Metabolic syndrome among young adults at high and low familial risk for depression.

BACKGROUND: Our study examined whether the early-onset depression phenotype among young adults (probands) is associated with the metabolic syndrome (MetS) and its components, and if MetS characterizes unaffected but high-risk siblings of probands. METHODS: We studied three groups of young adults (Mage = 25 years, s.d. = 3.84 years): probands with histories of childhood onset depression - i.e. early-onset phenotype - (n = 293), their unaffected siblings (high-risk siblings, n = 273), and healthy controls (n = 171). Participants completed a full psychiatric interview, physical and laboratory assessments, and self-rating scales. MetS was defined using the criteria of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (). RESULTS: Early-onset depression phenotype and being a high-risk sibling were associated with higher MetS composite scores relative to that of controls, but did not differ from one another. With regard to MetS components: Probands and siblings had similarly larger waist circumference and lower HDL than did controls, while siblings and controls had lower triglyceride levels than did probands but did not differ from one another. Groups did not differ on glucose levels and SBP. CONCLUSIONS: Our study extends the literature on the association between MetS and depression and underscores the importance of depression phenotypes: failure to account for the clinical heterogeneity of depression may partly underlie the inconsistent findings regarding its relation to MetS. The results also suggest that, in depression-prone populations, MetS may predate and possibly function as a risk factor for eventual depression.

High Level of Unwarranted Clinical Variation in the Use of Lower Extremity Revascularisation Procedures in Hungary (2013-2017).

OBJECTIVE: Assessment of variations in the use of lower extremity open vascular surgical procedures (LEOPEN) and lower extremity endovascular procedures (LEENDO) across small geographic areas in Hungary from 2013 to 2017. Introduction of a new metric giving a rough estimate of unwarranted clinical variation in revascularisation practice. METHODS: Spatial variation (at local administrative unit level) of referral for LEOPEN and LEENDO was evaluated through a retrospective analysis using healthcare administrative data of all beneficiaries in Hungary. The same assessment was performed for percutaneous coronary intervention in acute myocardial infarction (PCIAMI). The latter was considered a reasonable comparator (similar at risk population, well organised, guideline driven patient pathways, small room for referral discretion). Consequently, the ratio of spatial variations of LEOPEN and LEENDO to PCIAMI (as a reference) are thought to reflect unwarranted clinical variation. RESULTS: A total of 109 882 procedures were identified in the database (LEOPEN, LEENDO, PCIAMI) affecting 85 083 patients. While estimates of spatial variations for LEOPEN and LEENDO turned out to be high (systematic component of variation [SCV] 0.09 and 0.21, respectively), PCIAMI showed a low SCV value of 0.02. Consequently, the ratios of SCVs were SCV/SCVref = 4.67 (LEOPEN) and SCV/SCVref = 10.3 (LEENDO), indicating high levels of unwarranted clinical variation. CONCLUSION: The analysis showed that patients living in different locations of Hungary face very different odds of having lower extremity revascularisation procedures (open or endovascular). This spatial variation is thought to be related mainly to the failure in vascular service organisation. The newly introduced numerical estimate of unwarranted clinical variation may support within, and also between, system comparisons.

Level of advanced oxidation protein products is associated with subclinical atherosclerosis.

BACKGROUND: Oxidative stress is an important factor in the pathomechanism of atherosclerosis. Advanced oxidation protein products (AOPPs) are considered markers of oxidative stress. Thickening of the carotid intima-media layers indicates subclinical atherosclerosis and can be detected by carotid ultrasound. OBJECTIVE: Our aim was to examine the association between carotid intima-media thickness (CIMT) and the level of AOPPs. METHODS: Carotid duplex scans and measurements of AOPPs were performed on 476 participants of a cardiovascular population study. The presence of conventional cardiovascular risk factors was investigated with a questionnaire, physical examination, and laboratory tests. RESULTS: There was a positive correlation between maximum CIMT and the level of AOPPs only in the male population (r = 0.219, p = 0.033). Multivariate analysis has revealed that the association between AOPPs and mean or maximum CIMT was independent of cardiovascular risk factors (OR = 1.458, p = 0.004, and OR = 2.038, p < 0.001). CONCLUSIONS: Among males, the elevated level of AOPPs as a marker of oxidative stress may signal the existence of early atherosclerotic alterations.

Early and long-term results of the endovascular treatment of patients with isolated infrarenal aortic stenosis.

OBJECTIVE: The purpose of this study was to report our results of patients' characteristics, procedural complications, and long-term patency in treatment of isolated infrarenal aortic stenosis (IIAS). METHODS: Forty symptomatic patients (28 female, 12 male; median age, 60 years [54.8-68 years]) with IIAS who underwent endovascular intervention between 2001 and 2017 were retrospectively analyzed. Patient, lesion, procedure, and balloon/stent characteristics were assessed. Follow-up included clinical status evaluation and color Doppler ultrasound examination. RESULTS: The cause of IIAS was atherosclerosis in all patients. Twenty percent of the patients were younger than 50 years; 85% had hypertension, 80% were smokers, 38% had hyperlipidemia, 23% had diabetes mellitus, 15% were obese (body mass index ≥30 kg/m2), and 8% had chronic kidney disease. The median stenosis grade was 80% (70%-80%), and the median lesion length was 19.9 mm (13-29.4 mm). Severe calcification was present in 8% of the patients. Percutaneous transluminal angioplasty was performed in four cases (10%), whereas stenting was performed in 36 (90%). One complication, an aortic rupture requiring surgical repair, occurred. The median follow-up was 61 months (17-101 months). The primary patency rate was 100% at 6 months, 97% at 12 and 24 months, and 88% at 60 and 96 months. Restenosis developed in three patients (8%); reintervention was carried out in two cases (5%). CONCLUSIONS: Endovascular therapy for IIAS provides a safe and effective long-term treatment strategy.

Novel anti-inflammatory therapies to reduce cardiovascular burden of psoriasis.

Psoriasis mainly affects the skin and joints and has serious impacts on the physical, emotional, and financial life of patients. Recent studies have demonstrated that other comorbidities are frequently detected in psoriatic patients. A strong association with the development of cardiovascular diseases, such as hypertension, myocardial infarction, and stroke is responsible for the shortened (by 4.5-5 years) life expectancy of severe psoriatic patients. Systemic inflammation plays an important role in the interrelationship between psoriasis and atherosclerotic plaque formation, which is a common immunopathogenic pathway that explains the multiorgan involvement in psoriasis. As far life-threatening cardiovascular diseases are very often symptom-free, the treating dermatologist's responsibility is to initiate interdisciplinary holistic patient care, which may lead to directly saved patients' lives. Holistic care of severe psoriatic patients should include regular cardiac monitoring using cardiovascular imaging modalities and functional testing to detect even subclinical coronary artery disease. Effective anti-inflammatory treatment with biologic therapies may have beneficial effects on the cardiovascular state and may reduce the incidence of cardiac events. The authors review the latest findings on the shared immunopathogenic background of psoriasis and cardiovascular diseases and discuss the available data about the cardiovascular responses to the currently used biologic treatments.

The incidence and risk factors of stent fracture in patients treated for proximal common carotid artery stenosis.

OBJECTIVE: Our aim was to identify the incidence of and predictors for common carotid artery (CCA) stent fractures (SFs) and to examine the effect of SFs on the development of in-stent restenosis (ISR). METHODS: Seventy patients (37 women; median age, 60.9 years) who were stented for significant (≥60%) proximal CCA stenosis from 2006 to 2016 and revisited us to determine SF using fluoroscopy in 2018 were evaluated. Seventy stents were deployed; among them 87.1% were balloon-expandable and 12.9% were self-expandable. SFs were classified as type I (fracture of one strut), type II (fracture of multiple struts without stent deformity), type III (fracture of multiple struts with stent deformity), type IV (complete fracture of the stent without a gap), and type V (complete fracture of the stent with a gap). Duplex ultrasound examination was used for monitoring stent patency. Mann-Whitney U and Fisher's exact tests, Kaplan-Meier and logistic regression analyses, and a log-rank test and a gamma correlation analysis were applied as statistical methods. RESULTS: The patients were followed for 75.5 months (range, 47-109 months). Significant (≥70%) ISR was observed in eight patients (11.4%). Reintervention was performed in four cases (5.7%). Twenty-seven SFs (38.6%; type I, 8; type II, 10; type III, 4; type IV, 2; and type V, 3) were found. Calcification was shown to be a significant predictor for SF (odds ratio, 13.2; 95% confidence interval, 3.9-45.1; P < .001). There was no significant difference between the fractured and the nonfractured group regarding the number of patients with ISR and reintervention (P = .701 and P = .636, respectively). Neither did the primary patency rates differ significantly (P = .372) in patients with and without SF. CONCLUSIONS: Fractures frequently occur in a wide variety of stent devices deployed in the proximal CCA, but SFs seem to have no effect on ISR and reintervention.

Lower Limb Amputations and Revascularisation Procedures in the Hungarian Population: A 14 Year Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to assess the long term trends of lower limb amputation and revascularisation in Hungary over 14 years. METHODS: This was a retrospective cohort study that included all patients who underwent lower limb amputation or revascularisation over a 14 year period (2004-2017) in Hungary. Inpatient administrative data claims covering the entire beneficiary population were incorporated. Lower limb amputations (both minor and major) and revascularisation procedures (both open and endovascular) were identified in the claims files. Incidence rates were calculated and time trends were assessed via a generalised additive model. RESULTS: From 2004 to 2017, a total of 121 351 lower limb amputations (61 154 minor; 60 197 major) and 149 355 revascularisation procedures (89 243 open; 60 112 endovascular) were detected in 140 581 patients. The number of minor amputations decreased moderately in the last few years of the study period, while major amputations showed a slight decline (15%) beginning after 2013, which was more marked (22%) following adjustment for age. While the crude incidence of open vascular surgery procedures decreased by 31% (from 74.5/105 to 51.4/105), endovascular procedures showed growth by 79% (from 33.7/105 to 60.4/105) over the whole observation period. CONCLUSION: Observed amputation and revascularisation trends in Hungary are similar to the international experience. The major difference is a more than one decade lag in the starting point of the decline of amputations and in the move towards endovascular procedures. The number of amputations is more than twofold higher and the number of revascularisations is close to half that reported internationally. This comprehensive report of two vascular care performance indicators reveals an east/west vascular health divide in Europe and indicates the need to improve amputation prevention.

["Risk factors of childhood depression" research grant - past, present, future].

The authors summarize the last 10 years of an ongoing collaborative study between the Universities of Szeged and Pittsburgh on early onset major depression. First, the "Risk factors of childhood depression" grant is presented briefly as an initial research study in which the subjects of the current studies were recruited. This is a prominently large clinical sample in the field of child psychiatry even on an international level. In addition to the follow-up of the prognosis of the disorder, recent studies continue to explore the early onset depression in two directions. On the one hand, two studies investigate the role of biobehavioral inflexibility markers in the development of major depression ("Biobehavioral inflexibility and risk for juvenile-onset depression" and "Biobehavioral inflexibility and risk for juvenile-onset depression - renewal grant"). On the other hand, the authors would like to have a better understanding of the possible relationship between the major depression and cardiovascular diseases ("Pediatric depression and subsequent cardiac risk factors: a longitudinal study"). The most significant aims of the three studies will be demonstrated, as well as how the studies were prepared and organized along with the already existing experience concerning research management and involvement of new collaborating partners and experts.

The presence of long and heavily calcified lesions predisposes for fracture in patients undergoing stenting of the first part of the subclavian artery.

OBJECTIVE: To determine the prevalence and risk factors of subclavian artery stent fractures and to investigate their impact on in-stent restenosis development. METHODS: One hundred eight patients (65 females; median age, 58.3 years [interquartile range, 53.4-65.5 years]) with steno-occlusive disease of the first part of the subclavian artery who underwent stenting (N = 108 stents; balloon-expandable, 83.3%; self-expandable, 16.7%) between 2005 and 2015 and returned for a fluoroscopic examination of the implanted stents in 2017 were included in our study. Fractures were type I (single strut fracture), type II (multiple strut fractures without deformation), type III (multiple strut fractures with deformation), type IV (multiple strut fractures with acquired transection but without gap), or type V (multiple strut fractures with acquired transection with gap in the stent body). Stent patency was monitored by duplex ultrasound imaging. The Mann-Whitney U and Fisher's exact tests; Kaplan-Meier, receiver operating characteristic, and logistic regression analyses; as well as a log-rank test were used as statistical methods. RESULTS: The median follow-up was 73.8 months (interquartile range, 35.6-104.2 months). Thirty-eight fractures (35.2%) were detected; fractures were type I in 13, type II in 12, type III in 6, type IV in 4, and type V in 3 cases. Multivariable logistic regression analysis revealed the presence of long (≥20 mm) lesions (odds ratio, 3.3; 95% confidence interval, 1.3-8.4; P = .012) and heavy calcification (odds ratio, 4.7; 95% confidence interval, 1.7-12.7; P = .002) to be significant independent predictors of stent fracture. The primary patency rates were significantly worse (P = .035) in patients with stent fracture compared with those without stent fracture. CONCLUSIONS: Stent fractures frequently occur. Patients with long and/or heavily calcified lesions require closer follow-up.

Stent Protrusion >20 mm Into the Aorta: A New Predictor for Restenosis After Kissing Stent Reconstruction of the Aortoiliac Bifurcation.

PURPOSE: To determine the long-term patency of aortoiliac kissing stents and to identify predisposing factors for the development of in-stent restenosis (ISR). METHODS: A retrospective analysis was conducted of 105 patients (median age 60.9 years; 64 women) with symptomatic aortoiliac occlusive disease who had kissing stents implanted between 2001 and 2015. The indication for kissing stents was severe claudication in 91 (86.7%) patients and critical limb ischemia in 14 (13.3%). Lesions were TASC A in 52 (49.5%), B in 29 (27.6%), C in 4 (3.8%), and D in 20 (19%) patients. Twenty-five (23.8%) patients had heavily calcified lesions. In all, 210 stents were deployed [180 (85.7%) self-expanding and 30 (14.3%) balloon-expandable]. Follow-up included clinical evaluation, ankle-brachial index measurement, and duplex ultrasonography. RESULTS: The median follow-up was 45 months. The primary patency rates were 93%, 86%, and 77% at 12, 24, and 60 months, respectively. Significant ISR developed in 23 (21.9%) patients (12 unilateral and 11 bilateral). Univariate Cox regression analysis revealed older age [hazard ratio (HR) 0.5, 95% confidence interval (CI) 0.31 to 0.81, p=0.004] and larger aortic diameter (HR 0.42, 95% CI 0.25 to 0.7, p<0.001) to be variables favoring long-term patency, while a longer aortic stent segment (HR 1.56, 95% CI 1.16 to 2.09, p=0.003) and a larger discrepancy between the summed stent diameters and the aortic diameter (HR 1.64, 95% CI 1.01 to 2.65, p=0.043) were associated with ISR development. Multivariate analysis showed a longer aortic stent segment to be the only significant determinant of ISR (HR 1.44, 95% CI 1.02 to 2.01, p=0.035). CONCLUSION: The kissing stent technique can be performed with good long-term patency. Patients whose iliac stents protrude too far into the aorta need closer follow-up.

Current and potential imaging applications of ferumoxytol for magnetic resonance imaging.

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.

[Endovascular treatment of acute iliofemoral deep venous thrombosis - our results with catheter-directed thrombolysis and AngioJet]. / Az akut proximális mélyvénás thrombosis endovascularis kezelése ­ a lokális katéteres lysissel és az AngioJet-tel szerzett tapasztalataink.

INTRODUCTION: Most of the patients with iliofemoral thrombosis treated with anticoagulants only are affected with postthrombotic syndrome (PTS) that worsens the patients' quality of life. In the acute phase of proximal deep venous thrombosis (DVT) catheter-directed (CDT) and pharmacomechanical thrombolysis may be a reasonable alternative therapeutic method. Our aim was to summarize our results using these methods. METHODS: Since 2009 twenty-four patients with iliofemoral DVT were treated with these endovascular procedures and with stenting at our Institution. RESULTS: The median age of the patients was 35.83 ± 15.9 years, the female: male ratio was approximately 2:1. The mean time between the onset of the symptoms and the procedures was eleven days. CDT alone was performed in 8 patients, thrombus aspiration in addition to CDT using AngioJet device in 16 patients; in 19 cases the procedure was completed with venous stenting. During the follow-up we performed US examinations and estimated the severity of PTS by Villalta-scale. The total recanalization-rate was more than 50%, which even improved during the follow-up. The total lysis time and the amount of used recombinant tissue plasminogen activator decreased significantly by applying the AngioJet. We did not find any severe PTS among our patients during the follow-up visits. CONCLUSION: Our data suggests that these methods can be used efficiently and safely in the treatment of acute iliofemoral DVT.

[Interventional radiology treatment of extensive pulmonary embolism and thromboembolic diseases]. / Masszív pulmonalis embolia és thromboemboliás kórképek intervenciós radiológiai kezelése.

The authors discuss interventional radiological methods in the field of vascular interventions applied in venous system diseases. Venous diseases can be life threatening without appropriate treatment and can lead to chronic venous diseases and venous insufficiency with long-term reduction in the quality of life. In addition, recurrent clinical symptoms require additional treatments. Interventional radiology has several methods that can provide fast and complete recovery if applied in time. The authors summarize these methods hoping that they will be available for a wide range of patients through the establishment of Interventional Radiological Centres and will be a part of the daily routine of patient care. Regarding the frequency of venous diseases and its influance on life quality the authors would like to draw attention to interventional radiological techniques and modern therapeutic possibilities.

High frequency of brachiocephalic trunk stent fractures does not impair clinical outcome.

OBJECTIVE: Stenting is the preferred, minimally invasive treatment for innominate artery (IA) stenosis or occlusion. Stent fractures in the IA have not been assessed in larger cohorts. In this retrospective study, we examined the frequency and risk factors of IA stent fractures. METHODS: The final analysis included 32 patients (15 women; mean age, 59.4 ± 12.0 years) with 32 balloon-expandable stents (2000 to 2009). In 2010, the patients were asked to come back for a fluoroscopic examination of the implanted stents. Stent fractures and their relationship to atherosclerotic risk factors, lesion characteristics, postprocedural symptoms, and in-stent restenosis were analyzed. Fisher exact test and univariate Cox regression analysis were used in the statistical evaluation. RESULTS: Lesions were >20 mm in 14 patients (44%) or heavily calcified in 13 (41%). The mean follow-up time was 33.4 ± 21.0 months. Postprocedural symptoms were noted in nine patients (28%). Significant restenosis was detected in 22% of the implanted stents, and 11 stent fractures (34%) were found. The prevalence of heavily calcified lesions, postprocedural symptoms, and in-stent restenosis did not differ significantly between groups with and without fracture. Long lesions were associated with an increased incidence of stent fracture (hazard ratio, 5.09; 95% confidence interval, 1.33-19.48; P = .017). No correlation was observed between stent fractures and old age (≥70 years), female gender, smoking, hypertension, hyperlipidemia, or diabetes mellitus. CONCLUSIONS: IA stent fractures are common but seem to have no effect on symptoms and in-stent restenosis rates.

Effect of Sex, Age, and Cardiovascular Risk Factors on Aortoiliac Segment Geometry.

Background: To investigate the geometry of the aortoiliac (AI) segment and its correlation with sex, age, and cardiovascular (CV) risk factors. Methods: Abdominal and pelvic CTA/MRA scans of 204 subjects (120 males; median age: 53 [IQR, 27-75] years) without AI steno-occlusive disease or scoliosis were retrospectively analyzed. The participants were enrolled consecutively, ensuring the representation of each age decade. An in-house written software was developed to assess AI elongation using the tortuosity index (TI) and absolute average curvature (AAC). Aortic bifurcation angle, common iliac artery (CIA) take-off and planarity angles, bifurcation asymmetry, and deviation from optimal bifurcation were calculated and evaluated. Demographic data, CV risk factors, and medical history were collected from electronic health records. Results: The elongation of the iliac arteries was more pronounced in males (TI: left CIA, p = 0.011; left EIA, p < 0.001; right CIA, p = 0.023; right EIA, p < 0.001; AAC: left EIA, p < 0.001; right EIA, p = 0.001). Age significantly influenced TI and AAC in all AI segments (all p < 0.001), but was also positively associated with the aortic bifurcation angle (p < 0.001), both CIA planarities (left, p < 0.001; right, p = 0.002), aortic bifurcation asymmetry (p = 0.001), and radius discrepancy (p < 0.001). Significant positive correlations were found between infrarenal aortic TI/AAC and chronic kidney disease (CKD) (p = 0.027 and p = 0.016), AAC of both CIAs and hypertension (left, p = 0.027; right, p = 0.012), right CIA take-off angle and CKD (p = 0.031), and left CIA planarity and hyperlipidemia (p = 0.006). Conclusion: Sex, age, and CV risk factors have a significant effect on the geometry of the AI segment.

Growth and differentiation factor-15: A link between inflammaging and cardiovascular disease.

Age-related disorders are closely linked to the accumulation of senescent cells. The senescence-associated secretory phenotype (SASP) sustains and progresses chronic inflammation, which is involved in cellular and tissue dysfunction. SASP-related growth and differentiation factor-15 (GDF-15) is an immunoregulatory cytokine that is coupled to aging and thus may have a regulatory role in the development and maintenance of atherosclerosis, a major cause of cardiovascular disease (CVD). Although the effects of GDF-15 are tissue-specific and dependent on microenvironmental changes such as inflammation, available data suggest that GDF-15 has a significant role in CVD. Thus, GDF-15 is a promising biomarker and potential therapeutic target for atherosclerotic CVD.

Association of growth and differentiation factor-15 with coronary artery calcium score and ankle-brachial index in a middle-aged and elderly Caucasian population sample free of manifest cardiovascular disease.

Growth and differentiation factor-15 (GDF-15) is a stress-associated cytokine of the transforming growth factor-ß superfamily. The inflammatory and angiogenic effects of GDF-15 in atherosclerosis are controversial, and its correlation with the long asymptomatic phase of the disease is not well understood. Coronary artery calcium score (CACS) and ankle-brachial index (ABI) are sensitive markers of subclinical atherosclerosis. To date, only a few studies have examined the impact of GDF-15 on coronary artery calcification, and the association between GDF-15 and ABI has not been evaluated. Therefore, we aimed to investigate the possible relationship between serum GDF-15 concentrations and CACS and ABI in a Caucasian population sample of middle-aged (35-65 years) and elderly (> 65 years) people. In addition to recording demographic and anthropometric characteristics, atherosclerotic risk factors, and laboratory tests including serum HDL-cholesterol, LDL-cholesterol, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and N-terminal pro-B-type natriuretic peptide (NT-proBNP); GDF-15 level, cardiac computed tomography, and ABI measurements were also performed. A total of 269 asymptomatic individuals (men, n = 125; median age, 61.5 [IQR, 12.7] years) formed the basis of this study. Participants were divided into two groups according to their age (middle-aged, n = 175 and elderly, n = 94). Hypertension and diabetes mellitus were significantly more prevalent and CACS values and HbA1c, NT-proBNP, and GDF-15 levels were significantly higher (all p < 0.001) in the elderly group compared to the middle-aged group. Multivariate ridge regression analysis revealed a significant positive association between GDF-15 and CACS (middle-aged group: ß = 0.072, p = 0.333; elderly group: ß = 0.148, p = 0.003), and between GDF-15 and ABI (middle-aged group: ß = 0.062, p = 0.393; elderly group: ß = 0.088, p = 0.041) only in the elderly group. Our results show that GDF-15 is not only a useful biomarker of inflammation but can also predict early signs of asymptomatic atherosclerosis, especially in elderly people with chronic systemic inflammation associated with aging (inflammaging).

Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: a pilot study.

OBJECTIVE: Macrophages play a critical role in cerebral aneurysm formation and rupture. The purpose of this study is to demonstrate the feasibility and optimal parameters of imaging macrophages within human cerebral aneurysm wall using ferumoxytol-enhanced MRI. METHODS AND RESULTS: Nineteen unruptured aneurysms in 11 patients were imaged using T2*-GE-MRI sequence. Two protocols were used. Protocol A was an infusion of 2.5 mg/kg of ferumoxytol and imaging at day 0 and 1. Protocol B was an infusion of 5 mg/kg of ferumoxytol and imaging at day 0 and 3. All images were reviewed independently by 2 neuroradiologists to assess for ferumoxytol-associated loss of MRI signal intensity within aneurysm wall. Aneurysm tissue was harvested for histological analysis. Fifty percent (5/10) of aneurysms in protocol A showed ferumoxytol-associated signal changes in aneurysm walls compared to 78% (7/9) of aneurysms in protocol B. Aneurysm tissue harvested from patients infused with ferumoxytol stained positive for both CD68+, demonstrating macrophage infiltration, and Prussian blue, demonstrating uptake of iron particles. Tissue harvested from controls stained positive for CD68 but not Prussian blue. CONCLUSIONS: Imaging with T2*-GE-MRI at 72 hours postinfusion of 5 mg/kg of ferumoxytol establishes a valid and useful approximation of optimal dose and timing parameters for macrophages imaging within aneurysm wall. Further studies are needed to correlate these imaging findings with risk of intracranial aneurysm rupture.

Long-term prognostic value of left atrial longitudinal strain in an elderly community-based cohort.

Despite the well-known importance of left atrial (LA) mechanics in diastolic function, data are scarce regarding the prognostic power of LA longitudinal strain and its potential added value in the risk stratification of an elderly population. Accordingly, our aim was to determine the long-term prognostic importance of 2D speckle-tracking echocardiography-derived peak atrial longitudinal strain (PALS) in a community-based screening sample. Three hundred and fourteen volunteers were retrospectively identified from a population-based screening program (mean age 62 ± 11 years; 58% female) with a median follow-up of 9.5 years. All subjects who participated in the screening program underwent 2D echocardiography to measure left ventricular (LV) ejection fraction (EF), global longitudinal strain (GLS), and PALS, as well as low-dose cardiac CT to determine the Agatston score. The primary endpoint was all-cause mortality. Thirty-nine subjects (12.4%) met the primary endpoint. Subjects with adverse outcomes had significantly lower LV GLS (dead vs. alive; - 19.2 ± 4.3 vs. - 20.6 ± 3.5%, p < 0.05) and PALS (32.3 ± 12.0 vs. 41.8 ± 14.2%, p < 0.001), whereas LV EF did not show a difference between the two groups (51.1 ± 7.0 vs. 52.1 ± 6.2, %, p = NS). By multivariable Cox regression analysis, PALS was found to be a significant predictor of adverse outcomes independent of LV GLS, and Agatston and Framingham scores. In subjects with PALS values below the standard cut-off of 39%, the risk of all-cause mortality was almost 2.5 times higher (hazard ratio: 2.499 [95% confidence interval: 1.334-4.682], p < 0.05). Beyond the assessment of LV EF and LV GLS, PALS offers incremental value in cardiovascular risk stratification in a community-based elderly cohort. PALS was found to be a significant and independent predictor of long-term mortality among other classical cardiovascular risk estimators.

Dual contrast perfusion MRI in a single imaging session for assessment of pediatric brain tumors.

Ferumoxytol, an iron nanoparticle used as an intravascular contrast agent for perfusion magnetic resonance imaging (MRI), has never been explored in the pediatric population. The purpose of this prospective study is to characterize the vascular and permeability properties of pediatric brain tumors using two contrast agents during a single imaging session: ferumoxytol for dynamic susceptibility weighted contrast (DSC) MRI and gadoteridol for dynamic contrast-enhanced (DCE) MRI. In a single imaging session, patients received intravenous ferumoxytol for DSC MRI followed by gadoteridol for DCE MRI. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), transfer coefficient (K(trans)), and extravascular extracellular space volume fraction (v(e)) of the brain lesions were calculated. Patients underwent serial imaging sessions over the course of 2 years. Of the 7 patients enrolled thus far, none has experienced an adverse event. Two patients with medulloblastoma were enrolled preoperatively. In the first, rCBV(max), rCBF, K(trans) max, and v(e) max values were 3.74, 3.12, 0.47 min (-1), and 0.08, respectively, while in the second patient, rCBV(max), rCBF, K(trans) max, and v(e) max values were 4.72, 3.47, 0.60 min(-1), and 0.05, respectively. Four patients were enrolled after new gadolinium enhancement was noted in the tumor resection cavity. In 80 % of these lesions, rCBV was <1 suggestive of pseudoprogression secondary to radiochemotherapy. These preliminary results demonstrate that use of ferumoxytol and gadoteridol contrast agents during a single imaging session is feasible, safe, and appears useful for assessing tumor perfusion and permeability characteristics in children.