[Effects of electroacupuncture pretreatment on long-term postoperative cognitive dysfunction and neuron-inflammation in aged rats].

OBJECTIVE: To observe the effects of electroacupuncture pretreatment on postoperative cognitive dysfunction (POCD), neuronal apoptosis and neuron-inflammation in aged rats. METHODS: Thirty-six male SD rats aged 20 months were randomly divided into sham operation group, model group and electroacupuncture (EA) group, with 12 rats in each group. The POCD rats model was prepared by internal fixation of left tibial fracture. Five days before modeling, EA stimulation (2 Hz/15 Hz, 1 mA, 30 min) was applied to "Zusanli" (ST36), "Hegu" (LI4) and "Neiguan" (PC6) on the unaffected side of rats in the EA group, once a day for consecutive 5 d. The learning and memory abilities of rats were evaluated by water maze test 31-35 days after operation. The apoptosis of hippocampal neurons was observed by Tunel/NeuN double staining. The expressions of high mobility group protein B1 (HMGB1) and phosphorylated (p)-nuclear factor (NF)-κB in microglia cells in hippocampal dentate gyrus were detected by immunofluorescence staining. The expression levels of interleukin (IL)-6 and IL-1ß in the hippocampus were detected by Western blot. RESULTS: Compared with the sham operation group, the escape latency was prolonged (P<0.05); the frequency of crossing the original platform, ratio of the swimming distance and the time in the target quadrant of the Morris water maze were significantly decreased (P<0.05); the apoptosis rate of hippocampal neurons was significantly increased (P<0.05); the expressions of HMGB1 and p-NF-κB in microglia cells in the dentate gyrus and the expression levels of IL-6 and IL-1ß in hippocampus were increased (P<0.05) in the model group. Compared with the model group, the results of the above indexes were all opposite (P<0.05) in the EA group. CONCLUSION: EA preconditioning can regulate hippocampal inflammatory response, alleviate neuronal apoptosis rate and long-term cognitive dysfunction in aged rats with POCD, the mechanisms may be related to the inhibition of microglia HMGB1/NF-κB pathway in hippocampal dentate gyrus.

Electroacupuncture modulates gut microbiota in mice: A potential target in postoperative cognitive dysfunction.

The detailed mechanism of inflammation in postoperative cognitive dysfunction (POCD) is unclear. This study aimed to determine whether electroacupuncture (EA) ameliorates POCD by modulating gut microbial dysbiosis. Compared to the control group, mice in the EA group were treated at the acupoints Zusanli (ST36), Quchi (L111), Baihui (GV20), and Dazhui (GV14) 1 week before appendectomy. Novel object recognition and the Morris water maze tests were used to assess learning and spatial reference memory deficits, whereas hippocampus samples and stool samples were collected for central inflammatory tests and 16S-rRNA sequencing of intestinal flora, respectively. In amyloid precursor protein/presenilin 1 (APP/PS1) mice, EA enhanced spatial memory and learning deficits. The fecal microbial community was altered in APP/PS1 mice in the absence of EA following surgery. Among them, Coprococcus and Bacteroidetes were more abundant in the EA groups than in the control groups; however, Actinobacteriota, Helicobacteraceae, and Escherichia/shigella constitute the minor bacterial colonization in the EA groups. Furthermore, we found a significant negative correlation between Firmicutes and escape latency (Pearson correlation coefficient - 0.551, p < 0.01) and positive correlation between Proteobacteria and escape latency (Pearson correlation coefficient 0.462, p < 0.05). Electron microscopy revealed signs of blood-brain barrier (BBB) impairments and immunofluorescence images showed glial cells activated in the hippocampus of APP/PS mice without EA, and serum diamine oxidase levels were increased in these mice; whereas EA treatment significantly relieved the above pathological changes. Our findings implied that EA decreases hippocampal inflammation of APP/PS1 by upregulating benificial  gut microbiota, reducing BBB and intestinal barrier dysfunction, thus alleviates postoperative cognitive dysfunction. This may provide a novel target in POCD management.

Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is associated with worsened prognosis especially in aged population. Clinical and animal studies suggested that electroacupuncture (EA) could improve POCD. However, the underlying mechanisms especially EA's regulatory role of inflammasomes remain unclear. METHODS: The model of POCD was established by partial hepatectomy surgery in 18-month mice with or without postoperative EA treatment to the Baihui acupoint (GV20) for 7 days. Cognitive functions were assessed by Morris water maze test, and proinflammatory cytokines IL-1ß and IL-6 and microglia activity were assayed by qPCR, ELISA, or immunohistochemistry. Tight junction proteins, NLRP3 inflammasome and downstream proteins, and NF-κB pathway proteins were evaluated by western blotting. RESULTS: EA markedly preserved cognitive dysfunctions in POCD mice, associated with the inhibition of neuroinflammation as evidenced by reduced microglial activation and decreased IL-1ß and IL-6 levels in brain tissue. EA also preserved hippocampal neurons and tight junction proteins ZO-1 and claudin 5. Mechanistically, the activation of NLRP3 inflammasome and NF-κB was inhibited by EA, while NLRP3 activation abolished EA's treatment effects on cognitive function. CONCLUSION: EA alleviates POCD-mediated cognitive dysfunction associated with ameliorated neuroinflammation. Mechanistically, EA's treatment effects are dependent on NLRP3 inhibition.

Effect of electroacupuncture on postoperative cognitive dysfunction for patients undergoing total knee arthroplasty: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Electroacupuncture is increasingly used in rehabilitation for postoperative cognitive dysfunction (POCD), but relevant evidence remains unclear for patients receiving total knee arthroplasty (TKA). METHODS: The databases research of PubMed, EMBASE, CINAHL, and China National Knowledge Infrastructure (CNKI) will be conducted from inception to December 31, 2020. The relevant randomized controlled trials (RCTs) from data will be screened one by one. The remaining studies that meet the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software. Paired 2 reviewers will assess quality of the included studies and publication bias by using the Cochrane Collaboration risk of bias tool, and Egger test and Begg test respectively. And grading of recommendations assessment, development and evaluation (GRADE) will be used to estimate the quality of evidence. RESULTS: In this study, we will analyze the effect of electroacupuncture on Mini-Mental State Examination (MMSE), interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), S100-ß protein, and adverse events for patients with TKA. CONCLUSION: Our findings will provide evidence for the effectiveness of electroacupuncture on the treatment and prevention of POCD for TKA patients. REGISTRATION NUMBER: Available at: https://osf.io/azyt9 (DOI number: 10.17605/OSF.IO/AZYT9).

CSF disturbances and other neurosurgical complications after interdisciplinary reconstructions of large combined scalp and skull deficiencies.

Combined scalp and skull deficiency due to malignant scalp tumors or sequelae of intracranial surgery present challenging entities for both neurosurgeons and reconstructive treatment. In complex cases, an interdisciplinary approach is needed between neurosurgeons and cranio-maxillofacial surgeons. We present a considerably large series for which we identify typical complications and pitfalls and provide evidence for the importance of an interdisciplinary algorithm for chronic wound healing complications and malignomas of the scalp and skull. We retrospectively reviewed all patients treated by the department of neurosurgery and cranio-maxillofacial surgery at our hospital for complex scalp deficiencies and malignant scalp tumors affecting the skull between 2006 and 2019, and extracted data on demographics, surgical technique, and perioperative complications. Thirty-seven patients were treated. Most cases were operated simultaneously (n: 32) and 6 cases in a staged procedure. Nineteen patients obtained a free flap for scalp reconstruction, 15 were treated with local axial flaps, and 3 patients underwent full thickness skin graft treatment. Complications occurred in 62% of cases, mostly related to cerebrospinal fluid (CSF) circulation disorders. New cerebrospinal fluid (CSF) disturbances occurred in 8 patients undergoing free flaps and shunt dysfunction occurred in 5 patients undergoing local axial flaps. Four patients died shortly after the surgical procedure (perioperative mortality 10.8%). Combined scalp and skull deficiency present a challenging task. An interdisciplinary treatment helps to prevent severe and specialty-specific complications, such as hydrocephalus. We therefore recommend a close neurological observation after reconstructive treatment with focus on symptoms of CSF disturbances.

Timing of thoracic endovascular aortic repair for uncomplicated acute type B aortic dissection and the association with complications.

OBJECTIVE: Previous publications have clearly established a correlation between timing of thoracic endovascular aortic repair (TEVAR) and complications after treatment of complicated acute type B aortic dissection (ATBAD). However, the temporal association of TEVAR with morbidity after uncomplicated presentations is poorly understood and has not previously been examined using real-world national data. Therefore, the objective of this analysis was to determine whether TEVAR timing of uncomplicated ATBAD (UATBAD) is associated with postoperative complications. METHODS: The Vascular Quality Initiative TEVAR and complex endovascular aneurysm repair registry was analyzed from 2010 to 2019. Procedures performed for non-dissection-related disease as well as for ATBAD with malperfusion or rupture were excluded. Because of inherent differences between timing cohorts, propensity score matching was performed to ensure like comparisons. Univariate and multivariable analysis after matching was used to determine differences between timing groups (symptom onset to TEVAR: acute, 1-14 days; subacute, 15-90 days) for postoperative mortality, in-hospital complications, and reintervention. RESULTS: A total of 688 cases meeting inclusion criteria were identified. After matching 187 patients in each of the 1- to 14-day and 15- to 90-day treatment groups, there were no statistically significant differences between groups. On univariate analysis, the 1- to 14-day treatment group had a higher proportion of cases requiring reintervention within 30 days (15.3%) compared with UATBAD patients undergoing TEVAR within 15 to 90 days (5.2%; P = .02). There was also a difference (P = .007) at 1 year, with 33.8% of the 1- to 14-day UATBAD patients undergoing reintervention compared with 14.5% for the 15- to 90-day group. There were no statistically significant differences on multivariable analysis for long-term survival, complications, or long-term reintervention. There was a trend toward significance (P = .08) with the 1- to 14-day group having 2.3 times the odds of requiring an in-hospital reintervention compared with the 15- to 90-day group. CONCLUSIONS: Timing of TEVAR for UATBAD does not appear to predict mortality or postoperative complications. However, there is a strong association between repair within 1 to 14 days and higher risk of reintervention. This may in part be related to the 1- to 14-day group's representing an inherently higher anatomic or physiologic risk population that cannot be entirely accounted for with propensity analysis. The role of optimal timing to intervention should be incorporated into future study design of TEVAR trials for UATBAD.

Application of Acupuncture to Attenuate Immune Responses and Oxidative Stress in Postoperative Cognitive Dysfunction: What Do We Know So Far?

Postoperative cognitive dysfunction (POCD) is a common sequela following surgery and hospitalization. The prevention and management of POCD are important during clinical practice. POCD more commonly affects elderly patients who have undergone major surgery and can result in major decline in quality of life for both patients and their families. Acupuncture has been suggested as an effective intervention for many neurological disorders. In recent years, there are increasing interest in the use of acupuncture to prevent and treat POCD. In this review, we summarized the clinical and preclinical evidence of acupuncture on POCD using a narrative approach and discussed the potential mechanisms involved. The experimental details and findings of studies were summarized in tables and analyzed. Most of the clinical studies suggested that acupuncture before surgery could reduce the incidence of POCD and reduce the levels of systematic inflammatory markers. However, their reliability is limited by methodological flaws. Animal studies showed that acupuncture reduced cognitive impairment and the associated pathology after various types of surgery. It is possible that acupuncture modulates inflammation, oxidative stress, synaptic changes, and other cellular events to mitigate POCD. In conclusion, acupuncture is a potential intervention for POCD. More clinical studies with good research design are required to confirm its effectiveness. At the same time, findings from animal studies will help reveal the protective mechanisms, in which systematic inflammation is likely to play a major role.

Computerised cognitive training to improve cognition including delirium following coronary artery bypass grafting surgery: protocol for a blinded randomised controlled trial.

INTRODUCTION: Coronary artery bypass grafting (CABG) surgery is known to improve vascular function and cardiac-related mortality rates; however, it is associated with high rates of postoperative cognitive decline and delirium. Previous attempts to prevent post-CABG cognitive decline using pharmacological and surgical approaches have been largely unsuccessful. Cognitive prehabilitation and rehabilitation are a viable yet untested option for CABG patients. We aim to investigate the effects of preoperative cognitive training on delirium incidence, and preoperative and postoperative cognitive training on cognitive decline at 4 months post-CABG. METHODS AND ANALYSIS: This study is a randomised, single-blinded, controlled trial investigating the use of computerised cognitive training (CCT) both pre-CABG and post-CABG (intervention group) compared with usual care (control group) in older adults undergoing CABG in Adelaide, South Australia. Those in the intervention group will complete 1-2 weeks of CCT preoperatively (45-60 min sessions, 3.5 sessions/week) and 12 weeks of CCT postoperatively (commencing 1 month following surgery, 45-60 min sessions, 3 sessions/week). All participants will undergo cognitive testing preoperatively, over their hospital stay including delirium, and postoperatively for up to 1 year. The primary delirium outcome variable will be delirium incidence (presence vs absence); the primary cognitive decline variable will be at 4 months (significant decline vs no significant decline/improvement from baseline). Logistic regression modelling will be used, with age and gender as covariates. Secondary outcomes include cognitive decline from baseline to discharge, and at 6 months and 1 year post-CABG. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Central Adelaide Local Health Network Human Research Ethics Committee (South Australia, Australia) and the University of South Australia Human Ethics Committee, with original approval obtained on 13 December 2017. It is anticipated that approximately two to four publications and multiple conference presentations (national and international) will result from this research. TRIAL REGISTRATION NUMBER: This clinical trial is registered with the Australian New Zealand Clinical Trials Registry and relates to the pre-results stage. Registration number: ACTRN12618000799257.

Amelioration of postoperative cognitive dysfunction in mice by mesenchymal stem cell-conditioned medium treatments is associated with reduced inflammation, oxidative stress and increased BDNF expression in brain tissues.

OBJECTIVE: Mesenchymal stem cells (MSCs) are widely used in regeneration and repair of various tissues and organs, and whether MSC-conditioned medium (MSC-CM) has protective effects in postoperative cognitive dysfunction (POCD) remains largely unknown. We aimed to assess the therapeutic effect and explore the mechanisms of MSC-CM therapy in a POCD mouse model. METHODS: Sixty C57BL/6 mice were randomly assigned to 3 groups: control, POCD and POCD + MSC-CM. The POCD mouse model was established by left liver lobectomy. While mice in the control group were sham-operated, mice in the POCD + MSC-CM group were immediately administrated with MSC-CM after operation. The Morris water maze was used to determine cognitive function of mice at 1, 3, and 7 days after operation. The levels of IL-1ß, IL-6, TNF-α and malondialdehyde in brain tissues at 3 days after operation were assessed by ELISA, while the protein level of brain derived neurotrophic factor (BDNF) was determined by western blot. RESULTS: Left liver lobectomy induced POCD in mice resulted in decrease of cognitive function, increase of brain IL-1ß, IL-6, TNF-α and malondialdehyde levels, and decreased BDNF expression, while administration of MSC-CM significantly reversed these changes. CONCLUSION: MSC-CM ameliorates POCD in mice, and its protective roles are associated with reduced levels of inflammatory factors, attenuated oxidative stress, and increased BDNF expression.

Exendin-4 improves behaviorial deficits via GLP-1/GLP-1R signaling following partial hepatectomy.

Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists exhibit neurotrophic and neuroprotective effects. The aim of this study was to explore whether the GLP-1R agonist exendin-4 can alter surgery-induced behavioral deficits and exert neuroprotective effects via the activation of the hippocampal GLP-1/GLP-1R pathway. 120 male Sprague-Dawley rats (aged 18-20 months old) were randomly divided into four groups: control group, exendin-4 group, surgery group, and surgery + exendin-4 group. The animals received either exendin-4 (5 µg/kg/day) or saline intra-peritoneally for 14 days, and then were subjected to partial hepatectomy 24 h after the last injection. Behavioral changes were evaluated with Morris Water Maze and Open field testing on postoperative days 7 and 14. The levels of IL-1ß, NF-κB, Iba-1, Synaptophysin, GLP-1/GLP-1R, GSK-3ß, p-GSK-3ß (Ser9), p-Tau (Ser396), and p-Tau (Ser202/199) in the hippocampus were measured at the same time point. Surgical trauma induced an exacerbated spatial learning and memory impairment, increased the levels of depressive performance, and enhanced hippocampal NF-κB and IL-1ß expression in the aged rats on postoperative day 7. A corresponding decline in GLP-1R was also found following surgical challenge on postoperative day 7. Exendin-4 treatment partly reversed surgery-induced postoperative behavioral impairment, downregulated the levels of NF-κB and IL-1ß, ameliorated tau hyperphosphorylation and enhanced the activity of p-GSK-3ß (Ser9). Together, the downregulation of GLP-1R exacerbated surgery-induced behavior deficits. Exendin-4 treatment attenuated these effects by inhibiting neuroinflammation and tau hyperphosphorylation. These findings suggest that pretreatment with exendin-4 is a potential adjuvant for preventing surgery-induced behavioral deficits.

Unmet supportive care needs in patients treated with total laryngectomy and its associated factors.

BACKGROUND: The purpose of this study was to investigate unmet supportive care needs in patients treated with total laryngectomy and its associated factors. METHODS: In this cross-sectional study, 283 patients who underwent total laryngectomy completed questions on supportive care needs (Supportive Care Needs Survey [SCNS]). Median time since total laryngectomy surgery was 7 years (range 0-37 years). The prevalence of unmet supportive care needs and its associated factors were investigated using logistic regression analyses. RESULTS: Unmet supportive care needs were highest for the head and neck cancer-specific functioning domain (53%), followed by the psychological (39%), physical and daily living (37%), health system, information, and patient support (35%), sexuality (23%), and lifestyle (5%) domains. Seventy-one percent reported at least one low, moderate, or high unmet need. Female sex, living alone, and having a voice prosthesis were positively associated with unmet needs on 1 domain (P < .05). A worse health-related quality of life was associated with unmet needs on all domains. CONCLUSION: The majority of patients who underwent total laryngectomy report at least one low, moderate, or high unmet supportive care need.