Reproducibility analysis of the computerized tomography angiography-derived left atrial wall thickness maps.

BACKGROUND: Adapting the ablation index (AI) to the left atrial wall thickness (LAWT) derived from computed tomography angiography (CTA) allows for a personalized approach that showed to improve PVI safety and outcomes. METHODS: Three observers with different degrees of experience performed complete LAWT analysis of CTA for 30 patients and repeated the analysis for 10 of these patients. Intra- and inter-observer reproducibility of these segmentations was assessed. RESULTS: Geometric congruence of repeated reconstruction of LA endocardial surface showed that 99.4% of points in the 3D reconstructed mesh were within < 1 mm distance for the intra-observer variability and 95.1% for the inter-observer. For the LA epicardial surface, an 82.4% of points were within < 1 mm for intra-observer and a 77.7% for inter-observer. A 1.99% of points were further than 2 mm for the intra-observer and a 4.1% for the inter-observer. Colour agreement between LAWT maps showed that a 95.5% and a 92.9% intra- and inter-observer respectively presented the same colour or a change to the colour immediately above or below. The ablation index (AI), which was adapted to this LAWT colour maps to perform a personalized pulmonary vein isolation (PVI), showed an average difference in the derived AI lower than 25 units in all cases. For all analyses, the concordance increased with user-experience. CONCLUSION: Geometric congruence of LA shape was high, for both endocardial and epicardial segmentations. LAWT measurements were reproducible, increasing with user experience. This translated into a negligible impact in the target AI.

Scientists' warning against the society of waste.

The metabolism of contemporary industrialized societies, that is their energy and material flows, leads to the overconsumption and waste of natural resources, two factors often disregarded in the global ecological equation. In this Discussion article, we examine the amount of natural resources that is increasingly being consumed and wasted by humanity, and propose solutions to reverse this pattern. Since the beginning of the 20th century, societies, especially from industrialized countries, have been wasting resources in different ways. On one hand, the metabolism of industrial societies relies on non-renewable resources. On the other hand, yearly, we directly waste or mismanage around 78% of the total water withdrawn, 49% of the food produced, 31% of the energy produced, 85% of ores and 26% of non-metallic minerals extracted, respectively. As a consequence, natural resources are getting depleted and ecosystems polluted, leading to irreversible environmental changes, biological loss and social conflicts. To reduce the anthropogenic footprint in the planet, and live in harmony with other species and ourselves, we suggest to shift the current economic model based on infinite growth and reduce inequality between and within countries, following a degrowth strategy in industrialized countries. Public education to reduce superfluous consumption is also necessary. In addition, we propose a set of technological strategies to improve the management of natural resources towards circular economies that, like ecosystems, rely only upon renewable resources.

SYLVIUS: A multimodal and multidisciplinary platform for epilepsy surgery.

BACKGROUND AND OBJECTIVE: We present SYLVIUS, a software platform intended to facilitate and improve the complex workflow required to diagnose and surgically treat drug-resistant epilepsies. In complex epilepsies, additional invasive information from exploration with stereoencephalography (SEEG) with deep electrodes may be needed, for which the input from different diagnostic methods and clinicians from several specialties is required to ensure diagnostic efficacy and surgical safety. We aim to provide a software platform with optimal data flow among the different stages of epilepsy surgery to provide smooth and integrated decision making. METHODS: The SYLVIUS platform provides a clinical workflow designed to ensure seamless and safe patient data sharing across specialities. It integrates tools for stereo visualization, data registration, transfer of electrode plans referred to distinct datasets, automated postoperative contact segmentation, and novel DWI tractography analysis. Nineteen cases were retrospectively evaluated to track modifications from an initial plan to obtain a final surgical plan, using SYLVIUS. RESULTS: The software was used to modify trajectories in all 19 consulted cases, which were then imported into the robotic system for the surgical intervention. When available, SYLVIUS provided extra multimodal information, which resulted in a greater number of trajectory modifications. CONCLUSIONS: The architecture presented in this paper streamlines epilepsy surgery allowing clinicians to have a digital clinical tool that allows recording of the different stages of the procedure, in a common multimodal 2D/3D setting for participation of different clinicians in defining and validating surgical plans for SEEG cases.

On the Use of Digital Subtraction Angiography in Stereoelectroencephalography Surgical Planning to Prevent Collisions with Vessels.

OBJECTIVE: Stereoelectroencephalography (SEEG) consists of the implantation of microelectrodes for the electrophysiological characterization of epileptogenic networks. To reduce a possible risk of intracranial bleeding by vessel rupture during the electrode implantation, the stereotactic trajectories must follow avascular corridors. The use of digital subtraction angiography (DSA) for vascular visualization during planning is controversial due to the additional risk related to this procedure. Here we evaluate the utility of this technique for planning when the neurosurgeon has it available together with gadolinium-enhanced T1-weighted magnetic resonance sequence (T1-Gd) and computed tomography angiography (CTA). METHODS: Twenty-two implantation plans for SEEG were initially done using T1-Gd imaging (251 trajectories). DSA was only used later during the revision process. In 6 patients CTA was available at this point as well. We quantified the position of the closest vessel to the trajectory in each of the imaging modalities. RESULTS: Two thirds of the trajectories that appeared vessel free in the T1-Gd or CTA presented vessels in their proximity, as shown by DSA. Those modifications only required small shifts of both the entry and target point, so the diagnostic aims were preserved. CONCLUSIONS: T1-Gd and CTA, despite being the most commonly used techniques for SEEG planning, frequently fail to reveal vessels that are dangerously close to the trajectories. Higher-resolution vascular imaging techniques, such as DSA, can provide the neurosurgeon with crucial information about vascular anatomy, resulting in safer plans.

Reparación mitral transcatéter mediante dispositivo PASCAL: experiencia inicial / Transcatheter mitral valve repair with the PASCAL system: initial experience

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A new aggressive xenograft model of human colon cancer using cancer-associated fibroblasts.

BACKGROUND: Colorectal cancer is the second leading cause of cancer death. Almost half of the patients present recurrence within 5 years after the treatment of the primary tumor, the majority, with metastasis. On the other hand, in the search for new animal models that simulate metastatic cancer, it has been suggested that fibroblasts immersed in the peritumoral stroma (cancer-associated fibroblasts (CAFs)), play a relevant role in the development of cancer. The objective of this study was to identify an adequate animal model to study metastatic colon cancer and the application of new treatments. METHODS: Human CAFs and normal fibroblasts (NF) for transplant and culture were obtained from surgical fresh samples of patients with adenocarcinoma of sigmoid colon. Stromal cell purity was evaluated by morphology and immunostaining with vimentin (VIM) as a fibroblast marker and anti-proColXIα1 as a specific human CAF marker. Phenotypic characterization of cultured stromal cells was performed by co-staining with mesenchymal and epithelial cell markers. For identification in mice, human CAFs were labeled with the PKH26 red fluorescence dye. Cell line HT-29 was used as tumor cells. Transplant in the head of the pancreas of 34 SCID mice was performed in four different groups, as follows: I. 150,000 CAFS (n = 12), IIa. 1.5 million HT29 cells (n = 7), IIb. 150,000 NF+1.5 million HT29 cells (n = 5), III. 150,000 CAFS+1.5 million HT29 cells (n = 10). After euthanasia performed one month later, histological analysis was made using hematoxylin-eosin and anti-proColXIα1. A histopathological score system based on three features (tumor volume, desmoplasia and number of metastasized organs) was established to compare the tumor severity. RESULTS: The CAFs and NF cultured were proColXIα1+/VIM+, proColXIα1/alphaSMA+ and proColXIα1+/CK19+ in different proportions without differences among them, but the CAFs growth curve was significantly larger than that of the NF (p < 0.05). No tumor developed in those animals that only received CAFs. When comparing group II (a + b) vs. group III, both groups showed 100% hepatic metastases. Median hepatic nodules, tumor burden, lung metastases and severity score were bigger in group III vs group II (a + b), although without being significant, except in the case of the median tumor volume, that was significantly higher in group III (154.8 (76.9-563.2) mm3) vs group II (46.7 (3.7-239.6) mm3), p = 0.04. A correlation was observed between the size of the tumor developed in the pancreas and the metastatic tumor burden in the liver and with the severity score. CONCLUSION: Our experiments demonstrate that cultured CAFs have a higher growth than NF and that when human CAFs are associated to human tumor cells, larger tumors with liver and lung metastases are generated than if only colon cancer cells with/without NF are transplanted. This emphasizes the importance of the tumor stroma, and especially the CAFs, in the development of cancer.

Transcatheter Mitral Repair for Functional Mitral Regurgitation According to Left Ventricular Function: A Real-Life Propensity-Score Matched Study.

BACKGROUND: Transcatheter mitral valve repair (TMVR) could improve survival in functional mitral regurgitation (FMR), but it is necessary to consider the influence of left ventricular ejection fraction (LVEF). Therefore, we compare the outcomes after TMVR with Mitraclip® between two groups according to LVEF. METHODS: In an observational registry study, we compared the outcomes in patients with FMR who underwent TMVR with and without LVEF <30%. The primary endpoint was the combined one-year all-cause mortality and unplanned hospital readmissions due to HF. The secondary end-points were New York Heart Association (NYHA) functional class and mitral regurgitation (MR) severity. Propensity-score matching was used to create two groups with the same baseline characteristics, except for baseline LVEF. RESULTS: Among 535 FMR eligible patients, 144 patients with LVEF <30% (group 1) and 144 with LVEF >30% (group 2) had similar propensity scores and were included in the analyses. The primary study endpoint was significantlly higher in group 1 (33.3% vs. 9.4%, p = 0.002). There was a maintained improvement in secondary endpoints without significant differences among groups. CONCLUSION: FMR patients with LVEF <30% treated with MitraClip® had higher mortality and readmissions than patients with LVEF ≥30% treated with the same device. However, both groups improved the NYHA functional class and MR severity.

Scar Characterization to Predict Life-Threatening Arrhythmic Events and Sudden Cardiac Death in Patients With Cardiac Resynchronization Therapy: The GAUDI-CRT Study.

OBJECTIVES: The aim of this study was to analyze whether scar characterization could improve the risk stratification for life-threatening ventricular arrhythmias and sudden cardiac death (SCD). BACKGROUND: Among patients with a cardiac resynchronization therapy (CRT) indication, appropriate defibrillator (CRT-D) therapy rates are low. METHODS: Primary prevention patients with a class I indication for CRT were prospectively enrolled and assigned to CRT-D or CRT pacemaker according to physician's criteria. Pre-procedure contrast-enhanced cardiac magnetic resonance was obtained and analyzed to identify scar presence or absence, quantify the amount of core and border zone (BZ), and depict BZ distribution. The presence, mass, and characteristics of BZ channels in the scar were recorded. The primary endpoint was appropriate defibrillator therapy or SCD. RESULTS: 217 patients (39.6% ischemic) were included. During a median follow-up of 35.5 months (12 to 62 months), the primary endpoint occurred in 25 patients (11.5%) and did not occur in patients without myocardial scar. Among patients with scar (n = 125, 57.6%), those with implantable cardioverter-defibrillator (ICD) therapies or SCD exhibited greater scar mass (38.7 ± 34.2 g vs. 17.9 ± 17.2 g; p < 0.001), scar heterogeneity (BZ mass/scar mass ratio) (49.5 ± 13.0 vs. 40.1 ± 21.7; p = 0.044), and BZ channel mass (3.6 ± 3.0 g vs. 1.8 ± 3.4 g; p = 0.018). BZ mass (hazard ratio: 1.06 [95% confidence interval: 1.04 to 1.08]; p < 0.001) and BZ channel mass (hazard ratio: 1.21 [95% confidence interval: 1.10 to 1.32]; p < 0.001) were the strongest predictors of the primary endpoint. An algorithm based on scar mass and the absence of BZ channels identified 148 patients (68.2%) without ICD therapy/SCD during follow-up with a 100% negative predictive value. CONCLUSIONS: The presence, extension, heterogeneity, and qualitative distribution of BZ tissue of myocardial scar independently predict appropriate ICD therapies and SCD in CRT patients.

Response to chemoradiotherapy and lymph node involvement in locally advanced rectal cancer.

AIM: To establish the association between lymph node involvement and the response to neoadjuvant therapy in locally advanced rectal cancer. METHODS: Data of 130 patients with mid and low locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation followed by radical surgery over a 5-year period were reviewed. Tumor staging was done by endorectal ultrasound and/or magnetic resonance imaging. Tumor response to neoadjuvant therapy was determined by T-downstaging and tumor regression grading (TRG). Pathologic complete response (pCR) is defined as the absence of tumor cells in the surgical specimen (ypT0N0). The varying degrees TRG were classified according to Mandard's scoring system. The evaluation of the response is based on the comparison between previous clinico-radiological staging and the results of pathological evaluation. χ (2) and Spearman's correlation tests were used for the comparison of variables. RESULTS: Pathologic complete response (pCR, ypT0N0, TRG1) was observed in 19 cases (14.6%), and other 18 (13.8%) had only very few residual malignant cells in the rectal wall (TRG2). T-downstaging was found in 63 (48.5%). Mean lymph node retrieval was 9.4 (range 0-38). In 37 cases (28.5%) more than 12 nodes were identified in the surgical specimen. Preoperative lymph node involvement was seen in 77 patients (59.2%), 71 N1 and 6 N2. Postoperative lymph node involvement was observed in 41 patients (31.5%), 29 N1 and 12 N2, while the remaining 89 were N0 (68.5%). In relation to ypT stage, we found nodal involvement of 9.4% in ypT0-1, 22.2% in ypT2 and 43.7% in ypT3-4. Of the 37 patients considered "responders" to neoadjuvant therapy (TRG1 and 2), there were only 4 N+ (10.8%) and the remainder N0 (89.2%). In the "non responders" group (TRG 3, 4 and 5), 37 cases were N+ (39.8%) and 56 (60.2%) were N0 (P < 0.001). CONCLUSION: Response to neoadjuvant chemoradiation in rectal cancer is associated with lymph node involvement.

Computation of the change in length of a braided device when deployed in realistic vessel models.

PURPOSE: An important issue in the deployment of braided stents, such as flow diverters, is the change in length, also known as foreshortening, underwent by the device when is released from the catheter into a blood vessel. The position of the distal end is controlled by the interventionist, but knowing a priori the position of the proximal end of the device is not trivial. In this work, we assess and validate a novel computer method to predict the length that a braided stent will adopt inside a silicon model of an anatomically accurate vessel. METHODS: Three-dimensional rotational angiography images of aneurysmatic patients were used to generate surface models of the vessels (3D meshes) and then create accurate silicon models from them. A braided stent was deployed into each silicon model to measure its length. The same stents deployed on the silicon models were virtually deployed on the 3D meshes using the method being evaluated. RESULTS: The method was applied to five stent placements on three different silicon models. The length adopted by the real braided device in the silicon models varies between 15 and 30% from the stent length specified by the manufacturer. The final length predicted by the method was within the estimated error of the measured real stent length. CONCLUSIONS: The method provides, in a few seconds, the length of a braided stent deployed inside a vessel, showing an accurate estimation of the final length for the cases studied. This technique could provide useful information for planning the intervention and improve endovascular treatment of intracranial aneurysms in the future.

COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human invasive carcinoma-associated stromal cells and carcinoma progression.

The COL11A1 human gene codes for the α1 chain of procollagen 11A1 and mature collagen 11A1, an extracellular minor fibrillar collagen. Under regular conditions, this gene and its derived products are mainly expressed by chondrocytes and mesenchymal stem cells as well as osteoblasts. Normal epithelial cells and quiescent fibroblasts from diverse locations do not express them. Mesenchyme-derived tumors and related conditions, such as scleroderma and keloids, are positive for COL11A1/(pro)collagen 11A1 expression, as well as high-grade human gliomas/glioblastomas. This expression is almost absent in benign pathological processes such as breast hyperplasia, sclerosing adenosis, idiopathic pulmonary fibrosis, cirrhosis, pancreatitis, diverticulitis, and inflammatory bowel disease. By contrast, COL11A1/(pro)collagen 11A1 is highly expressed by activated stromal cells of the desmoplastic reaction of different human invasive carcinomas, and this expression is correlated with carcinoma aggressiveness and progression, and lymph node metastasis. COL11A1 upregulation has been shown to be associated to TGF-ß1, Wnt, and Hh signaling pathways, which are especially active in cancer-associated stromal cells. At the front of invasive carcinomas, neoplastic epithelial cells, putatively undergoing epithelial-to-mesenchymal transition, and carcinoma-derived cells with highly metastatic capabilities, can express COL11A1. Thus, in established metastases, the expression of COL11A1/(pro)collagen 11A1 could rely on both the metastatic epithelial cells and/or the accompanying activated stromal cells. COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human carcinoma-associated stromal cells and carcinoma progression.

Predictive markers of response to neoadjuvant therapy in rectal cancer.

BACKGROUND: Neoadjuvant therapy followed by radical surgery is the standard treatment in locally advanced rectal cancer. It is important to predict the response because the treatment has side effects and is costly. The aim of this study was to establish the relationship among clinical, pathologic, and molecular biomarkers and the response to neoadjuvant therapy. METHOD: A total of 130 patients with locally advanced mid and low rectal cancer who underwent long-course radiotherapy with 5-FU based chemotherapy followed by radical surgical resection were included in the study. Clinical and pathologic data were collected. Paraffin-embedded sections obtained in diagnostic biopsies were assessed by immunohistochemical staining for molecular markers and classified using a semiquantitative method. Results were related with T-downstaging and tumor regression grade using Mandard scoring system on surgical specimens. RESULTS: Pathologic complete response was found in 19 patients (14.6%), while in another 18 (13.8%) only minor residual disease was seen in the rectal wall. T-downstaging was observed in 63 (48.5%). The average of lymph node retrieval in the surgical specimens was 9.4. Regarding predictive markers of response, there was significant correlation between the expression of B-cell lymphoma 2 (P = 0.005), ß-catenin (P = 0.03), vascular endothelial growth factor (P = 0.048) and apoptotic protease activating factor 1 (P = 0.03), tumor differentiation grade (P < 0.001), and response in the univariate analysis. T-downstaging was associated with vascular endothelial growth factor expression (P = 0.03) and tumor differentiation grade (P < 0.001). Significant parameters found in the multivariate analysis were tumor differentiation grade and Bcl-2 expression. CONCLUSIONS: Pathologic and molecular biomarkers in the diagnostic biopsies may help us predict tumor response to chemoradiation in rectal cancer patients.

A three-dimensional computer-based perspective of the skull base.

OBJECTIVE: To describe our designed protocol for the reconstruction of three-dimensional (3D) models applied to various endoscopic endonasal approaches that allows performing a 3D virtual dissection of the desired approach and analyzing and quantifying critical surgical landmarks. METHODS: All human cadaveric heads were dissected at the Laboratory of Surgical Neuroanatomy of the University of Barcelona. The dissection anatomic protocol was designed as follows: 1) virtual surgery simulation systems, 2) navigated cadaver dissection, and 3) postdissection analysis and quantification of data. RESULTS: The virtual dissection of the selected approach, the preliminary exploration of each specimen, the real dissection laboratory experience, and the analysis of data retrieved during the dissection step provide a complete method to improve general knowledge of the main endoscopic endonasal approaches to the skull base, at the same time allowing the development of new surgical techniques. CONCLUSIONS: The methodology for surgical training in the anatomic laboratory described in this article has proven to be very effective, producing a depiction of anatomic landmarks as well as 3D visual feedback that improves the study, design, and execution in various neurosurgical approaches. The Dextroscope as a virtual surgery simulation system can be used as a preoperative planning tool that can allow the neurosurgeon to perceive, practice reasoning, and manipulate 3D representations using the transsphenoidal perspective acquiring specifically visual information for endoscopic endonasal approaches to the skull base. The Dextroscope also can be used as an advanced tool for analytic purposes to perform different types of measurements between surgical landmarks before, during, and after dissection.

Validation of COL11A1/procollagen 11A1 expression in TGF-ß1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma.

BACKGROUND: The human COL11A1 gene has been shown to be up-regulated in stromal cells of colorectal tumours, but, so far, the immunodetection of procollagen 11A1, the primary protein product of COL11A1, has not been studied in detail in human colon adenocarcinomas. Some cancer-associated stromal cells seem to be derived from bone marrow mesenchymal cells; the expression of the COL11A1 gene and the parallel immunodetection of procollagen 11A1 have not been evaluated in these latter cells, either. METHODS: We used quantitative RT-PCR and/or immunocytochemistry to study the expression of DES/desmin, VIM/vimentin, ACTA2/αSMA (alpha smooth muscle actin) and COL11A1/procollagen 11A1 in HCT 116 human colorectal adenocarcinoma cells, in immortalised human bone marrow mesenchymal cells and in human colon adenocarcinoma-derived cultured stromal cells. The immunodetection of procollagen 11A1 was performed with the new recently described DMTX1/1E8.33 mouse monoclonal antibody. Human colon adenocarcinomas and non-malignant colon tissues were evaluated by immunohistochemistry as well. Statistical associations were sought between anti-procollagen 11A1 immunoscoring and patient clinicopathological features. RESULTS: Procollagen 11A1 was immunodetected in human bone marrow mesenchymal cells and in human colon adenocarcinoma-associated spindle-shaped stromal cells but not in colon epithelial or stromal cells of the normal colon. This immunodetection paralleled, in both kinds of cells, that of the other mesenchymal-related biomarkers studied: vimentin and alpha smooth muscle actin, but not desmin. Thus, procollagen 11A1(+) adenocarcinoma-associated stromal cells are similar to "activated myofibroblasts". In the series of human colon adenocarcinomas here studied, a high procollagen 11A1 expression was associated with nodal involvement (p = 0.05), the development of distant metastases (p = 0.017), and advanced Dukes stages (p = 0.047). CONCLUSION: The immunodetection of procollagen 11A1 in cancer-associated stromal cells could be a useful biomarker for human colon adenocarcinoma characterisation.

Extended endoscopic endonasal approaches for cerebral aneurysms: anatomical, virtual reality and morphometric study.

INTRODUCTION: The purpose of the present contribution is to perform a detailed anatomic and virtual reality three-dimensional stereoscopic study in order to test the effectiveness of the extended endoscopic endonasal approaches for selected anterior and posterior circulation aneurysms. METHODS: The study was divided in two main steps: (1) simulation step, using a dedicated Virtual Reality System (Dextroscope, Volume Interactions); (2) dissection step, in which the feasibility to reach specific vascular territory via the nose was verified in the anatomical laboratory. RESULTS: Good visualization and proximal and distal vascular control of the main midline anterior and posterior circulation territory were achieved during the simulation step as well as in the dissection step (anterior communicating complex, internal carotid, ophthalmic, superior hypophyseal, posterior cerebral and posterior communicating, basilar, superior cerebellar, anterior inferior cerebellar, vertebral, and posterior inferior cerebellar arteries). CONCLUSION: The present contribution is intended as strictly anatomic study in which we highlighted some specific anterior and posterior circulation aneurysms that can be reached via the nose. For clinical applications of these approaches, some relevant complications, mainly related to the endonasal route, such as proximal and distal vascular control, major arterial bleeding, postoperative cerebrospinal fluid leak, and olfactory disturbances must be considered.

Use of perfusion bioreactors and large animal models for long bone tissue engineering.

Tissue engineering and regenerative medicine (TERM) strategies for generation of new bone tissue includes the combined use of autologous or heterologous mesenchymal stem cells (MSC) and three-dimensional (3D) scaffold materials serving as structural support for the cells, that develop into tissue-like substitutes under appropriate in vitro culture conditions. This approach is very important due to the limitations and risks associated with autologous, as well as allogenic bone grafiting procedures currently used. However, the cultivation of osteoprogenitor cells in 3D scaffolds presents several challenges, such as the efficient transport of nutrient and oxygen and removal of waste products from the cells in the interior of the scaffold. In this context, perfusion bioreactor systems are key components for bone TERM, as many recent studies have shown that such systems can provide dynamic environments with enhanced diffusion of nutrients and therefore, perfusion can be used to generate grafts of clinically relevant sizes and shapes. Nevertheless, to determine whether a developed tissue-like substitute conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation, and for this reason, the use of animal models is often an essential step in the testing of orthopedic implants before clinical use in humans. This review provides an overview of the concepts, advantages, and challenges associated with different types of perfusion bioreactor systems, particularly focusing on systems that may enable the generation of critical size tissue engineered constructs. Furthermore, this review discusses some of the most frequently used animal models, such as sheep and goats, to study the in vivo functionality of bone implant materials, in critical size defects.

A novel bidirectional continuous perfusion bioreactor for the culture of large-sized bone tissue-engineered constructs.

This works reports the development and preliminary assessment of a new bioreactor for culturing large-sized three-dimensional constructs in bone tissue engineering. The bidirectional continuous perfusion bioreactor (BCPB) promotes mechanical stimulation of cells through the creation of shear forces induced by flow perfusion. The main innovation consists in the possibility of culturing scaffolds of large dimensions that can be suitable for the regeneration of critical sized defects. The functionality of BCPB was preliminarily evaluated by culturing starch-polycaprolactone scaffolds/goat bone marrow stromal cells for 14 and 21 days. Cylindrical blocks were stacked (42 mm thick). Static culture was used as controls. The samples were collected for DNA, alkaline phosphatase (ALP), scanning electron microscopy (SEM), and histological analysis. The results showed higher ALP levels in the bioreactor cultures than those obtained under static conditions. The number of cells in constructs cultured in the bioreactor showed lower values compared to static cultures, suggesting that static conditions tend to privilege the metabolic path way for cellular proliferation while dynamic conditions tend to privilege the metabolic path for osteogenic differentiation. SEM observations show that, the migration and cell distribution was observed in the bioreactor. These results demonstrate the feasibility and the benefit of culturing constructs in BCPB.

Three-dimensional architecture of scar and conducting channels based on high resolution ce-CMR: insights for ventricular tachycardia ablation.

BACKGROUND: Conducting channels are the target for ventricular tachycardia (VT) ablation. Conducting channels could be identified with contrast enhanced-cardiac magnetic resonance (ce-CMR) as border zone (BZ) corridors. A 3-dimensional (3D) reconstruction of the ce-CMR could allow visualization of the 3D structure of these BZ channels. METHODS AND RESULTS: We included 21 patients with healed myocardial infarction and VT. A 3D high-resolution 3T ce-CMR was performed before CARTO-guided VT ablation. The left ventricular wall was segmented and characterized using a pixel signal intensity algorithm at 5 layers (endocardium, 25%, 50%, 75%, epicardium). A 3D color-coded shell map was obtained for each layer to depict the scar core and BZ distribution. The presence/characteristics of BZ channels were registered for each layer. Scar area decreased progressively from endocardium to epicardium (scar area/left ventricular area: 34.0±17.4% at endocardium, 24.1±14.7% at 25%, 16.3±12.1% at 50%, 13.1±10.4 at 75%, 12.1±9.3% at epicardium; P<0.01). Forty-five BZ channels (2.1±1.0 per patient, 23.7±12.0 mm length, mean minimum width 2.5±1.5 mm) were identified, 85% between the endocardium and 50% shell and 76% present in ≥1 layer. The ce-CMR-defined BZ channels identified 74% of the critical isthmus of clinical VTs and 50% of all the conducting channels identified in electroanatomic maps. CONCLUSIONS: Scar area in patients with healed myocardial infarction decreases from the endocardium to the epicardium. BZ channels, more commonly seen in the endocardium, display a 3D structure within the myocardial wall that can be depicted with ce-CMR. The use of ce-CMR-derived maps to guide VT ablation warrants further investigation.

Synthesis of trigeneration systems: sensitivity analyses and resilience.

This paper presents sensitivity and resilience analyses for a trigeneration system designed for a hospital. The following information is utilized to formulate an integer linear programming model: (1) energy service demands of the hospital, (2) technical and economical characteristics of the potential technologies for installation, (3) prices of the available utilities interchanged, and (4) financial parameters of the project. The solution of the model, minimizing the annual total cost, provides the optimal configuration of the system (technologies installed and number of pieces of equipment) and the optimal operation mode (operational load of equipment, interchange of utilities with the environment, convenience of wasting cogenerated heat, etc.) at each temporal interval defining the demand. The broad range of technical, economic, and institutional uncertainties throughout the life cycle of energy supply systems for buildings makes it necessary to delve more deeply into the fundamental properties of resilient systems: feasibility, flexibility and robustness. The resilience of the obtained solution is tested by varying, within reasonable limits, selected parameters: energy demand, amortization and maintenance factor, natural gas price, self-consumption of electricity, and time-of-delivery feed-in tariffs.