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Numerous cardioprotective interventions have been reported to reduce myocardial infarct size (IS) in pre-clinical studies. However, their translation for the benefit of patients with acute myocardial infarction (AMI) has been largely disappointing. One reason for the lack of translation is the lack of rigor and reproducibility in pre-clinical studies. To address this, we have established the European IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) pig AMI network with centralized randomization and blinded core laboratory IS analysis and validated the network with ischemic preconditioning (IPC) as a positive control. Ten sites in the COST Innovators Grant (IG16225) network participated in the IMPACT network. Three sites were excluded from the final analysis through quality control of infarct images and use of pre-defined exclusion criteria. Using a centrally generated randomization list, pigs were allocated to myocardial ischemia/reperfusion (I/R, N = 5/site) or IPC + I/R (N = 5/site). The primary endpoint was IS [% area-at-risk (AAR)], as quantified by triphenyl-tetrazolium-chloride (TTC) staining in a centralized, blinded core laboratory (5 sites), or IS [% left-ventricular mass (LV)], as quantified by a centralized, blinded cardiac magnetic resonance (CMR) core laboratory (2 sites). In pooled analyses, IPC significantly reduced IS when compared to I/R (57 ± 14 versus 32 ± 19 [%AAR] N = 25 pigs/group; p < 0.001; 25 ± 13 versus 14 ± 8 [%LV]; N = 10 pigs/group; p = 0.021). In site-specific analyses, in 4 of the 5 sites, IS was significantly reduced by IPC when compared to I/R when quantified by TTC and in 1 of 2 sites when quantified by CMR. A pig AMI multicenter European network with centralized randomization and core blinded IS analysis was established and validated with the aim to improve the reproducibility of cardioprotective interventions in pre-clinical studies and the translation of cardioprotection for patient benefit., Competing Interests: Declarations. Conflict of interest: P.F. is the founder and CEO and ZG is involved in the management of Pharmahungary Group, a group of R&D companies. Pharmahungary Group has a conflict of interest as it may be organizing multicenter studies on cardioprotection on external request and potentially including the here validated sites of the current COST action (IG16225). D.J.H. has received: consultant fees from Faraday Pharmaceuticals Inc. and Boehringer Ingelheim International GmbH; honoraria from Servier; and research funding from Astra Zeneca, Merck Sharp & Dohme Corp and Novonordisk. J. L. Z. received speaker honoraria from Pfizer, Bayer, Novartis, and Amgem. All other authors declare no competing interests. Ethical statements: The experimental protocols conformed to the EU directive 2010/63EU on the protection of animals used for scientific purposes and the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines [49]. The experimental protocols were formally approved by the appropriate national or institutional ethics committees (see Suppl. Data sheet experimental design)., (© 2024. The Author(s).)

Objective: Hemodialysis patients usually receive an arteriovenous fistula (AVF) in the arm as vascular access conduit to allow dialysis 2-3 times a week. This AVF introduces the high flow necessary for dialysis, but over time the ever-present supraphysiological flow is the leading cause of complications. This study aims to develop an implantable device able to non-invasively remove the high flow outside dialysis sessions., Methods: The developed prototype features a magnetic ring allowing external coupling and torque transmission to non-invasively control an AVF valve. Mock-up devices were implanted into arm and sheep cadavers to test sizes and locations. The transmission torque, output force, and valve closure are measured for different representative skin thicknesses., Results: The prototype was placed successfully into arm and sheep cadavers. In the prototype, a maximum output force of 78.9 ± 4.2 N, 46.7 ± 1.9 N, 25.6 ± 0.7 N, 13.5 ± 0.6 N and 6.3 ± 0.4 N could be achieved non-invasively through skin thicknesses of 1-5 mm respectively. The fistula was fully collapsible in every measurement through skin thickness up to the required 4 mm., Conclusion: The prototype satisfies the design requirements. It is fully implantable and allows closure and control of an AVF through non-invasive torque transmission. In vivo studies are pivotal in assessing functionality and understanding systemic effects., Significance: A method is introduced to transfer large amounts of energy to a medical implant for actuation of a mechanical valve trough a closed surface. This system allows non-invasive control of an AVF to reduce complications related to the permanent high flow in conventional AVFs.

Currently, tissue engineering has been dedicated to the development of 3D structures through bioprinting techniques that aim to obtain personalized, dynamic, and complex hydrogel 3D structures. Among the different materials used for the fabrication of such structures, proteins and polysaccharides are the main biological compounds (biopolymers) selected for the bioink formulation. These biomaterials obtained from natural sources are commonly compatible with tissues and cells (biocompatibility), friendly with biological digestion processes (biodegradability), and provide specific macromolecular structural and mechanical properties (biomimicry). However, the rheological behaviors of these natural-based bioinks constitute the main challenge of the cell-laden printing process (bioprinting). For this reason, bioprinting usually requires chemical modifications and/or inter-macromolecular crosslinking. In this sense, a comprehensive analysis describing these biopolymers (natural proteins and polysaccharides)-based bioinks, their modifications, and their stimuli-responsive nature is performed. This manuscript is organized into three sections: (1) tissue engineering application, (2) crosslinking, and (3) bioprinting techniques, analyzing the current challenges and strengths of biopolymers in bioprinting. In conclusion, all hydrogels try to resemble extracellular matrix properties for bioprinted structures while maintaining good printability and stability during the printing process.

Background: Congenital obstructive hydrocephalus generates progressive irreversible fetal brain damage by ventricular enlargement and incremental brain tissue compression that leads to maldevelopment and poor clinical outcomes. Intrauterine treatments such as ventriculo-amniotic shunting have been unsuccessfully tried in the eighties., Objective: To assess if prenatal endoscopic third ventriculostomy (ETV) is feasible in a large animal model and optimize this technique for ventricular decompression and potential arrest of fetal brain damage in fetal lambs., Methods: We generated hydrocephalus in 50 fetal lambs by injecting a polymeric agent into the cisterna magna at midgestation (E85). Subsequently, 3 weeks later (E105), fetal ETV was performed using a small rigid fetoscope. The endoscopy entry point was located anterior to the coronal suture, 7 mm from the midline., Results: We obtained clear visualization of the enlarged lateral ventricles by endoscopy in the hydrocephalic fetal lambs. The floor of the third ventricle was bluntly perforated and passed with the scope for a successful ETV. Total success was achieved in 32/50 cases (64%). Causes of failure were blurred vision or third ventricle obliteration by BioGlue in 10/50 (20%) cases, anatomic misdirection of the endoscope in 5 (10%) cases, 2 cases of very narrow foramen of Monro, and 1 case of choroid plexus bleeding. If we exclude the cases artificially blocked by the polymer, we had a successful performance of prenatal-ETV in 80% (32/40) of hydrocephalic fetuses., Conclusion: Despite the inherent difficulties arising from ovine brain anatomy, this study shows that innovative fetal ETV is technically feasible in hydrocephalic fetal lambs., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Tissue engineering is a promising methodology to produce advanced therapy medicinal products (ATMPs). We have developed personalized tissue engineered veins (P-TEV) as an alternative to autologous or synthetic vascular grafts utilized in reconstructive vein surgery. Our hypothesis is that individualization through reconditioning of a decellularized allogenic graft with autologous blood will prime the tissue for efficient recellularization, protect the graft from thrombosis, and decrease the risk of rejection. In this study, P-TEVs were transplanted to vena cava in pig, and the analysis of three veins after six months, six veins after 12 months and one vein after 14 months showed that all P-TEVs were fully patent, and the tissue was well recellularized and revascularized. To confirm that the ATMP product had the expected characteristics one year after transplantation, gene expression profiling of cells from P-TEV and native vena cava were analyzed and compared by qPCR and sequencing. The qPCR and bioinformatics analysis confirmed that the cells from the P-TEV were highly similar to the native cells, and we therefore conclude that P-TEV is functional and safe in large animals and have high potential for use as a clinical transplant graft.

The use of allogeneic adipose-derived mesenchymal stromal cells (alloADSCs) represents an attractive approach for treating myocardial infarction (MI). Furthermore, adding a natural support improves alloADSCs engraftment and survival in heart tissues, leading to a greater therapeutic effect. We aimed to examine the safety and immunological reaction induced by epicardial implantation of a clinical-grade collagen scaffold (CS) seeded with alloADSCs for its future application in humans. Thus, cellularized scaffolds were myocardially or subcutaneously implanted in immunosuppressed rodent models. The toxicological parameters were not significantly altered, and tumor formation was not found over the short or long term. Furthermore, biodistribution analyses in the infarcted immunocompetent rats displayed cell engraftment in the myocardium but no migration to other organs. The immunogenicity of alloADSC-CS was also evaluated in a preclinical porcine model of chronic MI; no significant humoral or cellular alloreactive responses were found. Moreover, CS cellularized with human ADSCs cocultured with human allogeneic immune cells produced no alloreactive response. Interestingly, alloADSC-CS significantly inhibited lymphocyte responses, confirming its immunomodulatory action. Thus, alloADSC-CS is likely safe and does not elicit any alloreactive immunological response in the host. Moreover, it exerts an immunomodulatory action, which supports its translation to a clinical setting.

Myocardial infarction is caused by an interruption of coronary blood flow, leading to one of the main death causes worldwide. Current therapeutic approaches are palliative and not able to solve the loss of cardiac tissue. Cardiosphere derived cells (CDCs) reduce scarring, and increase viable myocardium, with safety and adequate biodistribution, but show a low rate engraftment and survival after implantation. In order to solve the low retention, we propose the encapsulation of CDCs within three-dimensional alginate-poly-L-lysine-alginate matrix as therapy for cardiac regeneration. In this work, we demonstrate the encapsulation of CDCs in alginate matrix, with no decrease in viability over a month, and showing the preservation of CDCs phenotype, differentiation potential, gene expression profile and growth factor release after encapsulation, moving a step forward to clinical translation of CDCs therapy in regeneration in heart failure., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: We assessed an antireflux biodegradable heparin-coated ureteral stent (BraidStent ® -H) in an animal model comparative study after endoscopic treatment of ureteral strictures., Methods: A total of 24 female pigs underwent initial endoscopic, nephrosonographic, and contrast fluoroscopy assessment of the urinary tract. Afterward, unilateral laparoscopic ureteral stricture model was performed. Three weeks later, the animals underwent laser endoureterotomy and were randomly assigned to Group-I, in which a double-pigtail stent was placed for 6 weeks, or Group-II, in which a BraidStent®-H was placed. Follow-up was carried out by ultrasonography, contrast fluoroscopy, ureteroscopy, urinalysis and bacteriuria assessment at 3, 6, 12 and 5 months. Finally, a pathological study of the urinary system was performed., Results: There were no animals in Group-II with vesicoureteral reflux, with significance at 6 weeks with Group-I. Distal ureteral peristalsis was maintained in 50-75% in Group-II at 1-6 weeks. The 91.7% of stents in Group-II were degraded between 3-6 weeks, without obstructive fragments. Bacteriuria in Group II was 33.3-50% at 3 and 6 weeks. The global success rate by groups was 91.6% and 87.5% in groups I and II, respectively, with no statistical significance., Conclusions: BraidStent ® -H has been shown to be as efficacious as current ureteral stents in the treatment of benign ureteral strictures following laser endoureterotomy. In addition, it reduces the morbidity associated with current stents and has a homogeneous and predictable degradation rate of about 6 weeks, with no obstructive fragments. Future studies are required to improve the antibacterial coating to reduce BraidStent ® -H contamination in view of the results obtained with the heparin coating., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-21-19). Dr. Soria reports that he has a patent EP2749311 issued to JUMISC. Dr. Sanchez-Margallo reports that he has a patent EP2749311 issued to JUMISC. The other authors have no conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

Background: Double J ureteral stents are widely used on urological patients to provide drainage of the upper urinary tract. Unfourtunately, ureteral stents are not free from complications, as bacterial colonization and require a second procedure for removal. The purpose of the current comparative experimental study is to evaluate a new heparin-coated biodegradable antireflux ureteral stent (BraidStent®-H) to prevent urinary bacterial colonization., Methods: A total of 24 female pigs were underwent determination of bacteriuria and nephrosonographic, endoscopic and contrast fluoroscopy assessment of the urinary tract. Afterward, were randomly assigned animals to Group-I, in which a 5Fr double-pigtail ureteral stent was placed for 6 weeks, or Group-II, in which a BraidStent®-H was placed. Follow-up assessments were performed at 1, 3, 6, 8, 12 weeks. The final follow-up includes the above methods and an exhaustive pathological study of the urinary tract was accomplished after 20 weeks., Results: Bacteriuria findings in the first 48 h were significant between groups at 6 h and 12 h. Asymptomatic bacteriuria does not reach 100% of the animals in Group-II until 48 h versus Group-I where it appears at 6 h. The weekly bacteriuria mean rate was 27.7% and 44.4% in Group I and II respectively, without statistical significance. In Group II there were no animals with vesicoureteral reflux, with statistical significance at 3 and 6 weeks with Group-I. The 91.2% of stents in Group-II were degraded between 3 and 6 weeks, without obstructive fragments. Distal ureteral peristalsis was maintained in 66.6-75% in Group-II at 1-6 weeks., Conclusions: The heparin coating of BraidStent® allows an early decrease of bacterial colonization, but its effectiveness is low at the long term. Heparin coating did not affect scheduled degradation rate or size of stents fragments. BraidStent®-H avoids the side effects associated with current ureteral stents, thus should cause less discomfort to patients.

Objective: The aim was to assess a new biodegradable and antireflux intraureteral stent (BraidStent ® ) design in a swine model after ureteral laparoscopic operation. Materials and Methods: A total of 24 female pigs underwent initial endoscopic, nephrosonographic, and contrast fluoroscopy assessment of the urinary tract. Afterward, unilateral ureteropelvic junction obstruction was performed by laparoscopic approach. Six weeks later, the animals underwent laparoscopic Anderson-Hynes pyeloplasty, and were randomly assigned to Group-I, in which a double-pigtail ureteral stent was inserted for 6 weeks, or Group-II, in which a BraidStent ® , a biodegradable intraureteral stent design, was placed. Follow-up assessments were performed at 3 and 6 weeks and 5 months. Results: In terms of therapeutic success, complete resolution was observed in 91.6% of Group-I animals and 88.8% in Group-II. No evidence of vesicoureteral reflux (VUR) was observed in Group-II animals and statistical significance in VUR and ureteral orifice damage were observed between groups. BraidStent ® degradation occurred in a controlled manner between 3 and 6 weeks, without obstructive fragments. Distal ureteral peristalsis was maintained in 66.6% and 83.3% in Group-II at 3 and 6 weeks of follow-up, respectively. In Group-II, the positive bacteriuria rate was 41.6% and the migration rate 25%. Pathological assessment showed a significant improvement in ureteral healing in Group-II vs Group-I. Conclusions: The results of this comparative study in a porcine model indicate that the intraureteral BraidStent performed similarly to conventional ureteral stents. It avoids complete ureteral length intubation, the adverse effects associated with conventional ureteral stents, and maintains a high level of distal ureteral peristalsis. Moreover, the BraidStent ® exhibited a predictable and controlled degradation rate and did not cause any obstructive fragments. However, further studies are needed to improve the anchoring system and reduce the risk of bacterial colonization.

Objective: The authors hypothesized that new agents such as BioGlue would be as efficacious as kaolin in the induction of hydrocephalus in fetal sheep., Methods: This study was performed in 34 fetal lambs randomly divided into 2 studies. In the first study, fetuses received kaolin, BioGlue (2.0 mL), or Onyx injected into the cisterna magna, or no injection (control group) between E85 and E90. In the second study, fetuses received 2.0-mL or 2.5-mL injections of BioGlue into the cisterna magna between E85 and E90. Fetuses were monitored using ultrasound to assess lateral ventricle size and progression of hydrocephalus. The fetuses were delivered (E120-E125) and euthanized for histological analysis. Selected brain sections were stained for ionized calcium binding adaptor 1 (Iba1) and glial fibrillary acidic protein (GFAP) to assess the presence and activation of microglia and astroglia, respectively. Statistical comparisons were performed with Student's t-test for 2 determinations and ANOVA 1-way and 2-way repeated measures for multiple determinations., Results: At 30 days after injection, the lateral ventricles were larger in all 3 groups that had undergone injection than in controls (mean diameter in controls 3.76 ± 0.05 mm, n = 5). However, dilatation was greater in the fetuses injected with 2 mL of BioGlue (11.34 ± 4.76 mm, n = 11) than in those injected with kaolin (6.4 ± 0.98 mm, n = 7) or Onyx (5.7 ± 0.31 mm, n = 6) (ANOVA, *p ≤ 0.0001). Fetuses injected with 2.0 mL or 2.5 mL of BioGlue showed the same ventricle dilatation but it appeared earlier (at 10 days postinjection) in those injected with 2.5 mL. The critical threshold of ventricle dilatation was 0.1 for all the groups, and only the BioGlue 2.0 mL and BioGlue 2.5 mL groups exceeded this critical value (at 30 days and 18 days after injection, respectively) (ANOVA, *p ≤ 0.0001). Moderate to severe hydrocephalus with corpus callosum disruption was observed in all experimental groups. All experimental groups showed ventriculomegaly with significant microgliosis and astrogliosis in the subventricular zone around the lateral ventricles. Only kaolin resulted in significant microgliosis in the fourth ventricle area (ANOVA, *p ≤ 0.005)., Conclusions: The results of these studies demonstrate that BioGlue is more effective than Onyx or kaolin for inducing hydrocephalus in the fetal lamb and results in a volume-related response by obstructive space-occupancy without local neuroinflammatory reaction. This novel use of BioGlue generates a model with potential for new insights into hydrocephalus pathology and the development of therapeutics in obstructive hydrocephalus. In addition, this model allows for the study of acute and chronic obstructive hydrocephalus by using different BioGlue volumes for intracisternal injection.

Objectives: To assess the efficacy of a new anti-reflux intraureteral stent design in a swine model after minimally invasive treatment of ureteral stricture to reduce ureteral stent morbidity, previous to manufacture this design in a biodegradable fashion., Methods: Twenty-eight female pigs were included. The study began with a cystoscopic, nephrosonographic and contrast fluoroscopic assessment. Afterwards, obstructive uropathy model in right ureter was created. Obstruction was confirmed 6 weeks later and animals were randomly distributed into 2 groups. Group I underwent laser endopyelotomy and Group-II laparoscopic pyeloplasty A 3Fr anti-reflux intraureteral stent was placed 6 weeks. Follow-up evaluations were performed at 3-6 weeks. The final follow-up was completed at 5 months and included the aforementioned diagnostic methods and pathological study., Results: None of the study animals showed any vesicoureteral reflux signs or ureteral orifice injury. There were no urinomas or ureteric fistulas. The dislodgement rate was 10.7%. After 6 weeks of stenting, 71.4% of ureters showed ureteral peristalsis below the stent, and 100% at the final follow-up. After pathological assessment, no differences were shown at UPJ and healing in the incised area was correct in both groups., Conclusions: The new stent design avoids vesicoureteral reflux and bladder trigone irritation, consequently might reduce morbidity associated with double pigtail ureteral stents. This study also shows that it is only necessary temporary scaffolding the incised ureteral segment and not the entire length of the ureter after minimally invasive surgery. It is also necessary to manufacture this design in a biodegradable material, thus avoiding its removal.

Objective: To determine the effects in urinary tract of a new antireflux-biodegradable ureteral stent., Materials and Methods: Thirty six ureters belonging to 24 pigs were used. The study began with endoscopic, nephrosonographic, and fluoroscopic assessments. Three study groups of ureters (n = 12) were then specified. In group I, a biodegradable antireflux ureteral stent (BDG-ARS) was inserted in the right ureter of 12 pigs. Group II comprised the left ureter of the same animals, in which a double-pigtail stent was placed for 6 weeks. Group III ureters, belonging to 12 additional animals, were subjected to a ureteropelvic junction obstruction model that was then treated by endopyelotomy and stenting with BDG-ARS. Follow-ups were performed at 3-6 weeks and at 5 months., Results: None of the ureters receiving the BDG-ARS showed any evidence of vesicoureteral reflux (VUR). BDG-ARS degradation took place in a controlled and predictable fashion from the third to the sixth weeks, and no obstructive fragments appeared. No differences were found between groups I and II regarding passive ureteral dilation, but significant differences were found regarding VUR and ureteral orifice damage. BDG-ARS always maintained distal ureteral peristalsis. BDG-ARS in group III showed a 50% positive urine culture rate and a 16.6% migration rate in both BDG-ARS groups., Conclusion: BDG-ARS avoided VUR and bladder trigone irritation. In addition, this polymer combination and stent-braided design achieved a consistent biodegradation rate with no obstructive fragments and with uniform degradation between the third and the sixth weeks. Consequently, morbidity associated with ureteral stents might be reduced., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The traditional method of surgical training has followed the 'observe, practice, and teach' model, which is useful for open surgery, but is insufficient for minimally invasive surgery. This study presents the validation of a new simulator designed for TMJ arthroscopy training. A group of 10 senior maxillofacial surgeons performed an arthroscopy procedure using the simulator. They then completed a questionnaire analyzing the realism of the simulator, its utility, and the educational quality of the audiovisual software. The mean age of the 10 surgeons was 42.6 years, and they had performed a mean 151 arthroscopies. With regard to the realism of the simulator, 80% reported that it was of an appropriate size and design and 70% referred to the very realistic positions and relationships between the internal structures. Regarding its educational potential, 80% reported the simulator to be very useful for acquiring the basic skills and to acquire the sensation of depth during access to the TMJ. Finally, 90% reported the prototype to be very useful for TMJ arthroscopy training. These preliminary results showed a high degree of approval. The general opinion of the group of experts was that the experience was rewarding and inspiring, and that the prototype has the educational potential for the achievement of basic TMJ arthroscopy skills., (Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study is to validate a training model that combines the use of nonbiologic and biologic simulators as well as live porcine animal model in endoscopic retrograde intrarenal surgery (RIRS)., Materials and Methods: A total of 60 urologists took part in this study, and the activity lasted for 2 days. The training model was divided into three modules: Module-I, related to the acquisition of basic theoretical knowledge; Module-II, consisting of an internship with bench models; and Module III, in which animal models were used. First, trainees practiced with animals without using a lesion model (placement of an ureteral access sheath under fluoroscopic guidance and flexible ureterorenoscopy). Afterward, they practiced on a porcine animal model of bilateral renal lithiasis. Performance was measured using a validated global rating score and RIRS checklist score. Face and content validation as well as constructive validation provided by trainees in front of 15 experts were performed during the practice., Results: Face and content validations were satisfactory. "Individual" constructive validity showed statistical significance between the first and the last time that trainees practiced on an animal model. Statistical significance was also found between trainees and expert scores. There were 73.4% of trainees who increased their skills by more than 40%., Conclusion: This RIRS training model allows for the acquisition of technical knowledge and skills as face, content, and constructive validation show. A structured use of nonbiologic, biologic, and animal model simulators allows the increase of RIRS skills.

The aim of the study was to evaluate the possibility to use live anesthetized pigs as a model for laparoscopic liver resection. During two days laparoscopy course two trainees were operating on two live animals performing exposure of the liver, Pringle manoeuver, division of liver ligaments, dissecting of the structures inside the hepatoduodenal ligament, dissection of the hepatic veins and left lateral liver sectionectomy. Exposure of the liver and Pringle manoeuver were performed correctly within 50 and 35 minutes. Left lateral sectionectomy has been performed correctly within 2 hours. The full dissection of the hepatoduodenal ligament and exposure of the hepatic veins were judged as insufficient by experienced laparoscopic tutors. There was one injury to the suprahepatic vena cava that was managed laparoscopically. The porcine model can be used as an advanced training for laparoscopic liver surgery.

Objective: To assess a new antireflux ureteral stent in animal model. The design expects to reduce morbidity associated with JJ ureteral stents., Materials and Methods: Twelve pigs were used in this study. The study began with a nephrosonographic assessment and excretory urography. Afterward, measurement of the internal diameter of both ureteropelvic junctions (UPJ) by retrograde ureteropyelography was performed. A 3 Fr (ARS group) antireflux ureteral stent was placed in the right kidney and a JJ 4 Fr (JJ group) stent was placed in the left. Follow-ups were performed at 3-6 weeks; both stents were removed at 6 weeks. The final follow-up was completed at 5 months. This includes the above-mentioned diagnostic methods and an anatomopathological study., Results: There were no significant differences in UPJ diameter evolution between groups. During renal damage assessment, significant differences at 3 and 6 weeks were found, renal dilation being larger in JJ group. The JJ group shows a higher degree of vesicoureteral reflux at 3 and 6 weeks. After assessment of ureteral orifice, significant differences between groups were found at 3 weeks, 6 weeks, and 5 months, damage being more severe in the JJ group. After anatomopathological assessment, no statistical significance at UPJ was observed. However, statistical significance was found at ureterovesical junction, damage being more severe in the JJ group., Conclusion: The antireflux ureteral stent design dilates the upper urinary tract without affecting ureterovesical junction, and consequently reduces morbidity associated with JJ ureteral stents. Therefore, its patient tolerance will possibly be better than that to existent designs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The optimal timing of cardiac stem cells administration is still unclear. We assessed the safety of same-day and delayed (one week) delivery and the possible influence of the timing on the therapeutic outcomes of allogeneic porcine cardiac stem cells administration after acute myocardial infarction in a closed-chest ischemia-reperfusion model., Methods: Female swine surviving 90 min occlusion of the mid left anterior descending coronary artery received an intracoronary injection of 25x10(6) porcine cardiac stem cells either two hours (n = 5, D0) or 7 days (n = 6, D7) after reperfusion. Controls received intracoronary injection of vehicle on day 7 (n = 6, CON). Safety was defined in terms of absence of major cardiac events, changes to the ECG during injection, post-administration coronary flow assessed using the TIMI scale and cardiac troponin I determination after the intervention. Cardiac Magnetic Resonance was performed for morphological and functional assessment prior to infarction, before injection (D7 and CON groups only), at one and 10 weeks. Samples were taken from the infarct and transition areas for pathological examination., Results: No major adverse cardiac events were seen during injection in any group. Animals receiving the therapy on the same day of infarction (D0 group) showed mild transient ST changes during injection (n = 4) and, in one case, slightly compromised coronary flow (TIMI 2). Cardiac function parameters and infarct sizes were not significantly different between groups, with a trend towards higher ejection fraction in the treated groups. Ventricular volumes indexed to body surface area increased over time in control animals, and decreased by the end of the study in animals receiving the therapy, significantly so when comparing End Diastolic Volume between CON and D7 groups (CON: 121.70 ml/m(2) ± 26.09 ml/m(2), D7: 98.71 ml/m(2) ± 8.30 ml/m(2), p = 0.037). The treated groups showed less organization of the collagenous scar, and a significantly (p = 0.019) higher amount of larger, more mature vessels at the infarct border., Conclusions: The intracoronary injection of 25x10(6) allogeneic cardiac stem cells is generally safe, both early and 7 days after experimental infarction, and alleviates myocardial dysfunction, with a greater limitation of left ventricular remodeling when performed at one week.

Myocardial infarction, even after reperfusion, leads to significant loss of cardiomyocytes and to a maladaptive remodeling process. A possibility gaining attention as an ancillary therapy is the use of cardiac-derived cell products, with early stage clinical trials reporting highly promising results with autologous cells. However, an autologous therapy presents limitations, such as timeframe of therapy, cell processing and culture costs, risks posed to the patient by the tissue harvesting, etc. Allogeneic cells may represent an answer, providing an off-the-shelf product that could be used in the acute stage, before the myocardial damage is irrevocable. To date, allogeneic cardiac-derived cell products are being tested extensively, but the questions of their immunogenicity (and therefore safety), efficacy, cost-effectiveness, etc. are only partially elucidated. Small Phase I/II clinical trials (ALLSTAR, CAREMI) have started and their results will shed the much needed light on the feasibility and safety of a much needed therapy.

Aim: To evaluate if application of failure mode and effect analysis (FMEA) to laparoscopy training can help surgeons acquire laparoscopy skills., Methods: After preparing a FMEA matrix of laparoscopic sigmoidectomy, we have introduced it during three laparoscopy courses. Forty-eight surgeons, divided into 24 teams of two surgeons, have participated in three courses. During each course, every team has performed three laparoscopic sigmoidectomies in three experimental animals (1 OR session every day). Risk priority number (RPN) has been calculated for every surgery, and the results have been discussed at the end of each training day with all participants., Results: We have observed a decline in the median RPN from 1339 during the first OR session through 62 during second OR session to reach 0 in the third OR session. Only two teams out of 24 were not able to reach a RPN of less than 300 during third OR session. When the type of failures were analysed, we have observed a shift from procedure-type failures to technical failures that depended on each participant technical abilities., Conclusion: Application of FMEA principles to laparoscopy training can help acquire non-technical skills necessary for safe laparoscopic surgery.

In the recent years, it has been demonstrated that the biological activity of mesenchymal stem cells (MSCs) is mediated through the release of paracrine factors. Many of these factors are released into exosomes, which are small membranous vesicles that participate in cell-cell communication. Exosomes from MSCs are thought to have similar functions to MSCs such as repairing and regeneration of damaged tissue, but little is known about the immunomodulatory effect of these vesicles. Based on an extensive bibliography where the immunomodulatory capacity of MSCs has been demonstrated, here we hypothesized that released exosomes from MSCs may have an immunomodulatory role on the differentiation, activation and function of different lymphocyte subsets. According to this hypothesis, in vitro experiments were performed to characterize the immunomodulatory effect of human adipose MSCs derived exosomes (exo-hASCs) on in vitro stimulated T cells. The phenotypic characterization of cytotoxic and helper T cells (activation and differentiation markers) together with functional assays (proliferation and IFN-γ production) demonstrated that exo-hASCs exerted an inhibitory effect in the differentiation and activation of T cells as well as a reduced T cell proliferation and IFN-γ release on in vitro stimulated cells. In summary, here we demonstrate that MSCs-derived exosomes are a cell-derived product that could be considered as a therapeutic agent for the treatment of inflammation-related diseases.

Purpose: The aim of the present study was to validate a model of training, which combines the use of non-biological and ex vivo biological bench models, as well as the modelling of urological injuries for endourological treatment in a porcine animal model., Material and Methods: A total of 40 participants took part in this study. The duration of the activity was 16 hours. The model of training was divided into 3 levels: level I, concerning the acquisition of basic theoretical knowledge; level II, involving practice with the bench models and level III, concerning practice in the porcine animal model. First, trainees practiced with animals without using a model of injured (ureteroscopy, management of guide wires and catheters under fluoroscopic control) and later practiced in lithiasic animal model. During the activity, an evaluation of the face and content validity was conducted, as well as constructive validation provided by the trainees versus experts. Evolution of the variables during the course within each group was analysed using the Student's t test for paired samples, while comparisons between groups, were performed using the Student's t test for unpaired samples., Results: The assessments of face and content validity were satisfactory. The constructive validation, "within one trainee" shows that were statistical significant differences between the first time the trainees performed the tasks in the animal model and the last time, mainly in the knowledge of procedure and Holmium laser lithotripsy cathegories. At the beginning of level III, there are also statistical significant differences between trainee's scores and the expert's scores., Conclusions: This realistic Endourology training model allows the acquisition of knowledge and technical and non-technical skills as evidenced by the face, content and constructive validity. Structured use of bench models (biological and non biological) and animal model simulators increase the endourological basic skills.

Objective: To investigate the feasibility and safety of laparoscopy-assisted transvaginal resection of sigmoid cancer., Methods: From 2009 to 2011 we performed 21 laparoscopy-assisted transvaginal resections of sigmoid cancers., Results: The resected tumours were T1(6), T2(7) and T3(8). The median number of resected lymph nodes was 15. Median operative time was 150 min and no conversion to open technique was necessary. A total of eighteen patients tolerated a liquid diet 24 h after surgery. The average VAS pain score (0 = no pain, 10 = unbearable pain) was 1.8 after 24 h and 1.1 after 48 h. One patient experienced a postoperative ileus, two patients had vaginal spotting with serous flow and three patients suffered urinary tract infections. One patient developed a hernia at the umbilical trocar site that was operated on. None of the sexually active patients reported any differences in sexual activity pre-op and postop on a postoperative questionnaire. After a median of 25 (10-41) months of follow-up, all patients are alive and well, with no evidence of recurrent disease., Conclusion: Laparoscopy-assisted transvaginal resection of sigmoid cancer is feasible and safe in a selected group of patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Sutures are commonly used for surgical procedures and new sutures are being developed to improve wound healing. In the past decade, it has been extensively shown that mesenchymal stem cells (MSCs) have a wound healing potential. To benefit the overall wound healing process, we aimed to analyze the usage of pretreated sutures for improving the implantation of MSCs in the tissues. Our results firstly showed that suture pretreatments with gelatin, poly-L-lysine, and NaOH improved the adhesive strength of MSCs to sutures. These cells remained surrounding the sutured tissue and no significant phenotypic changes were found in those cells cultured onto pretreated sutures. In vivo experiments showed that the implantation of MSCs by suturing increases the collagen content in the sutured tissue. Moreover, proteomics analysis of secreted proteins showed that collagen alpha-1(I) chain was the most abundant collagen found. To our knowledge, this is the first report that aimed to improve the implantation of MSCs in tissue by suture pretreatments. Moreover, in vivo experiments suggest that MSC-coated sutures may enhance wound healing and tissue remodeling through the release of different collagen types being applicable for those patients that tend to have difficulty healing., (© 2014 by the Wound Healing Society.)

Objectives: The aim of the study was to evaluate early (the first 30 days) postoperative complications after transvaginal resection of the sigmoid colon., Material and Methods: A total of 23 laparoscopy-assisted transvaginal resections of the sigmoid colon and 1 NOTES transvaginal sigmoid resection were performed in the course of 3 years. Postoperative complications were recorded in a prospective manner., Results: In the group of 24 patients operated on using the transvaginal approach, 6 (25%) complications were recorded, including 3 urinary tract infections, 2 vaginal bleedings, and 1 abdominal trocar site hernia., Conclusion: Early postoperative complication rate after transvaginal resection of the sigmoid colon is relatively low and the clinical complications are not severe.

Several clinical trials are currently evaluating the safety and efficacy of mesenchymal stem cells (MSCs) in different diseases. The MSCs are guided by inflammatory mediators and specific interactions with immune cells occur, especially between MSCs and the cells of the innate immune system. At the present many of these interactions remain to be determined. This review summarizes the current knowledge in relation to the susceptibility of MSCs to NK cell mediated lysis as well as the immunomodulatory activity of MSCs and its control over NK cell function. Here we hypothesize that the inflammatory context will regulate the outcome of NK-MSC interactions.

Objective: To evaluate a new design for a hybrid, dynamic, metallic ureteral stent that might avoid the formation of urothelial hyperplasia after ureteral metallic stenting in an experimental study., Materials and Methods: A total of 30 healthy female pigs were included in the present study, and an experimental obstructive uropathy in the right lumbar ureter was created in each pig. Obstruction was confirmed using percutaneous ultrasonography and retrograde ureteral pyelography and endoluminal ultrasonography 6 weeks after obstructive uropathy model creation. Then, the pigs were randomly distributed into 2 groups. Group 1 underwent standard metallic ureteral self-expanding internally covered stent deployment. Group 2 received a new hybrid metallic ureteral self-expanding internally covered stent. The follow-up period was 6 months., Results: The hybrid metallic ureteral self-expanding internally covered stent group had a lower rate of urothelial hyperplasia (21% vs 70%), reduced stent migration (6.6% vs 33.3%), and a greater success rate after 6 months of follow-up (86.6% vs 47%) compared with the standard metallic ureteral self-expanding internally covered stent deployment group, with statically significant differences between the 2 groups., Conclusion: Our experimental results have indicated that the use of the hybrid metallic ureteral self-expanding internally covered stent in ureteral strictures is feasible, safe, and effective and reduces the formation of urothelial hyperplasia without secondary interventions to maintain ureteral patency., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Several minimally invasive techniques using natural orifices as an entrance site to the peritoneal cavity have been described recently. Pure natural orifice translumenal endoscopic surgery (NOTES) techniques have been mainly implemented to perform cholecystectomies and appendectomies, while more complex operations like colon resections have been described in a hybrid setting and with the use of the transumbilical approach. Here we describe the technique of transvaginal sigmoid colon resection for cancer with standard laparoscopy equipment., Materials and Methods: After developing the transvaginal technique of sigmoid colon resection in an experimental sheep model, we have performed this operation in a human patient for cancer. Twelve months of follow-up is reported., Results: A totally transvaginal R0 resection of the sigmoid colon for adenocarcinoma has been successfully performed in a female patient with laparoscopy equipment. The specimen included 13 lymph nodes, all of which were free of metastasis. Twelve months after surgery the patient is alive with no evidence of disease., Conclusion: A pure transvaginal NOTES approach to sigmoid colon cancer is feasible in human patients.

Mesenchymal stem cells have demonstrated their potentiality for therapeutic use in treating diseases or repairing damaged tissues. However, in some cases, the results of clinical trials have been disappointing or have not worked out as well as hoped. These disappointing results can be attributed to an inadequate or insufficient preclinical study. For medical and surgical purposes, the similarities between the anatomy of pig and human make this animal an attractive preclinical model. In this sense, for mesenchymal stem cell-based therapy, it is strongly necessary to have well characterized animal-derived mesenchymal stem cell lines to validate preclinical effectiveness of these cells. In this work, porcine mesenchymal stem cells (pMSCs) were isolated from bone marrow, adipose tissue and peripheral blood and compared in terms of differentiation potential, cell surface markers and gene expression. Our results demonstrated that the isolation and in vitro expansion protocols were feasible and effective. The data presented in this work are relevant because they provide an extensive phenotypic characterization; genetic study and differentiation behavior of the most commonly used stem cell lines for clinical practices. These pMSCs are widely available to scientists and could be a valuable tool to evaluate the safety and efficacy of adoptively transferred cells., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Natural orifice translumenal endoscopic surgery (NOTES), although in its embryonic phase, is currently experiencing important developments. The technique has been successfully applied for cholecystectomies and appendectomies. However, several doubts exist as to the technical limitations and feasibility of NOTES in other clinical settings., Methods: The authors have performed totally transvaginal colon resections in a sheep model. Although completion of the surgery was possible through the transvaginal route, the addition of a transumbilical laparoscope was used as an added safety measure., Results: Totally transvaginal resection of the sigmoid colon was performed for two sheep with no intra- or postoperative complications., Conclusion: Totally transvaginal resection of the colon (pure NOTES) is feasible in a sheep model.

The purpose of this study was to evaluate the feasibility of hybrid natural orifice translumenal endoscopic surgery (NOTES) transvaginal cholecystectomy in a porcine model of acute cholecystitis. We have developed an experimental model of acute cholecystitis in 8 female pigs (33.37±3.11 kg) through the surgical occlusion of the common bile duct. After 4 days, hybrid NOTES cholecystectomy was performed in all animals with the assistance of only one 5 mm trocar. The transvaginal approach and the abdomen exploration were performed without any complication. The hybrid NOTES cholecystectomy was successfully completed in all animals. The mean operative time was 76.50±10 minutes. Gallbladder rupture appeared in 2 cases, and there was no bleeding or laceration of adjacent organs. Our experiments showed the feasibility of hybrid NOTES cholecystectomy in an experimental model of acute cholecystitis. Additional research and training on experimental models of pathology will be necessary to validate NOTES surgery.

Human perceptual capabilities related to the laparoscopic interaction paradigm are not well known. Its study is important for the design of virtual reality simulators, and for the specification of augmented reality applications that overcome current limitations and provide a supersensing to the surgeon. As part of this work, this article addresses the study of laparoscopic pulling forces. Two definitions are proposed to focalize the problem: the perceptual fidelity boundary, limit of human perceptual capabilities, and the Utile fidelity boundary, that encapsulates the perceived aspects actually used by surgeons to guide an operation. The study is then aimed to define the perceptual fidelity boundary of laparoscopic pulling forces. This is approached with an experimental design in which surgeons assess the resistance against pulling of four different tissues, which are characterized with both in vivo interaction forces and ex vivo tissue biomechanical properties. A logarithmic law of tissue consistency perception is found comparing subjective valorizations with objective parameters. A model of this perception is developed identifying what the main parameters are: the grade of fixation of the organ, the tissue stiffness, the amount of tissue bitten, and the organ mass being pulled. These results are a clear requirement analysis for the force feedback algorithm of a virtual reality laparoscopic simulator. Finally, some discussion is raised about the suitability of augmented reality applications around this surgical gesture.