Interaction of AI-Enabled Quantitative Coronary Plaque Volumes on Coronary CT Angiography, FFRCT, and Clinical Outcomes: A Retrospective Analysis of the ADVANCE Registry.

BACKGROUND: Luminal stenosis, computed tomography-derived fractional-flow reserve (FFRCT), and high-risk plaque features on coronary computed tomography angiography are all known to be associated with adverse clinical outcomes. The interactions between these variables, patient outcomes, and quantitative plaque volumes have not been previously described. METHODS: Patients with coronary computed tomography angiography (n=4430) and one-year outcome data from the international ADVANCE (Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care) registry underwent artificial intelligence-enabled quantitative coronary plaque analysis. Optimal cutoffs for coronary total plaque volume and each plaque subtype were derived using receiver-operator characteristic curve analysis. The resulting plaque volumes were adjusted for age, sex, hypertension, smoking status, type 2 diabetes, hyperlipidemia, luminal stenosis, distal FFRCT, and translesional delta-FFRCT. Median plaque volumes and optimal cutoffs for these adjusted variables were compared with major adverse cardiac events, late revascularization, a composite of the two, and cardiovascular death and myocardial infarction. RESULTS: At one year, 55 patients (1.2%) had experienced major adverse cardiac events, and 123 (2.8%) had undergone late revascularization (>90 days). Following adjustment for age, sex, risk factors, stenosis, and FFRCT, total plaque volume above the receiver-operator characteristic curve-derived optimal cutoff (total plaque volume >564 mm3) was associated with the major adverse cardiac event/late revascularization composite (adjusted hazard ratio, 1.515 [95% CI, 1.093-2.099]; P=0.0126), and both components. Total percent atheroma volume greater than the optimal cutoff was associated with both major adverse cardiac event/late revascularization (total percent atheroma volume >24.4%; hazard ratio, 2.046 [95% CI, 1.474-2.839]; P<0.0001) and cardiovascular death/myocardial infarction (total percent atheroma volume >37.17%, hazard ratio, 4.53 [95% CI, 1.943-10.576]; P=0.0005). Calcified, noncalcified, and low-attenuation percentage atheroma volumes above the optimal cutoff were associated with all adverse outcomes, although this relationship was not maintained for cardiovascular death/myocardial infarction in analyses stratified by median plaque volumes. CONCLUSIONS: Analysis of the ADVANCE registry using artificial intelligence-enabled quantitative plaque analysis shows that total plaque volume is associated with one-year adverse clinical events, with incremental predictive value over luminal stenosis or abnormal physiology by FFRCT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02499679.

Arthroscopic management of ankle primary synovial chondromatosis (Reichel's syndrome): A case report with literature review.

INTRODUCTION AND IMPORTANCE: Primary Synovial chondromatosis is a rare disease characterized by metaplastic cartilaginous nodules originating from the synovium, which rarely involves the ankle joint. To date, there has been a limited number of reported cases regarding the arthroscopic treatment of this disease, which can be attributed to its rare incidence. This article aims to illuminate the advantages and challenges of this technique by presenting a case study. Furthermore, we delve into the existing literature to assess the different treatments used for this disease and their outcomes. CASE PRESENTATION: A 59-year-old male patient presented with ankle pain, swelling and limited dorsiflexion. Subsequent imaging findings led to the diagnosis of anterior ankle primary synovial chondromatosis. Following this, the patient underwent arthroscopic assisted loose body removal and partial anterior synovectomy, conducted via anteromedial and anterolateral portals. During the five-year follow-up period, no recurrence was observed, and the American Orthopedic Foot and Ankle Score (AOFAS) was assessed as 88. CLINICAL DISCUSSION: Given the uncommon occurrence of this disease, no standardized treatment approach has been established in the literature. While many researchers advocate for surgical intervention to alleviate symptoms and prevent potential complications like osteoarthritis and malignancy, there exists a diversity of perspectives concerning the specific strategies and techniques to employ. CONCLUSION: Partial anterior synovectomy and loose body removal using arthroscopy via anteromedial and anterolateral portals demonstrate a notably efficacious and low-risk technique for addressing primary synovial chondromatosis affecting the anterior chamber of the ankle.

Association between metabolic syndrome and stroke: a population based cohort study.

Both metabolic syndrome (MetS) and stroke are associated with increased risk of mortality. Here, we aimed to assess the prevalence of MetS among adults using three definitions (Adult Treatment Panel III (ATP-III), International Diabetes Federation (IDF) and IDF ethnic specific cut-off for Iranian criteria) and its association with stroke. We performed a cross-sectional study of a total of 9991 adult participants of Rafsanjan Cohort Study (RCS), as part of the Prospective epidemiological research studies in Iran (PERSIAN cohort study). The MetS prevalence was evaluated in participants according to the different criteria. Multivariate logistic regression analyses were conducted to assess the association between three definitions of MetS with stroke. We found that MetS was significantly associated with higher odds of stroke according to NCEP-ATP III (odds ratio (OR): 1.89, 95% confidence interval (CI) 1.30-2.74), international IDF (OR:1.66, 95% CI: 1.15-2.40) and Iranian IDF (OR:1.48, 95% CI: 1.04-2.09) after adjusted for variables confounders. Furthermore, after adjustment, in receiver operating characteristic (ROC) curve, the AUROC was 0.79 (95% CI = 0.75-0.82), 0.78(95% CI = 0.74-0.82) and 0.78(95% CI = 0.74-0.81) for presence of MetS according to NCEP-ATP III, international IDF and Iranian IDF, respectively. ROC analyses revealed that all of these three criteria for MetS are "moderately accurate" for the identification of increased stroke risk.In conclusion, our results showed that MetS was associated with increased odds of stroke. Our findings implicate the importance of early identification, treatment, and ultimately prevention of the metabolic syndrome.

The contribution of amyloid deposition in the aortic valve to calcification and aortic stenosis.

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits associated with CAVD, which could allow the use of antisense oligonucleotides and/or isotype gene therapies for the prevention and/or treatment of CAVD.

Early Failure of Arteriovenous Fistula (AVF): The Effect of Diabetes and Hypertension in a Cross-Sectional Study.

Background: Identification and control of clinical predictors of arteriovenous (AVF) failure can improve the long-term outcome of hemodialysis patients. The effects of these factors on the outcome of AVF are not still clear. So, we aimed this study to compare the effect of hypertension and diabetes on early failure of AVF. Methods: In this retrospective study, we evaluated 400 patients with ESRD referred to our clinic for the creation of the first AVF from July 14, 2001, through August 7, 2018. One month after AVF creation, the patients were referred to the clinic for patency control. Demographic characteristics, previous history of diabetes and hypertension, and laboratory data of all patients were recorded preoperatively. Data were entered to SPSS v.24 and Study data were analyzed with chi-square and independent student t-test. Then, early failure of AVF and its relationship with a history of diabetes and hypertension were assessed. Results: There was no statistically significant relationship between the history of diabetes and early AVF failure risk in ESRD patients (OR, 0.78; 95% CI, 0.25 to 2.43). Furthermore, the history of hypertension was significantly lower in the early failure of AVF group (OR, -2.82; 95% CI, -1.42 to -5.59). Although, this effect faded when using regression analysis (OR, -2.67; 95% CI, -0.97 to -7.36). There was a higher Body mass index in the non-early failure group (p = 0.041). There was no significant difference in age (p = 0.512), gender (p = 0.091), history of smoking (p = 0.605), treatment with insulin (p = 0.683), oral antidiabetic agents (p = 0.734), duration of diabetes (p = 0.384), and duration of hypertension (p = 0.093). Conclusion: We reported that the history of diabetes was not higher in the early failure group, while there was a lower risk of AVF failure in patients with a previous history of hypertension.

Early and mid-term outcomes of carotid angioplasty and stent placement in 579 patients.

BACKGROUND AND PURPOSE: Carotid angioplasty and stenting (CAS) could be considered for preventing stroke in patients with carotid artery stenosis. This study aimed to determine the incidence and the risk factors of the early and mid-term complications associated with CAS. METHODS: This is a retrospective cohort study conducted at Shiraz University of Medical Sciences from March 2011 to March 2019. Patients at high risk and standard risk for carotid endarterectomy were included. The primary composite outcome was defined as stroke, myocardial infarction (MI), and death in the first 30 days after CAS. All-cause mortality, vascular mortality, and stroke were investigated during mid-term follow-up. RESULTS: A total of 579 patients (618 CAS) were recruited (mean age: 71.52 years). Overall, 394 (68.40%), 211 (36.63%), 179 (31.07%), and 96 (16.72%) patients had hypertension, dyslipidemia, diabetes mellitus, or were cigarette smokers, respectively. Primary composite outcomes were observed in 2.59% of patients (1.55% stroke, 0.69% MI, and 1.72% death). Atrial fibrillation was a predictor of primary composite outcome in multivariate logistic regression (p = .048). The presence of total occlusion in the contralateral carotid artery was significantly associated with the risk of stroke in univariate logistic regression (p = .041). The patients were followed for a period ranging from 1 to 83 months. The overall survival rate for all-cause mortality was 93.48% at 1 year, 77.24% at 5 years, and 52.92% at 8 years. All-cause mortality was significantly higher among patients with symptomatic carotid stenosis (p = .014). CONCLUSION: CAS provides acceptable short-term and mid-term outcomes in a unique population of high- and standard-surgical-risk, symptomatic and asymptomatic, octogenarian, and nonoctogenarian patients.

Risk factors of kidney stone disease: a cross-sectional study in the southeast of Iran.

BACKGROUND: The prevalence of kidney stones in the world is increasing and environmental factors seem to play a major role in this issue. The aim of the present study was to investigate the prevalence of risk factors of kidney stones in the adult population of Rafsanjan city based on the data of the Rafsanjan Cohort Study (RCS). METHODS: In the baseline phase of this study, 10,000 people aged 35 to 70 years are enrolled in the RCS, as one of the prospective epidemiological research studies in Iran. From this population, 9932 participants completed related demographic questionnaires as well as reported a history of diabetes mellitus, kidney stone, and hypertension diseases. The obtained data were analyzed using univariable and multivariable logistics regression. RESULTS: According to the obtained results, 46.54% of the studied population were male and 53.46% were female. The mean age of the participants was 49.94 ± 9.56 years. 2392 people accounting for 24.08% of the population had kidney stones. After adjustment of the variables, six variables of gender, WSI, no consumption of purified water, BMI, and history of hypertension and diabetes were found to be significant related factors of kidney stone disease. CONCLUSIONS: Gender, hypertension, obesity, diabetes, and personal habits like alcohol consumption, opium use and, cigarette smoking are effective in the development of kidney stones. So, by identifying the susceptible patients and teaching them, the burden of the disease on society and the individual can be reduced. The results of this study are helpful to health care providers for preventive planning for kidney stone disease.

Primary Testis Leiomyosarcoma: A Case Report.

Primary leiomyosarcoma in testis is an uncommon tumor with few cases reported. It generally develops after radiotherapy or long-term taking anabolic steroid medication. We report a 53-year-old male patient with primary testis leiomyosarcoma who presented with painless testicular enlargement without any known predisposing factors. Ultrasound revealed a large heterogeneous left testicular solid lesion. Alpha-fetoprotein (AFP) and beta-human chorionic gonadotrophin (beta-HCG) levels in serum were normal. Left radical orchidectomy following with histology assessment established a diagnosis of primary leiomyosarcoma of testis. No data of cancer metastasis was established. The patient didn't receive any adjuvant therapy. There wasn't any evidence of recurrence after 1 year follow-up. Leiomyosarcoma must be one of the differential diagnoses of seronegative tumors in testis. The motivation for this paper is the extreme infrequency of the situation and the differential diagnosis by all expansive inguinoscrotal tumors.

Brain magnetic resonance imaging without contrast significantly increased serum levels of IL-6, but not IL-10, IL-17A and TGF-ß.

Introduction: Magnetic Resonance Imaging (MRI) is a non-invasive imaging modality. However, the effects of MRI on the immune system in the in vivo conditions are yet to be clarified. In this study we explored the effects of routine brain MRI on the protein and mRNA peripheral blood levels of interleukin-6 (IL-6), IL-10, IL-17A and transforming growth factor-beta (TGF-ß).Material and methods: 40 subjects, who referred for brain MRI, were entered for evaluating effects of routine brain MRI on the protein and mRNA peripheral blood levels of IL-6, IL-10, IL-17A and TGF-ß. Accordingly, peripheral blood were collected before and 3 hours after MRI from the participants. Protein levels of the cytokines were evaluated using ELISA. Also, mRNA levels were analyzed using Real-Time PCR techniques.Results: Brain MRI without contrast led to an increase in protein levels of IL-6 in the peripheral serum, but did not change protein and mRNA levels of IL-10, IL-17A and TGF-ß. IL-6 mRNA levels after MRI were higher in the participants with mild anxiety compared to those without anxiety.Conclusion: brain MRI without contrast can induce secretion of IL-6 and may be associated with its functions, such as development of plasma cells or induction of inflammation.

Photobiomodulation for spinal cord injury: A systematic review and meta-analysis.

In recent years, photobiomodulation therapy (PBMT) has found many applications in various medical fields. Studies of PBMT on spinal cord injury (SCI) have mostly used laser sources in experimental animal models. The purpose of this study was to summarize studies that have employed PBMT for various kinds of SCI in animals. A thorough search in databases including MEDLINE, EMBASE, SCOPUS, and Web of Science, with the removal of unrelated articles, yielded 16 relevant articles. The meta-analysis showed that PBMT was effective in improving post-SCI movement in the first 14 days (MD = 1.593 (95% CI: 1.110 to 2.075; p <0.001, I2 = 51.9%) and this improvement became even greater thereafter (MD = 2.086 (95% CI: 1.570 to 2.603; p = <0.001. I2= 90.3%). Time of irradiation (<300 sec or >300 sec), gender (male or female), injury model (contusion or compression, radiation protocol (<14 days or ≥14days), laser wavelength (<800nm or >800nm) and injury severity (moderate or severe) were found to be factors that can affect PBM efficacy for SCI treatment. PBMT has an anti-inflammatory effect, is effective in reducing the size of spinal cord lesions and helps to absorb administrated proteins and stem cells to the lesion site.

Adverse Plaque Characteristics Relate More Strongly With Hyperemic Fractional Flow Reserve and Instantaneous Wave-Free Ratio Than With Resting Instantaneous Wave-Free Ratio.

OBJECTIVES: The current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)-derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices. BACKGROUND: Next to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR. METHODS: Of 120 patients (62% men, age 58.3 ± 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements. RESULTS: Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to ≥70% stenosis (-0.10, p < 0.001 and -0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (-0.10, p < 0.001 and -0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR. CONCLUSIONS: CT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.

Impact of opium dependency on clinical and neuropsychological indices of multiple sclerosis patients.

The aim of this study was to determine the effect of opium on clinical and neuropsychological parameters in multiple sclerosis (MS) patients with substance dependency. A cross-sectional study was conducted on MS patients in Rafsanjan, Iran. Forty opium-addict MS patients (10 males and 30 females) aged between 18 and 50 years were compared with 40 MS patients with no addiction. Word-Pair Learning, Mini-Mental State Examination (MMSE), Wisconsin Card-Sorting Test (WCST), Depression, Anxiety, Expanded Disability Status Scale (EDSS), Fatigue, and the Multiple Sclerosis Functional Composite (MSFC) were measured and compared in the two groups. The comparison of two groups showed a significant increase trait anxiety (P < 0.001), fatigue (P = 0.009) and significant decrease in the executive function (P = 0.003), MMSE (P = 0.003), and working memory (P < 0.001) in addicted MS. It indicates the better efficiency of processing in the non-addicted MS patients. The MSFC z-score also was significantly higher in the non-addicted group (P < 0.001). The opium addiction has a negative impact on the clinical and neuropsychological outcome in MS patients.

Advanced Imaging in Cardiac Sarcoidosis.

Sarcoidosis is a chronic disease of unknown etiology characterized by the presence of noncaseating granulomas. Cardiac involvement in sarcoidosis may lead to adverse outcomes such as advanced heart block, arrhythmias, cardiomyopathy, or death. Cardiac sarcoidosis can occur in patients with established sarcoidosis, or it can be the sole manifestation of the disease. Traditional diagnostic techniques, including echocardiography, have poor sensitivity for diagnosing cardiac sarcoidosis. The accumulating evidence supports the essential role of advanced cardiac imaging modalities such as MRI and PET in diagnosis, risk stratification, and management of patients with cardiac sarcoidosis. The current review highlights important theoretic and practical aspects of using cardiac imaging tools in the evaluation of patients with suspected or established cardiac sarcoidosis.

Is Cardiac Diastolic Dysfunction a Part of Post-Menopausal Syndrome?

Post-menopausal women exhibit an exponential increase in the incidence of heart failure with preserved ejection fraction compared with men of the same age, which indicates a potential role of hormonal changes in subclinical and clinical diastolic dysfunction. This paper reviews the preclinical evidence that demonstrates the involvement of estrogen in many regulatory molecular pathways of cardiac diastolic function and the clinical data that investigates the effect of estrogen on diastolic function in post-menopausal women. Published reports show that estrogen deficiency influences both early diastolic relaxation via calcium homeostasis and the late diastolic compliance associated with cardiac hypertrophy and fibrosis. Because of the high risk of diastolic dysfunction and heart failure with preserved ejection fraction in post-menopausal women and the positive effects of estrogen on preserving cardiac function, further clinical studies are needed to clarify the role of endogenous estrogen or hormone replacement in mitigating the onset and progression of heart failure with preserved ejection fraction in women.

Comparison of Postural Balance between Subgroups of Nonspecific Low-back Pain Patients Based on O'Sullivan Classification System and Normal Subjects during Lifting.

BACKGROUND: Balance disorder is one of the most-studied fields in low-back pain patients (LBP). However, there is insufficient information regarding the effect of LBP subgrouping on postural control. The purpose of the present study was to compare postural control between subgroups of chronic nonspecific LBP and healthy subjects during lifting. METHODS: A total of 35 men with chronic LBP (19 active extension pattern [AEP] and 16 flexion pattern [FP]) and 15 healthy controls were enrolled in this cross-sectional study. Pooled LBP was subdivided based on the O'Sullivan's classification system (OCS). The participants were asked to lift a box from the ground to the waist level and hold it for 20 seconds. The load was 10% of the subject's weight. Force plate system was used to record balance parameters, including standard deviations (SDs) of center of pressure (COP) amplitude and COP velocity in anterior-posterior and medial-lateral directions and mean total velocity. The test was divided into two static and dynamic phases. Data were analyzed using one-way analysis of variance and independent t-test. RESULTS: There were no significant differences between pooled LBP and control groups in any of the variables, except for the SD of the anterior-posterior direction velocity in the X-plane in the static phase (P=0.017). After classifying LBP, the results showed that the healthy and AEP groups were significantly different in SD of COP velocity in the frontal plane (P=0.021), mean total velocity (P=0.010), and SD of COP velocity in the sagittal plane (P=0.039). CONCLUSION: The present study showed that postural control was not different between the pooled LBP and normal groups. After classifying pooled LBP based on OCS, we found that the AEP showed different postural control as compared to healthy controls in the dynamic phase. The FP and AEP exhibited different postural control relative to the healthy controls in the static phase, and COP velocity was lower in those groups compared to the control group. The results of this study support the concept of LBP classification.

Abnormal Fractional Flow Reserve in Nonobstructive Coronary Artery Disease.

Background The basis of discordance between invasive coronary angiographic (ICA) anatomic stenosis and fractional flow reserve (FFR) is not fully understood. We analyzed coronary computed tomography angiography (CTA) characteristics of ICA-verified nonobstructive lesions in the proximal or midleft anterior descending artery with FFR ≤0.8, that is, anatomy-physiology mismatch. Methods and Results CTA and ICA were performed in 108 patients. FFR was measured during intravenous ATP (180 µg/[kg·min]) infusion. CTA-verified plaque characteristics between 53 consecutive ICA-FFR mismatch (ICA-quantitative coronary angiography <50%, FFR≤0.8) and 55 ICA-FFR match (ICA-quantitative coronary angiography<50%, FFR>0.8) vessels were compared. CTA-verified vessel area (20.7±6.7 versus 16.9±4.8 mm2; P=0.0007), positive area remodeling index (ARI; 1.38±0.23 versus 1.06±0.11; P<0.0001), %plaque area (64.7±12.7 versus 57.4±8.5%; P<0.0007), jeopardized myocardial mass (46.2±18.5 versus 37.1±14.3 g; P= 0.006), and the prevalence of low attenuation plaque (45.3% versus 9.1%; P<0.0001) at the minimum lumen area were significantly higher in the ICA-FFR mismatch than the match group. By receiver operation curve analysis, the areas under the curve for positive area remodeling index, %plaque area and jeopardized myocardial mass were 0.921, 0.681, and 0.641, respectively, for the diagnosis of mismatch (cutoff values 1.13, 66% and 58.7 g, respectively). The sensitivity and specificity of area remodeling index >1.13 for predicting ICA-FFR mismatch were 88.7% and 78.2%, respectively. Conclusions In the absence of anatomically significant stenosis, abnormal FFR is more frequently encountered in patients with CTA-derived positive remodeling, larger plaque burden, and low attenuation plaque. These findings contribute to a better understanding of how FFR-based decision-making might translate into demonstrated superior clinical outcomes.

Is there a role for fractional flow reserve in coronary artery bypass graft (CABG) planning?

The concept of significant lesions has substantially evolved over the last decade. With growing evidence for use of fractional flow reserve (FFR) as a determinant of lesion-specific ischemia and its superiority to angiography-guided revascularization and medical therapy, the field of percutaneous revascularization has shifted to rely exclusively on FFR instead of luminal stenosis alone in guiding revascularization. This transition to physiological assessment has not yet made it to the realm of surgical revascularization. FFR-guided therapy has been shown to be superior to angiography-guided therapy mainly by safe deferral of about 1/3rd of lesions, leading to less periprocedural events and better outcomes. Is it possible that utilization of FFR-guided CABG would lead to less complicated procedures, shorter operating times, more frequent off pump CABG procedures and more hybrid procedures? Can FFR-guided CABG improve the cardiovascular outcomes as compared to current standard of practice? In the following paragraphs we review the concept of FFR, the evidence behind FFR-guided therapy, the emerging data regarding use FFR-guided CABG and discuss where the revascularization field is headed.

JZL184, as a monoacylglycerol lipase inhibitor, down-regulates inflammation in a cannabinoid pathway dependent manner.

INTRODUCTION: Stroke is a prevalent disorder which is associated with several complications including inflammation. JZL-184 (JZL) inhibits arachidonic acid (AA) production and consequently results in two-arachidonoylglycerol (2-AG) accumulation. Both reduced production of AA metabolic products and increased 2-AG, the agonist of type 1 cannabinoid receptor (CB1), can result in reduced inflammation. In this study, we investigated the mechanisms of JZL in the improvement of stroke complications in mouse permanent cerebral ischemia (PPMCAO) model using AM251, the antagonist of CB1. MATERIAL AND METHODS: PMCAO mice were divided into six groups including intact, controls, vehicle, JZL, AM251 and JZL plus AM251 administrated groups. Brain infarction and edema, brain levels of matrix metalloperoteinase-9 (MMP9), interleukin (IL)-10 and tumor necrosis factor-α (TNF-α) and behavioral functions have been examined in all groups. RESULTS: The results showed that JZL lowered brain infarction, neurological disorders, TNF-α and MMP9 more effectively than JZL plus AM251. JZL and JZL plus AM251 reduced brain edema and increased brain IL-10. JZL, AM251 and JZL plus AM251 improve behavioral functions. DISCUSSION: JZL reduces brain infarction and brain pro-inflammatory molecules in CB1 pathway dependent manner. JZL also reduces brain edema and increased IL-10 in CB1 pathways or decreased AA metabolites. Further, AM251 improves behavioral functions via unknown mechanisms.

Monoacylglycerol lipase inhibitor, JZL-184, confers neuroprotection in the mice middle cerebral artery occlusion model of stroke.

INTRODUCTION: Investigators are searching to find new therapeutic strategies to reduce stroke secondary injury. JZL-184 (JZL) is an inhibitory factor for production of arachidonic acid (AA). Thus, it suppresses production of AA metabolites which are the cause of inflammation and tissue edema. Therefore, JZL may be considered for suppression of stroke secondary injury in mice middle cerebral artery occlusion (MCAO) model. Additionally, Aspirin is a known anti-inflammatory factor which is used to reduce pro-inflammatory secondary injury. The aim of this study was to determine the effects of JZL on the reduction of stroke secondary injury and to compare them with Aspirin effects. MATERIAL AND METHODS: MCAO model has been induced and accordingly 83 male MCAO induced mice have been introduced to the study. The animals were divided to seven groups including intact, controls, vehicle, Aspirin, JZL 4, 8 and 16 mg/kg administrated groups. Brain edema and infarction, behavioral functions and brain levels of IL-10, TNF-α and matrix metaloperoteinase-9 (MMP9) have been examined in the evaluated groups. RESULTS: The results revealed that JZL reduced brain edema, infarction, brain levels of TNF-α and MMP9 and also increased brain levels of IL-10 as well as improved behavioral functions in all three concentrations. The therapeutic effects of JZL were observed as well as Aspirin. DISCUSSION: Based on the results, it seems that JZL can be considered as a good candidate for inhibition of stroke secondary injury in the case of delayed treatment.