Impact of breastfeeding on ICU admissions and need for mechanical ventilation in infants younger than 6 months with RSV+ bronchiolitis. An observational study.

INTRODUCTION: This work aimed to analyze whether breastfeeding is a predictive factor for admission to ICU or needing mechanical ventilation in children under 6 months with RSV+ respiratory infection. METHODS: A retrospective cohort study was performed in three hospitals. Binary and multiple logistic regression analyses were performed to evaluate the association of variables with admission to the ICU or receiving mechanical ventilation. RESULTS: We analyzed 414 admissions, of which 293 (70.8%) had received breastfeeding, 43 (8.1%) were admitted to the ICU, and 26 (5.4%) required mechanical ventilation. Bivariate analysis showed that breastfeeding for at least 15 days and a longer duration of breastfeeding were associated with a lower risk of admission to the ICU and requiring mechanical ventilation. Multivariate analysis showed that not having been breastfed for at least 1 month was predictive of ICU admission; not having been breastfed for at least 2 months was predictive of needing mechanical ventilation. CONCLUSIONS: Breastfeeding for as little as 15-28 days could be associated with a lower risk of ICU admission and requiring mechanical ventilation in infants younger than 6 months admitted for RSV+ bronchiolitis. Since breastfeeding is one of the few protective factors that can be promoted, this finding is relevant for current clinical practice and the development of health promotion programs. Future studies can compare their results to ours.

Biomechanical Behavior of Dynamic vs. Static Distal Locking Intramedullary Nails in Subtrochanteric Femur Fractures.

OBJECTIVE: Hip fractures are one of the most frequent fractures presenting to the emergency department and orthopedic trauma teams. The aim of this study was to determine the best indication and therapeutic technique for subtrochanteric fractures and unifying criteria when choosing the most suitable type of nail. MATERIALS AND METHODS: To analyze the influence of the material and the type of distal locking of intramedullary nails (static or dynamic), a femur model with a fracture in the subtrochanteric region stabilized with a long Gamma intramedullary nail was applied using finite element method (FEM) simulation. RESULTS: The mechanical study shows that titanium nails allow for greater micromobility at the fracture site, which could act as a stimulus for the formation of callus and consolidation of the fracture. In the mechanical study, the type of distal locking mainly affects mobility at the fracture site and stress in the cortical bone around the distal screws, without in any case exceeding values that may compromise the viability of the assembly or that may result in detrimental effects (in terms of mobility at the fracture site) for the consolidation process. CONCLUSION: Subtrochanteric fractures treated with titanium nail and static distal locking is safe and does not hinder consolidation.

European Database of Explanted UHMWPE Liners from Total Joint Replacements: Correlations among Polymer Modifications, Structure, Oxidation, Mechanical Properties and Lifetime In Vivo.

This contribution lays the foundation for the European database of explanted UHMWPE liners from total joint replacements. Three EU countries (Czech Republic, Italy and Spain) have joined their datasets containing anonymized patient data (such as age and BMI), manufacturer data (such as information on UHMWPE crosslinking, thermal treatment and sterilization), orthopedic evaluation (such as total duration of the implant in vivo and reasons for its revision) and material characterization (such as oxidative degradation and micromechanical properties). The joined database contains more than 500 entries, exhibiting gradual growth, and it is beginning to show interesting trends, which are discussed in our contribution, including (i) strong correlations between UHMWPE oxidative degradation, degree of crystallinity and microhardness; (ii) statistically significant differences between UHMWPE liners with different types of sterilization; (iii) realistic correlations between the extent of oxidative degradation and the observed reasons for total joint replacement failures. Our final objective and task for the future is to continuously expand the database, involving researchers from other European countries, in order to create a robust tool that will contribute to the better understanding of structure-properties-performance relationships in the field of arthroplasty implants.

Therapeutic potential of topical administration of siRNAs against HIF-1α for corneal neovascularization.

Given the implications of the problem of neovascularization on ocular health, as well as the growth in the number of cases, the purpose of the present study has been testing the efficacy of siRNAs (small interfering RNA) designed to silence Hypoxia Inducible Factor -1α (HIF-1α) and to demonstrate that their use stops neovascularization in a model of corneal burn. Corneal wounds in the limbic zone were made in the eyes of New Zealand white rabbits. Topical applications of siRNAs were done the next day to the wound for four consecutive days and eyes were examined with a slit lamp. Evaluation of neovascularization progress was done by analyzing images by ImageJTM and to determine the neovascular area in Matlab ® was used. At the same time, a rabbit corneal cell line was used for in vitro study of hypoxia exposure and Western blot analysis of the cell's extracts were done. Under normal cell culture oxygenation, the expression of HIF-1α was lower than that observed under hypoxic conditions. After 2 h of hypoxia, there was a significant increase in the HIF-1α expression, effect that was maintained up to 6 h. The increased in HIF-1α was mimicked by a cell permeable prolyl-4-hydroxylase inhibitor. Cobalt chloride showed no capacity to increase HIF-1α in vitro. The effect of three different siRNA on HIF-1α was tested after 4 h of hypoxia. siRNA#1 was able to silence 80% of HIF-1α expression, siRNA#2 and siRNA#3 reduce the expression in 45% and 40% respectively. In addition, the three siRNA were tested in a corneal model of neovascularization. scrambledsiRNA#2 was the most effective inhibitor of blood vessel production, followed by siRNA#3 and siRNA#1. Compared to the scrambled siRNA (100% of blood vessel generation), siRNA#2 blocked the presence of blood vessels by 83 ± 2%, siRNA#3 inhibited 45 ± 7% and siRNA#1 only inhibited 18 ± 5%. The necessary time to observe the 50% of effect showed values of NV50 of 10.2 ± 2.4 days for the scrambled siRNA, 9.1 ± 1.4 for siRNA#1, 6.5 ± 1.85 for siRNA#2 and 4.8 ± 1.8 days for siRNA#3. In conclusion, the topical application of siRNA towards HIF-1α seems to be an effective and reliable method to stop neovascularization.

Analysis of 18F-Sodium Fluoride Positron Emission Tomography Signal Sources in Atherosclerotic Minipigs Shows Specific Binding of 18F-Sodium Fluoride to Plaque Calcifications.

Objective: 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) imaging is thought to visualize active atherosclerotic plaque calcification. This is supported by the binding of 18F-NaF to plaque calcification ex vivo, but no prior studies have examined binding of 18F-NaF to human-like plaque in vivo. Our aim was to validate the specificity of 18F-NaF PET for plaque calcifications in atherosclerotic minipigs. Approach and Results: Gain-of-function PCSK9D374Y (proprotein convertase/subtilisin kexin type 9) transgenic Yucatan minipigs (n=4) were fed high-fat diet for 2.5 years to develop atherosclerosis and then subjected to 18F-NaF PET/computed tomography imaging. The heart, aorta, and iliac arteries were immediately re-scanned ex vivo after surgical extraction. Lesions from the abdominal aorta, iliac arteries, and coronary arteries were cryo-sectioned for autoradiography. Histological plaque characteristics, PET/computed tomography signal, and autoradiography were linked through regression and co-localization analysis. Arterial 18F-NaF PET signal had intensities comparable to clinical scans and colocalized moderately with calcification detected by computed tomography. Histological analysis showed calcification spanning from microcalcifications near lipid pools and necrotic core to more homogenous macrocalcifications. Comparison with arteries from autopsy cases confirmed the resemblance in localization and appearance with early human plaque calcification. Regression analysis in the abdominal aorta showed correlations with calcified plaque but could not rule out contributions from noncalcified plaque. This was resolved by autoradiography, which showed specific accumulation in plaque calcifications in all examined arteries. In the context of porcine abdominal aorta, 18F-NaF PET imaging was, however, less accurate than computed tomography for detecting small calcifications. Conclusions: 18F-NaF accumulates specifically in calcifications of atherosclerotic plaques in vivo.

Effects of Colchicine on Atherosclerotic Plaque Stabilization: a Multimodality Imaging Study in an Animal Model.

Colchicine demonstrated clinical benefits in the treatment of stable coronary artery disease. Our aim was to evaluate the effects of colchicine on atherosclerotic plaque stabilization. Atherosclerosis was induced in the abdominal aorta of 20 rabbits with high-cholesterol diet and balloon endothelial denudation. Rabbits were randomized to receive either colchicine or placebo. All animals underwent MRI, 18F-FDG PET/CT, optical coherence tomography (OCT), and histology. Similar progression of atherosclerotic burden was observed in the two groups as relative increase of normalized wall index (NWI). Maximum 18F-FDG standardized uptake value (meanSUVmax) decreased after colchicine treatment, while it increased in the placebo group with a trend toward significance. Animals with higher levels of cholesterol showed significant differences in favor to colchicine group, both as NWI at the end of the protocol and as relative increase in meanSUVmax. Colchicine may stabilize atherosclerotic plaque by reducing inflammatory activity and plaque burden, without altering macrophage infiltration or plaque typology.

Bone Remodeling of Two Anatomic Stems: Densitometric Study of the Redesign of the ABG-II Stem.

BACKGROUND: Periprosthetic bone remodeling, which is a phenomenon observed in all femoral stems, has a multifactorial origin as it depends on factors related to the patient, the surgical technique, and the design of the implant. To determine the pattern of remodeling produced by 2 models of anatomic cementless implants, we quantified the changes in bone mineral density (BMD) in the 7 areas of Gruen observed at different moments after surgery during the first postoperative year. METHODS: A prospective, comparative, controlled, 1-year follow-up densitometric study was carried out in 2 groups of patients suffering from primary unilateral hip osteoarthritis. In the first group, with 68 patients, an ABG-II stem was implanted. In the second, with 66 patients, the ANATO stem was used. The contralateral, healthy hip was taken as a control. RESULTS: Both groups showed a decrease in BMD at 3 months in all the areas, which recovered at the end of the study, except in zone 7: there was a 17.7% decrease in the ABG-II group and a 5.9% decrease in the ANATO group. In zones 2 and 6, where more loads are transmitted, conservation of BMD is observed in response to Wolff's law. The differences in the pattern of remodeling between groups were maintained despite the age, gender, and BMI of the patients or the size of the implants. CONCLUSION: The ANATO stem achieved a more efficient transmission of loads at the metaphyseal level, which promotes bone preservation at the proximal femur, than the ABG-II stem.

Plasma Metabolic Signature of Atherosclerosis Progression and Colchicine Treatment in Rabbits.

Balloon catheter endothelial denudation in New Zealand white rabbits fed high cholesterol diet is a validated atherosclerosis model. Well-characterized in terms of atherosclerosis induction and progression, the metabolic changes associated with the atherosclerosis progression remain indeterminate. Non-targeted metabolomics permits to develop such elucidation and allows to evaluate the metabolic consequences of colchicine treatment, an anti-inflammatory drug that could revert these changes. 16 rabbits underwent 18 weeks of atherosclerosis induction by diet and aortic denudation. Thereafter animals were randomly assigned to colchicine treatment or placebo for 18 weeks while on diet. Plasma samples were obtained before randomization and at 36 weeks. Multiplatform (GC/MS, CE/MS, RP-HPLC/MS) metabolomics was applied. Plasma fingerprints were pre-processed, and the resulting matrixes analyzed to unveil differentially expressed features. Different chemical annotation strategies were accomplished for those significant features. We found metabolites associated with either atherosclerosis progression, or colchicine treatment, or both. Atherosclerosis was profoundly associated with an increase in circulating bile acids. Most of the changes associated with sterol metabolism could not be reverted by colchicine treatment. However, the variations in lysine, tryptophan and cysteine metabolism among others, have shown new potential mechanisms of action of the drug, also related to atherosclerosis progression, but not previously described.

Translational large animal model of hibernating myocardium: characterization by serial multimodal imaging.

Nonrevascularizable coronary artery disease is a frequent cause of hibernating myocardium leading to heart failure (HF). Currently, there is a paucity of therapeutic options for patients with this condition. There is a lack of animal models resembling clinical features of hibernating myocardium. Here we present a large animal model of hibernating myocardium characterized by serial multimodality imaging. Yucatan minipigs underwent a surgical casein ameroid implant around the proximal left anterior descending coronary artery (LAD), resulting in a progressive obstruction of the vessel. Pigs underwent serial multimodality imaging including invasive coronary angiography, cardiac magnetic resonance (CMR), and hybrid 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT). A total of 43 pigs were operated on and were followed for 120 ± 37 days with monthly multimodality imaging. 24 pigs (56%) died during the follow-up. Severe LAD luminal stenosis was documented in all survivors. In the group of 19 long-term survivors, 17 (90%) developed left ventricular systolic dysfunction [median LVEF of 35% (IQR 32.5-40.5%)]. In 17/17, at-risk territory was viable on CMR and 14 showed an increased glucose uptake in the at-risk myocardium on 18FDG-PET/CT. The present pig model resembles most of the human hibernated myocardium characteristics and associated heart failure (systolic dysfunction, viable myocardium, and metabolic switch to glucose). This human-like model might be used to test novel interventions for nonrevascularizable coronary artery disease and ischemia heart failure as a previous stage to clinical trials.

Explicit measurement of multi-tracer arterial input function for PET imaging using blood sampling spectroscopy.

BACKGROUND: Conventional PET imaging has usually been limited to a single tracer per scan. We propose a new technique for multi-tracer PET imaging that uses dynamic imaging and multi-tracer compartment modeling including an explicitly derived arterial input function (AIF) for each tracer using blood sampling spectroscopy. For that purpose, at least one of the co-injected tracers must be based on a non-pure positron emitter. METHODS: The proposed technique was validated in vivo by performing cardiac PET/CT studies on three healthy pigs injected with 18FDG (viability) and 68Ga-DOTA (myocardial blood flow and extracellular volume fraction) during the same acquisition. Blood samples were collected during the PET scan, and separated AIF for each tracer was obtained by spectroscopic analysis. A multi-tracer compartment model was applied to the myocardium in order to obtain the distribution of each tracer at the end of the PET scan. Relative activities of both tracers and tracer uptake were obtained and compared with the values obtained by ex vivo analysis of excised myocardial tissue segments. RESULTS: A high correlation was obtained between multi-tracer PET results, and those obtained from ex vivo analysis (18FDG relative activity: r = 0.95, p < 0.0001; SUV: r = 0.98, p < 0.0001). CONCLUSIONS: The proposed technique allows performing PET scans with two tracers during the same acquisition obtaining separate information for each tracer.

Quantitative assessment of myocardial blood flow and extracellular volume fraction using 68Ga-DOTA-PET: A feasibility and validation study in large animals.

BACKGROUND: Here we evaluated the feasibility of PET with Gallium-68 (68Ga)-labeled DOTA for non-invasive assessment of myocardial blood flow (MBF) and extracellular volume fraction (ECV) in a pig model of myocardial infarction. We also aimed to validate MBF measurements using microspheres as a gold standard in healthy pigs. METHODS: 8 healthy pigs underwent three sequential 68Ga-DOTA-PET/CT scans at rest and during pharmacological stress with simultaneous injection of fluorescent microspheres to validate MBF measurements. Myocardial infarction was induced in 5 additional pigs, which underwent 68Ga-DOTA-PET/CT examinations 7-days after reperfusion. Dynamic PET images were reconstructed and fitted to obtain MBF and ECV parametric maps. RESULTS: MBF assessed with 68Ga-DOTA-PET showed good correlation (y = 0.96x + 0.11, r = 0.91) with that measured with microspheres. MBF values obtained with 68Ga-DOTA-PET in the infarcted area (LAD, left anterior descendant) were significantly reduced in comparison to remote ones LCX (left circumflex artery, P < 0.0001) and RCA (right coronary artery, P < 0.0001). ECV increased in the infarcted area (P < 0.0001). CONCLUSION: 68Ga-DOTA-PET allowed non-invasive assessment of MBF and ECV in pigs with myocardial infarction and under rest-stress conditions. This technique could provide wide access to quantitative measurement of both MBF and ECV with PET imaging.

Optimization of purification techniques for lumen-loaded magnetoliposomes.

Liposomes encapsulating magnetic nanoparticles (MNPs), known as magnetoliposomes (MLs), have become a hot topic in biomedical research for applications in remote-triggered drug delivery and diagnostic imaging. One of the most crucial steps in the preparation of MLs is the purification of non-encapsulated MNPs, as a non-efficient purification can lead to misleading results. Purification is challenging especially when MNPs are loaded in the liposome lumen due to the small size differences between the MLs and the non-encapsulated MNPs. This work presents a comparison of three well known purification techniques, namely size exclusion chromatography, centrifugation and salt-induced aggregation, using five commercial MNPs with different configurations. The optimal purification techniques for two MNPs were studied further in the synthesis of MLs. In conclusion, we show that an efficient MLs purification requires the performance of a detailed study to select a valid method that is strongly dependent upon MNPs choices.

Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy.

BACKGROUND: Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. RESULTS: The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson's correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. CONCLUSIONS: Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

The use of Barthel index for the assessment of the functional recovery after osteoporotic hip fracture: One year follow-up.

The Barthel index evolution was analyzed in a sample of older people with osteoporotic hip fracture in order to verify the influence of comorbidities and cognitive impairment on the physical recovery of those patients, during the first year following the fracture. A prospective observational study was carried out between October 1, 2012 and March 31, 2013. A sample of 247 individuals was initially selected. After a primary revision, 39 participants were excluded (clearly not meeting inclusion criteria, lack of data, or not agree to participate in the study), and finally a total of 208 participants were included in the analysis, 166 women, with an average age of 84.59 years, and 42 men, with an average age of 82.05. 54.80% of all cases were older than 85 years. The mean Barthel index value prior to fracture was 76.63, decreasing to 64.91 at one-year follow-up. Only 22.12% of patients achieved a full recovery for activities of daily living. A statistical analysis was performed by comparing Barthel index recovery depending on the values of Charlson and Pfeiffer indexes, respectively. The mean differences in Barthel index drop between the one-year follow-up and the hospital admission values were found statistical significant (p<0.01). These findings indicate that Charlson and Pfeiffer indexes clearly influence the Barthel index recovery. Low values of Charlson and Pfeiffer indexes resulted in better Barthel index recovery. In conclusion, the Barthel index is a good tool to evaluate the physical recovery after osteoporotic hip fracture.

Efficacy of topical tranexamic acid within a blood-saving programme for primary total hip arthroplasty: a pragmatic, open-label randomised study.

BACKGROUND: Total hip arthroplasty entails considerable peri-operative blood loss, which may lead to acute post-operative anaemia and red blood cell transfusion. This study was aimed at assessing whether the addition of topical tranexamic acid to our ongoing blood-saving protocol for total hip arthroplasty was effective and safe. MATERIALS AND METHODS: A pragmatic, prospective, open-label randomised study of patients scheduled for total hip arthroplasty at a single centre was conducted. Consecutive patients were randomly assigned to receive topical tranexamic acid (2 g) at the end of surgery (tranexamic group, n=125) or not (control group, n=129). A restrictive transfusion protocol was applied. Outcome measures were red blood cell loss at 24 hours after surgery, in-hospital transfusion rate, and incidence of thromboembolic complications. RESULTS: Topical tranexamic acid was effective in reducing both red cell loss (mean difference: 138 mL [95% CI 87-189 mL]; p<0.001) in the 24h after surgery and in-hospital transfusion rates (12 vs 32.6%, for the tranexamic acid and control groups, respectively; p<0.001; relative risk=0.37 [95% CI 0.22-0.63]). However, relative red cell loss and transfusion rates were higher in females than in males, irrespectively of tranexamic acid use. The beneficial effect of tranexamic acid on transfusion was restricted to patients with pre-operative haemoglobin ≥13 g/dL (5.1 vs 24.8%; p<0.001). Topical tranexamic acid was well tolerated and no clinically apparent thromboembolic complications were witnessed. DISCUSSION: The use of topical tranexamic acid after hip arthroplasty reduced red cell loss and transfusion rates; the efficacy of this strategy may be improved by reinforcing both pre-operative haemoglobin optimisation and adherence to the practice of transfusing single units of red cells.

Protein corona and phospholipase activity drive selective accumulation of nanomicelles in atherosclerotic plaques.

ApoB-100 and Phosphatidylcholine-specific phospholipase C (PC-PLC) are important contributors to atherosclerosis development. ApoB-100 is the main structural protein of LDL, being directly associated with atherosclerosis plaque generation. PC-PLC is highly expressed in atherosclerosis lesions and contributes to their progression. We show how phosphatidylcholine-coated nanomicelles can be used for specific characterisation of atherosclerosis plaque. Results show that ApoB-100 in the protein corona of the nanomicelle targets the particles to atherosclerotic areas in apolipoprotein E-/- mice. Furthermore, PC-PLC selectively removes the polar heads from the phospholipid coating of the nanomicelles leading to their accumulation. To fully characterise the behaviour of the nanomicelles, we developed multimodal probes using a nanoemulsion step. Hybrid imaging revealed plaque accumulation of the nanomicelles and colocalisation with PC-PLC expression and ApoB-100 in the plaque. This study shows how protein corona composition and enzyme-driven nanomaterial accumulation can be used for detection of atherosclerosis.

Assessment of regional pulmonary blood flow using 68Ga-DOTA PET.

BACKGROUND: In vivo determination of regional pulmonary blood flow (PBF) is a valuable tool for the evaluation of many lung diseases. In this study, the use of 68Ga-DOTA PET for the in vivo quantitative determination of regional PBF is proposed. This methodology was implemented and tested in healthy pigs and validated using fluorescent microspheres. The study was performed on young large white pigs (n = 4). To assess the reproducibility and consistency of the method, three PET scans were obtained for each animal. Each radiotracer injection was performed simultaneously to the injection of fluorescent microspheres. PBF images were generated applying a two-compartment exchange model over the dynamic PET images. PET and microspheres values were compared by regression analysis and Bland-Altman plot. RESULTS: The capability of the proposed technique to produce 3D regional PBF images was demonstrated. The correlation evaluation between 68Ga-DOTA PET and microspheres showed a good and significant correlation (r = 0.74, P < 0.001). CONCLUSIONS: Assessment of PBF with the proposed technique allows combining the high quantitative accuracy of PET imaging with the use of 68Ga/68Ge generators. Thus, 68Ga-DOTA PET emerges as a potential inexpensive method for measuring PBF in clinical settings with an extended use.

New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans.

Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease.

Comparative Analysis of the Biomechanical Behaviour of Two Cementless Short Stems for Hip Replacement: Linea Anatomic and Minihip.

A comparative study between two stems (Linea Anatomic and Minihip) has been performed in order to analyse the differences in their biomechanical behaviour, concerning stem micromotions and load transmission between stem and bone. From the corresponding finite element models, a parametric study was carried out to quantify ranges of micromotions taking into account: friction coefficient in the stem-bone interface, press-fit and two types of gait cycle. Micromotions were evaluated for each stem at six different levels along repeated gait cycles. An initial and marked stem subsidence at the beginning of the simulation was observed, followed by an asymptotic decrease due to friction forces. Once migration occurs, a repeated reversible cyclic micromotion is developed and stabilized as gait cycle times are simulated. The general motion pattern exhibited higher amplitude of micromotion for Minihip compared to Linea stem. The load transmission mechanism was analyzed, identifying the main internal forces. The results show higher local forces for Minihip stem up to 80% greater than for Linea stem. The differences of design between Minihip and Linea conditioned different distributions of load, influencing the posterior stress-shielding. Consequently, short stems require high bone stock and quality should, being indicated for young patients with high bone quality.

Accurate quantification of atherosclerotic plaque volume by 3D vascular ultrasound using the volumetric linear array method.

INTRODUCTION: Direct quantification of atherosclerotic plaque volume by three-dimensional vascular ultrasound (3DVUS) is more reproducible than 2DUS-based three-dimensional (2D/3D) techniques that generate pseudo-3D volumes from summed 2D plaque areas; however, its accuracy has not been reported. We aimed to determine 3DVUS accuracy for plaque volume measurement with special emphasis on small plaques (a hallmark of early atherosclerosis). METHODS: The in vitro study consisted of nine phantoms of different volumes (small and medium-large) embedded at variable distances from the surface (superficial vs. >5 cm-depth) and comparison of 3DVUS data generated using a novel volumetric-linear array method with the real phantom volumes. The in vivo study was undertaken in a rabbit model of atherosclerosis in which 3DVUS and 2D/3D volume measurements were correlated against gold-standard histological measurements. RESULTS: In the in vitro setting, there was a strong correlation between 3DVUS measures and real phantom volume both for small (3.0-64.5 mm(3) size) and medium-large (91.1-965.5 mm(3) size) phantoms embedded superficially, with intraclass correlation coefficients (ICC) of 0.99 and 0.98, respectively; conversely, when phantoms were placed at >5 cm, the correlation was only moderate (ICC = 0.67). In the in vivo setting there was strong correlation between 3DVUS-measured plaque volumes and the histological gold-standard (ICC = 0.99 [4.02-92.5 mm(3) size]). Conversely, the correlation between 2D/3D values and the histological gold standard (sum of plaque areas) was weaker (ICC = 0.87 [49-520 mm(2) size]), with large dispersion of the differences between measurements in Bland-Altman plots (mean error, 79.2 mm(2)). CONCLUSIONS: 3DVUS using the volumetric-linear array method accurately measures plaque volumes, including those of small plaques. Measurements are more accurate for superficial arterial territories than for deep territories.