results from this trial will be disseminated in peer-reviewed journals and presented at professional symposiums. TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry (ChiCTR2300071062).

Effect of intravenous lidocaine on chronic postoperative pain in patients undergoing breast cancer surgery: a prospective, double-blind, randomized, placebo-controlled clinical trial.

Background: Chronic postoperative pain (CPSP) is one of the common complications of breast cancer patients, which can seriously affect the quality of life and long-term prognosis of patients. The purpose of this study was to investigate whether perioperative intravenous lidocaine infusion could reduce the incidence of CPSP in patients with breast cancer. Methods: Female patients undergoing radical breast cancer surgery were randomly assigned to the 2% lidocaine group (L) and the control group (S). group L received an intravenous infusion of 1.5 mg/kg lidocaine 10 minutes prior to induction, followed by a continuous infusion of 2 mg/kg/h until the end of surgery. The control group received an equal amount of saline. The primary outcome was the incidence of CPSP at 3 months. Secondary outcomes included VAS pain scores and frequency of remedial analgesia within 24 hours postoperatively; incidence of CPSP at 1 and 6 months; and scores on the Brief Pain Inventory (BPI), Simplified McGill Pain Questionnaire (SF-MPQ), and Neuropathic Pain Score (DN-4) at 1, 3, and 6 months postoperatively. Results: Eighty-two patients participated in this study. A total of 78 patients completed the 3-month postoperative follow-up (39 in group S and 39 in group L). At 3 months, the incidence of CPSP was significantly lower in the L group than in the S group (33.3% in the S group and 12.8% in the L group, P=0.032). Pain scores at rest and during exercise were significantly lower in the L group than in the S group at different time points (P≤0.001 and P<0.001). The need for remedial analgesia at 24 hours postoperatively also differed significantly between the two groups (P=0.036). At 6 months, the incidence of CPSP was also lower in the L group than in the S group (29.7% in the S group and 10.5% in the L group, P=0.038). The differences in SF-MPQ scores were statistically significant at both 3 and 6 months postoperatively (P=0.022, P=0.037). Conclusions: Intravenous infusion of lidocaine reduces the incidence of CPSP in breast cancer patients at 3 and 6 months and is effective in relieving acute postoperative pain. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100050445.

Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome.

Colorectal cancer (CRC) is currently the third most common cancer with a high mortality rate. The underlying molecular mechanism of CRC, especially advanced CRC, remains poorly understood, resulting in few available therapeutic plans. To expand our knowledge of the molecular characteristics of advanced CRC and explore possible new therapeutic strategies, we herein conducted integrated proteomics and metabolomics analyses of 40 serum samples collected from 20 advanced CRC patients before and after treatment. The mass spectrometry-based proteomics analysis was performed under data-independent acquisition (DIA), and the metabolomics analysis was performed by ultra-performance liquid chromatography coupled with time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS). Trace elements including Mg, Zn, and Fe were measured by inductively coupled plasma spectrometry (ICP-MS) analysis. Four of the 20 patients had progressive disease (PD) after treatment, and clinical test results indicated that they all had impaired liver functions. In the proteomics analysis, 64 proteins were discovered to be significantly altered after treatment. These proteins were enriched in cancer-related pathways and pathways participating immune responses, such as MAPK signaling pathway and complement/coagulation cascades. In the metabolomics analysis, 128 metabolites were found to be significantly changed after treatment, and most of them are enriched in pathways associated with lipid metabolism. The cholesterol metabolism pathway was significantly enriched in both the proteomics and metabolomics pathway enrichment analyses. The concentrations of Mg in the serums of CRC patients were significantly lower than those in healthy individuals, which returned to the normal range after treatment. Correlation analysis linked key lipids, proteins, and Mg as immune modulators in the development of advanced CRC. The results of this study not only extended our knowledge on the molecular basis of advanced CRC but also provided potential novel therapeutic targets for CRC treatment.

Effect of intravenous lidocaine infusion on perioperative cellular immunity and the quality of postoperative recovery in breast cancer patients: a randomized controlled trial.

Background: Breast cancer has become the most common malignancy worldwide. Experimental and, retrospective, clinical data indicate that anaesthetic technique might influence the risk of metastasis after cancer surgery by modulating the immune system. The purpose of this study is to investigate the effect of perioperative lidocaine injection on immune cells such as T lymphocytes and natural killer cells (NK cells) and the quality of postoperative recovery in breast cancer patients and to propose new ideas and relevant theoretical evidence for the selection of anesthetic protocols for perioperative tumor patients. Methods: Women (n=68) undergoing primary breast tumour resection were randomly assigned to received 2% lidocaine (n=34; group L) or placebo (normal saline; n=34; group S). Venous blood was collected thirty minutes before surgery (T0), after tumor removal (T1), immediately after surgery (T2), 24 h after surgery (T3), and 48 h after surgery (T4). The percentages of NK cells and T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) in peripheral blood were detected by flow cytometry. Patients' quality of recovery-15 (QoR-15) scores were recorded by questionnaire before and 24 h after the operation, as well as intraoperative propofol and remifentanil dosages, the frequency of 24 h postoperative remedial analgesia, and the incidence of nausea and vomiting, dizziness, and chest tightness. Results: There were 62 patients included in the study, and 60 patients were finally analyzed. The difference in the changing trend of NK cell levels in the 2 groups over time was statistically significant (F=7.675, P=0.008). The intraoperative changing trends of CD3+ T cells, CD4+ T cells, and the CD4+/CD8+ ratio over time differed significantly between the 2 groups of patients (P<0.05), whereas the trends of CD8+ T cells did not differ significantly (P>0.05). The QoR-15 score at 24 h after surgery was higher in Group L (128.50±20.25) than in Group S (117.50±19.50), and the difference was statistically significant (P=0.005). No adverse events such as cardiac arrhythmia and lidocaine toxicity occurred in both groups during the perioperative period. Conclusions: Continuous intravenous pumping of lidocaine during the perioperative period has little effect on immune function in breast cancer patients and promotes postoperative recovery. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100050445.

Development and Validation of a Risk Nomogram Model for Perioperative Respiratory Adverse Events in Children Undergoing Airway Surgery: An Observational Prospective Cohort Study.

PURPOSE: The aim of this study was to explore the associated risk factors of perioperative respiratory adverse events (PRAEs) in children undergoing airway surgery and establish and validate a nomogram prediction model for PRAEs. PATIENTS AND METHODS: This study involved 709 children undergoing airway surgery between November 2020 and July 2021, aged ≤18 years in the affiliated hospital of Xuzhou Medical University. They were divided into training (70%; n = 496) and validation (30%; n = 213) cohorts. The least absolute shrinkage and selection operator (LASSO) was used to develop a risk nomogram model. Concordance index values, calibration plot, decision curve analysis, and the area under the curve (AUC) were examined. RESULTS: PRAEs were found in 226 of 496 patients (45.6%) and 88 of 213 patients (41.3%) in the training and validation cohorts, respectively. The perioperative risk factors associated with PRAEs were age, obesity, degree of upper respiratory tract infection, premedication, and passive smoking. The risk nomogram model showed good discrimination power, and the AUC generated to predict survival in the training cohort was 0.760 (95% confidence interval, 0.695-0.875). In the validation cohort, the AUC of survival predictions was 0.802 (95% confidence interval, 0.797-0.895). Calibration plots and decision curve analysis showed good model performance in both datasets. The sensitivity and specificity of the risk nomogram model were calculated, and the result showed the sensitivity of 69.5% and 64.8% and specificity of 73.3% and 81.6% for the training and validation cohorts, respectively. CONCLUSION: The present study showed the proposed nomogram achieved an optimal prediction of PRAEs in patients undergoing airway surgery, which can provide a certain reference value for predicting the high-risk population of perioperative respiratory adverse events and can lead to reasonable preventive and treatment measures.