Leucine-rich alpha-2-glycoprotein 1 affects bone destruction via IL-6 in mouse periodontitis model.

OBJECTIVE: To investigate the production of leucine-rich α-2-glycoprotein-1 (LRG1) in periodontitis patients and its effectiveness as a new diagnostic marker for periodontitis. SUBJECTS AND METHODS: In vitro experiments were conducted to analyze LRG1 mRNA expression in human gingival epithelial cells and fibroblasts via quantitative real-time PCR. In vivo experiments were conducted to analyze LRG1 localization in periodontitis patients. The correlation between the serum LRG1 levels and alveolar bone resorption in the mouse periodontitis model was also investigated. RESULTS: A positive correlation existed between the periodontal inflamed surface area and serum LRG1 levels (Spearman's rank correlation coefficient: 0.60). LRG1 mRNA expression in human gingival epithelial cells and fibroblasts was upregulated by Porphyromonas gingivalis stimulation or tumor necrosis factor-α stimulation. Interleukin-6 in human gingival epithelial cells and fibroblasts induced the production of LRG1 and transforming growth factor-ß. LRG1 levels in the periodontal tissue and serum in the periodontitis model were higher than those in control mice. LRG1 local administration resulted in alveolar bone resorption, whereas the administration of interleukin-6R antibody inhibited bone resorption. CONCLUSIONS: LRG1 levels in serum and periodontal tissue are upregulated in periodontitis and are implicated in periodontal tissue destruction through interleukin-6 production.

A Case of Multiple Brain Tuberculomas in the Subarachnoid Cisterns: Recognition of Radiological Characteristics Regarding the Development of Paradoxical Response during Antituberculosis Treatment.

Brain tuberculoma and its occurrence within the subarachnoid cisterns is rare in Japan. Serological and cerebrospinal fluid (CSF) examinations and imaging findings lack specificity; thus, preoperative diagnosis is often challenging. This report presents the case of a 70-year-old woman admitted to our hospital with a one-month history of low-grade fever and altered mental status. Based on the CSF analysis and her history of latent tuberculosis infection seven years ago, she was strongly suspected of suffering from tuberculous meningitis (TBM). Consequently, the patient was enrolled in a clinical trial for antituberculosis treatment (ATT). CSF soluble interleukin-2 receptor level decreased from 2,926 U/mL on day 1 to 225 U/mL 42 days after initiating ATT. Her condition improved after five weeks; however, contrast-enhanced T1-weighted magnetic resonance imaging (MRI) revealed multiple enhanced lesions within the basal subarachnoid cisterns 25 days after admission. As the number and size of these lesions increased, a biopsy confirmed brain tuberculoma diagnosis, and the treatment was continued. In conclusion, when intracisternal scattered mass lesions are identified during TBM treatment, we should consider the possibility of tuberculoma developments arising from a paradoxical response (PR) during the treatment. Serial MRIs are crucial in monitoring PR development in cisternal tuberculomas, an extension of severe TBM. Finally, a PR can be effectively managed by continuing ATT with adjunctive corticosteroids.

Hypothermia Attenuates Neurotoxic Microglial Activation via TRPV4.

Therapeutic hypothermia (TH) provides neuroprotection. However, the cellular mechanisms underlying the neuroprotective effects of TH are not fully elucidated. Regulation of microglial activation has the potential to treat a variety of nervous system diseases. Transient receptor potential vanilloid 4 (TRPV4), a nonselective cation channel, is activated by temperature stimulus at 27-35 °C. Although it is speculated that TRPV4 is associated with the neuroprotective mechanisms of TH, the role of TRPV4 in the neuroprotective effects of TH is not well understood. In the present study, we investigated whether hypothermia attenuates microglial activation via TRPV4 channels. Cultured microglia were incubated under normothermic (37 °C) or hypothermic (33.5 °C) conditions following lipopolysaccharide (LPS) stimulation. Hypothermic conditions suppressed the expression of pro-inflammatory cytokines, inducible nitric oxide synthase, and the number of phagocytic microglia. AMP-activated protein kinase (AMPK)-NF-κB signaling was inhibited under hypothermic conditions. Furthermore, hypothermia reduced neuronal damage induced by LPS-treated microglial cells. Treatment with TRPV4 antagonist in normothermic culture replicated the suppressive effects of hypothermia on microglial activation and microglia-induced neuronal damage. In contrast, treatment with a TRPV4 agonist in hypothermic culture reversed the suppressive effect of hypothermia. These findings suggest that TH suppresses microglial activation and microglia-induced neuronal damage via the TRPV4-AMPK-NF-κB pathway. Although more validation is needed to consider differences according to age, sex, and specific central nervous system regions, our findings may offer a novel therapeutic approach to complement TH.

Incidence and factors associated with newly implemented do-not-attempt-resuscitation orders among deteriorating patients after rapid response system activation: A retrospective observational study using a Japanese multicenter database.

Aim: The rapid response system (RRS) was initially aimed to improve patient outcomes. Recently, some studies have implicated that RRS might facilitate do-not-attempt-resuscitation (DNAR) orders among patients, their families, and healthcare providers. This study aimed to examine the incidence and factors independently associated with DNAR orders newly implemented after RRS activation among deteriorating patients. Methods: This observational study assessed patients who required RRS activation between 2012 and 2021 in Japan. We investigated patients' characteristics and the incidence of new DNAR orders after RRS activation. Furthermore, we used multivariable hierarchical logistic regression models to explore independent predictors of new DNAR orders. Results: We identified 7904 patients (median age, 72 years; 59% male) who required RRS activation at 29 facilities. Of the 7066 patients without pre-existing DNAR orders before RRS activation, 394 (5.6%) had new DNAR orders. Multivariable hierarchical logistic regression analyses revealed that new DNAR orders were associated with age category (adjusted odds ratio [aOR], 1.56; 95% confidence interval, 1.12-2.17 [65-74 years old reference to 20-64 years old], aOR, 2.56; 1.92-3.42 [75-89 years old], and aOR, 6.58; 4.17-10.4 [90 years old]), malignancy (aOR, 1.82; 1.42-2.32), postoperative status (aOR, 0.45; 0.30-0.71), and National Early Warning Score 2 (aOR, 1.07; 1.02-1.12 [per 1 score]). Conclusion: The incidence of new DNAR orders was one in 18 patients after RRS activation. The factors associated with new DNAR orders were age, malignancy, postoperative status, and National Early Warning Score 2.

Malposition of a pulmonary artery catheter in the left ventricle: a case report.

BACKGROUND: Placement of pulmonary artery catheters may be associated with a variety of complications. We present a case where a pulmonary artery catheter was accidentally advanced into the left ventricle by perforating the intraventricular septum. CASE PRESENTATION: A 73-year-old woman underwent mitral valve dysfunction. A pulmonary artery catheter could not pass the tricuspid valve under general anesthesia, which was manually advanced via the right ventricle during surgery. After valve replacement, systolic pulmonary artery pressure was higher than radial arterial blood pressure. Transesophageal echocardiography (TEE) revealed the tip of the catheter in the left ventricle. The catheter was withdrawn and then advanced to the pulmonary artery under monitoring of TEE. Transseptal shunt flow gradually decreased and finally disappeared. The surgery was completed without additional procedures. CONCLUSIONS: Although ventricular septal perforation is rare, it should be recognized as a potential complication of pulmonary artery catheter insertion.

Efficacy and safety of colorectal endoscopic submucosal dissection in patients with sarcopenia.

BACKGROUND: Endoscopic submucosal dissection (ESD) for early-stage colorectal cancer (CRC) has become a common and useful treatment. Although sarcopenia has been identified as an independent risk factor for complications after surgery for CRC, whether sarcopenia is also an independent risk factor for complications after colorectal ESD remains to be clarified. The aim of this study was to compare the outcomes of colorectal ESD in patients with and those without sarcopenia. METHODS: This is a retrospective cohort study. A total of 334 patients underwent colorectal ESD for 361 neoplasms at Hiratsuka City Hospital from March 2012 to October 2018. The neoplasms were divided into two groups depending on the presence or absence of sarcopenia in the patients. RESULTS: Overall, 334 patients underwent colorectal ESD for 361 neoplasms during the study period. We excluded 90 patients (90 neoplasms), and 244 patients (277 neoplasms) were included in the final analysis (134 from the sarcopenia group, 137 from the non-sarcopenia group). The en-bloc resection rate was high and was not significantly different between the sarcopenia group [126/134 (94.1%)] and the non-sarcopenia group [133/137 (97.1%)], P = 0.1778). The rate of perforation and the rate of delayed bleeding were not significantly different between the sarcopenia group and the non-sarcopenia group [6/134 (4.5%) vs. 9/137 (6.6%), P = 0.314, 4/134 (3%) vs. 6/137 (4.4%), P = 0.3885, respectively]. CONCLUSIONS: The presence of sarcopenia did not influence the rate of complications after ESD. Colorectal ESD is safe and effective even in patients with sarcopenia. Prospective multicenter studies are necessary to confirm our results.

Hypothermia Attenuates Neuronal Damage via Inhibition of Microglial Activation, Including Suppression of Microglial Cytokine Production and Phagocytosis.

Although therapeutic hypothermia (TH) provides neuroprotection, the cellular mechanism underlying the neuroprotective effect of TH has not yet been fully elucidated. In the present study, we investigated the effect of TH on microglial activation to determine whether hypothermia attenuates neuronal damage via microglial activation. After lipopolysaccharide (LPS) stimulation, BV-2 microglia cells were cultured under normothermic (37 °C) or hypothermic (33.5 °C) conditions. Under hypothermic conditions, expression of pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) was suppressed. In addition, phagocytosis of latex beads was significantly suppressed in BV-2 cells under hypothermic conditions. Moreover, nuclear factor-κB signaling was inhibited under hypothermic conditions. Finally, neuronal damage was attenuated following LPS stimulation in neurons co-cultured with BV-2 cells under hypothermic conditions. In conclusion, hypothermia attenuates neuronal damage via inhibition of microglial activation, including microglial iNOS and pro-inflammatory cytokine expression and phagocytic activity. Investigating the mechanism of microglial activation regulation under hypothermic conditions could contribute to the development of novel neuroprotective therapies.

General Anesthetic Management of a Patient With Hypertrophic Cardiomyopathy for Oral Surgery: Did Digitalis Contribute to Bradycardia?

Stabilization of circulatory dynamics is a critical issue in the anesthetic management of patients with hypertrophic cardiomyopathy (HCM). In this report, we managed general anesthesia for a 74-year-old male patient with nonobstructive HCM who developed circulatory instability intraoperatively. Severe bradycardia measuring 35 beats/min and hypotension measuring 78 mm Hg systolic were observed during surgery. Using stroke volume variation and stroke volume from the FloTrac as indices, successful circulatory management was performed with dopamine. The hypotension and bradycardia were thought to be the result of methyldigoxin and possibly associated with our perioperative management. Cardiology consult should have been obtained. We demonstrated that the FloTrac can be beneficial in diagnosing and managing cardiovascular instability and administration of dopamine in the anesthetic management of nonobstructive HCM patients.

Neuroprotective erythropoietin attenuates microglial activation, including morphological changes, phagocytosis, and cytokine production.

Erythropoietin (EPO), a hematopoietic hormonal cytokine induced in response to hypoxia, has neuroprotective effects. EPO receptor (EPOR) is expressed in microglia, resident immune cells in the brain. However, the effect of EPO on microglial activation is not clear. In the present study, we demonstrated that the EPOR is highly expressed in microglia, rather than in neurons or astrocytes, in in vitro experiments. Therefore, we investigated whether EPO could attenuate lipopolysaccharide (LPS)-mediated activation of microglia in vitro. The BV-2 microglial cell line was treated with LPS in the absence or presence of EPO. In the presence of EPO, microglial expression of LPS-induced inflammatory cytokine genes was significantly decreased. In addition, EPO suppressed the LPS-induced phagocytic activity of BV-2 cells towards fluorescent beads, as well as induction of inducible nitric oxide synthase. In in vivo experiments, EPO significantly decreased the LPS-induced expression of inflammatory cytokine genes in mouse brains. Furthermore, morphological analysis of cortical microglia in the brains of mice stimulated with LPS revealed that combined treatment with EPO alleviated LPS-induced morphological changes in the microglia. These data indicate that EPO attenuates microglial activation, including morphological changes in vivo, phagocytosis in vitro, and the production of inflammatory cytokines in vivo and in vitro. Further investigation of EPO modulation of LPS-induced microglial activation may contribute to the development of novel neuroprotective therapies.

Inflammatory cytokine tumor necrosis factor α suppresses neuroprotective endogenous erythropoietin from astrocytes mediated by hypoxia-inducible factor-2α.

Interest in erythropoietin (EPO) as a neuroprotective mediator has grown since it was found that systemically administered EPO is protective in several animal models of disease. However, given that the blood-brain barrier limits EPO entry into the brain, alternative approaches that induce endogenous EPO production in the brain may be more effective clinically and associated with fewer untoward side-effects. Astrocytes are the main source of EPO in the central nervous system. In the present study we investigated the effect of the inflammatory cytokine tumor necrosis factor α (TNFα) on hypoxia-induced upregulation of EPO in rat brain. Hypoxia significantly increased EPO mRNA expression in the brain and kidney, and this increase was suppressed by TNFα in vivo. In cultured astrocytes exposed to hypoxic conditions for 6 and 12 h, TNFα suppressed the hypoxia-induced increase in EPO mRNA expression in a concentration-dependent manner. TNFα inhibition of hypoxia-induced EPO expression was mediated primarily by hypoxia-inducible factor (HIF)-2α rather than HIF-1α. The effects of TNFα in reducing hypoxia-induced upregulation of EPO mRNA expression probably involve destabilization of HIF-2α, which is regulated by the nuclear factor (NF)-κB signaling pathway. TNFα treatment attenuated the protective effects of astrocytes on neurons under hypoxic conditions via EPO signaling. The effective blockade of TNFα signaling may contribute to the maintenance of the neuroprotective effects of EPO even under hypoxic conditions with an inflammatory response.

Using miglitol at 30 min before meal is effective in hyperinsulinemic hypoglycemia after a total gastrectomy.

A 45-year-old woman who had undergone total gastrectomy for gastric cancer presented with a history of postprandial hypoglycemic episodes with loss of consciousness after meals. Laboratory findings revealed marked hyperinsulinemia and hypoglycemia after a meal. We first treated the patient with octreotide; however, she was unable to continue the treatment because of adverse effects of the drug, such as nausea and headache. Diazoxide was used next for preventing hyperinsulinemia; however, this was not effective for suppressing the postprandial insulin secretion. Since hypoglycemia following gastrectomy is thought to be caused by rapid delivery of nutrients into the duodenum, we performed a meal tolerance test while varying the timing of administration of miglitol in relation to the meal. Miglitol was administered 30 min before, just before, or both 30 min and just before a meal. In the case of administration just before a meal, insulin secretion was suppressed, although hypoglycemia was not prevented. Administration of the drug 30 min before a meal prevented postprandial hypoglycemia by slowing the increase of the blood glucose and serum insulin levels following the meal to a greater degree than administration just before a meal. Miglitol administration both 30 min and just before a meal caused an even smoother increase in blood glucose and serum insulin levels following the meal. In this report, we propose a new therapeutic approach for reactive hypoglycemia after gastrectomy, namely, administration of miglitol 30 min before meals.

Reduction of endothelial tight junction proteins is related to cerebral aneurysm formation in rats.

OBJECTIVE: The formation of cerebral aneurysms is associated with endothelial damage and macrophage migration. Hypothesizing that the opening of tight junctions due to the disappearance of the tight junction proteins occludin and zona occludens-1 (ZO-1) in damaged endothelia allows macrophage migration, leading to cerebral aneurysm formation, we investigated the role of tight junction proteins. METHODS: The vascular wall of female rats subjected to hypertension, oophorectomy (OVX), and hemodynamic stress to induce cerebral aneurysms was evaluated morphologically, immunohistochemically, and by quantitative RT-PCR. We also assessed the regulation of tight junction proteins in human brain endothelial cells (HBECs). RESULTS: In the very early stage before aneurysm formation, the expression of occludin and ZO-1 was reduced in injured endothelial cell junctions exhibiting gaps. In the course of aneurysmal progression their reduction progressed and was correlated with macrophage migration. In hypertension along with OVX rats we observed an increase in angiotensin II and the degradation molecules matrix metalloproteinase-9 (MMP-9), nicotinamide-adenine dinucleotide phosphate oxidases and monocyte chemoattractant protein-1. The mineralocorticoid receptor blocker eplerenone increased occludin and ZO-1 expression; this was associated with a reduction in angiotensin II and the degradation molecules and resulted in the inhibition of macrophage exudation and aneurysm formation. In HBECs, occludin and ZO-1 downregulation by angiotensin II and estrogen deficiency was reversed by eplerenone, the MMP inhibitor SB3CT, and apocynin. Our results suggest that macrophage migration is associated with the reduction in tight junction proteins induced by the degradation molecules. CONCLUSION: In rats, the destruction of tight junctions may facilitate macrophage migration and cerebral-aneurysm formation.

Ibudilast inhibits cerebral aneurysms by down-regulating inflammation-related molecules in the vascular wall of rats.

OBJECTIVE: Phosphodiesterase-4 (PDE-4) is a cyclic adenosine monophosphate-specific enzyme involved in various inflammatory diseases. We studied its role in and the effect of ibudilast, which predominantly blocks PDE-4, on rat cerebral aneurysms. METHODS: Cerebral aneurysms were induced at the anterior cerebral artery-olfactory artery bifurcation of female rats subjected to hypertension, increased hemodynamic stress, and estrogen deficiency. The effect of ibudilast (30 or 60 mg/kg/d for 3 months) on their cerebral aneurysms was studied by morphological and immunohistochemical assessment and quantitative real-time polymerase chain reaction assay. In our in vitro study, we grew endothelial cells stimulated by angiotensin II under estrogen-free conditions and examined the effect of ibudilast on PDE-4 activation and the cyclic adenosine monophosphate level. RESULTS: Morphological evaluation using vascular corrosion casts showed ibudilast significantly suppressed cerebral aneurysms in a dose-dependent manner. In rats with induced cerebral aneurysms, the gene and protein expression of PDE-4 was high, and endothelial leukocyte adhesion molecules (P-selectin, intracellular adhesion molecule 1, and vascular adhesion molecule 1), matrix metalloproteinase-9, and tumor necrosis alpha were expressed. Macrophage migration was also increased. Treatment with ibudilast down-regulated these molecules, suppressed macrophage migration into the aneurysm wall, and inhibited PDE-4 activation and the elevation of cyclic adenosine monophosphate in endothelial cells. CONCLUSION: These results suggest that blocking of PDE4 is associated with the reduction of inflammation-related molecules and macrophage migration, thereby reducing the progression of cerebral aneurysms. It may represent a new conservative therapy to treat patients with cerebral aneurysms.

Traumatic pseudoaneurysm of superficial temporal artery.

An 83-year-old man reported falling and bumping his right lateral forehead on the ground 3 weeks previously. Physical examination revealed a soft, reddish swelling on the lateral forehead. Computed tomography confirmed a hematoma of the right lateral forehead. On the seventh hospital day, the swelling showed slight enlargement. Re-examination revealed a pulsatile mass with a palpable thrill and systolic bruit. Doppler echo showed pulsation of the swelling, which disappeared with compression of the anterior branch of the superficial temporal artery (STA). Surgical exploration was performed, and the pseudoaneurysm was resected. Pathological findings confirm a pseudoaneurysm.

Severe hyponatremia occurring after surgical stress in a patient with mitochondrial disease.

A 53-year-old man with mitochondrial disease underwent gastrectomy because of gastric cancer. Three days after the surgery, he developed severe hyponatremia (Na, 106 mmol l(-1)) together with hypovolemic shock and lactic acidosis. Despite the hyponatremia, his urine sodium concentration was high, suggesting renal salt wasting. Although mitochondrial diseases are not common and hyponatremia in patients with these diseases is not well known, clinicians should pay close attention to serum sodium levels and maintain them properly.

Role of mineralocorticoid receptor on experimental cerebral aneurysms in rats.

Activation of the renin-angiotensin (Ang)-aldosterone system is involved in the pathology of vascular diseases. Although the blockade of the mineralocorticoid receptor protects against vascular diseases, its role in cerebral aneurysms remains to be elucidated. We treated female rats subjected to renal hypertension, increased hemodynamic stress, and estrogen deficiency for 3 months with the mineralocorticoid receptor blocker eplerenone (30 or 100 mg/kg per day) or vehicle (vehicle control). Eplerenone reduced the incidence of cerebral aneurysms and saline intake without lowering of the blood pressure. In the aneurysmal wall, the production of Ang II and nitrotyrosine was increased. The mRNA levels of Ang-converting enzyme 1 and NADPH oxidase subunits NOX4, Rac1, monocyte chemoattractant protein 1, and matrix metalloproteinase 9 were increased. Eplerenone brought about a reduction in these molecules, suggesting that mineralocorticoid receptor blockade suppresses cerebral aneurysm formation by inhibiting oxidative stress, inflammatory factors, local renin-Ang system activation, and saline intake. Other female rats implanted with pellets of the mineralocorticoid receptor agonist deoxycorticosterone acetate manifested a high incidence of cerebral aneurysm formation and the upregulation of molecules related to oxidative stress, inflammatory factors, and the local renin-Ang system; their saline intake was increased. We demonstrate that mineralocorticoid receptor activation at least partly contributes to the pathogenesis of cerebral aneurysms.

Endothelial damage due to impaired nitric oxide bioavailability triggers cerebral aneurysm formation in female rats.

OBJECTIVE: Epidemiological data indicate a high incidence of cerebral aneurysms in postmenopausal women. To elucidate the pathogenesis of cerebral aneurysms, we focused on the contribution of endothelial damage in rats. METHODS: We induced estradiol deficiency by oophorectomy (OVX), hypertension, or both, and hemodynamic stress in 7-week-old female Sprague-Dawley rats. They were then given hormone-replacement therapy with 17beta-estradiol or an angiotensin II type 1 receptor blocker (ARB). The effects of estradiol, angiotensin II type 1 receptor blocker, or both on cultured endothelial cells were also examined. RESULTS: The number of anomalously shaped endothelial cells was higher in OVX than hypertensive rats (P < 0.05). Rats subjected to hypertension and OVX exhibited a marked increase in the incidence of saccular cerebral aneurysms. Estradiol or angiotensin II type 1 receptor blocker treatment reduced this incidence (P < 0.05). The endothelial nitric oxide synthase (eNOS) mRNA level in the intracranial artery of OVX and hypertensive and OVX rats was low (P < 0.05). Immunohistochemically, the expression of eNOS and estrogen receptor alpha (ERalpha) in the vascular wall of hypertensive and OVX rats was decreased; angiotensin II and the nicotinamide adenine dinucleotide phosphate oxidase subunits nicotinamide adenine dinucleotide phosphate oxidase 4 and p22phox were strongly expressed in cerebral aneurysms. In the absence of estradiol, eNOS was downregulated and nicotinamide adenine dinucleotide phosphate oxidase expression was increased in endothelial cells; angiotensin II augmented these phenomena. The regulation of eNOS was mediated by ERalpha. These results suggest that estrogen deficiency induces endothelial dysfunction and reactive oxygen species generation, triggering endothelial damage that leads to cerebral aneurysms and that hypertension is an additional risk factor. CONCLUSION: A therapy targeted at the endothelium and management of hypertension may help to prevent cerebral aneurysms.

Comparison between early and late carotid endarterectomy for symptomatic carotid stenosis in relation to oxidized low-density lipoprotein and plaque vulnerability.

OBJECTIVE: Although carotid endarterectomy (CEA), the gold standard in stroke prevention, has been performed in the late stage after the insult, its optimal timing remains unclear. Using biomarkers in plaque and plasma, we evaluated oxidative stress and plaque vulnerability between early and late CEA in symptomatic patients. METHODS: We compared symptomatic stroke patients who underwent early CEA within 4 weeks of the last insult (group A; n = 15) with those who received CEA in the late stage beyond 4 weeks from the last symptom (group B; n = 57). They were divided into vulnerable (group Av, n = 13; group Bv, n = 33) and stable (group As, n = 2; group Bs, n = 24) subgroups according to the pathologic findings on their plaques. We studied the relationships among their primary symptoms, clinical findings, oxidized low-density lipoprotein levels, and gelatinase A (matrix metalloproteinase [MMP]-9) activity in their plaques and plasma. RESULTS: Group A had a variety of symptoms; there was no difference in the outcome of CEA between groups A and B. The plaque and plasma oxidized low-density lipoprotein levels were higher in group A than in group B (P < .05). The incidence of pathologically vulnerable plaque was higher in group A than in group B. Plaque oxidized low-density lipoprotein levels and MMP-9 activity were similar in group Av and group Bv and were higher in those groups than in group As and Bs. CONCLUSIONS: We first demonstrated that vulnerable plaques in patients subjected to early CEA manifested a remarkable increase in oxidized low-density lipoprotein and MMP-9 activation. Our findings suggest that early CEA may be beneficial in the aspect of oxidative stress.