Menstrual blood-derived mesenchymal stromal cells: impact of preconditioning on the cargo of extracellular vesicles as potential therapeutics.

BACKGROUND: Mesenchymal stromal cells (MSCs) have been shown to exert their therapeutic effects through the secretion of broad spectrum of paracrine factors, including extracellular vesicles (EVs). Accordingly, EVs are being pursued as a promising alternative to cell-based therapies. Menstrual blood-derived stromal cells (MenSCs) are a type of MSC that, due to their immunomodulatory and regenerative properties, have emerged as an innovative source. Additionally, new strategies of cell priming may potentially alter the concentration and cargo of released EVs, leading to modification of their biological properties. In this study, we aimed to characterize the EVs released by MenSCs and compare their therapeutic potential under three different preconditioning conditions (proinflammatory stimuli, physioxia, and acute hypoxia). METHODS: MenSCs were isolated from five healthy women. Following culturing to 80% confluence, MenSCs were exposed to different priming conditions: basal (21% O2), proinflammatory stimuli (IFNγ and TNFα, 21% O2), physioxia (1-2% O2), and acute hypoxia (< 1% O2) for 48-72 h. Conditioned media from MenSCs was collected after 48 h and EVs were isolated by a combination of ultra-filtration and differential centrifugation. An extensive characterization ranging from nano-flow cytometry (nFC) to quantitative high-throughput shotgun proteomics was performed. Bioinformatics analyses were used to derive hypotheses on their biological properties. RESULTS: No differences in the morphology, size, or number of EVs released were detected between priming conditions. The proteome analysis associated with basal MenSC-EVs prominently revealed their immunomodulatory and regenerative capabilities. Furthermore, quantitative proteomic analysis of differentially produced MenSC-EVs provided sufficient evidence for the utility of the differential preconditioning in purpose-tailoring EVs for their therapeutic application: proinflammatory priming enhanced the anti-inflammatory, regenerative and immunomodulatory capacity in the innate response of EVs, physioxia priming also improves tissue regeneration, angiogenesis and their immunomodulatory capacity targeting on the adaptive response, while acute hypoxia priming, increased hemostasis and apoptotic processes regulation in MenSC-EVs, also by stimulating immunomodulation mainly through the adaptive response. CONCLUSIONS: Priming of MenSCs under proinflammatory and hypoxic conditions affected the cargo proteome of EVs released, resulting in different therapeutic potential, and thus warrants experimental exploration with the aim to generate better-defined MSC-derived bioproducts.

Comparative anatomy of the ovine and human pelvis for laparoscopic sacrocolpopexy: evaluating the effectiveness of the ovine model.

INTRODUCTION AND HYPOTHESIS: Laparoscopic sacrocolpopexy (LSC) is a functional reconstructive surgery used to treat pelvic organ prolapse (POP) in middle-aged women. Although LSC is widely used, its implementation is hindered by perceived technical difficulties and surgical learning curves. Surgeons require adequate experience with LSC prior to performing the procedure on patients to improve their quality of life. This study is aimed at demonstrating the effectiveness of the ovine model (OM) for training and research in LSC, while also comparing anatomical differences between ovine and human models during the procedure. METHODS: The animal model and training were provided by the Jesús Usón Minimally Invasive Surgery Centre. Urologists and gynecologists with experience in LSC participated in a course and their findings were recorded and documented. RESULTS: Differences in patient positioning, trocar placement, and reperitonealization were identified between the ovine and human models. Hysterectomy is always performed in the ovine model, whereas it is not mandatory in humans. There are also differences in the dissection of the levator ani muscle and attachment point of the posterior mesh to the uterus between the two models. Despite differences in some areas, the ovine pelvic structure and vagina are similar in size to those of humans. CONCLUSIONS: The ovine model is a valuable tool for surgeons in their learning curve for LSC, allowing for safe and effective practice prior to performing the procedure on patients. The use of the OM can help to improve the quality of life for women affected by pelvic organ prolapse.

Comparative efficacy and safety of prostatic urethral lift vs prostatic artery embolization for benign prostatic hyperplasia: a systematic review and network meta-analysis.

OBJECTIVE: To assess and compare the clinical efficacy and safety of prostatic urethral lift (PUL) and prostatic artery embolization (PAE) for the treatment of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) by means of a systematic review and network meta-analysis. METHODS: A systematic literature search was performed using PubMed and Web of Science from inception to March 2021 to identify randomized controlled trials (RCTs) that compared PUL or PAE with either transurethral resection of the prostate (TURP) or sham procedures as control interventions. Qualitative and quantitative analyses were performed to pool the data on direct and indirect comparisons between interventions using STATA 14. RESULTS: Eight RCTs with 675 participants were included in our network meta-analysis. Quantitative synthesis revealed that TURP was the most efficacious intervention for clinical (International Prostate Symptoms Score and quality of life) and functional outcomes (maximum urinary flow rate and post-void residual urine volume), and was associated with a lower reintervention rate compared with PAE (risk ratio [RR] 2.08 with 95% confidence interval [CI] 0.96 to 4.51) and PUL (RR 2.33 with 95% CI 0.50 to 10.86), although the difference were not statistically significant. Indirect comparison indicated that PUL and PAE resulted in similar outcomes. PAE was associated with fewer minor adverse events (AEs; RR 0.75 with 95% CI 0.48 to 1.18) and PUL with fewer major AEs (RR 0.72 with 95% CI 0.17 to 3.13) when compared with TURP. Whilst PAE had a better ranking with regard to improvement of most clinical and functional outcomes, PUL was the best ranked procedure regarding erectile function, as measured by the International Index of Erectile Function 5, but no significant difference was observed. CONCLUSION: Current evidence suggests that PUL and PAE have similar clinical efficacy and safety profiles in the management of LUTS associated with BPH. However, the quality of evidence is relatively low because of the paucity of RCTs available, and results should be interpreted with caution.

Popliteal Vascular Lymph Node Resection in the Rabbit Hindlimb for Secondary Lymphedema Induction.

Lymphedema is a common condition often associated with cancer and its treatment, which leads to damage to the lymphatic system, and current treatments are mostly palliative rather than curative. Its high incidence among oncologic patients indicates the need to study both normal lymphatic function and pathologic dysfunction. To reproduce chronic lymphedema, it is necessary to choose a suitable experimental animal. Attempts to establish animal models are limited by the regenerative capacity of the lymphatic system. Among the potential candidates, the rabbit hindlimb is easy to handle and extrapolate to the human clinical scenario, making it advantageous. In addition, the size of this species allows for better selection of lymphatic vessels for vascularized lymph node resection. In this study, we present a procedure of vascular lymph node resection in the rabbit hindlimb for inducing secondary lymphedema. Anesthetized animals were subjected to circumferential measurement, patent blue V infiltration, and indocyanine green lymphography (ICG-L) using real-time near-infrared fluorescence, a technique that allows the identification of single popliteal nodes and lymphatic channels. Access to the identified structures is achieved by excising the popliteal node and ligating the medial and lateral afferent lymphatics. Special care must be taken to ensure that any lymphatic vessel that joins the femoral lymphatic system within the thigh without entering the popliteal node can be identified and ligated. Postoperative evaluation was performed at 3, 6, and 12 months after induction using circumferential measurements of the hindlimb and ICG-L. As demonstrated during follow-up, the animals developed dermal backflow that was maintained until the 12th month, making this experimental animal useful for novel long-term evaluations in the management of lymphedema. In conclusion, the approach described here is feasible and reproducible. Additionally, during the time window presented, it can be representative of human lymphedema, thus providing a useful research tool.

Cytotoxicity Assessment of a New Design for a Biodegradable Ureteral Mitomycin Drug-Eluting Stent in Urothelial Carcinoma Cell Culture.

Urothelial tumour of the upper urinary tract is a rare neoplasm, but unfortunately, it has a high recurrence rate. The reduction of these tumour recurrences could be achieved by the intracavitary instillation of adjuvant chemotherapy after nephron-sparing treatment in selected patients, but current instillation methods are ineffective. Therefore, the aim of this in vitro study is to evaluate the cytotoxic capacity of a new instillation technology through a biodegradable ureteral stent/scaffold coated with a silk fibroin matrix for the controlled release of mitomycin C as an anti-cancer drug. Through a comparative study, we assessed, in urothelial carcinoma cells in a human cancer T24 cell culture for 3 and 6 h, the cytotoxic capacity of mitomycin C by viability assay using the CCK-8 test (Cell counting Kit-8). Cell viability studies in the urothelial carcinoma cell line confirm that mitomycin C embedded in the polymeric matrix does not alter its cytotoxic properties and causes a significant decrease in cell viability at 6 h versus in the control groups. These findings have a clear biomedical application and could be of great use to decrease the recurrence rate in patients with upper tract urothelial carcinomas by increasing the dwell time of anti-cancer drugs.

Assessment of a Coated Mitomycin-Releasing Biodegradable Ureteral Stent as an Adjuvant Therapy in Upper Urothelial Carcinoma: A Comparative In Vitro Study.

A major limitation of the treatment of low-grade upper tract urothelial carcinoma is the difficulty of intracavitary instillation of adjuvant therapy. Therefore, the aim of this in vitro study was to develop and to assess a new design of biodegradable ureteral stent coated with a silk fibroin matrix for the controlled release of mitomycin C as a chemotherapeutic drug. For this purpose, we assessed the coating of a biodegradable ureteral stent, BraidStent®, with silk fibroin and subsequently loaded the polymeric matrix with two formulations of mitomycin to evaluate its degradation rate, the concentration of mitomycin released, and changes in the pH and the weight of the stent. Our results confirm that the silk fibroin matrix is able to coat the biodegradable stent and release mitomycin for between 6 and 12 h in the urinary environment. There was a significant delay in the degradation rate of silk fibroin and mitomycin-coated stents compared to bare biodegradable stents, from 6-7 weeks to 13-14 weeks. The present study has shown the feasibility of using mitomycin C-loaded silk fibroin for the coating of biodegradable urinary stents. The addition of mitomycin C to the coating of silk fibroin biodegradable stents could be an attractive approach for intracavitary instillation in the upper urinary tract.

Prostatic artery occlusion versus prostatic artery embolisation for the management of benign prostatic hyperplasia: early results in a canine model.

OBJECTIVE: To compare the technical efficacy and safety between prostatic artery occlusion (PAO) with ethylene vinyl alcohol copolymer (EVOH) and prostatic artery embolizsation (PAE) with microspheres in a canine model. METHODS: 17 adult male beagles underwent PAO (n = 7) with Onyx-18 or PAE (n = 10) with microspheres (300-500 µm). To evaluate the primary outcomes (technical efficacy and safety), MRI evaluations were performed immediately before and 1 week, 2 weeks, and 1 month after procedures to document prostate volume (PV); and all dogs were inspected for procedure-related complications during 1 month follow-up. The secondary outcomes included the prostate ischaemia size detected by MRI and recanalisation of prostatic artery by follow-up angiography. Differences between groups were statistically analysed. RESULTS: Both procedures were bilaterally successful in all animals. Compared with PAE, the mean fluoroscopy time (23.80 vs 36.24 min, p = 0.014) and radiation dose (68.19 vs 125.26 mGy, p = 0.003) were significantly less in PAO procedure. The mean percentage of PV change significantly decreased in both groups at 2 weeks (30.71% vs 37.89%) and 1 month (56.41% %vs 55.56%) after PAO and PAE respectively), without significant differences between groups at either time point. No major complications were observed except one animal after PAO with transient haematuria and acute urinary retention. The mean prostate ischaemia induced by PAO was significant greater compared with PAE at 1 week (43.44% vs 18.91%, p=0.001). PAO with EVOH is technically feasible and with comparable efficacy and safety with PAE. There are possible benefits to PAO over PAE. ADVANCES IN KNOWLEDGE: A new technical modification of the PAE consisting of the use of liquid embolic agent to occlude the prostatic artery trunk and its branches has been developed in pre-clinical study, showing to be an effective and safe procedure which can induce a significant prostate shrinkage for the management of symptomatic benign prostatic hyperplasia in patients. In addition, the findings have showed a similar therapeutic effect comparable with the conventional PAE using microspheres.

Swine Models of Aneurysmal Diseases for Training and Research.

Large animal models, specifically swine, are widely used to research cardiovascular diseases and therapies, as well as for training purposes. This paper describes two different aneurysmal swine models that may help researchers to study new therapies for aneurysmal diseases. These aneurysmal models are created by surgically adding a pouch of tissue to carotid arteries in swine. When the model is used for research, the pouch must be autologous; for training purposes, a synthetic pouch suffices. First, the right external jugular vein (EJV) and right common carotid artery (CCA) must be surgically exposed. The EJV is ligated and a vein pouch fashioned from a short segment. This pouch is then sutured to an elliptical arteriotomy performed in the CCA. Animals must be kept heparinized during model creation, and local vasodilators may be used to decrease vasospasms. Once the suture is completed, correct blood flow should be inspected, checking for bleeding from the suture line and vessel patency. Finally, the surgical incision is closed by layers and an angiography performed to image the aneurysmal model. A simplification of this aneurysmal carotid model that decreases invasiveness and surgical time is the use of a synthetic, rather than venous, pouch. For this purpose, a pouch is tailored in advance with a segment of a polytetrafluoroethylene (PTFE) prosthesis, one end of which is sutured close using polypropylene vascular suture and sterilized prior to surgery. This "sac" is then attached to an arteriotomy performed in the CCA as described. Although these models do not reproduce many of the physiopathological events related to aneurysm formation, they are hemodynamically similar to the situation found in the clinical setting. Therefore, they can be used for research or training purposes, allowing physicians to learn and practice different endovascular techniques in animal models that are close to the human system.

A Fibrin Coating Method of Polypropylene Meshes Enables the Adhesion of Menstrual Blood-Derived Mesenchymal Stromal Cells: A New Delivery Strategy for Stem Cell-Based Therapies.

Polypropylene (PP) mesh is well-known as a gold standard of all prosthetic materials of choice for the reinforcement of soft tissues in case of hernia, organ prolapse, and urinary incontinence. The adverse effects that follow surgical mesh implantation remain an unmet medical challenge. Herein, it is outlined a new approach to allow viability and adhesion of human menstrual blood-derived mesenchymal stromal cells (MenSCs) on PP surgical meshes. A multilayered fibrin coating, based on fibrinogen and thrombin from a commercial fibrin sealant, was optimized to guarantee a homogeneous and stratified film on PP mesh. MenSCs were seeded on the optimized fibrin-coated meshes and their adhesion, viability, phenotype, gene expression, and immunomodulatory capacity were fully evaluated. This coating guaranteed MenSC viability, adhesion and did not trigger any change in their stemness and inflammatory profile. Additionally, MenSCs seeded on fibrin-coated meshes significantly decreased CD4+ and CD8+ T cell proliferation, compared to in vitro stimulated lymphocytes (p < 0.0001). Hence, the proposed fibrin coating for PP surgical meshes may allow the local administration of stromal cells and the reduction of the exacerbated inflammatory response following mesh implantation surgery. Reproducible and easy to adapt to other cell types, this method undoubtedly requires a multidisciplinary and translational approach to be improved for future clinical uses.

IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells.

Mesenchymal stromal cells isolated from menstrual blood (MenSCs) exhibit a potent pro-angiogenic and immunomodulatory capacity. Their therapeutic effect is mediated by paracrine mediators released by their secretomes. In this work, we aimed to evaluate the effect of a specific priming condition on the phenotype and secretome content of MenSCs. Our results revealed that the optimal condition for priming MenSCs was the combination of interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) that produced a synergistic and additive effect on IDO1 release and immune-related molecule expression. The analyses of MenSC-derived secretomes after IFNγ and TNFα priming also revealed an increase in EV release and in the differentially expressed miRNAs involved in the immune response and inflammation. Proliferation assays on lymphocyte subsets demonstrated a decrease in CD4+ T cells and CD8+ T cells co-cultured with secretomes, especially in the lymphocytes co-cultured with secretomes from primed cells. Additionally, the expression of immune checkpoints (PD-1 and CTLA-4) was increased in the CD4+ T cells co-cultured with MenSC-derived secretomes. These findings demonstrate that the combination of IFNγ and TNFα represents an excellent priming strategy to enhance the immunomodulatory capacity of MenSCs. Moreover, the secretome derived from primed MenSCs may be postulated as a therapeutic option for the regulation of adverse inflammatory reactions.

Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy.

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.

Laparoscopic Diagnosis and Treatment of Gossypiboma Postconventional Ovariohysterectomy in a Bitch.

Introduction. Gossypiboma is a rare surgical complication in small animals. The authors reported the laparoscopic diagnosis and treatment of an abdominal gossypiboma and chronic draining fistula postopen ovariohysterectomy (OVH) unresponsive to medical treatment in a bitch. Case Presentation. The patient had undergone OVH and exploratory laparotomy in other veterinary practice 3 years previously. The animal, presenting a chronic fistula, was then referred to UFSM Veterinary Hospital. Ultrasonographic examination revealed a structure compatible with a granuloma. For the laparoscopic procedure, a 3-port (two at 11 mm; one at 6 mm) access was used. Adhesiolysis and mass removal were performed by blunt dissection and bipolar electrocoagulation. The fistula was treated by mobilising the omentum through it. There were no intra- or postoperative complications. The chronic wound showed first intention healing. The mass was composed of fibrous tissues surrounding one surgical gauze. Discussion and Conclusion. The removal of a retained surgical gauze in the abdomen by laparoscopy has already been described in medicine. However, a laparoscopic approach for treating a fistulous draining tract due to a gossypiboma has not been previously reported in dogs. Laparoscopic exploration of the fistula allowed the use of a pedicled omental flap through infected sites to control chronic infection. Laparoscopic surgery can be used to identify and treat abdominal gossypiboma in dogs, including those with chronic abdominal sinus.

Assessment of the Grades of Vesicoureteral Reflux in Stented Ureters: An Experimental Study.

INTRODUCTION: The aim of this experimental study is to assess, in a porcine model, the onset and grades of vesicoureteral reflux associated with ureteral stents. METHODS: Twenty-four female porcine models were used. A 4.7-Fr ureteral stent was placed in all right ureters and kept in place for 6 weeks. Follow-ups were performed on weeks 1, 3, 6, and 12. Ultrasonography, cystoscopy, and fluoroscopy were used to analyze grade of hydronephrosis, presence and grade of vesicoureteral reflux, bacteriuria, and macroscopic changes of the ureteral orifices. Vesicoureteral reflux was classified using a modification of the International Reflux Study Committee grades. RESULTS: 91.7% animals present vesicoureteral reflux, 89.5% grade IA, 3.5% grade IB, and 7% grade II. There is a significant increase in reflux during follow-ups at 3 and 6 weeks, whereas 6 weeks after removal, 26.3% of the ureters still present vesicoureteral reflux. Hydronephrosis and macroscopic changes of the ureteral orifice increase significantly with stenting, but there is no significant association between them and vesicoureteral reflux; the relationship between bacteriuria and the presence of vesicoureteral reflux is not significant either. CONCLUSION: Vesicoureteral reflux caused by ureteral stents in an animal model is mostly low grade and mainly affects the distal ureter.

Comparative Study of the Influence of Three-Dimensional Versus Two-Dimensional Urological Laparoscopy on Surgeons' Surgical Performance and Ergonomics: A Systematic Review and Meta-Analysis.

Objective: The objective of this study is to compare the use of three-dimensional (3D) vision systems with traditional two-dimensional systems in laparoscopic urological surgery, analyzing the benefits, limitations, and impact of introducing this medical technology with regard to surgical performance and the surgeon's ergonomics. Methods: A systematic review with a structured bibliographic search was conducted in the electronic libraries (PubMed and EMBASE) until August 2019 and with no language restrictions. Studies on 3D visualization technology in laparoscopic urologic surgery, randomized controlled trials, and observational comparative studies were included. Relevant data were extracted and analyzed. Results: A total of 25 articles were obtained, of which 4 were clinical studies with patients, 2 studies were carried out in experimental animal models, and the remaining 19 were conducted in simulated environments. Regarding the European training program in basic laparoscopic urological skills, the results showed no significant differences in execution time using either imaging system. Three-dimensional vision led to a significant reduction in surgery time in pyeloplasty and radical nephrectomy. In addition, there was a reported decrease in blood loss in adrenalectomy, nephron-sparing nephrectomy, radical nephrectomy, simple nephrectomy, and pyeloplasty using 3D vision. Regarding ergonomics, the studies generally described no differences in side effects (headache, nausea, eye strain) when comparing the two types of visualization systems. Surgeons reported reduced workloads and stress with 3D vision than with traditional laparoscopy. Conclusions: Three-dimensional laparoscopic systems essentially advance surgical performance in less-experienced laparoscopic surgeons. Three-dimensional laparoscopy leads to improvements in surgery time, which is important for specific surgical procedures involving intracorporeal ligatures and sutures. The results achieved on the surgeons' ergonomics showed better depth perception and decreased stress and workloads during 3D vision with no differences in potential side effects.

Laparoscopy for the Treatment of Congenital Hernia: Use of Surgical Meshes and Mesenchymal Stem Cells in a Clinically Relevant Animal Model.

More than a century has passed since the first surgical mesh for hernia repair was developed, and, to date, this is still the most widely used method despite the great number of complications it poses. The purpose of this study was to combine stem cell therapy and laparoscopy for the treatment of congenital hernia in a swine animal model. Porcine bone marrow-derived mesenchymal stem cells (MSCs) were seeded on polypropylene surgical meshes using a fibrin sealant solution as a vehicle. Meshes with (cell group) or without (control group) MSCs were implanted through laparoscopy in Large White pigs with congenital abdominal hernia after the approximation of hernia borders (implantation day). A successive laparoscopic biopsy of the mesh and its surrounding tissues was performed a week after implantation, and surgical meshes were excised a month after implantation. Ultrasonography was used to measure hernia sizes. Flow cytometry, histological, and gene expression analyses of the biopsy and necropsy samples were performed. The fibrin sealant solution was easy to prepare and preserved the viability of MSCs in the surgical meshes. Ultrasonography demonstrated a significant reduction in hernia size 1 week after implantation in the cell group relative to that on the day of implantation (p < 0.05). Flow cytometry of the mesh-infiltrated cells showed a non-significant increase of M2 macrophages when the cell group was compared with the control group 1 week after implantation. A significant decrease in the gene expression of VEGF and a significant increase in TNF expression were determined in the cell group 1 month after implantation compared with gene expressions in the control group (p < 0.05). Here, we propose an easy and feasible method to combine stem cell therapy and minimally invasive surgical techniques for hernia repair. In this study, stem cell therapy did not show a great immunomodulatory or regenerative effect in overcoming hernia-related complications. However, our clinically relevant animal model with congenital hernia closely resembles the clinical human condition. Further studies should be focused on this valuable animal model to evaluate stem cell therapies in hernia surgery.

Clinical predictive factors in prostatic artery embolization for symptomatic benign prostatic hyperplasia: a comprehensive review.

Prostatic artery embolization (PAE) has been established as a routine treatment for symptomatic benign prostatic hyperplasia (BPH) all over the world. With increasing clinical experience in the last decade, investigators have sufficient data to assess predictive factors with the purpose to guide patient selection and counseling for PAE or to individualize therapeutic plans after PAE. This paper is a comprehensive review to introduce the concept of clinical predictors and give a systemic classification of various predictive factors in PAE. The authors review each individual factor and its predictive capability and discuss the possible reasons for the inconsistent or conflicting findings in the literature. Based on current evidence, the baseline prostate volume, in particular the transition zone volume and transition zone index; 24 h post-PAE prostate-specific antigen (PSA) level; and prostate infarction and prostate volume reduction at 1-3 months have potential in prediction of treatment outcomes. Patients with Adenomatous-dominant BPH or with indwelling bladder catheter before PAE may have more benefits from PAE. Baseline intravesical prostatic protrusion (IPP), C-reactive protein (CRP) level at 48 h and early detection of prostate infarct at 1 day and 1 week after PAE need further investigating.

A Pre-clinical Rat Model for the Study of Ischemia-reperfusion Injury in Reconstructive Microsurgery.

Ischemia-reperfusion injury is the main cause of flap failure in reconstructive microsurgery. The rat is the preferred preclinical animal model in many areas of biomedical research due to its cost-effectiveness and its translation to humans. This protocol describes a method to create a preclinical free skin flap model in rats with ischemia-reperfusion injury. The described 3 cm x 6 cm rat free skin flap model is easily obtained after the placement of several vascular ligatures and the section of the vascular pedicle. Then, 8 h after the ischemic insult and completion of the microsurgical anastomosis, the free skin flap develops the tissue damage. These ischemia-reperfusion injury-related damages can be studied in this model, making it a suitable model for evaluating therapeutic agents to address this pathophysiological process. Furthermore, two main monitoring techniques are described in the protocol for the assessment of this animal model: transit-time ultrasound technology and laser speckle contrast analysis.

[Validity studies in laparoscopic simulation. Methodology and design considerations.] / Validación en simulación laparoscópica. Consideraciones metodológicas y de diseño.

OBJECTIVES: To describe a roadmap of the most representative milestones and considerations in the validation of surgical simulators, especially those of laparoscopic surgery. And additionally, help determine when in this process a simulator can be considered as validated. METHODS: A non-systematic review was carried out searching terms like simulation, validation, training, assessment, skills and learning curve, as well as providing the experience accumulated by our center. RESULTS: An ideal classical validation process should consist of the following steps: fidelity, verification/calibration/ reliability, subjective and objective strategies. Baseline tests of fidelity and verification/calibration/ technological reliability are not always detailed in the simulation literature. A simulator can be considered validated if, at least, satisfactorily completed any of the two main objective strategies, that is, constructive and/or criterion validity. CONCLUSIONS: The methodologies to validate simulators as useful and reliable for the improvement of psychomotor/ technical skills are widely analyzed, although there is a variety of approaches depending on the scientific reference consulted, not being implemented equally in all works. This apparent arbitrariness should be considered in advance because it can lead the researcher to misunderstandings, especially when the simulator will be regarded as valid.

OBJETIVOS: Describir una hoja de ruta de los hitos y consideraciones más representativos en la validación de simuladores quirúrgicos, especialmente los de cirugía laparoscópica. Y adicionalmente contribuir a determinar en qué momento de este proceso puede considerarse un simulador como validado.MÉTODOS: Se realizó una revisión no sistemática con los términos simulación, validación, formación, entrenamiento, evaluación, habilidades y curva de aprendizaje, además de aportar la experiencia acumulada por nuestro centro. RESULTADOS: Un proceso ideal clásico de validación debería constar de los siguientes pasos: Fidelidad, Verificación/ Calibración/Fiabilidad, estrategias subjetivas y objetivas. Las pruebas de inicio tanto de Fidelidad como de Verificación/Calibración/Fiabilidad tecnológica no siempre están descritas de manera explícita en los trabajos de validación de simuladores. Un simulador puede considerarse validado si al menos ha completado satisfactoriamente una validación de cualquiera de los dos grandes bloques de tipo objetivo, es decir, constructiva y/o de criterio. CONCLUSIONES: Los métodos que permiten validar simuladores como útiles y fiables para la mejora de habilidades de tipo psicomotor/técnico están ampliamente documentados aunque existe cierta variedad de enfoques en función de la referencia científica que se consulte, no aplicándose por igual en todos los trabajos. Esta aparente arbitrariedad debería ser conocida de antemano porque puede llevar al investigador a ciertos equívocos, especialmente a la hora de afirmar cuándo el simulador se considera plenamente validado.

Laparoscopic uterine graft procurement and surgical autotransplantation in ovine model.

Currently, uterus transplantation (UTx) is a clinical option for infertile women. Over the past three decades, treating benign or malignant gynecological diseases with minimally invasive gynecological surgery has improved, providing significant advantages over conventional open surgery. This study addresses the method used for laparoscopic live-donor ovariohysterectomy and graft harvest from a sheep model. Using a microsurgical practice, ten grafts were autotransplanted after uterine perfusion. End-to-end anastomosis techniques were used to approximate veins and arteries. Follow-ups were carried out 2-months after surgery and postoperative studies included ultrasound scan, diagnostic hysteroscopy, vascular angiography, and exploratory laparoscopy. All transplants were completed without complications. After vascular anastomosis, total reperfusion of the tissue was accomplished in all animals without confirmation of arterial or venous thrombosis. Angiographic explorations did not show any statistically significant dissimilarity in the arterial diameters between the different examination times. 3-months after uterine transplantation all animals underwent assisted reproduction techniques. Patent uterine arteries were observed 4, 8 and 12 months after the transplant. 6-months after transplantation, six sheep (60%) became pregnant with assisted reproduction practices. We noticed an increase in the degree of fibrosis of the cervix samples in non-pregnant animals of the transplant group. Laparoscopic surgery can be an advantageous approach for the uterus retrieval procedure during uterine transplantation. However, larger sample sized reports are needed in order to accomplish validation, standardization and wider use of this route.