Mönckeberg's medial arteriosclerosis in the oral and maxillofacial region: A pilot study.

OBJECTIVE: To evaluate the prevalence of medial vascular calcifications in the oral and maxillofacial region and their association with systemic diseases. MATERIALS AND METHODS: The study included 211 consecutive patients with systemic diseases (January 2015-May 2016). Medical history and radiographic images were evaluated. Univariate analysis (t-test) was performed for continuous variables (age). The Chi square test was applied for the categorical variables (Mönckeberg medial arteriosclerosis [MMA], gender). RESULTS: There was a 6.2% prevalence of MMA. The mean age of patients with MMA was 65.46 ± 13.38. The prevalence of kidney disease in patients with MMA was significantly higher than in those without MMA (p < 0.001). This finding was maintained even after adjusting for other systemic diseases (OR = 31.84 [8.63-136.78]). CONCLUSION: A significant prevalence of MMA in kidney disease patients was observed in this pilot study.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

Clinical characteristics and risk factors for primary Sjögren's syndrome complicated with pulmonary arterial hypertension. / åŽŸå‘æ€§å¹²ç‡¥ç»¼åˆå¾åˆå¹¶è‚ºåŠ¨è„‰é«˜åŽ‹çš„ä¸´åºŠç‰¹å¾å’Œå±é™©å› ç´ .

OBJECTIVES: Primary Sjögren's syndrome (pSS) is involved in pulmonary tissue. Pulmonary arterial hypertension (PAH) is one of the pulmonary complications caused by pSS. This study aims to investigate the clinical characteristics and risk factors for pSS complicated with PAH. METHODS: We retrospectively analyzed 165 patients in the Second Xiangya Hospital of Central South University. They were divided into a pSS-PAH group (n=86) and a pSS group (n=79) according to pulmonary artery pressure detected by color doppler echocardiography. The clinical characteristics, laboratory test indexes, and risk factors were compared between the 2 groups. RESULTS: Among 165 patients with pSS, 86 patients (52.12%) had PAH. Females were 79 (91.90%) patients in the pSS-PAH group, more than males. The patients in the pSS-PAH group were older than those in the pSS group (all P<0.05). The incidence of keratoconjunctivitis, alopecia, Raynaud's phenomenon, cough, chest tightness, shortness of breath, and dry skin was higher (all P<0.05), and the incidence of pulmonary infection, pulmonary cystic degeneration, respiratory failure, osteoporosis, arteriosclerosis, and hypertension were higher in the pSS-PAH group than those in the pSS group (all P<0.05). The laboratory indicators of pulmonary artery diameter, right atrium diameter, right ventricular contractile diameter and pulmonary artery systolic pressure were higher in the pSS-PAH group than those in the pSS group (all P<0.05), and the positive rates of anti-nuclear antibody, anti-SSA antibody, and anti-Ro-52 antibody were higher (all P<0.05). The incidence of restrictive ventilatory dysfunction and decreased lung diffusion volume in the pSS-PAH group was higher than that in the pSS group (both P<0.05). Advanced age (OR=1.094, 95% CI 1.053 to 1.137, P<0.001), concomitant keratoconjunctivitis (OR=2.075, 95% CI 1.054 to 4.088, P=0.035), hair loss (OR=2.655, 95% CI 1.368 to 5.152, P=0.004), dry skin (OR=2.696, 95% CI 1.364 to 5.332, P=0.004), high pulmonary artery systolic pressure (OR=1.185, 95% CI 1.125 to 1.248, P<0.001), respiratory failure (OR=2.279, 95% CI 1.137 to 4.570, P=0.020), osteoporosis (OR=2.087, 95% CI 1.025 to 4.248, P=0.043), atherosclerosis (OR=2.251, 95% CI 1.146 to 4.423, P=0.018), hypertension (OR=2.370, 95% CI 1.190 to 4.718, P=0.014), the increased antinuclear antibody (OR=2.155, 95% CI 1.094 to 4.245, P=0.026), the increased anti-SSA antibody (OR=2.565, 95% CI 1.292 to 5.091, P=0.007), the increased anti-RO-52 antibody (OR=2.623, 95% CI 1.278 to 5.383, P=0.009), and the decreased lung dispersion (OR=2.602, 95% CI 1.386 to 4.884, P=0.003), were all risk factors for PAH in pSS patients. CONCLUSIONS: The incidence of pSS-PAH is high in this study. The advanced age, elevated pulmonary artery systolic pressure, concomitant keratoconjunctivitis, alopecia, dry skin, respiratory failure, osteoporosis, arteriosclerosis, and hypertension, increased anti-nuclear antibody, anti-SSA antibody, and anti-Ro-52 antibody, and decreased pulmonary dispersion suggest that the risk of PAH is significantly increased in patients with pSS.

Association between Arteriosclerosis and Uncontrolled Blood Pressure in Patients with Essential Hypertension: Cross-Sectional Observational Study Results of the BEST Study.

Whether arteriosclerosis can influence the hypertension control remains incompletely understood. We hypothesized that higher arteriosclerosis may be associated with uncontrolled hypertension. Arteriosclerosis was assessed by carotid femoral artery pulse wave velocity (CF-PWV) and uncontrolled hypertension (systolic blood pressure [BP] ≥130 mm Hg or diastolic BP ≥80 mm Hg). The multivariable-adjusted logistic regression was used for analysis. A total of 1,428 patients with essential hypertension (mean age 68 years, 49.6% male) were enrolled into the study from 2010 to 2017. The BP was uncontrolled in 50.7% of the participants and the mean level of CF-PWV was 12.3 m/s. All the cardiovascular risk factors were worse and CF-PWV was higher in patients with uncontrolled hypertension (all p < 0.05). Multivariable-adjusted logistic regression analysis showed that CF-PWV as a continuous variable (odd ratio [OR] 1.093, 95% confidence interval [CI] 1.046-1.142) was independently associated with uncontrolled hypertension, after male (OR 1.511) and total cholesterol (OR 1.167), followed by body mass index (OR 1.092), fasting plasma glucose (OR 1.075), and creatinine (OR 1.010) (all p < 0.05). As a binary variable, CF-PWV >12 m/s was also independently associated with uncontrolled hypertension (OR 1.690, 95% CI 1.320-2.164, p < 0.05). Arteriosclerosis is independently associated with uncontrolled BP in patients with hypertension.

The Severity of Obstructive Sleep Apnea Increases the Risk of Arteriosclerosis.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder worldwide. It is associated with myocardial remodeling and arteriosclerosis in patients with hypertension. Our study investigated the relationship between OSA severity and arteriosclerosis and blood pressure in an Asian population. METHODS: We enrolled 365 subjects from July 2018 to December 2020 at Ruijin Hospital. We recorded data from the medical history and collected blood samples from all participants. We performed 24-hour ambulatory Blood Pressure (BP) monitoring and Carotid-femoral pulse wave velocity (cf-PWV) measurements. Overnight polysomnography (PSG) was performed using Respironics Alice PDxSleepware. RESULTS: PSG was performed in a total of 365 subjects; mean age of 49.1 ± 12.8 years and Body Mass Index (BMI) 28.1 ± 3.8 kg/m2. The majority (89.3%) were male. The office systolic BP was significantly higher in the moderate to severe group than mild OSA group (148 ± 21 mmHg vs 139 ± 19 mmHg, p < 0.01). The subjects with moderate to severe OSA presented higher cf-PWV values than those in the mild group (10.03 ± 3.67 m/s vs 7.62 ± 1.48 m/s, p < 0.01). BMI was significantly higher in the moderate to severe than the mild OSA groups (28.3 ± 4.0 kg/m2 vs 27.5 ± 3.2 kg/m2, p < 0.05). The Pearson correlation showed that the apnea-hypopnea index (AHI) was significantly and positively correlated with cf-PWV (r = 0.217, p < 0.01), Age (r = 0.148, p < 0.01), BMI (r = 0.228, p < 0.01) and HbA1c (r = 0.172, p < 0.01). After adjusting for age, BMI, low density lipoprotein cholesterin (LDL-c), FGB, AHI, estimated Glomerular Filtration Rate (eGFR), Night BP, office diastolic BP and Day BP in Logistic regression model, AHI (OR = 1.03, 95% CI: 1.01-1.05) and office diastolic pressure (OR = 1.04, 95% CI: 1.00-1.08) and age (OR = 1.12, 95% CI: 1.06-1.19) were independent risk factors for arteriosclerosis. CONCLUSIONS: The severity of OSA was positively correlated with pulse wave velocity. AHI, office BP and age were independent risk factors for arteriosclerosis.

A patient with Silver-Russell syndrome with multilocus imprinting disturbance, and Schimke immuno-osseous dysplasia unmasked by uniparental isodisomy of chromosome 2.

Silver-Russell syndrome (SRS) is a congenital disorder characterized by prenatal and postnatal growth failure and craniofacial features. Hypomethylation of the H19/IGF2:IG-differential methylated region (H19LOM) is observed in 50% of SRS patients, and 15% of SRS patients with H19LOM had multilocus imprinting disturbance (MLID). Schimke immuno-osseous dysplasia (SIOD), characterized by spondyloepiphyseal dysplasia and nephropathy, is an autosomal recessive disorder caused by mutations in SMARCAL1 on chromosome 2. We report a patient with typical SRS-related features, spondyloepiphyseal dysplasia, and severe nephropathy. Molecular analyses showed H19LOM, paternal uniparental isodisomy of chromosome 2 (iUPD(2)pat), and a paternally inherited homozygous frameshift variant in SMARCAL1. Genome-wide methylation analysis showed MLID in this patient, although it showed no MLID in another patient with SIOD without SRS phenotype. These results suggest that iUPD(2)pat unmasked the recessive mutation in SMARCAL1 and that the SMARCAL1 gene mutation may have no direct effect on the patient's methylation defects.

High-resolution MRI of the vessel wall helps to distinguish moyamoya disease from atherosclerotic moyamoya syndrome.

AIM: To evaluate the value of high-resolution magnetic resonance imaging of the vessel wall (VWI) for differentiating moyamoya disease (MMD) from atherosclerotic moyamoya syndrome (AS-MMS). MATERIALS AND METHODS: Twenty-one patients with MMD or AS-MMS were assessed retrospectively by two independent raters regarding and magnetic resonance angiography (MRA) stage grading score; collateral development in the lateral fissure and basal ganglia on MRA; and pattern of the thickening of the arterial wall; presence, degree, and pattern of enhancement; presence and distribution of deep tiny flow voids (DTFVs) and collateral development in the lateral fissure and basal ganglia on VWI. After univariate analysis between the two groups, logistic regression models based on imaging findings of MRA or VWI were implemented respectively, and receiver operating characteristic (ROC) curves were generated to compare the discriminatory power of the two imaging methods for diagnosis of MMD. Interrater agreement was analysed using an unweighted Cohen's κ or interclass correlation coefficient (ICC). RESULTS: MMD manifested as more concentric thickening, more homogeneous enhancement, higher presence of DTFV, smaller outer-wall boundary area of stenosis or occlusion, and smaller remodelling index on VWI. After Bonferroni-Holm correction for multiple comparisons, for AS-MMS, collaterals in both the lateral fissure and basal ganglia were not usually present on either MRA or VWI. The diagnostic performance of the multivariate logistic regression model based on VWI with an accuracy of 87.1% for classification was higher than MRA. Interrater agreement was moderate or substantial for all the imaging findings. CONCLUSIONS: VWI might be a useful and feasible method for differentiating MMD from AS-MMS and a prospective tool for guiding first-line treatment.

Correlation among cystatin C, homocysteine and arteriosclerosis indexes in patients with chronic kidney disease. / æ ¢æ€§è‚¾è„ç— æ‚£è€ èƒ±æŠ‘ç´ Cã€åŒåž‹åŠèƒ±æ°¨é ¸ä¸ŽåŠ¨è„‰ç¡¬åŒ–æŒ‡æ ‡çš„ç›¸å ³æ€§.

OBJECTIVES: Chronic kidney disease (CKD) has become an important public health problem in the world. The occurrence of cardiovascular events is the main cause of death in patients with CKD, and arteriosclerosis is an important pathophysiological basis for cardiovascular diseases. Nowadays, brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) are clinically important indicators to reflect early atherosclerosis. Cystatin C (Cys C)and homocysteine (Hcy) are related to arteriosclerosis in healthy, hypertensive, and diabetic people, while there are few studies on the correlation among Hcy, CysC and arteriosclerosis in patients with CKD. This study aims to investigate the relationship between Cys C, Hcy and atherosclerosis in patients with CKD. METHODS: A total of 611 individuals, who met the diagnostic criteria for CKD and underwent physical examination in the Health Management Center of Third Xiangya Hospital, Central South University from June 2019 to June 2020, were selected as the research subjects. Height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured and recorded, and body mass index (BMI) was calculated. Blood samples (5 mL) were collected and Cys C, Hcy, fasting blood glucose (FBG), total cholesterol (TC), serum creatinine (SCr), and other blood indexes were tested. Urine was collected to detect microalbumin and creatinine, and the albumin/creatinine ratio (UACR) was calculated. baPWV and ABI were measured by automatic arteriosclerosis detector. The quartiles of Cys C and Hcy were divided into groups, and the proportion of baPWV and ABI abnormalities among groups was compared pairwise. The correlation between Cys C, Hcy, and baPWV was analyzed by Pearson correlation analysis. Univariate and multivariate logistic regression were used to analyze the effects of Cys C and Hcy on ABI and baPWV. RESULTS: Among 611 patients with CKD, 435 (71.19%) had abnormal baPWV and 48 (7.86%) had abnormal ABI. With the increase of Cys C and Hcy levels, the proportion of baPWV and ABI abnormalities were gradually increased. BaPWV was positively correlated with Cys C (r=0.32) and Hcy (r=0.20). After adjusting for confounding factors such as gender, BMI, and FBG, Cys C (OR=6.54, 95% CI 1.93 to 22.14, P<0.01) and Hcy (OR=1.08, 95% CI 1.01 to 1.16, P=0.02) were independent risk factors for abnormal baPWV. Also, after adjusting for confounding factors such as age, sex, BMI, and FBG, Cys C (OR=9.95, 95% CI 2.84 to 34.92, P<0.01) and Hcy (OR=1.06, 95% CI 1.01 to 1.11, P=0.02) were independent risk factors for abnormal ABI. CONCLUSIONS: In patients with CKD, baPWV and ABI are significantly correlated with Cys C and Hcy levels. Detection of Cys C and Hcy levels is helpful for the early diagnosis of arteriosclerosis.

Knockout of AKAP150 improves impaired BK channel-mediated vascular dysfunction through the Akt/GSK3ß signalling pathway in diabetes mellitus.

Vascular dysfunction resulting from diabetes is an important factor in arteriosclerosis. Previous studies have shown that during hyperglycaemia and diabetes, AKAP150 promotes vascular tone enhancement by intensifying the remodelling of the BK channel. However, the interaction between AKAP150 and the BK channel remains open to discussion. In this study, we investigated the regulation of impaired BK channel-mediated vascular dysfunction in diabetes mellitus. Using AKAP150 null mice (AKAP150-/- ) and wild-type (WT) control mice (C57BL/6J), diabetes was induced by intraperitoneal injection of streptozotocin. We found that knockout of AKAP150 reversed vascular remodelling and fibrosis in mice with diabetes and in AKAP150-/- diabetic mice. Impaired Akt/GSK3ß signalling contributed to decreased BK-ß1 expression in aortas from diabetic mice, and the silencing of AKAP150 increased Akt phosphorylation and BK-ß1 expression in MOVAS cells treated with HG medium. The inhibition of Akt activity caused a decrease in BK-ß1 expression, and treatment with AKAP150 siRNA suppressed GSK3ß expression in the nuclei of MOVAS cells treated with HG. Knockout of AKAP150 reverses impaired BK channel-mediated vascular dysfunction through the Akt/GSK3ß signalling pathway in diabetes mellitus.

Large-scale network dysfunction in vascular cognitive disorder supports connectional diaschisis in advanced arteriosclerosis.

BACKGROUND AND PURPOSE: The interrelation of cognitive performance, cerebrovascular damage and brain functional connectivity (FC) in advanced arteriosclerosis remains unclear. Our aim was to investigate the associations between FC, white matter damage and cognitive impairment in carotid artery disease. METHODS: Seventy-one participants with a recent cerebrovascular event and with written informed consent underwent resting-state functional magnetic resonance imaging and the Addenbrooke's Cognitive Examination - Revised (ACE-R). Network and inter-hemispheric FC metrics were compared between cognitively normal and impaired subjects, and interrelated with cognition. In order to explore the nature of FC changes, their associations with microstructural damage of related white matter tracts and cognitive performance were investigated, followed by mediation analysis. RESULTS: Participants with global cognitive impairment showed reduced FC compared to the cognitively intact subjects within the central executive network (CEN), and between hemispheres. Patients with executive dysfunction had decreased CEN FC whilst patients with memory loss demonstrated low FC in both the CEN and the default mode network (DMN). Global performance correlated with connectivity metrics of the CEN hub with DMN nodes, and between hemispheres. Cingulum mean diffusivity (MD) was negatively correlated with ACE-R and CEN-DMN FC. The cingulum MD-cognition association was partially mediated by CEN-DMN FC. CONCLUSIONS: Long-range functional disconnection of the CEN with DMN nodes is the main feature of cognitive impairment in elderly subjects with symptomatic carotid artery disease. Our findings provide further support for the connectional diaschisis concept of vascular cognitive disorder, and highlight a mediation role of functional disconnection to explain associations between microstructural white matter tract damage and cognitive impairment.

High-intensity vessel sign on fluid-attenuated inversion recovery imaging: a novel imaging marker of high-risk carotid stenosis-a MRI and SPECT study.

BACKGROUND: Measurement of luminal stenosis and determination of plaque instability using MR plaque imaging are effective strategies for evaluating high-risk carotid stenosis. Nevertheless, new methods are required to identify patients with carotid stenosis at risk of future stroke. We aimed to clarify the mechanisms and clinical implications of the hyperintense vessel sign (HVS) as a marker of high-risk carotid stenosis. METHODS: We included 148 patients who underwent carotid stent (CAS) or carotid endarterectomy (CEA). MRI FLAIR was performed to detect HVS prior to and within 7 days after CAS/CEA. MR plaque imaging and 123I-iodoamphetamine SPECT was performed prior to CEA/CAS. Detailed characteristics of HVS were categorized in terms of symptomatic status, hemodynamic state, plaque composition, and HVS on time series. RESULTS: Forty-six of 80 symptomatic hemispheres (57.5%) and 5 of 68 asymptomatic hemispheres (7.4%) presented HVS (P < 0.01). Of the 46 symptomatic hemispheres with HVS, 19 (41.3%) presented with hemodynamic impairment and 27 (58.7%) presented without hemodynamic impairment. Of 19 hemispheres with hemodynamic impairment, 12 subjects (63.2%) showed high intensity and 7 (36.8%) showed iso-intensity plaques on T1WI. All 27 hemispheres without hemodynamic impairment showed high-intensity plaques. Of the five asymptomatic and HVS-positive hemispheres, one showed hemodynamic impairment; MR plaque imaging revealed T1 iso-intensity. The other four hemispheres that did not show hemodynamic impairment showed T1WI high-intensity plaques. CONCLUSION: There are two possible mechanisms of HVS, hemodynamic impairment due to severe carotid stenosis and micro-embolism from unstable plaques. HVS could be a radiological marker for high-risk carotid stenosis.

Schimke immunoosseous dysplasia and management considerations for vascular risks.

Schimke immunoosseous dysplasia (SIOD) is a multisystemic condition characterized by early arteriosclerosis and progressive renal insufficiency, among other features. Many SIOD patients have severe, migraine-like headaches, transient neurologic attacks, or cerebral ischemic events. Cerebral events could be exacerbated or precipitated by hypertension, and it is unclear how these are related to arteriosclerotic changes as dyslipidemia is also a feature of SIOD. The correlation between hypercholesterolemia and cardiovascular risk in SIOD is unclear. Also, the etiology and management of headaches is not well characterized. Here we report our clinical observations in the management of SIOD in a patient who was diagnosed in school age despite early signs and symptoms. We describe biallelic variants, including a previously unreported c.1931G>A (p.Arg644Gln) variant in SMARCAL1. We specifically investigated whether migraine-like headaches and progressive nephropathy may be related to blood pressure dysregulation. We found a correlation between tighter blood pressure regulation using ambulatory blood pressure monitoring and a subjective decrease in headache symptoms. We discuss blood pressure medication management in SIOD. We also characterize dyslipidemia relative to atherosclerosis risks and provide new management strategies to consider for optimizing care.

Downregulation of MicroRNA-4463 Attenuates High-Glucose- and Hypoxia-Induced Endothelial Cell Injury by Targeting PNUTS.

BACKGROUND/AIMS: Vascular complications are the main reasons for disability and mortality associated with type 2 diabetes mellitus (T2DM) and numerous microRNAs (miRNAs) are involved in this process. Our previous study demonstrated that miR-4463 was increased in the plasma of T2DM patients combined with arteriosclerosis of low extremity artery (ASO). However, the role of miR-4463 remains unclear. METHODS: miR-4463 expression in the vascular tissues of patients with ASO and T2DM and in human umbilical vein endothelial cells (HUVECs) was detected by qPCR. Cell survival and apoptosis was analyzed via Cell Counting Kit-8 and flow cytometry assays, respectively. Protein expression was determined by Western blot and protein subcellular localization was detected with immunofluorescence. A dual-luciferase assay was used to elucidate the target gene of miR-4463. RESULTS: miR-4463 was elevated in the vascular tissues of patients with T2DM and ASO. In HUVECs, both 25 mmol/L glucose (high glucose, HG) and hypoxia induced miR-4463 expression. Downregulation of miR-4463 promoted HUVEC survival and reduced cell apoptosis under HG and/or hypoxic conditions by facilitating the expression of protein phosphatase-1 nuclear targeting subunit (PNUTS), X-linked inhibitor of apoptosis protein (XIAP), p-AKT, p-Bad, increased the Bcl-2/Bax ratio, as well as downregulated cleaved caspase 3 expression. Mechanistically, we identified PNUTS as a direct target gene of miR-4463. Both the inhibition of AKT phosphorylation and silencing of PNUTS diminished the effect of miR-4463 on HUVEC apoptosis. Moreover, downregulation of miR-4463 enhanced PNUTS to enable PTEN nuclear localization, which resulted in AKT phosphorylation. CONCLUSION: Our results suggest that downregulation of miR-4463 attenuates cell apoptosis by directly enhancing PNUTS expression to promote PTEN nuclear localization, subsequently activating AKT signaling pathway in HUVECs under HG and/ or hypoxic conditions.

Interaction between Albuminuria and Treatment Group Outcomes for Patients with Renal Artery Stenosis: The NITER Study.

PURPOSE: To perform a post-hoc analysis of the Nephropathy Ischemic Therapy (NITER) trial, which enrolled patients with atherosclerotic renal artery stenosis, to evaluate whether medical therapy plus stent placement is superior to medical therapy alone in patients without elevated albuminuria. MATERIALS AND METHODS: Data from 51 patients were analyzed and stratified into 2 cohorts by median urinary albumin (UAlb) levels: cohort 1 ("low albuminuria," UAlb ≤0.04 g/24h) and cohort 2 ("high albuminuria," UAlb >0.04g/24h). Interaction effect between treatment arms and UAlb cohorts was calculated using Cox regression analysis. Survival analysis was followed by test for effect size, power analysis, and construction of a Kaplan-Meier survival table. RESULTS: At study completion, 13 patients had an outcome event: 6 (23%) from cohort 1 and 7 (28%) from cohort 2. Patients in cohort 1 had event-free survival of 83% at 3.9 ± 0.3 years from the primary endpoints of all-cause mortality, dialysis, and cardiovascular events when treated with interventional therapy, compared to 45% when treated with medical therapy alone (P = .501), which showed a 62% treatment effect for stent placement. In cohort 2, event-free survival rates were 64% for medical therapy versus 52% for medical plus interventional therapy (P = .64). Using Cox regression analysis, the interaction effect between treatment arms and UAlb cohorts was not significant (P = .32). The power of the study to detect an interaction effect, if one existed, was only 15%. CONCLUSIONS: Inference cannot be drawn for similar populations because of inadequate sample size, but, in this sample, patients treated with stent placement who had low albuminuria had better outcomes than patients treated with medical therapy alone.

Arteriosclerosis Is a Major Predictor of Small Bowel Vascular Lesions.

BACKGROUND: Most studies have focused on evaluating the association between the presence of small bowel vascular lesions (SBVLs) and patients' comorbidities. AIMS: We sought to uncover a more fundamental indicator that may predict the presence of SBVLs by considering atherosclerosis qualitatively and quantitatively. METHODS: We enrolled 79 consecutive patients with obscure gastrointestinal bleeding who had undergone computed tomography (CT) and capsule endoscopy or double-balloon endoscopy from January 2015 to June 2017. The SBVL frequency, type, and location, and the relationship between the presence of SBVLs and the patients' clinical characteristics were evaluated. Arterial wall calcification was assessed on unenhanced CT images, and a modified Agatston scoring system was used to determine the abdominal aorta calcium scores. RESULTS: Of the 27 (34%) patients with SBVLs, 15 (19%) had type 1a, 12 (15%) had type 1b, and 2 (3%) had type 2a SBVLs. Most of the lesions were located in the jejunum. Cardiovascular disease (P = .017), chronic kidney disease (P = .025), and arteriosclerosis (P = .0036) were associated with the presence of SBVLs. Subsequent multivariate analysis revealed that arteriosclerosis (odds ratio [OR] 7.29; 95% confidence interval [CI] 1.13-143.9) and superior mesenteric artery calcification (OR 16.3; 95% CI 3.64-118.6) were independent predictors of the presence of SBVLs. The modified Agatston score was significantly higher in SBVL cases than in non-SBVL cases (6384 vs. 2666, P = .0023). CONCLUSIONS: Arteriosclerosis, especially increased superior mesenteric artery calcification, is associated with an increased likelihood of SBVLs.

Toe Brachial Pressure Index as Alternative Method to Correlate Arteriosclerotic Disease in Type 2 Diabetes.

AIM: To investigate the association between the ankle brachial pressure index and toe brachial pressure index with the findings of carotid Doppler ultrasonography in patients with diabetes and coronary ischaemic disease. METHODS AND RESULTS: The objective was to evaluate the relationship between insulin resistance and serum homocysteine in subjects with polycystic ovarian syndrome (PCOS). CONCLUSION: We studied 81 type 2 diabetic patients, with established cardiovascular disease, consecutively admitted to our outpatient clinic in the Division of Diabetes of La Paz Hospital. We collected clinic and demographic data, ABI and TBI were measured and at the same time a carotid Doppler ultrasound was performed. Multiple linear regression analysis was used to investigate the association of ABI and TBI with carotid disease. We found a negative correlation between TBI and internal carotid artery peak systolic velocity (ICA PSV) (r = -0,300, p= 0,007), common carotid artery resistance index (CCA RI) (r = -0,232, p= 0,038) and intima-media thickness (IMT) (r -0,236, p=0,035). Toe blood pressure and ICA PSV showed an inverse association (r=- 0,226, p=0,042). Adjusting for clinical and demographic characteristic, only low TBI index is associated with a higher ICA PSV.

[Contrast-enhanced ultrasonographic study in patients with lower limb arterial lesions]. / Ul'trazvukovoe issledovanie s kontrastnym usileniem u patsientov s porazheniiami arterii nizhnikh konechnostei.

BACKGROUND: The introduction into clinical practice of contrast-enhanced ultrasonographic examination made it possible to assess patency of tibial arteries and perfusion of crural muscles in patients with occlusive lesions of lower-limb arteries. These findings are important for planning optimal treatment policy and assessing efficacy of operative or medicamentous treatment. OBJECTIVE: The study was aimed at investigating a possibility of contrast-enhanced ultrasound examination for assessment of patency of tibial arteries and quantitative assessment of perfusion of crural muscles in patient with occlusive lesions of lower-limb arteries. PATIENTS AND METHODS: We examined a total of 30 patients presenting with atherosclerotic-genesis occlusive lesions of lower limb arteries and symptomatic intermittent claudication. Five patients were examined in the postoperative period. All patients were subjected to quantitative analysis of crural muscle perfusion in the pre- and postoperative periods, determining the time of onset of contrast medium accumulation and the time to the peak of intensity. RESULTS: Contrast-enhanced ultrasound examination demonstrated that in patients with occlusive lesions of lower-limb arteries the start of contrast medium accumulation appeared to occur later than in apparently healthy people: on second 30-88, depending on the degree of limb ischaemia. The contrasting time-to-peak was also increased (from 36 to 120 s). In the postoperative period all patients were found to have improved perfusion of the crural muscles, which was confirmed by a decrease in time-to-peak contrasting. CONCLUSION: Contrast-enhanced ultrasonographic examination is currently the only non-invasive, safe method of determining perfusion of crural muscles, which may be used many times for assessment of viability of the ischaemised extremity, as well as for assessment of efficacy of the treatment performed.

Characterization of mild and severe post-radical nephrectomy renal functional deterioration utilizing histopathological evaluation of non-neoplastic nephrectomized renal parenchyma.

BACKGROUND: We investigated factors affecting mild (MRFD) and severe renal functional deterioration (SRFD) after radical nephrectomy with a special focus on the histopathology of nephrectomized non-neoplastic renal parenchyma. METHODS: MRFD was defined as a postoperative decline of percent estimated glomerular filtration rate (eGFR) lower than the value of the mean minus standard deviation (SD). SRFD was defined as a rate greater than the value of the mean plus SD. The histopathological factors of global glomerulosclerosis (GS) and arteriosclerosis in non-neoplastic renal parenchyma and multiple clinical factors were analyzed to determine whether they affected postoperative renal functional deterioration in 100 renal cell carcinoma cases. The prognoses, including non-cancer mortality, were collected from long-term follow-up data. RESULTS: A higher preoperative eGFR and a higher global GS extent in non-neoplastic renal parenchyma were independently associated with MRFD and SRFD, respectively. The cardiovascular disease-specific survival rates of the SRFD group and the group with global GS extent >14 % were significantly worse than those of their counterparts. CONCLUSIONS: This is the first report to identify global GS extent in nephrectomized non-neoplastic renal parenchyma as a factor affecting the development of life-threatening post-nephrectomy renal functional deterioration. Moreover, we are the first to advocate the importance of the characterization of favorable post-nephrectomy renal functional deterioration. The identification of MRFD and SRFD by histopathological evaluation of nephrectomized non-neoplastic renal parenchyma will contribute to personalized postoperative follow-up. It may improve follow-up of individual patients with SRFD by permitting collaboration with other clinical departments such as cardiology.

Does arteriosclerosis contribute to hemifacial spasm?

BACKGROUND: Hemifacial spasm (HFS) is caused by pulsative vascular compression of the root exit zone (REZ) of the facial nerve. However, the mechanism that causes the offending vessels to compress the REZ has not been clarified. Elongation of intracranial arteries due to arteriosclerosis is one possibility, but such arteriosclerotic changes are not observed very frequently among patients with HFS. The aim of the present study was to investigate whether arteriosclerotic changes would contribute to the pathogenesis of HFS. METHODS: This study included 111 HFS patients, all of whom were Japanese. The prevalence rates of hypertension, hyperlipidemia, and diabetes mellitus were examined as risk factors of atherosclerosis, and the cardio-ankle vascular index (CAVI) was measured as an indicator of arteriosclerotic change. The severity of white matter lesions (WMLs) in HFS patients was measured by magnetic resonance imaging. These data were compared with data from healthy Japanese controls. RESULTS: The prevalence rates of the risk factors for atherosclerosis in the HFS patients were not higher than those in the general Japanese population. The CAVI scores for the HFS patients were similar to, or lower than those in the healthy controls for all age groups except 60 to 69-year-old men. The severity of WMLs in the HFS patients was not significantly worse than that in the controls. CONCLUSIONS: It is suggested that arteriosclerotic changes are not involved in the pathogenesis of HFS, and that vascular compression syndromes are attributable to anatomical features of the intracranial arteries and facial nerves formed during the prenatal stage.