1.Long-term survival of surgical versus non-surgical treatment for esophageal squamous cell carcinoma in patients ≥70 years: A retrospective cohort study
Kexun LI ; Changding LI ; Xin NIE ; Wenwu HE ; Chenghao WANG ; Kangning WANG ; Guangyuan LIU ; Junqiang CHEN ; Zefen XIAO ; Qiang FANG ; Yongtao HAN ; Lin PENG ; Qifeng WANG ; Xuefeng LENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):619-625
Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.
2.Incidence of venous thromboembolism in esophageal cancer: a real-world study of 8 458 cases
Kunyi DU ; Xin NIE ; Kexun LI ; Changding LI ; Kun LIU ; Zhiyu LI ; Kunzhi LI ; Simiao LU ; Kunhan NI ; Wenwu HE ; Chenghao WANG ; Jialong LI ; Haojun LI ; Qiang ZHOU ; Kangning WANG ; Guangyuan LIU ; Wenguang XIAO ; Qiang FANG ; Qiuling SHI ; Yongtao HAN ; Lin PENG ; Xuefeng LENG
Chinese Journal of Digestive Surgery 2024;23(1):109-113
Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.
3.Tick-borne pathogens infection of rodents at the border of China and the Democratic People's Republic of Korea
Zhuo WANG ; Qiong WU ; Xiao-Yang HUANG ; Guan-Peng HUANG ; You-Xin MA ; En-Rong MAO ; Guo-Shuang LENG ; Hong-Min ZHAO ; Bing LI ; Yi-Min WU
Chinese Journal of Zoonoses 2024;40(4):323-327
To investigate the existence of tick-borne pathogens infection of rodents at the border of China and the Demo-cratic People's Republic of Korea(DPRK).PCR was used to detect the spotted fever group rickettsiae(SFGR)ompA gene,Ehrlichia chaffeensis(Ec)and Anaplasma phagocytophilum(Ap)16S rRNA,Candidatus Neoehrlichia mikurensis(CNm)groEL gene,Bartonella(Ba)rpoB gene,and Francisella tularensis(Ft)fopA gene in rodents samples collected from Ji'an of Jilin province and Kuandian of Liaoning Province.The positivity rates of 132 wild rats spleen samples,SFGR,Ec,Ap,CNm,Ba,and Ft were 9.85%,12.88%,5.30%,3.79%,51.52%,and 6.06%,respectively,with statistical differences in in-fection rates(x2=149.236,P=0.000).The infection rate of Ba was the highest in wild rats in this area.There was no signifi-cant difference in the infection rate of SFGR,Ec,Ap,CNm,and Ft among different rats species,but there were significant differences in the infection rate of Ba(x2=13.36,P=0.010).The infection rate of Apodemus agrarius was the highest.A-mong 132 wild rats specimens,the coinfection rate of the two pathogens was 15.9%(21/132),with Ba as the main species(15/132),and two cases of coinfection with three pathogens were detected.The infection of six tick-borne pathogens is common in wild rats at the China/DPRK border.Co-infection of two or three pathogens indicates a risk of multiple tick-borne pathogens and mixed natural foci of multiple tick-borne infec-tious diseases.
4.Curcumol Mediates the Programmed Cell Death in Acute Myeloid Leukemia through PI3K/AKT Signaling Pathway
Zuo-Tao LI ; Xiao-Yun CHEN ; Hai-Liang LI ; Gui-Xiang LENG ; Yan-Quan LIU ; Ling GUO ; Yi-Li WANG
Journal of Experimental Hematology 2024;32(6):1682-1688
Objective:To investigate the effects of Curcumol on the malignant biological characteristics of acute myeloid leukemia (AML)cells and its molecular mechanism,and to provide theoretical and experimental evidence for the anti-leukemia treatment of traditional Chinese medicine.Methods:After the AML cell lines HL-60 and KG-1 cells were treated different concentrations of with Curcumol.The proliferation activity of cells was detected by CCK-8 method,and the expression changes of apoptotic proteins and PI3 K/AKT signaling pathway proteins were detected by Western blot. Real-time quantitative fluorescence polymerase chain reaction (RT-qPCR ) was used to detect the expression of Caspase family mRNA.Results:Curcumol could inhibit the proliferation and induce apoptosis of HL-60 and KG-1 cells,promote apoptosis by up-regulating the expression of Bax and down-regulating the expression of Bcl-2 protein (P<0.05).When Curcumol interferes with HL-60 and KG-1 cells,it can also induce programmed cell death of AML by inhibiting PI3 K/AKT signaling pathway.In addition,after the intervention of Curcumol,the expression of Caspase 3,Caspase 6,Caspase 8 and Caspase 9 were up-regulated in HL-60 cells (P<0.05 ),the expression of Caspase 3,Caspase 8 and Caspase 9 were significantly up-regulated in KG-1 cells (P<0.01),while the expression of Caspase 6 was weakly affected (P<0.05 ),but low concentration of Curcumol (<60 μg/ml)had no effect on the expression of Caspase 6 in KG-1 cells (P>0.05).Conclusion:Curcumol may mediate the programmed death of AML cells by inhibiting the PI3K/AKT signaling pathway,affecting the expression of Bcl-2 family proteins,and promoting the activation of core members of Caspase family,so as to play an anti-leukemia role.
5.Clinical results of 100 cases of modified eversion carotid endarterectomy
Leng NI ; Wenzhuo LIAN ; Rong ZENG ; Xiao DI ; Xitao SONG ; Fangda LI ; Liqiang CUI ; Guoqiang SUN ; Yuehong ZHENG ; Changwei LIU
Chinese Journal of Surgery 2024;62(12):1143-1149
Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.
6.Inhibitory effects of hesperidin on estrogen-and progestin-induced mammary hyperplasia in female rats
Yang YANG ; Xiao-Fen YANG ; Pei-Sen HUANG ; Jie LENG ; Fan YANG ; Yong-Jia LI
The Chinese Journal of Clinical Pharmacology 2024;40(1):77-81
Objective To investigate the therapeutic effect of hesperidin(Hsp)on mammary gland hyperplasia(MGH)rats and the possible mechanism.Methods Sixty female rats were randomly divided into blank,model,control and experimental-L,-M,-H groups.Except for blank group,all other groups were injected intramuscularly with estrogen and progestin to induce MGH model in rats.The experimental-L,-M and-H groups were given 25,50,100 mg·kg-1 Hsp by gavage.The control group was given 5 mg·kg-1 tamoxifen by gavage.The blank and control groups were given an equal volume of 0.9%NaCl by gavage.Six groups of rats were administered once a day for 30 days.After the administration,the height and diameter of nipples and the uterine coefficient were measured.The serum sex hormone content was detected using enzyme-linked immunosorbent assay,the levels of oxidative stress indicators were detected using corresponding kits,and the expressions of related proteins were detected using Western blot.Results The nipple diameters of rats in experimental-M and-H groups,control group,model group and blank group were(1.41±0.20),(1.18±0.21),(1.23±0.20),(1.75±0.13)and(1.02±0.06)mm;the nipple heights were(1.62±0.24),(1.41±0.19),(1.47±0.16),(1.87±0.32)and(1.23±0.14)mm;the uterine indexes were(0.55±0.08),(0.37±0.05),(0.41±0.04),(0.72±0.11)and(0.34±0.03)mg·g-1;the relative expression levels of estrogen receptor alpha(ERα)were 0.54±0.05,0.13±0.02,0.13±0.03,0.89±0.08 and 0.10±0.02;the relative expression levels of progesterone receptor(PR)were 0.43±0.03,0.08±0.01,0.87±0.07,0.20±0.04 and 0.14±0.03;the phosphorylated-extracellular-regulated kinase 1/2(ERK1/2)/ERK1/2 were 0.50±0.03,0.06±0.02,0.83±0.05,0.09±0.04 and 0.04±0.01,respectively.Compared with model group,the differences of above indexes in the experimental-M,-H groups and control group were statistically significant(all P<0.05).Conclusion Hsp could reduce nipple diameter,height,and uterine coefficient,regulate sex hormone levels,resist oxidative stress,and inhibit the expression of ERα,PR and p-ERK1/2 proteins in rats.
7.Clinical trial of ritodrine hydrochloride,phloroglucinol and magnesium sulfate in patients with threatened abortion after 20 gestational weeks
Juan LI ; Jin-Mei DENG ; Jiang-Nan LIU ; Xiao-Lan LI ; Ying LENG
The Chinese Journal of Clinical Pharmacology 2024;40(2):175-179
Objective To observe the effects of ritodrine hydrochloride,phloroglucinol and magnesium sulfate on serum sex hormones and fetal protection effect in patients with threatened abortion after 20 gestational weeks.Methods Patients with threatened abortion(after 20 gestational weeks)underwent fetal protection treatment were retrospectively enrolled.According to cohort method,they were divided into group A(ritodrine hydrochloride injection 100 mg+5%glucose injection 500 mL for intravenous drip,continued infusion after uterine contraction inhibition for 12-18 h,oral ritodrine hydrochloride tablets),group B(of phloroglucinol injection 40 mg+5%glucose injection 500 mL for intravenous drip,drug withdrawal after uterine contraction inhibition)and group C(magnesium sulfate injection 20 mL+5%glucose injection 100 mL,magnesium sulfate injection 40 mL+5%glucose injection 500 mL for intravenous drip after rapid intravenous drip,continued infusion after uterine contraction inhibition for 12 h).The onset time,disappearance time of uterine contraction,levels of serum sex hormones[progesterone(P),estradiol(E2),human chorionic gonadotrophin β-subunit(β-hCG)],adverse drug reactions and response rate of fetal protection in the three groups were observed.Results There were 40 cases in group A,38 cases in group B and 42 cases in group C.The onset time in group A,group B and group C were(1.71±0.34),(2.29±0.23)and(4.51±1.12)h,and the difference was statistically significant(P<0.05).The disappearance time of uterine contraction in groups A,B and C were(1.34±0.32),(2.24±0.26)and(2.36±0.28)d,and the difference between group B and group A,between group C and group A were statistically significant(all P<0.05).After 3 d of treatment,levels of serum P in group A,group B and group C were(78.64±10.34),(69.35±10.52)and(68.76±11.13)ng·mL-1;E2 levels were(672.25±85.63),(623.25±92.31)and(624.12±93.65)pg·mL-1;β-hCG levels were(6.95×104±1 258.65),(6.75×104±1 274.43)and(6.70×104±1 327.59)mU·mL-1;the difference between group B and group A,between group C and group A were statistically significant(all P<0.05).The incidence rates of palpitation in groups A,B and C were 25.00%,0 and 9.52%,the difference between group A and group B was statistically significant(P<0.05).The incidence rates of headache in groups A,B and C were 2.50%,2.63%and 26.19%;the difference between group A and group C,and between group B and group C was statistically significant(P<0.05).The incidence rates of fatigue in groups A,B and C were 5.00%,0 and 19.05%,and the difference between group B and group C was statistically significant(P<0.05).The incidence rates of gastrointestinal discomfort were 5.00%,0 and 11.90%,and the difference between group B and group C was statistically significant(all P<0.05).The response rates of fetal protection in groups A,B and C were 92.50%,94.74%and 73.81%,and the difference between group A and group C,between group B and group C was statistically significant(all P<0.05).Conclusion The onset time of ritodrine hydrochloride is short,which can be the first choice for disease control.Phloroglucinol is comparable to ritodrine hydrochloride in terms of fetal protection effect,which has better advantages in adverse drug reactions.Clinically,phloroglucinol can be considered for patients with poor tolerance to ritodrine hydrochloride.
8.Clinical results of 100 cases of modified eversion carotid endarterectomy
Leng NI ; Wenzhuo LIAN ; Rong ZENG ; Xiao DI ; Xitao SONG ; Fangda LI ; Liqiang CUI ; Guoqiang SUN ; Yuehong ZHENG ; Changwei LIU
Chinese Journal of Surgery 2024;62(12):1143-1149
Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.
9.Effects of Polygoni multiflori Radix Preparata on the neurological function improvement in a rat model of post-stroke depression
Yang LIU ; Yang TIAN ; Qin-Jie LENG ; Jing PENG ; Xiao-Qing WU ; Rui TAN
Chinese Traditional Patent Medicine 2024;46(7):2211-2219
AIM To explore the effects and mechanism of Polygoni multiflori Radix Preparata(PMRP)ona rat model of post-stroke depression(PSD).METHODS The models of middle cerebral artery occlusion(MCAO)established by thread embolism method were then randomly divided into the model group,the positive drug(fluoxetine)group,and the low-dose and high-dose PMRP groups,with 10 rats in each group,in contrast to the 10 rats of the sham operation group.After 7 days of MCAO modeling,the rats underwent their 21-day PSD modeling except those of the sham operation group,during which the rats had their the neurological functions and behaviors assessed on the 1st,7th,14th and 21st day;and their cerebral infarction area and brain water content detected on the 21st day.HE staining,Nissl staining and immunohistochemical staining were used to observe the pathological morphology of cerebral ischemic penumbra.ELISA and Western blot were applied in the detections of the cerebral protein expressions of aquaporins(AQP3,AQP4,AQP5)and brain-derived neurotrophic factor(BDNF).RESULTS Compared with the model group,the high-dose PMRP group displayed improved neurological functions and behavioral scores(P<0.05,P<0.01),and reduced cerebral infarction area and brain water content(P<0.05).Compared with the model group,each treatment group demonstrated clearer brain structure in ischemic penumbra,smaller intercellular space,increased neuron counts,decreased cerebral protein expressions of AQP3,AQP4 and AQP5(P<0.05,P<0.01),and increased BDNF protein expression(P<0.05).CONCLUSION PMRP can reduce the depression of PSD rats by improving the microenvironment of neurons to promote their growth and survival,and eliminating the brain edema to enhance neurological functions via reduced protein expressions of AQP3,AQP4 and AQP5,and increased BDNF protein expression.
10.Diabetes mellitus and adverse outcomes after carotid endarterectomy: A systematic review and meta-analysis.
Fengshi LI ; Rui ZHANG ; Xiao DI ; Shuai NIU ; Zhihua RONG ; Changwei LIU ; Leng NI
Chinese Medical Journal 2023;136(12):1401-1409
BACKGROUND:
There is still uncertainty regarding whether diabetes mellitus (DM) can adversely affect patients undergoing carotid endarterectomy (CEA) for carotid stenosis. The aim of the study was to assess the adverse impact of DM on patients with carotid stenosis treated by CEA.
METHODS:
Eligible studies published between 1 January 2000 and 30 March 2023 were selected from the PubMed, EMBASE, Web of Science, CENTRAL, and ClinicalTrials databases. The short-term and long-term outcomes of major adverse events (MAEs), death, stroke, the composite outcomes of death/stroke, and myocardial infarction (MI) were collected to calculate the pooled effect sizes (ESs), 95% confidence intervals (CIs), and prevalence of adverse outcomes. Subgroup analysis by asymptomatic/symptomatic carotid stenosis and insulin/noninsulin-dependent DM was performed.
RESULTS:
A total of 19 studies (n = 122,003) were included. Regarding the short-term outcomes, DM was associated with increased risks of MAEs (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 5.1%), death/stroke (ES = 1.61, 95% CI: [1.13-2.28], prevalence = 2.3%), stroke (ES = 1.55, 95% CI: [1.16-1.55], prevalence = 3.5%), death (ES = 1.70, 95% CI: [1.25-2.31], prevalence =1.2%), and MI (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 1.4%). DM was associated with increased risks of long-term MAEs (ES = 1.24, 95% CI: [1.04-1.49], prevalence = 12.2%). In the subgroup analysis, DM was associated with an increased risk of short-term MAEs, death/stroke, stroke, and MI in asymptomatic patients undergoing CEA and with only short-term MAEs in the symptomatic patients. Both insulin- and noninsulin-dependent DM patients had an increased risk of short-term and long-term MAEs, and insulin-dependent DM was also associated with the short-term risk of death/stroke, death, and MI.
CONCLUSIONS
In patients with carotid stenosis treated by CEA, DM is associated with short-term and long-term MAEs. DM may have a greater impact on adverse outcomes in asymptomatic patients after CEA. Insulin-dependent DM may have a more significant impact on post-CEA adverse outcomes than noninsulin-dependent DM. Whether DM management could reduce the risk of adverse outcomes after CEA requires further investigation.
Humans
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Endarterectomy, Carotid/adverse effects*
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Carotid Stenosis/surgery*
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Risk Factors
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Treatment Outcome
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Time Factors
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Stents/adverse effects*
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Diabetes Mellitus, Type 2/complications*
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Diabetes Mellitus, Type 1
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Stroke/complications*
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Insulin/therapeutic use*
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Myocardial Infarction/complications*
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Risk Assessment

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