The research progress of perioperative non-pharmacological interventions on postoperative cognitive dysfunction: a narrative review.

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery and general anesthesia. The occurrence of POCD seriously affects the postoperative recovery of patients, and leads to prolonged hospital stay, reduced quality of life, increased medical costs, and even higher mortality. There is no definite and effective drug treatment for POCD. More evidence shows that perioperative non-pharmacological intervention can improve postoperative cognitive function and reduce the incidence of POCD. Therefore, our studies summarize the current non-pharmacological interventions of POCD from the aspects of cognitive training, physical activity, transcutaneous electrical acupoint stimulation, noninvasive brain stimulation, non-pharmacological sleep improvement, music therapy, environment, and multimodal combination Interventions, to provide more data for clinical application and research.

Effect of thoracic paravertebral nerve block on delirium in patients after video-assisted thoracoscopic surgery: a systematic review and meta-analysis of randomized controlled trials.

Background: Nerve blocks are widely used in various surgeries to alleviate postoperative pain and promote recovery. However, the impact of nerve block on delirium remains contentious. This study aims to systematically evaluate the influence of Thoracic Paravertebral Nerve Block (TPVB) on the incidence of delirium in patients post Video-Assisted Thoracoscopic Surgery (VATS). Methods: We conducted a systematic search of PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases in June 2023. The search strategy combined free-text and Medical Subject Headings (MeSH) terms, including perioperative cognitive dysfunction, delirium, postoperative cognitive dysfunction, paravertebral nerve block, thoracic surgery, lung surgery, pulmonary surgery, and esophageal/esophagus surgery. We utilized a random effects model for the analysis and synthesis of effect sizes. Results: We included a total of 9 RCTs involving 1,123 participants in our study. In VATS, TPVB significantly reduced the incidence of delirium on postoperative day three (log(OR): -0.62, 95% CI [-1.05, -0.18], p = 0.01, I2 = 0.00%) and postoperative day seven (log(OR): -0.94, 95% CI [-1.39, -0.49], p < 0.001, I2 = 0.00%). Additionally, our study indicates the effectiveness of TPVB in postoperative pain relief (g: -0.82, 95% CI [-1.15, -0.49], p < 0.001, I2 = 72.60%). Conclusion: The comprehensive results suggest that in patients undergoing VATS, TPVB significantly reduces the incidence of delirium and notably diminishes pain scores. Systematic review registration: CRD42023435528. https://www.crd.york.ac.uk/PROSPERO.

Minimal alveolar concentration of sevoflurane in combination with remimazolam in adults during laryngeal mask insertion: an up-down sequential allocation study.

BACKGROUND: Remimazolam is a novel ultrashort-acting intravenous benzodiazepine sedative-hypnotic. The combination of remimazolam and sevoflurane does not increase respiratory sensitivity, produce bronchospasm, or cause other adverse conditions. We aimed to observe the effects of different remimazolam doses on the minimum alveolar concentration (MAC) of sevoflurane at end-expiration during laryngeal mask insertion and evaluate the effect of sex on the efficacy of the combination of remimazolam on the suppression of laryngeal mask insertion in adult patients. METHODS: We included 240 patients undergoing laparoscopic surgery under general anesthesia with elective placement of a laryngeal mask (120 males and 120 females). The patients were randomly divided into four groups according to sex: a control group (randomization for female patients, RF0; randomization for male patients, RM0) and three remimazolam groups (RF1, RM1 / RM2, RF2 / RM3, RF3), with 30 patients in each group. Induction was established by vital capacity rapid inhalation induction (VCRII), using 8% sevoflurane and 100% oxygen (6 L/min) in all patients. The (RF1, RM1), (RM2, RF2), and (RM3, RF3) groups were continuously injected with remimazolam at doses of 1, 1.5, and 2.0 mg/kg/h, respectively, while the (RM0, RF0) group was injected with an equal volume of normal saline. The end-expiratory concentration of sevoflurane was adjusted to a preset value after the patient's eyelash reflex disappeared. After the end-expiratory concentration of sevoflurane was kept stable for at least 15 min, the laryngeal mask was placed, and the patient's physical response to the mask placement was observed immediately and within 30 s of placement. The MAC of sevoflurane was measured using the up-and-down sequential method of Dixon. RESULTS: The calculated MAC of end-expiratory sevoflurane during laryngeal mask insertion in adult females was (2.94 ± 0.18)%, (2.69 ± 0.16)%, (2.32 ± 0.16)% and (1.83 ± 0.15)% in groups RF0, RF1, RF2 and RF3; (2.98 ± 0.18)%, (2.80 ± 0.19)%, (2.54 ± 0.15)% and (2.15 ± 0.15)% in male groups RM0, RM1, RM2 and RM3, respectively. The MAC values were significantly lower in the (RF1-RF3, RM1-RM3) group when compared to the (RF0, RM0) group. There was no significant difference between (RF0, RF1) and (RM0, RM1), but the MAC value of the RF2-RF3 group was significantly lower than that of the RM2-RM3 group. CONCLUSIONS: Remimazolam can effectively reduce end-expiratory sevoflurane MAC values during laryngeal mask placement in adults. When remimazolam was measured above 1.5 mg/kg/h, the effect of inhibiting laryngeal mask implantation in female patients was stronger than that in male patients. Remimazolam at a dose of 1-2 mg/kg/h combined with sevoflurane induction can be safely and effectively used in these patients.

Design, Synthesis, and Anti-Osteoporotic Characterization of Arginine N-Glycosylated Teriparatide Analogs via the Silver-catalyzed Solid-Phase Glycosylation Strategy.

In spite of effective antiosteoporosis potency, teriparatide, a bone-building agent approved by the FDA (Food and Drug Administration), was proven to exhibit various side effects. In our previous work, we developed a universal strategy for synthesizing arginine N-glycosylated peptides termed silver-promoted solid-phase glycosylation (SSG) strategy. However, it is unknown whether the SSG strategy can be applied in the peptide drug design. Herein, we first reported the optimization of teriparatide via SSG strategy. Using Arg20 and/or Arg25 as the modifying positions, three series of arginine N-glycosylated teriparatide analogs were successfully synthesized, of which the introduced sugar groups included glucose, galactose, mannose, rhamnose, ribose, 2-acetamino-2-deoxy-glucose, xylose, lactose, and maltose. Among the 27 arginine N-glycosylated derivatives, Arg20-xylose and Arg25-maltose teriparatide analogs, termed PTH-1g and PTH-2i, respectively, indicated enhanced serum stability and significantly improved antiosteoporotic activities in vitro and in vivo compared with the native counterpart. They may serve as effective therapeutic candidates for treating osteoporosis.

A toolbox of diverse arginine N-glycosylated peptides and specific antibodies.

Among posttranslational modifications, atypical arginine N-glycosylation has drawn increasing interest due to its fundamental role in various cellular procedures and signaling pathways. The efficient synthesis of arginine N-glycosylated substrates, as well as the generation of specific antibodies, remains challenging. This work describes the efficient synthesis of diverse arginine N-glycosylated peptides, in a process termed silver-promoted solid-phase glycosylation (SGG). There are two key features of the SSG strategy: (i) robust synthesis of gram-scale S-alkyl-isothiourea glycosyl donors facilitates the subsequent SSG procedure and (ii) the simultaneous introduction of both the side-chain sugar motif and arginine residue. Notably, our findings, combined with our previous results, provide a toolbox containing diverse S-alkyl-isothiourea glycosyl donors (glucose, galactose, mannose, ribose, xylose, lactose and maltose) as well as the corresponding Arg N-glycosylated peptides. In addition, our toolbox is shown to help investigate specific antibodies and identify multiple potent and precise biochemical tools for exploring arginine N-glycosylation.

Incidence and outcomes of acute kidney disease in patients after type A aortic dissection surgery.

BACKGROUND: Acute kidney injury (AKI), acute kidney disease (AKD) and CKD (chronic kidney disease) were a continuous process. There has been little discussion of risk factors for AKD in the population undergoing surgery for acute type A aortic dissection (AAAD). OBJECTIVE: The main objective of this study was to investigate the risk factors for AKD after surgery for acute type A aortic dissection and the impact of AKD on early and late mortality. DESIGN: AKI was to be defined as an increase in serum creatinine to >0.3 mg/dL or 1.5 times above baseline within 7 days. AKD was defined as the kidney damage within 90 days after AKI. Logistic regression models were performed to identify the risk factors of AKD and the association between AKD and early mortality after AAAD surgery. PARTICIPANTS: Patients with AKI after AAAD surgery admitted in ICU from March 2009 to September 2021 were included. KEY RESULTS: Among the 328 patients who developed AKI after AAAD surgery, 98 patients (29.9%) progressed to AKD. Multivariable analysis revealed that AKI stage 2 (OR, 3.032) and AKI stage 3 (OR, 4.001) have been shown to be independent risk factors for the development of AKD. AKD (OR, 3.175) proved to be an independent risk factor for early mortality, while no significant difference in late mortality was observed between patients in the AKD and non-AKD groups. CONCLUSION: The severity of AKI after surgery of AAAD was independently associated with AKD. The occurrence of AKD had a negative impact on early mortality. CLINICAL TRIAL REGISTRATION: ChiCTR, ChiCTR1900021290. Registered 12 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35795.

Machine learning prediction of postoperative unplanned 30-day hospital readmission in older adult.

Background: Although unplanned hospital readmission is an important indicator for monitoring the perioperative quality of hospital care, few published studies of hospital readmission have focused on surgical patient populations, especially in the elderly. We aimed to investigate if machine learning approaches can be used to predict postoperative unplanned 30-day hospital readmission in old surgical patients. Methods: We extracted demographic, comorbidity, laboratory, surgical, and medication data of elderly patients older than 65 who underwent surgeries under general anesthesia in West China Hospital, Sichuan University from July 2019 to February 2021. Different machine learning approaches were performed to evaluate whether unplanned 30-day hospital readmission can be predicted. Model performance was assessed using the following metrics: AUC, accuracy, precision, recall, and F1 score. Calibration of predictions was performed using Brier Score. A feature ablation analysis was performed, and the change in AUC with the removal of each feature was then assessed to determine feature importance. Results: A total of 10,535 unique surgeries and 10,358 unique surgical elderly patients were included. The overall 30-day unplanned readmission rate was 3.36%. The AUCs of the six machine learning algorithms predicting postoperative 30-day unplanned readmission ranged from 0.6865 to 0.8654. The RF + XGBoost algorithm overall performed the best with an AUC of 0.8654 (95% CI, 0.8484-0.8824), accuracy of 0.9868 (95% CI, 0.9834-0.9902), precision of 0.3960 (95% CI, 0.3854-0.4066), recall of 0.3184 (95% CI, 0.259-0.3778), and F1 score of 0.4909 (95% CI, 0.3907-0.5911). The Brier scores of the six machine learning algorithms predicting postoperative 30-day unplanned readmission ranged from 0.3721 to 0.0464, with RF + XGBoost showing the best calibration capability. The most five important features of RF + XGBoost were operation duration, white blood cell count, BMI, total bilirubin concentration, and blood glucose concentration. Conclusion: Machine learning algorithms can accurately predict postoperative unplanned 30-day readmission in elderly surgical patients.

Diagnostic, Prognostic, and Immunological Roles of HELLS in Pan-Cancer: A Bioinformatics Analysis.

Background: Inappropriate repair of DNA damage drives carcinogenesis. Lymphoid-specific helicase (HELLS) is an important component of the chromatin remodeling complex that helps repair DNA through various mechanisms such as DNA methylation, histone posttranslational modification, and nucleosome remodeling. Its role in human cancer initiation and progression has garnered recent attention. Our study aims to provide a more systematic and comprehensive understanding of the role of HELLS in the development and progression of multiple malignancies through analysis of HELLS in cancers. Methods: We explored the role of HELLS in cancers using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Multiple web platforms and software were used for data analysis, including R, Cytoscape, HPA, Archs4, TISIDB, cBioPortal, STRING, GSCALite, and CancerSEA. Results: High HELLS expression was found in a variety of cancers and differentially expressed across molecular and immune subtypes. HELLS was involved in many cancer pathways. Its expression positively correlated with Th2 and Tcm cells in most cancers. It also correlated with genetic markers of immunomodulators in various cancers. Conclusions: Our study elucidates the role HELLS plays in promotion, inhibition, and treatment of different cancers. HELLS is a potential cancer diagnostic and prognostic biomarker with immune, targeted, or cytotoxic therapeutic value. This work is a prerequisite to clinical validation and treatment of HELLS in cancers.

Silver-promoted solid-phase guanidinylation enables the first synthesis of arginine glycosylated Samoamide A cyclopeptide analogue.

Cyclization and glycosylation serve as effective approaches for enhancing the drug properties of peptides. Distinct from typical glycosylation, atypical arginine N-glycosylation has drawn increasing attention due to its fundamental role in various cellular procedures and signaling pathways. We previously developed a robust strategy for constructing arginine N-glycosylated peptides characterized by silver-promoted solid-phase guanidinylation. Modeled after cyclic octapeptide Samoamide A, an antitumor peptide composed of eight hydrophobic amino acids extracted from cyanobacteria, herein we first performed arginine scanning to determine an optimal position for replacement with arginine. Consequently, the first synthesis of arginine glycosylated Samoamide A cyclopeptide analogue was described combining solid-phase glycosylation with solution-phase cyclization. The resultant SA-HH-TT displayed enhanced water solubility compared with the non-glycosylated SA-HH-TT. Notably, our method provides a universal strategy for synthesizing arginine N-glycosylated cyclopeptides.

Incidence- and In-hospital Mortality-Related Risk Factors of Acute Kidney Injury Requiring Continuous Renal Replacement Therapy in Patients Undergoing Surgery for Acute Type a Aortic Dissection.

Background: Few studies on the risk factors for postoperative continuous renal replacement therapy (CRRT) in a homogeneous population of patients with acute type A aortic dissection (AAAD). This retrospective analysis aimed to investigate the risk factors for CRRT and in-hospital mortality in the patients undergoing AAAD surgery and to discuss the perioperative comorbidities and short-term outcomes. Methods: The study collected electronic medical records and laboratory data from 432 patients undergoing surgery for AAAD between March 2009 and June 2021. All the patients were divided into CRRT and non-CRRT groups; those in the CRRT group were divided into the survivor and non-survivor groups. The univariable and multivariable analyses were used to identify the independent risk factors for CRRT and in-hospital mortality. Results: The proportion of requiring CRRT and in-hospital mortality in the patients with CRRT was 14.6 and 46.0%, respectively. Baseline serum creatinine (SCr) [odds ratio (OR), 1.006], cystatin C (OR, 1.438), lung infection (OR, 2.292), second thoracotomy (OR, 5.185), diabetes mellitus (OR, 6.868), AKI stage 2-3 (OR, 22.901) were the independent risk factors for receiving CRRT. In-hospital mortality in the CRRT group (46%) was 4.6 times higher than in the non-CRRT group (10%). In the non-survivor (n = 29) and survivor (n = 34) groups, New York Heart Association (NYHA) class III-IV (OR, 10.272, P = 0.019), lactic acidosis (OR, 10.224, P = 0.019) were the independent risk factors for in-hospital mortality in patients receiving CRRT. Conclusion: There was a high rate of CRRT requirement and high in-hospital mortality after AAAD surgery. The risk factors for CRRT and in-hospital mortality in the patients undergoing AAAD surgery were determined to help identify the high-risk patients and make appropriate clinical decisions. Further randomized controlled studies are urgently needed to establish the risk factors for CRRT and in-hospital mortality.

The Incidence, Risk Factors and In-Hospital Mortality of Acute Kidney Injury in Patients After Surgery for Acute Type A Aortic Dissection: A Single-Center Retrospective Analysis of 335 Patients.

Background: Acute kidney injury (AKI) is a common complication of cardiac surgery, which could lead to increased morbidity and mortality. Acute type A aortic dissection (AAAD) is a life-threatening cardiac disease and can be closely related to post-operative AKI. However, data on the incidence of AKI defined by the newest Kidney Disease: Improving Global Outcomes (KDIGO) criteria and in-hospital mortality of a homogeneous population who underwent AAAD are limited. We aimed to investigate the incidence of AKI defined by the KDIGO criteria and the risk factors associated with the outcomes among AAAD-induced AKI patients. Methods: We reviewed 335 patients who underwent surgical treatment for AAAD between March 2009 and June 2016. We screened the patients' AKI status and analyzed probably risk factors of AKI and in-hospital mortality. Independent-sample t-test or Chi-square test was performed to identify differences between AKI and non-AKI groups and survivors with AKI and non-survivors with AKI, respectively. The logistic regression model was applied to identify independent risk factors. Results: AKI occurred in 71.94% of AAAD patients, including 85 stage 1 (35.26%), 77 stage 2 (31.95%), and 79 stage 3 (32.78%) patients. The in-hospital mortality rate was 21.16%. Logistic regression analysis showed that the body mass index, chronic kidney disease, chronic liver disease, cardiopulmonary bypass duration, red blood cell transfusion, and hypoproteinemia were the independent significant risk factors of the occurrence of post-operative AKI. The risk factors associated with in-hospital mortality among AAAD-induced AKI patients included AKI stage (odds ratio (OR), 3.322), deep hypothermic circulatory arrest (OR, 2.586), lactic acidosis (OR, 3.407), and continuous renal replacement therapy (OR, 3.156). Conclusion: For AAAD patients undergoing surgery, AKI was a common complication, and it increased patients' mortality risk. Therefore, identifying the risk factors of AKI and preventing post-operative AKI are important for improving the post-operative outcomes of AAAD patients. Clinical Trial Registration: ChiCTR, ChiCTR1900021290. Registered 12 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35795.