Axillary artery access for interventional procedures.

PURPOSE: To evaluate axillary artery access for the interventional treatment of carotid or splanchnic arteries that have angulated takeoff or complex anatomy when larger catheters (up to 9 F) are needed. TECHNIQUE: The axillary artery approach was used to treat the left internal carotid artery (ICA) in 3 patients (2 angulated takeoffs and 1 bovine arch) and a celiac axis aneurysm. An 8-F, 45-cm-long introducer sheath was inserted for the carotid procedures, whereas a 9-F, 90-cm sheath was chosen for the celiac aneurysm. Cerebral protection and stenting were successfully performed in all carotid patients; an 8x40-mm stent-graft was implanted to exclude the celiac artery aneurysm. An 8-F vascular closure device was used in the axillary arteries; hemostasis was immediate, and no hematoma or other complications were recorded in follow-up. CONCLUSIONS: This preliminary experience revisits the axillary approach as an alternative access route for interventional procedures. In association with a vascular closure device, this approach should be considered as a useful and safe option for those interventional procedures in which larger sheaths or catheters are required to cope with difficult arterial anatomies.     

Usefulness and safety of transcatheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy

Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HC) and predicts adverse outcome. Radiofrequency catheter ablation (RFCA) represents a potentially advantageous alternative to lifelong pharmacologic treatment. However, its efficacy in patients with HC is not established. In the present study, the feasibility, safety, and efficacy of RFCA of AF in patients with HC were evaluated. Twenty-six patients with HC with paroxysmal (n = 13) or permanent (n = 13) AF refractory to antiarrhythmic therapy (age 58 +/- 11 years, time from AF onset 7.3 +/- 6.2 years, left atrial volume 170 +/- 48 ml) underwent RFCA. A schema with pulmonary vein isolation plus linear lesions was used. No major periprocedural complication occurred. One patient died from a hemorrhagic stroke 4 weeks after RFCA while in sinus rhythm. During a 19 +/- 10-month follow-up, 9 of the remaining 25 patients (36%) experienced recurrence of AF (despite repeated RFCA in 3) and were considered failures, whereas 16 remained in sinus rhythm (i.e., 64% overall success rate). Ten of these 16 patients were off antiarrhythmic drug therapy at final evaluation. RFCA was highly successful in patients with paroxysmal AF (77% success rate compared with 50% in the subgroup with permanent AF). Patients with restoration of sinus rhythm showed marked symptomatic improvement (final New York Heart Association functional class 1.2 +/- 0.5 vs 1.7 +/- 0.7 before the procedure, p = 0.003). Conversely, patients for whom RFCA failed showed no change (final functional class 1.9 +/- 0.8 vs 1.7 +/- 0.9 before the procedure, p = 0.59). In conclusion, in most studied patients with HC, RFCA proved a safe and effective therapeutic option for AF, improved functional status, and was able to reduce or postpone the need for long-term pharmacologic treatment.     

The Portuguese Registry of Hypertrophic Cardiomyopathy: Overall results

Introduction

We report the results of the Portuguese Registry of Hypertrophic Cardiomyopathy, an initiative that reflects the current spectrum of cardiology centers throughout the territory of Portugal.

Effects of empagliflozin on cardiorespiratory fitness and significant interaction of loop diuretics

The effects of empagliflozin on cardiorespiratory fitness in patients with type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) are unknown. In this pilot study we determined the effects of empagliflozin 10 mg/d for 4 weeks on peak oxygen consumption (VO₂) in 15 patients with T2DM and HFrEF. As an exploratory analysis, we assessed whether there was an interaction of the effects of empagliflozin on peak VO₂ of loop diuretics. Empagliflozin reduced body weight (?1.7 kg; P = .031), but did not change peak VO₂ (from 14.5 mL kg^?1 min^?1 [12.6‐17.8] to 15.8 [12.5‐17.4] mL kg^?1 min^?1; P = .95). However, patients using loop diuretics (N = 9) demonstrated an improvement, whereas those without loop diuretics (N = 6) experienced a decrease in peak VO₂ (+0.9 [0.1‐1.4] vs ?0.9 [?2.1 to ?0.3] mL kg^?1 min^?1; P = .001), and peak VO₂ changes correlated with the baseline daily dose of diuretics (R = +0.83; P < .001). Empagliflozin did not improve peak VO₂ in patients with T2DM and HFrEF. However, as a result of exploratory analysis, patients concomitantly treated with loop diuretics experienced a significant improvement in peak VO₂.     

A new interactive design approach for concept selection based on expert opinion

Effective identification of the optimal design in the early stages of product development is critical in order to obtain the best chances of eventual customer satisfaction. Currently, the advancements in prototyping techniques offer unique chances to evaluate the features of different design candidates by means of product experts acting as assessors and/or customers enrolled as testers. In this paper, the candidate identification using virtual and physical prototypes is described and a practical fuzzy approach toward the evaluation of the optimal design is presented. The proposed methodology is tested on a full case study, namely the choice of optimal design for the traditional Neapolitan coffeemaker, inspired by the prototypes of the Italian designer Riccardo Dalisi. Several concepts are developed in a virtual environment and four alternatives among them are realized using Additive Manufacturing. By allowing experts to interact with virtual and physical prototypes, they were able to express their opinion on a custom fuzzy evaluation scale (i.e. they were freely choosing more or less coarse linguistic scales as well as the related shapes of fuzzy sets to adequately represent the level of fuzziness of their judgments). Once the opinions are collected, the set of best candidate(s) is easily identified and useful suggestion can be obtained for further developing the product.     

Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma

Aberrant somatic hypermutation (SHM) has been identified as a mechanism for genomewide instability in diffuse large B-cell lymphoma (DLBCL). To assess whether aberrant SHM plays a role in the molecular pathogenesis of Hodgkin lymphoma (HL), we investigated microdissected neoplastic cells of nodular lymphocyte-predominant HL (NLPHL; n = 10) and classic HL (cHL; n = 9) for the presence of mutations in the 5' sequences of 4 previously identified aberrant SHM targets (PIM1, PAX5, RhoH/TTF, c-MYC). Mutations in one or more genes were detected in 80% of NLPHLs and 55% of cHLs, with 50% and 30% of patients carrying mutations in 2 or more genes, respectively. The most frequently involved protooncogene was PAX5, mutated in 7 of 9 patients with NLPHL and 2 of 9 patients with cHL. In total, 34 mutations were detected in NLPHL (frequency, 1.04/1,000 bp) and 35 were detected in patients with cHL (frequency, 1.92/1,000 bp). Mutations were of somatic origin because they were absent in control T cells and shared most of the features of the immunoglobulin variable (IGV) gene-associated SHM mechanism-ie, single nucleotide substitutions (n = 63) with rare deletions/insertions (n = 6) and a predominance of transitions over transversions with preferential targeting motifs. Our finding that NLPHL and cHL are targeted by aberrant SHM, as is DLBCL, suggests that these lymphomas may share common molecular pathogenetic events.     

Bone mineral density and turnover in non-corticosteroid treated African American children with juvenile rheumatoid arthritis

OBJECTIVE: To determine bone mineral content (BMC), bone mineral density (BMD), Z scores, and markers of bone turnover in African American children with juvenile rheumatoid arthritis (JRA). METHODS: Eight children with JRA with no prior exposure to corticosteroids were evaluated. Lumbar spine (L1-L4) and total body and total hip BMC and BMD were determined using dual x-ray absorptiometry (DXA), and Z scores (BMD) were calculated. Serum samples of markers of bone turnover including pyridinoline (PYR), N-terminal propeptide of type I procollagen (P1NP), osteocalcin (OC), and bone-specific alkaline phosphatase (BSAP) were measured. RESULTS: The mean Z score (BMD) at the lumbar spine (L1-L4) in patients with JRA was -1.2+/-0.8. Z scores for total body and total hip were within 1 standard deviation of normal compared with healthy historical controls matched for age, sex, and race. CONCLUSION: BMD was normal for chronological age (defined as Z score >or= 2.0) in African American children with JRA who had not previously been treated with corticosteroids. Further studies are needed on the effects of JRA on skeletal health in African American children.     

Diabetic Cardiomiopathy Progression is Triggered by miR122-5p and Involves Extracellular Matrix: A 5-Year Prospective Study

ObjectivesThe purpose of this study was to follow the long-term progression of diabetic cardiomyopathy by combining cardiac magnetic resonance (CMR) and molecular analysis.BackgroundThe evolution of diabetic cardiomyopathy to heart failure affects patients’morbidity and mortality. CMR is the gold standard to assess cardiac remodeling, but there is a lack of markers linked to the mechanism of diabetic cardiomyopathy progression.MethodsFive-year longitudinal study on patients with type 2 diabetes mellitus (T2DM) enrolled in the CECSID (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes) trial compared with nondiabetic age-matched controls. CMR with tagging together with metabolic and molecular assessments were performed at baseline and 5-year follow-up.ResultsA total of 79 men (age 64 ± 8 years) enrolled, comprising 59 men with T2DM compared with 20 nondiabetic age-matched controls. Longitudinal CMR with tagging showed an increase in ventricular mass (ΔLVMi = 13.47 ± 29.66 g/m²; p = 0.014) and a borderline increase in end-diastolic volume (ΔEDVi = 5.16 ± 14.71 ml/m²; p = 0.056) in men with T2DM. Cardiac strain worsened (Δσ = 1.52 ± 3.85%; p = 0.033) whereas torsion was unchanged (Δθ = 0.24 ± 4.04°; p = 0.737), revealing a loss of the adaptive equilibrium between strain and torsion. Contraction dynamics showed a decrease in the systolic time-to-peak (ΔTtP = ?35.18 ± 28.81 ms; p < 0.001) and diastolic early recoil-rate (ΔRR = ?20.01 ± 19.07 s^-1; p < 0.001). The ejection fraction and metabolic parameters were unchanged. Circulating miR microarray revealed an up-regulation of miR122-5p. Network analysis predicted the matrix metalloproteinases (MMPs) MMP-16 and MMP-2 and their regulator (tissue inhibitors of metalloproteinases) as targets. In db/db mice we demonstrated that miR122-5p expression is associated with diabetic cardiomyopathy, that in the diabetic heart is overexpressed, and that, in vitro, it regulates MMP-2. Finally, we demonstrated that miR122-5p overexpression affects the extracellular matrix through MMP-2 modulation.ConclusionsWithin 5 years of diabetic cardiomyopathy onset, increasing cardiac hypertrophy is associated with progressive impairment in strain, depletion of the compensatory role of torsion, and changes in viscoelastic contraction dynamics. These changes are independent of glycemic control and paralleled by the up-regulation of specific microRNAs targeting the extracellular matrix. (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes [CECSID]; NCT00692237)     

Non-steroidal anti-inflammatory drugs and risk of cerebrovascular events in patients with osteoarthritis: a nested case–control study

Recent studies show that the risk of cardiovascular adverse events for certain traditional non-steroidal anti-inflammatory drugs (NSAIDs) is similar to that of rofecoxib. While these results are focused on ischemic cardiomyopathy, there is little evidence concerning the risk of ischemic stroke/transient ischemic attack and hemorrhagic stroke. Additionally, there is no information on nimesulide and ketoprofen, the most frequently prescribed NSAIDs in Italy, along with diclofenac. This study aims to determine whether the use of NSAIDs is associated with an increased risk of cerebrovascular events in Italy. We performed a case–control analysis nested in a cohort of patients with osteoarthritis between 2002 and 2011 who were newly treated with NSAIDs. The patients were followed until December 31, 2012. Conditional logistic regression was used to estimate odds ratios (ORs) with 95 % confidence intervals (95 % CI) of cerebrovascular events (index date) associated with current (until 30 days before the index date), recent (31–365 days) and past (>365 days) use of NSAIDs. Within a cohort of 29,722 patients, 1566 cases (1546 matched with controls) were identified (incidence rate = 11.0/1000 person–years). The overall rate of cerebrovascular event was not elevated with current NSAIDs overall when compared with past use. Among individual NSAIDs, diclofenac and ketoprofen were the molecules significantly associated with an increased rate of cerebrovascular events (OR = 1.53; 95 % CI 1.04–2.24; OR = 1.62; 95 % CI 1.02–2.58, respectively). The most frequent event was hemorrhagic stroke following the use of ketoprofen (OR = 2.09; 95 % CI 1.05–4.15). Diclofenac and ketoprofen seemed to increase the risk of cerebrovascular events. These findings might influence the choice of NSAIDs according to patient characteristics.     

Activation of ras oncogenes and expression of tumor-specific transplantation antigens in methylcholanthrene-induced murine fibrosarcomas

The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3-methylcholanthrene (3-MCA), was tested in NIH 3T3 transformation assay. Activation of K-ras and N-ras was found in 7 and 3 cases respectively. No H-ras activation was detected. Polymerase chain reaction and oligonucleotide hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K-ras mutation at codon 12, 3 at codon 13 and 1 at both codons. One case of K13 mutation was not detectable by transfection. Three cases of mutation at codon 61 of N-ras were also found, one of which was simultaneous with a K12 mutation. Tumor-specific transplantation antigens (TSTA) were assessed in the 22 original tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of TSTA+ tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3-MCA respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations occurred in the DNAs of 11 out of the 16 TSTA+ sarcomas, but none of the DNAs of the 6 TSTA- tumors showed ras mutation. The results suggest that 3-MCA-induced transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13 or 61 of K- and N- but not H-ras gene and that such mutation is accompanied by the expression of TSTA.