scholarly journals Metabolic reprogramming mediates hippocampal microglial M1 polarization in response to surgical trauma causing perioperative neurocognitive disorders

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Gang Luo ◽  
Xiaofeng Wang ◽  
Yongchen Cui ◽  
Yue Cao ◽  
Zhe Zhao ◽  
...  

Abstract Background Microglial polarization toward pro-inflammatory M1 phenotype are major contributors to the development of perioperative neurocognitive disorders (PNDs). Metabolic reprogramming plays an important role in regulating microglial polarization. We therefore hypothesized that surgical trauma can activate microglial M1 polarization by metabolic reprogramming to induce hippocampal neuroinflammation and subsequent postoperative cognitive impairment. Methods We used aged mice to establish a model of PNDs, and investigated whether surgical trauma induced metabolic reprograming in hippocampus using PET/CT and GC/TOF–MS based metabolomic analysis. We then determined the effect of the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) on hippocampal microglial M1 polarization, neuroinflammation, and cognitive function at 3 d after surgery. Results We found that surgery group had less context-related freezing time than either control or anesthesia group (P < 0.05) without significant difference in tone-related freezing time (P > 0.05). The level of Iba-1 fluorescence intensity in hippocampus were significantly increased in surgery group than that in control group (P < 0.05) accompanied by activated morphological changes of microglia and increased expression of iNOS/CD86 (M1 marker) in enriched microglia from hippocampus (P < 0.05). PET/CT and metabolomics analysis indicated that surgical trauma provoked the metabolic reprogramming from oxidative phosphorylation to glycolysis in hippocampus. Inhibition of glycolysis by 2-DG significantly alleviated the surgical trauma induced increase of M1 (CD86+CD206−) phenotype in enriched microglia from hippocampus and up-regulation of pro-inflammatory mediators (IL-1β and IL-6) expression in hippocampus. Furthermore, glycolytic inhibition by 2-DG ameliorated the hippocampus dependent cognitive deficit caused by surgical trauma. Conclusions Metabolic reprogramming is crucial for regulating hippocampal microglial M1 polarization and neuroinflammation in PNDs. Manipulating microglial metabolism might provide a valuable therapeutic strategy for treating PNDs.

2020 ◽  
Vol 10 (9) ◽  
pp. 2236-2241
Author(s):  
Chengyi Zhou ◽  
Junru Wang ◽  
Min Tao ◽  
Zhiqin Zhou ◽  
Wei Yang ◽  
...  

Objective: The objective is to study the effect of continuous nursing on the vomiting of patients with expectant vomiting of lung cancer, and to establish a three-dimensional segmentation model of PET-CT image, so as to provide an effective nursing intervention for patients with expectant vomiting of lung cancer. Methods: In this study, the sampling method is adopted. We collected 68 patients (over 18 years old) diagnosed with lung cancer from May 2016 to June 2018 as the study subjects. Patients are divided into experimental group and control group. Before discharge, the patients in the control group are given general discharge guidance and health knowledge guidance. The patients in the experimental group are treated with continuous nursing until the next admission, except for general discharge guidance and health knowledge guidance. The cycle is a period of intermittent chemotherapy. According to the general data questionnaire designed by the researchers themselves, the criteria of acute and subacute toxicity of anticancer drugs developed by the World Health Organization (WHO), and the simple coping style questionnaire, the data are collected. SPSS 22.0 is used for analysis. The rank sum test is used in the grading of expected nausea and vomiting. The score of self coping ability is compared within the group by paired sample t-test, and P < 0.05 is statistically significant. Results: First, before continuous nursing, there is no significant difference in the expected nausea and vomiting between the two groups (P = 0.299). After continuous nursing, in the experimental group, nausea and vomiting is significantly improved (P < 0.001). Second, the positive and negative coping scores of the two groups are 15.98±1.11 and 16.99±1.23, respectively. There is no significant difference between the two groups (P > 0.05). After continuous nursing, the experimental group is compared with the control group. There is a significant difference between positive coping score (19.21±2.12) and negative coping score (16.27±1.53) (P < 0.01). Thirdly, the pixels with the standard uptake value (SUV) > 1/4 of the maximum standard uptake value (SUVmax) are selected as the basic tumor range, which can accurately predict the tumor size and range. Conclusion: PET-CT image analysis and continuous nursing can reduce the degree of nausea and vomiting in patients with lung cancer expectant vomiting, predict the size of lung cancer tumor, improve the patients’ self-response ability and the cure rate of tumor, which is worth promoting in patients with lung cancer expectant vomiting.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3520-3520 ◽  
Author(s):  
Iradj Sobhani ◽  
Isabelle Baumgaertner ◽  
Emmanuel Itti ◽  
Alain Luciani ◽  
Richard Layese ◽  
...  

3520 Background: Curative surgery is the best therapy of CRC and recurrences. We assessed whether adding semi-annual PET-CT to the usual surveillance would be cost-effective in high risk recurrent CRC patients. Methods: CRC patients (stage II tumor perforated, stages III and IV) in remission after curative surgery were randomly assigned (1:1) to trimester usual surveillance (control) or usual surveillance + semi-annual course PET-CT (intervention) for a 3-yr follow up period. Every 3 months, multidisciplinary committee decided about recurrence by yes/no/doubtful. If yes, curative surgery alone (when relevant), or chemotherapy alone (unresecable recurrence) were conducted; additional exams could be performed if doubtful. Primary composite endpoint (failure) comprised unresectable recurrence & death. The economic assessments according to standards (CHEERS) were performed and costs were compared between groups. Statistical tests for calculation of the relative risk (RR) were used and survival was analyzed using Kaplan-Meier method, Log-Rang test and Cox models. Results: Baseline characteristics of 239 patients (120/119) enrolled in 12 centers were balanced. The failure rate was 29.2% (31 unresectable recurrences & 4 deaths) and 23.5% (27 & 1) in Interventional vs Control, respectively with no significant difference (RR = 1.24, 95% CI: 0.81-1.90; P = .32). Similar results were observed in multivariate analysis (Cox models) adjusted for stage and tumor differentiation (HR = 1.33, 95% CI: 0.8-2.19, P = .27). Period until the unresectable recurrence was significantly shorter in Interventional (median = 7; IQR: 3-20 months) than in Control group (14.3; 7.3-27; P= 0.016). This was consistent with lower elevation (median; IQR) of tumour marker in interventional (3.8; 2.8-19) than in control group (10; 5.2-28.6) at the first recurrence time as compared to the baseline (p = 0.007). Overall (mean; SD) cost (euros)/patient was higher in the PET-Scan (9385; 11658) than in the control group (7027; 7656). Conclusions: Although recurrences were detected earlier in PET-CT group, the strategy was less effective, more expensive. This exam should not be advised routinely. Clinical trial information: NCT 00624260.


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Jazyra Zynat ◽  
Yuyu Guo ◽  
Yingli Lu ◽  
Dongping Lin

Objectives. This study aimed to explore the expression of GLP-1 receptor in hypothalamus and gastrointestinal tissues after Roux-en-Y gastric bypass (RYGB) surgery in diabetic rats.Methods. Male 12-week-old Wistar rats (control) and Goto-Kakizaki rats (diabetic) were randomly divided into two groups, respectively: control sham surgery group (C), control RYGB group (C + R), diabetic sham surgery group (D), and diabetic RYGB group (D + R). Body weight and blood glucose were monitored before and after surgery every week. Eight weeks after surgery, all rats were sacrificed and the serum fasting GLP-1 concentrations were measured by ELISA. GLP-1R and DPP-4 expression in hypothalamus and ileum were measured by RT-PCR.Results. The body weight and fasting/random blood glucose in the D + R group decreased significantly compared with the D group (P<0.05). Serum GLP-1 levels in diabetic rats treated with RYGB were higher than the corresponding sham surgery rats. The expression of GLP-1R of hypothalamus in RYGB-treated diabetic rats was significantly higher than those of the sham surgery diabetic rats and both control group rats (P<0.05). We found a negative correlation between hypothalamus GLP-1R mRNA and blood glucose level. No significant difference was seen in ileum GLP-1R and DPP-4 expression among all groups.Conclusions. RYGB efficiently promoted serum GLP-1 levels and the expression of GLP-1 receptor in the hypothalamus in diabetic rats. These data suggest that the hypothalamus GLP-1R may play an important role in the GLP-1 system for improving glucose homeostasis after reconstruction of the gastrointestinal tract.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Bentsen ◽  
J K Jensen ◽  
R Ripa ◽  
P Hasbak ◽  
A Kjaer

Abstract Introduction Myocardial perfusion imaging using positron emission tomography (PET) with 82Rubidium (82Rb) is used as a standard clinical examination. 82Rb-PET provides important information for the correct diagnosis and aids in prognostic risk assessment in patients with ischemic heart disease. 82Rb enters the myocardial cells by active transport of the sodium/potassium adenosine triphosphate transporter. Some antiarrhythmic drugs inhibits sodium/potassium adenosine triphosphate transporter. Purpose To determent if the uptake of 82Rb-PET using standard uptake value (SUV) is affected by administration of antiarrhythmic drugs. Methods Twenty-one Sprague-Dawley rats were baseline PET/CT scanned with 82Rb, using a Siemens preclinical PET/CT Inveon MM system and a Cardiogen-82 Rb generator. After baseline scan, the rats were divided into three groups. One control group without any treatment, and two received treatment with either orally administered Metoprolol 50mg/kg/24h or orally administered Amiodarone 120mg/kg/24h for seven days. All three groups were again PET/CT scanned with 82Rb-PET after the last administration on day seven. Data are presented as mean ±SEM. Results In the control group, there was no difference in mean SUV in the heart from day one to day seven (SUVmean 3.47±0.11 vs 3.45±0.35 p=0.97). In the group treated with metoprolol, likewise there was no difference in mean SUV in the heart from day one to day seven (SUVmean 3.87±0.13 vs 4.4±0.21 p=0.096). In contrast, in the group treated with amiodarone there was a significant difference in mean SUV from day one to day seven (SUVmean 4.14±0.15 vs 3.38±0.18 p=0.001). In all three groups there was no difference in mean SUV from day one to day seven in the liver and kidney. Conclusions The antiarrhythmic drug amiodarone had a clear impact on SUVmean in the heart. To the best of our knowledge, this is the first time it has been shown, that amiodarone lowers the SUV in 82Rb-PET in the heart. Amiodarone therefore seems to change to uptake of 82Rb in the myocyte. This could potentially influence the calculation to estimate absolute flow through the coronary arteries and lead to wrong conclusions regarding myocardial perfusion in patients treated with amiodarone. Further studies are needed to characterize the mechanism and to confirm the effect clinically.


2019 ◽  
Author(s):  
Rispah Chomba ◽  
Maeyane Steve Moeng ◽  
Warren Lowman

Abstract Background: Biomarkers like procalcitonin (PCT) are an important antimicrobial stewardship tool for critically ill patients. The purpose of our study was to compare a procalcitonin guided antibiotic algorithm to standard antibiotic treatment in surgical trauma patients admitted to the intensive care unit (ICU).Methods: A prospective, two period cross-over study was conducted in a surgical trauma intensive care unit in South Africa. In the first period, 40 patients were recruited into the control group and antibiotics were discontinued as per standard of care. In the second period, 40 patients were recruited into the procalcitonin group and antibiotics were discontinued if the PCT decreased by ≥ 80% from the peak PCT level, or to an absolute value of less than 0.5 µg/L. Antibiotic duration of treatment was the primary outcome. Patients were followed up for 28 days from the first sepsis event.Results: For the first sepsis event the PCT group had a mean antibiotic duration of 9.3 days while the control group had a mean duration of 10.9 days (p=0.10). Patients in the intervention group had more antibiotic free days alive (mean 7.7±6.57 days) compared to the control group ﴾mean 3.8±5.22 days, (p=0.004﴿. The length of ICU stay and length of hospital stay for the two groups were similar. The in-hospital mortality was reduced in the intervention group (15%) compared to the control group (30%).Conclusion: There was no significant difference in duration of antibiotic treatment between the two groups. However, the PCT group had more antibiotic free days alive and lower in-hospital mortality compared to the control group.Trial registration: Pan African clinical trial registry, PACTR201909715467725, date of registration: 20.9.2019; retrospectively registered, https://pactr.samrc.ac.za/Search.aspx


2021 ◽  
Vol 7 (5) ◽  
pp. 902-910
Author(s):  
Yang Liu ◽  
Ting Cai ◽  
Ling Liu ◽  
Hong-Sheng Ma ◽  
Hui Ye ◽  
...  

Health economic evaluation of day surgery is helpful for patients and hospitals to choose reasonable surgery modes.By taking laparoscopic cholecystectomy (LC) in a no-smoking hospital, the top 2 hospital in China (West China hospital), as a case, this paper conducted a health economic evaluation of day surgery mode of no-smoking environment in China. The clinical data of patients undergoing LC with benign gallbladder diseases was collected in the case hospital, in which 838 patients were included in the day surgery group and 1,620 patients were included in the control group. Results showed that there was no statistically significant difference between the two groups in terms of gender and discharge approaches (p> 0.05). The age, hospitalization expenses, and LOS in the day surgery group were significantly lower than those in the control groupat p< 0.05. The cost-effectiveness ratiosof the day surgery group and the control group were 8,046.40 and 29,558.25, respectively.The day surgery mode for LC is more cost-effective than inpatient surgery mode, andday surgery is recommended for LC patients who meet the indications of day surgery in China.


2011 ◽  
Vol 18 (02) ◽  
pp. 275-279
Author(s):  
MUHAMMAD SAJID SHEIKH ◽  
MUHAMMAD FASIH UR REHMAN

Objectives: To evaluate the effectiveness of LMWH prophylaxis for DVT in high risk patients after general surgery. Study design: Randomized controlled study. Setting: Surgical Unit-IV, District Head Quarters Hospital, Faisalabad. Period: From March 2009 to August 2009. Patients and Methods: Sixty patients in the LMWH group were given perioperative enoxaparin (Clexane) as prophylaxis while compression stockings were used in another control group comprised of 60 patients. At 5th postoperative day, Doppler study was performed to detect DVT in both groups. Categorical data were analyzed for significance using Chi square test through SPSS. Results: There were significant difference in age factor, history of DVT, Medical factor, surgical trauma factor and interpretation on the basis of points. However, there is non significant difference between LMWH group and control group for chemoprophylasis. Conclusions: LMWH administration is effective for the prevention of venous thromboembolism in high risk patients and its practice should be the standard of care in the practice of surgery. 


1997 ◽  
Vol 78 (05) ◽  
pp. 1327-1331 ◽  
Author(s):  
Paul A Kyrle ◽  
Andreas Stümpflen ◽  
Mirko Hirschl ◽  
Christine Bialonczyk ◽  
Kurt Herkner ◽  
...  

SummaryIncreased thrombin generation occurs in many individuals with inherited defects in the antithrombin or protein C anticoagulant pathways and is also seen in patients with thrombosis without a defined clotting abnormality. Hyperhomocysteinemia (H-HC) is an important risk factor of venous thromboembolism (VTE). We prospectively followed 48 patients with H-HC (median age 62 years, range 26-83; 18 males) and 183 patients (median age 50 years, range 18-85; 83 males) without H-HC for a period of up to one year. Prothrombin fragment Fl+2 (Fl+2) was determined in the patient’s plasma as a measure of thrombin generation during and at several time points after discontinuation of secondary thromboprophylaxis with oral anticoagulants. While on anticoagulants, patients with H-HC had significantly higher Fl+2 levels than patients without H-HC (mean 0.52 ± 0.49 nmol/1, median 0.4, range 0.2-2.8, versus 0.36 ± 0.2 nmol/1, median 0.3, range 0.1-2.1; p = 0.02). Three weeks and 3,6,9 and 12 months after discontinuation of oral anticoagulants, up to 20% of the patients with H-HC and 5 to 6% without H-HC had higher Fl+2 levels than a corresponding age- and sex-matched control group. 16% of the patients with H-HC and 4% of the patients without H-HC had either Fl+2 levels above the upper limit of normal controls at least at 2 occasions or (an) elevated Fl+2 level(s) followed by recurrent VTE. No statistical significant difference in the Fl+2 levels was seen between patients with and without H-HC. We conclude that a permanent hemostatic system activation is detectable in a proportion of patients with H-HC after discontinuation of oral anticoagulant therapy following VTE. Furthermore, secondary thromboprophylaxis with conventional doses of oral anticoagulants may not be sufficient to suppress hemostatic system activation in patients with H-HC.


1979 ◽  
Author(s):  
G Cella ◽  
H de Haas ◽  
M Rampling ◽  
V Kakkar

Haemorrheological factors have been shown to be affected in many kings of vascular disease. The present study was undertaken to correlate these factors in normal subjects and patients suffering from peripheral arterial disease. Twenty-two patients were investigated; they had moderate or severe intermittent claudication, extent of disease being confirmed by aorto-arteriography and ankle-systolic pressure studies. Twenty-five controls with no symptoms or signs of arterial disease were selected with comparable age and sex distribution. Whole blood viscosity was measured at shear rates of 230 secs-1 and 23 secs-lat 37°c using a Wells Brookfield cone plate microvisco meter. Plasma viscosity was also measured in an identical manner. Erythrocyte flexibility was measured by centrifuge technique and fibrinogen concentration as well as haematocrit by standard techniques. The fibrinogen concentration appeared to be the only significant parameter; the mean concentration in patients with peripheral vascular disease of 463 ± 73mg/l00ml in the control group ( < 0.05). Although whole blood viscosity was high in patients, when corrected to a common haematocrit, there was no significant difference between patients and controls. The same megative correlation was found for plasma viscosity. The red cell flexibility was found to be increased in patients as compared to the control group, but this effect appeared to be simply proportional to the fibrinogen concentration.


Author(s):  
Elçin Bedeloğlu ◽  
Mustafa Yalçın ◽  
Cenker Zeki Koyuncuoğlu

The purpose of this non-random retrospective cohort study was to evaluate the impact of prophylactic antibiotic on early outcomes including postoperative pain, swelling, bleeding and cyanosis in patients undergoing dental implant placement before prosthetic loading. Seventy-five patients (45 males, 30 females) whose dental implant placement were completed, included to the study. Patients used prophylactic antibiotics were defined as the experimental group and those who did not, were defined as the control group. The experimental group received 2 g amoxicillin + clavulanic acid 1 h preoperatively and 1 g amoxicillin + clavulanic acid twice a day for 5 days postoperatively while the control group had received no prophylactic antibiotic therapy perioperatively. Data on pain, swelling, bleeding, cyanosis, flap dehiscence, suppuration and implant failure were analyzed on postoperative days 2, 7, and 14 and week 12. No statistically significant difference was detected between the two groups with regard to pain and swelling on postoperative days 2, 7, and 14 and week 12 ( p &gt;0.05), while the severity of pain and swelling were greater on day 2 compared to day 7 and 14 and week 12 in both groups ( p =0.001 and p &lt;0.05, respectively). Similarly, no significant difference was found between the two groups with regard to postoperative bleeding and cyanosis. Although flap dehiscence was more severe on day 7 in the experimental group, no significant difference was found between the two groups with regard to the percentage of flap dehiscence assessed at other time points. Within limitations of the study, it has been demonstrated that antibiotic use has no effect on implant failure rates in dental implant surgery with a limited number of implants. We conclude that perioperative antibiotic use may not be required in straightforward implant placement procedures. Further randomized control clinical studies with higher numbers of patients and implants are needed to substantiate our findings.


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