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Recurrent anal fistulae:Limited surgery supported by stem cells

World Journal of Gastroenterology 2015年第11期21卷 3330-3336页

作者： Damian garcia-Olmo Hector Guadalajara Ines Rubio-Perez Maria Dolores Herreros Paloma de-la-Quintana mariano garcia-arranz Hospital Fundación Jimenez Díaz Colorectal Surgery Unit University Hospital Fundación Jiménez Díaz Colorectal Surgery Unit La Paz University Hospital Cell Therapy Laboratory University Hospital Fundación Jiménez Díaz

AIM:To study the results of stem-cell therapy under a Compassionate-use Program for patients with recurrent anal ***:Under controlled circumstances,and approved by European and Spanish laws,a Compassionate-use Program allows the use of stem-cell therapy for patients with very complex anal *** had previously undergone multiple surgical interventions that had failed to resolve the fistulae,and presented symptomatic *** intervention consisted of limited surgery(with closure of the internal opening),followed by local implant of stem cells in the fistula-tract *** expanded adipose-derived stem cells were the main cell type selected for *** first evaluation was performed on the 8th postoperative week;outcome was classified as response or partial *** one year after the intervention confirmed if complete healing of the fistula was ***:Ten patients(8 male)with highly recurrent and complex fistulae were treated(mean age:49years,range:28-76 years).Seven cases were nonCrohn’s fistulae,and three were Crohn’s-associated *** surgical attempts ranged from 3to *** patients presented with preoperative incontinence(Wexner scores of 12 and 13 points).After the intervention,six patients showed clinical response on the 8th postoperative week,with a complete cessation of suppuration from the *** patients presented a partial response,with an evident decrease in suppuration.A year later,six patients(60%)remained healed,with complete reepithelization of the external *** Wexner Scores were 0 in six *** two patients with previous incontinence improved their scores from12 to 8 points and from 13 to 5 *** adverse reactions or complications related to stem-cell therapy were reported during the study ***:Stem cells are safe and useful for treating anal *** can be achieved in severe cases,sparing fecal incontinence risk,and impr

关键词： Adipose-derived stem cells Cell therapy Compassion

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Stem cell therapy for faecal incontinence: Current state and future perspectives

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World Journal of Stem Cells 2018年第7期10卷 82-105页

作者： Jacobo Trébol Ana Carabias-Orgaz mariano García-arranz Damián García-Olmo General and Digestive Tract Surgery Department Salamanca University Healthcare Centre Anaesthesiology Department Complejo Asistencial de ávila New Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez Díaz General and Digestive Tract Surgery Department Quiron-Salud Hospitals Surgery Department Universidad AutónomaMadrid

Faecal continence is a complex function involving different organs and systems. Faecal incontinence is a common disorder with different pathogeneses, disabling consequences and high repercussions for quality of life. Current management modalities are not ideal, and the development of new treatments is needed. Since 2008, stem cell therapies have been validated, 36 publications have appeared(29 in preclinical models and seven in clinical settings), and six registered clinical trials are currently ongoing. Some publications have combined stem cells with bioengineering technologies. The aim of this review is to identify and summarise the existing published knowledge of stem cell utilization as a treatment for faecal incontinence. A narrative or descriptive review is presented. Preclinical studies have demonstrated that cellular therapy, mainly in the form of local injections of muscle-derived(muscle derived stem cells or myoblasts derived from them) or mesenchymal(bone-marrow-or adipose-derived) stem cells, is safe. Cellular therapy has also been shown to stimulate the repair of both acute and subacute anal sphincter injuries, and some encouraging functional results have been obtained. Stem cells combined with normal cells on bioengineered scaffolds have achieved the successful creation and implantation of intrinsically-innervated anal sphincter constructs. The clinical evidence, based on adipose-derived stem cells and myoblasts, is extremely limited yet has yielded some promising results, and appears to be safe. Further investigation in both animal models and clinical settings is necessary to drawing conclusions. Nevertheless, if the preliminary results are confirmed, stem cell therapy for faecal incontinence may well become a clinical reality in the near future.

关键词： Faecal incontinence Anal sphincter Cell implantation Tissue engineering Cell therapy Stem cells

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Navigating medial patellotibial ligament reconstruction:Clinical perspectives and surgical strategies

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World Journal of Clinical Cases 2025年第1期13卷 6-10页

作者： Juan Pablo Zicaro Ignacio garcia-Mansilla Division of Knee Hospital Italiano de Buenos AiresBuenos Aires 1109Argentina

The surgical approach for patellar instability usually refers to reconstruction of the medial patellofemoral ligament associated with an osteotomy of the tibial tuberosity or a trochleoplasty when *** medial patellotibial ligament and the medial patellomeniscal ligament are secondary stabilizers of the *** this,both the medial patellotibial and patellofemoral ligaments aid in patellar rotation and tilt when the knee is flexed beyond 45°.The medial patellotibial ligament plays a particularly important role in the final stages of stretching in extension and between 40 degrees to 90 degrees of *** clinical relevance and surgical indications for medial patellotibial ligament reconstruction associated with medial patellofemoral ligament reconstruction are still *** editorial explores the surgical indications and clinical results for medial patellotibial ligament reconstruction to improve readers’understanding of this technique,especially because reported clinical outcomes have remained sparse.

关键词： Medial patellotibial ligament Patellar instability Reconstruction Surgical

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Challenges and improvement strategies in the hospitalization of chronic multimorbid patients

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World Journal of Clinical Cases 2025年第3期13卷 35-41页

作者： Andres Fontalba-Navas Francisco Pozo Muñoz Rogelio garcia Cisneros Maria Jose garcia Larrosa Maria del Mar Callejon Gil Ignacio garcia Delgado Maria Belen Jimenez Martinez Antequera Hospital Northern Málaga Integrated Healthcare AreaAntequera 29200AndalusiaSpain Department of Public Health and Psychiatry University of MálagaMálaga 29010Spain Antequera Hospital Northern Málaga Antequera Integrated Healthcare AreaAntequera 29200MálagaSpain

BACKGROUND Addressing the growing challenge of hospitalizing chronic multimorbid patients,this study examines the strain these conditions impose on healthcare systems at a local level,focusing on a pilot *** diseases and complex patients require comprehensive management strategies to reduce healthcare burdens and improve patient *** proven effective,this pilot model has the potential to be replicated in other healthcare settings to enhance the management of chronic multimorbid *** To evaluate the effectiveness of the high complexity unit(HCU)in managing chronic multimorbid patients through a multidisciplinary care model and to compare it with standard hospital *** The study employed a descriptive longitudinal approach,analyzing data from the Basic Minimum Data Set(BMDS)to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout *** HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity *** The study employed a descriptive longitudinal approach,analyzing data from the BMDS to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout *** HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity *** This study demonstrates the effectiveness of the HCU in managing patients with complex chronic diseases through a multidisciplinary *** coordinated care provided by the HCU results in improved patient outcomes,reduced unnecessary hospitalizations,and better management of patient *** superiority of the HCU compared to standard care is evident in key outcomes such as fewer readmissions and higher patient satisfaction,reinforcing its value as a model of ca

关键词： High complexity unit Chronic multimorbidity Patient-centered care Integrated care Healthcare management

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Epithelial-mesenchymal transition in prostate cancer： providing new targets for therapy

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Asian Journal of Andrology 2011年第2期13卷 179-180页

作者： Andrew J Armstrong Stephen，Freedland mariano garcia-Blanco Duke Cancer Institute Departments of Medicine and Surgery Duke Prostate Center Duke University Durham NC 27710 USA Section of Urology Durham VA Medical Center Duke Prostate Center Division of Urologic Surgery Departments of Surgery and Pathology Duke University Medical Center Durham NC 27710 USA Department of Molecular Genetics and Microbiology Department ol Medicine Center for RNA Biology Duke Universit＇ Medical Center NC 27710 USA

The ability of epithelial cells to undergo phenotypic transitions during embryo-genesis, wound healing and malignant pro- gression is now widely accepted as a core biological process termed epithelialmesenchymal transition （EMT）. During cancer progression, the process of EMT has been associated with the acquisition of stemness properties, treatment resistance and metastatic progression, hallmarks of malig- nancy.

关键词： Cells Lymphocytes Associations Cancer (genus) Neoplasms Processing Models Crossing over Proteins Castration

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Stem cell therapy applied for digestive anastomosis: Current state and future perspectives

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World Journal of Stem Cells 2022年第1期14卷 117-141页

作者： Jacobo Trébol Tihomir Georgiev-Hristov Isabel Pascual-Miguelañez Hector Guadalajara mariano García-arranz Damian García-Olmo Servicio de Cirugía General y del Aparato Digestivo Complejo Asistencial Universitario de SalamancaSalamanca 37007Spain Departamento de Anatomía e Histología Humanas Universidad de SalamancaSalamanca 37007Spain Servicio de Cirugía General y del Aparato Digestivo Hospital General Universitario de VillalbaMadrid 28400Spain Servicio de Cirugía General y del Aparato Digestivo Hospital Universitario La PazMadrid 28046Spain Servicio de Cirugía General y del Aparato Digestivo Hospital Universitario Fundación Jiménez DíazMadrid 28040Spain Grupo de Investigación en Nuevas Terapias Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain Damian García-Olmo Departamento de CirugíaUniversidad Autónoma de MadridMadrid 28029Spain Servicio de Cirugía General y del Aparato Digestivo Hospital Universitario Fundación Jiménez Díaz y Grupo Quiron-Salud MadridMadrid 28040Spain

BACKGROUND Digestive tract resections are usually followed by an *** leakage,normally due to failed healing,is the most feared complication in digestive surgery because it is associated with high morbidity and *** technical and technological advances and focused research,its rates have remained almost unchanged the last *** the last two decades,stem cells(SCs)have been shown to enhance healing in animal and human studies;hence,SCs have emerged since 2008 as an alternative to improve anastomoses *** To summarise the published knowledge of SC utilisation as a preventative tool for hollow digestive viscera anastomotic or suture *** PubMed,Science Direct,Scopus and Cochrane searches were performed using the key words“anastomosis”,“colorectal/colonic anastomoses”,“anastomotic leak”,“stem cells”,“progenitor cells”,“cellular therapy”and“cell therapy”in order to identify relevant articles published in English and Spanish during the years of 2000 to *** employing SCs,performing digestive anastomoses in hollow viscera or digestive perforation sutures and monitoring healing were finally *** lists from the selected articles were reviewed to identify additional pertinent *** Given the great variability in the study designs,anastomotic models,interventions(SCs,doses and vehicles)and outcome measures,performing a reliable meta-analysis was considered impossible,so we present the studies,their results and *** Eighteen preclinical studies and three review papers were identified;no clinical studies have been published and there are no registered clinical *** studies,mainly in rat and porcine models and occasionally in very adverse conditions such as ischaemia or colitis,have been demonstrated SCs as safe and have shown some encouraging morphological,functional and even clinical *** SCs are mostly employed,and delivery routes are mainly local

关键词： Surgical anastomosis Anastomotic leak Digestive system surgical procedure Cell transplantation Cell therapy Stem cells Tissue engineering

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A universal additive concept yields record-high efficient organic solar cells

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Science China Materials 2024年第5期67卷 1670-1671页

作者： mariano Campoy Quiles Institute of Materials Science of Barcelona ICMAB-CSICCampus UAB08193BellaterraSpain

Organic photovoltaics(OPVs)are an emerging light-to-electricity conversion technology that promises flexible,lightweight,semitransparent devices based on abundant and non-toxic organic *** power conversion efficiency under one sun has been increasing at an average pace of approximately 1%every year over the past 10 years,up to current values circa 20%.This has been possible through the continuous synthesis of improved semiconductors.

关键词： additive semiconductors approximate

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Artificial versus Natural Reuse of CO2 for DME Production：Are We Any Closer？

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Engineering 2017年第2期3卷 166-170页

作者： mariano Martin Department of Chemical Engineering University of Salamanca Salamanca 37008 Spain

This work uses a mathematical optimization approach to analyze and compare facilities that either capturecarbon dioxide （CO2） artificially or use naturally captured COs in the form of lignocellulosic biomass towardthe production of the same product, dimethyl ether （DME）. In nature, plants capture COs via photosynthesisin order to grow. The design of the first process discussed here is based on a superstructure optimizationapproach in order to select technologies that transform lignocellulosic biomass into DME. Biomass is gas-ified; next, the raw syngas must be purified using reforming, scrubbing, and carbon capture technologiesbefore it can be used to directly produce DME. Alternatively, CO2 can be captured and used to produce DMEvia hydrogenation. Hydrogen （H2） is produced by splitting water using solar energy. Facilities based on bothphotovoltaic （PV） solar or concentrated solar power （CSP） technologies have been designed; their monthlyoperation, which is based on solar availability, is determined using a multi-period approach. The currentlevel of technological development gives biomass an advantage as a carbon capture technology, since bothwater consumption and economic parameters are in its favor. However, due to the area required for growingbiomass and the total amount of water consumed （if plant growing is also accounted for）, the decision to use biomass is not a straightforward one.

关键词： Solar energy Photovoltaic Concentrated solar power Biomass Water electrolysis Dimethyl ether

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Rat model of anal sphincter injury and two approaches for stem cell administration

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World Journal of Stem Cells 2018年第1期10卷 1-14页

作者： Jacobo Trébol Tihomir Georgiev-Hristov Luz Vega-Clemente Ignacio García-Gómez Ana Carabias-Orgaz mariano García-arranz Damián García-Olmo Department of General and Digestive Tract Surgery University Hospital“La Paz”Madrid 28046Spain Department of General and Digestive Tract Surgery Villalba General HospitalMadrid 28400Spain New Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain Hektoen Institute of Medicine ChicagoIL 60612United States Department of Anaesthesiology Complejo Asistencial deávilaávila 05004Spain New Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain Department of General and Digestive Tract Surgery Quiron-Salud HospitalsMadrid 28040Spain Department of Surgery Madrid Autonomous UniversityMadrid 28029Spain

AIM To establish a rat model of anal sphincter injury and test different systems to provide stem cells to injured *** Adipose-derived stem cells(ASCs) were isolated from BDIX rats and were transfected with green fluorescent protein(GFP) for cell tracking. Biosutures(sutures covered with ASCs) were prepared with 1.5 × 10~6 GFPASCs, and solutions of 10~6 GFP-ASCs in normal saline were prepared for injection. Anorectal normal anatomy was studied on Wistar and BDIX female rats. Then, we designed an anal sphincter injury model consisting of a 1-cm extra-mucosal miotomy beginning at the anal verge in the anterior middle line. The sphincter lesion was confirmed with conventional histology(hematoxylin and eosin) and immunofluorescence with 4', 6-diamidino-2-phenylindole(commonly known as DAPI), GFP and α-actin. Functional effect was assessed with basal anal manometry, prior to and after injury. After sphincter damage, 36 BDIX rats were randomized to three groups for:(1) Cell injection without repair;(2) biosuture repair; and(3) conventional suture repair and cell injection. Functional and safety studies were conducted on all the animals. Rats were sacrificed after 1, 4 or 7 d. Then, histological and immunofluorescence studies were performed on the surgical *** With the described protocol, biosutures had been covered with at least 820000-860000 ASCs, with 100% viability. Our studies demonstrated that some ASCs remained adhered after suture passage through the muscle. Morphological assessment showed that the rat anal anatomy is comparable with human anatomy; two sphincters are present, but the external sphincter is poorly developed. Anal sphincter pressure data showed spontaneous, consistent, rhythmic anal contractions, taking the form of "plateaus" with multiple twitches(peaks) in each pressure wave. These basal contractions were very heterogeneous; their frequency was 0.91-4.17 per min(mean 1.6980, SD 0.57698), their mean duration was 26.67 s and mean numb

关键词： Fecal incontinence Experimental rat model Anal sphincter Cell implantation Cell therapy Stem cells Mesenchymal stem cell

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Stem cell therapy in the management of shoulder rotator cuff disorders

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World Journal of Stem Cells 2015年第4期7卷 691-699页

作者： Maria Valencia Mora Miguel A Ruiz Ibán Jorge Díaz Heredia Raul Barco Laakso Ricardo Cuéllar mariano García arranz Unidad de Hombro y Codo Hospital Universitario Ramón y Cajal Hospital Universitario La Paz Departamento de Traumatología y Cirugía Ortopédica Hospital Universitario Donostia Instituto de Investigación Sanitaria Fundación Jiménez Diaz Departamento de Cirugía Universidad Autónoma de Madrid

Rotator cuff tears are frequent shoulder problems that are usually dealt with surgical repair. Despite improved surgical techniques, the tendon-to-bone healing rate is unsatisfactory due to difficulties in restoring the delicate transitional tissue between bone and tendon. It is essential to understand the molecular mechanisms that determine this failure. The study of the molecular environment during embryogenesis and during normal healing after injury is key in devising strategies to get a successful repair. Mesenchymal stem cells(MSC) can differentiate into different mesodermal tissues and have a strong paracrine, anti-inflammatory, immunoregulatory and angiogenic potential. Stem cell therapy is thus a potentially effective therapy to enhance rotator cuff healing. Promising results have been reported with the use of autologous MSC of different origins in animal studies: they have shown to have better healing properties, increasing the amount of fibrocartilage formation and improving the orientation of fibrocartilage fibers with less immunologic response and reduced lymphocyte infiltration. All these changes lead to an increase in biomechanical strength. However, animal research is still inconclusive and more experimental studies are needed before human application. Future directions include expanded stem cell therapy in combination with growth factors or different scaffolds as well as new stem cell types and gene therapy.

关键词： Rotator cuff Enthesis Biologic Stem cells

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