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1.
Arthroscopy ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38897483

RESUMEN

PURPOSE: The purpose of this study is to evaluate the utility of meniscus allografts in combination with other procedures to delay knee arthroplasty in patients older than 50 years of age previously advised joint arthroplasty. METHODS: One hundred eight meniscus allograft transplants (MATs) using the arthroscopic three tunnel technique between 1997 and 2019 in patients over 50 years of age were retrospectively reviewed with two-year minimum follow-up period. Inclusion criteria were patients recommended knee arthroplasty with pain and preservation of some joint space by standing flexion x-rays. Exclusion criteria were lack of joint space, failure to comply with rehabilitation protocol or complete research questionnaires. International Knee Documentation Committee (IKDC) composite and isolated pain scale were evaluated longitudinally. Time from MAT to arthroplasty was measured with failure defined as allograft excision or revision, progression to arthroplasty, or same or increased pain. RESULTS: Eighty-six of 108 (79.6%) patients met eligibility criteria. Over the follow-up mean 8.55 (range of 0.68 to 25.2) years, 42 of 87 (48.2%) grafts progressed to arthroplasty with mean time of 8.64 (median 8.05) years. Concomitant procedures did not have significant impact on survival; however, survival medians were higher among paste graft and chondroplasty and lower among osteotomy groups. At the time of reporting, 41 of 84 (48.8%) patients had intact meniscus transplants, demonstrating significant improvements (p<0.001) in pain and function as assessed by IKDC. These improvements were sustained ten years post-operatively, correlated to a mean of 65.8 years of age. At least 50% of patients achieved Minimal Clinically Important Difference (MCID) through 10 years post-operatively. CONCLUSIONS: Meniscus allografts in combination with other arthroscopic interventions delay knee arthroplasty and improve knee symptoms of pain and function in a population of knee arthroplasty candidates over 50 years of age. Influences of concomitant procedures cannot be defined.

2.
Nucleic Acids Res ; 45(D1): D730-D736, 2017 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-27899677

RESUMEN

The Gene Expression Database (GXD; www.informatics.jax.org/expression.shtml) is an extensive and well-curated community resource of mouse developmental expression information. Through curation of the scientific literature and by collaborations with large-scale expression projects, GXD collects and integrates data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot and western blot experiments. Expression data from both wild-type and mutant mice are included. The expression data are combined with genetic and phenotypic data in Mouse Genome Informatics (MGI) and made readily accessible to many types of database searches. At present, GXD includes over 1.5 million expression results and more than 300 000 images, all annotated with detailed and standardized metadata. Since our last report in 2014, we have added a large amount of data, we have enhanced data and database infrastructure, and we have implemented many new search and display features. Interface enhancements include: a new Mouse Developmental Anatomy Browser; interactive tissue-by-developmental stage and tissue-by-gene matrix views; capabilities to filter and sort expression data summaries; a batch search utility; gene-based expression overviews; and links to expression data from other species.


Asunto(s)
Biología Computacional/métodos , Bases de Datos Genéticas , Perfilación de la Expresión Génica/métodos , Expresión Génica , Genómica/métodos , Animales , Ontología de Genes , Ratones , Especificidad de Órganos , Motor de Búsqueda , Interfaz Usuario-Computador , Navegador Web
3.
Arthroscopy ; 34(6): 1948-1949, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29804613

RESUMEN

The C-shaped meniscus cartilages normally insert into bone around the tibial spines of the knee. As the knee joint rotates and flexes, circumferential hoop stresses are generated within the tissue, resisted by the collagen fibers that define both the insertion points and the ultrastructure of the meniscus tissue itself. For a transplanted meniscus to work normally, the biomechanical interface of the collagen fibers to the bone must be recreated.


Asunto(s)
Articulación de la Rodilla , Meniscos Tibiales/cirugía , Aloinjertos , Análisis por Apareamiento , Técnicas de Sutura
4.
Knee Surg Sports Traumatol Arthrosc ; 25(12): 3824-3833, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27695904

RESUMEN

PURPOSE: The purpose of this study is to evaluate the clinical outcomes of the articular cartilage paste graft procedure at a minimum of 10 years from surgery. It is hypothesized that articular cartilage paste grafting can provide patients with a durable repair of severe full-thickness osteochondral injuries, measured by persistence of procedure-induced benefit and subjective outcome scores at 10 or more years. METHODS: Seventy-four patients undergoing paste grafting at a mean age of 45.3 ± 10.8 years (range 13-69 years) were followed up at a mean of 16.8 ± 2.4 years (range 10.6-23.2 years) post-operatively using validated subjective outcome measures; Kaplan-Meier survival analysis was performed to estimate expected population benefit time. RESULTS: Kaplan-Meier estimated median benefit time of 19.1 years (mean: 16.6 ± 0.9 years) for all patients undergoing paste grafting. Thirty-one (41.9 %) patients had progressed to arthroplasty at a mean of 9.8 ± 5.6 years (range 0.4-20.6 years). Ninety percent of patients reported that the procedure provided good to excellent pain relief. Median IKDC subjective score increased significantly at most recent follow-up (70.1) compared to preoperative (55.7, p = 0.013). Median WOMAC scores decreased significantly from 26 to 14 (p = 0.001). Median Tegner score increase from 4 to 6 was not found to be significant (ns). VAS pain averaged 23/100 at most recent follow-up. CONCLUSIONS: Patients who underwent the paste grafting reported improved pain, function, and activity levels for an expected mean of 16.6 years, and for those who ultimately progressed to knee replacement, surgical treatment including the paste graft was able to delay arthroplasty until a mean age of 60.2 years, an age at which the procedure is commonly performed. Full-thickness articular cartilage loss can be successfully treated, reducing pain, and improving function, using this single-step, inexpensive arthroscopic procedure. LEVEL OF EVIDENCE: IV.


Asunto(s)
Artroscopía , Cartílago Articular/cirugía , Articulación de la Rodilla/cirugía , Trasplantes , Resultado del Tratamiento , Adolescente , Adulto , Anciano , Cartílago/trasplante , Femenino , Estudios de Seguimiento , Humanos , Fracturas Intraarticulares/patología , Masculino , Persona de Mediana Edad , Osteoartritis/cirugía , Manejo del Dolor , Dimensión del Dolor , Periodo Posoperatorio , Trasplante Autólogo , Adulto Joven
5.
Nucleic Acids Res ; 42(Database issue): D818-24, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24163257

RESUMEN

The Gene Expression Database (GXD; http://www.informatics.jax.org/expression.shtml) is an extensive and well-curated community resource of mouse developmental expression information. GXD collects different types of expression data from studies of wild-type and mutant mice, covering all developmental stages and including data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot and western blot experiments. The data are acquired from the scientific literature and from researchers, including groups doing large-scale expression studies. Integration with the other data in Mouse Genome Informatics (MGI) and interconnections with other databases places GXD's gene expression information in the larger biological and biomedical context. Since the last report, the utility of GXD has been greatly enhanced by the addition of new data and by the implementation of more powerful and versatile search and display features. Web interface enhancements include the capability to search for expression data for genes associated with specific phenotypes and/or human diseases; new, more interactive data summaries; easy downloading of data; direct searches of expression images via associated metadata; and new displays that combine image data and their associated annotations. At present, GXD includes >1.4 million expression results and 250,000 images that are accessible to our search tools.


Asunto(s)
Bases de Datos Genéticas , Expresión Génica , Ratones/genética , Animales , Internet , Interfaz Usuario-Computador
6.
Knee Surg Sports Traumatol Arthrosc ; 23(1): 251-7, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25253235

RESUMEN

PURPOSE: The purpose of this study was to evaluate the efficacy of meniscus allograft transplantation in an active patient population with moderate to severe cartilage damage and the procedure's ability to allow sports participation postoperatively. METHODS: Forty-nine patients with moderate to severe cartilage damage who underwent meniscus allograft transplantation were included in this study; those with symptoms related to articular cartilage damage also underwent articular cartilage repair. Kaplan-Meier (KM) survival estimate, potential hazards to survival, and subjective clinical outcomes were analyzed. For KM survival, failure was defined as progression to knee arthroplasty, surgical removal of the meniscus transplant without revision, a self-reported follow-up pain level that was more than preoperative level, or constant moderate pain with no relief from non-operative treatment. RESULTS: The mean follow-up time was 8.6 ± 4.2 years. The mean age at surgery was 45.3 ± 12.9 years. Meniscus transplantation was performed in 37 medial cases and 12 lateral cases. There were 41 patients with Outerbridge Grade IV and 8 with Grade III. Thirty-six (73.5%) patients were able to participate in sporting activities postoperatively. Eleven (22.4%) meniscus transplants failed at an average of 5.2 ± 4.4 years. The KM mean estimated survival time was 12.6 ± 0.7 years. No tested risks were found to affect sports participation or procedure success. CONCLUSIONS: Meniscus transplantation is a viable surgical option for patients with severe cartilage damage and missing or irreparable menisci to provide significant improvements in pain and function levels in the medium to long term with the majority of patients achieving their goal of participation in sporting activities. These results indicate that symptomatic patients may be able to participate in sports activities for an average of 12.6 years following meniscus transplantation. LEVEL OF EVIDENCE: Case series, Level IV.


Asunto(s)
Enfermedades de los Cartílagos/cirugía , Cartílago Articular/cirugía , Traumatismos de la Rodilla/cirugía , Meniscos Tibiales/trasplante , Adulto , Cartílago/trasplante , Cartílago Articular/lesiones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Deportes , Trasplante Homólogo
7.
Nucleic Acids Res ; 39(Database issue): D849-55, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20929875

RESUMEN

The International Knockout Mouse Consortium (IKMC) aims to mutate all protein-coding genes in the mouse using a combination of gene targeting and gene trapping in mouse embryonic stem (ES) cells and to make the generated resources readily available to the research community. The IKMC database and web portal (www.knockoutmouse.org) serves as the central public web site for IKMC data and facilitates the coordination and prioritization of work within the consortium. Researchers can access up-to-date information on IKMC knockout vectors, ES cells and mice for specific genes, and follow links to the respective repositories from which corresponding IKMC products can be ordered. Researchers can also use the web site to nominate genes for targeting, or to indicate that targeting of a gene should receive high priority. The IKMC database provides data to, and features extensive interconnections with, other community databases.


Asunto(s)
Bases de Datos Genéticas , Ratones Noqueados , Alelos , Animales , Marcación de Gen , Vectores Genéticos , Genómica , Internet , Ratones , Anotación de Secuencia Molecular , Interfaz Usuario-Computador
8.
J Exp Orthop ; 10(1): 91, 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37672199

RESUMEN

PURPOSE: ACL reconstruction has a significant failure rate. To address the need for inexpensive strong tissue, a treatment process to "humanize" porcine tissue was developed and tested in primates and humans. This report describes the long-term outcomes from the first human clinical trial using a porcine xenograft ACL reconstruction device. METHODS: The study was performed with Z-Lig™ xenograft ACL device in 2003 as a pilot clinical feasibility study. This device was processed to slow its immune-mediated destruction by enzymatic elimination of α-gal epitopes and by partial crosslinking to slow the infiltration of macrophages into the biotransplant. RESULTS: Ten patients underwent reconstruction with the Z-Lig™ device. Five of 10 patients failed due to subsequent trauma (n = 3), arthrofibrosis (n = 1), and surgical technical error (n = 1). One patient was lost to follow-up after the 12-year evaluation. Each remaining patient reported a stable fully athletic knee. Physical exams are consistent with a score of less than one on the ACL stability tests. MRIs demonstrate mature remodeling of the device. There is no significant degradation in patient-reported outcome scores, physical exams, or MRI appearance from 12 to 20-year follow-ups. CONCLUSIONS: The studies in a small group of patients have demonstrated that implantation of porcine ligament bioprosthesis into patients with torn ACLs can result in the reconstruction of the bioprosthesis into autologous ACL that remains successful over 20 years. The possibility of humanizing porcine tissue opens the door to unlimited clinical material for tissue reconstructions if supported by additional clinical trials. LEVEL OF EVIDENCE: IV, case series.

9.
Bioengineering (Basel) ; 8(1)2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33445522

RESUMEN

This review describes the first studies on successful conversion of porcine soft-tissue bioprostheses into viable permanently functional tissue in humans. This process includes gradual degradation of the porcine tissue, with concomitant neo-vascularization and reconstruction of the implanted bioprosthesis with human cells and extracellular matrix. Such a reconstruction process is referred to in this review as "humanization". Humanization was achieved with porcine bone-patellar-tendon-bone (BTB), replacing torn anterior-cruciate-ligament (ACL) in patients. In addition to its possible use in orthopedic surgery, it is suggested that this humanization method should be studied as a possible mechanism for converting implanted porcine bioprosthetic heart-valves (BHV) into viable tissue valves in young patients. Presently, these patients are only implanted with mechanical heart-valves, which require constant anticoagulation therapy. The processing of porcine bioprostheses, which enables humanization, includes elimination of α-gal epitopes and partial (incomplete) crosslinking with glutaraldehyde. Studies on implantation of porcine BTB bioprostheses indicated that enzymatic elimination of α-gal epitopes prevents subsequent accelerated destruction of implanted tissues by the natural anti-Gal antibody, whereas the partial crosslinking by glutaraldehyde molecules results in their function as "speed bumps" that slow the infiltration of macrophages. Anti-non gal antibodies produced against porcine antigens in implanted bioprostheses recruit macrophages, which infiltrate at a pace that enables slow degradation of the porcine tissue, neo-vascularization, and infiltration of fibroblasts. These fibroblasts align with the porcine collagen-fibers scaffold, secrete their collagen-fibers and other extracellular-matrix (ECM) components, and gradually replace porcine tissues degraded by macrophages with autologous functional viable tissue. Porcine BTB implanted in patients completes humanization into autologous ACL within ~2 years. The similarities in cells and ECM comprising heart-valves and tendons, raises the possibility that porcine BHV undergoing a similar processing, may also undergo humanization, resulting in formation of an autologous, viable, permanently functional, non-calcifying heart-valves.

10.
Cartilage ; 13(1_suppl): 1058S-1065S, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-32396463

RESUMEN

OBJECTIVE: Patients undergoing articular cartilage paste grafting have been shown in studies to have significant improvement in pain and function in long-term follow-ups. We hypothesized that ex vivo impacting of osteochondral autografts results in higher chondrocyte matrix production versus intact osteochondral autograft plugs. DESIGN: This institutional review board-approved study characterizes the effects of impacting osteochondral plugs harvested from the intercondylar notch of 16 patients into a paste, leaving one graft intact as a control. Cell viability/proliferation, collagen type I/II, SOX-9, and aggrecan gene expression via qRT-PCR (quantitative reverse transcription-polymerase chain reaction) were analyzed at 24 and 48 hours. Matrix production and cell morphology were evaluated using histology. RESULTS: Paste samples from patients (mean age 39.7) with moderate (19%) to severe (81%) cartilage lesions displayed 34% and 80% greater cell proliferation compared to plugs at 24 and 48 hours post processing, respectively (P = 0.015 and P = 0.021). qRT-PCR analysis yielded a significant (P = 0.000) increase of aggrecan, SOX-9, collagen type I and II at both 24 and 48 hours. Histological examination displayed cell division throughout paste samples, with accumulation of aggrecan around multiple chondrocyte lacunae. CONCLUSIONS: Paste graft preparation resulted in increased mobility of chondrocytes by matrix disruption without loss of cell viability. The impaction procedure stimulated chondrocyte proliferation resulting in a cellular response to reestablish native extracellular matrix. Analysis of gene expression supports a regenerative process of cartilage tissue formation and contradicts long-held beliefs that impaction trauma leads to immediate cell death. This mechanism of action translates into clinical benefit for patients with moderate to severe cartilage damage.


Asunto(s)
Cartílago Articular , Adulto , Autoinjertos , Cartílago Articular/cirugía , Condrocitos/metabolismo , Colágeno Tipo II/metabolismo , Humanos , Trasplante Autólogo
11.
J Exp Orthop ; 6(1): 9, 2019 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-30805738

RESUMEN

Corrective lower limb osteotomies are innovative and efficient therapeutic procedures for restoring axial alignment and managing unicompartmental knee osteoarthritis. This review presents critical insights into the up-dated clinical knowledge on osteotomies for complex posttraumatic or congenital lower limb deformities with a focus on high tibial osteotomies, including a comprehensive overview of basic principles of osteotomy planning, biomechanical considerations of different implants for osteotomies and insights in specific bone deformity correction techniques. Emphasis is placed on complex cases of lower limb osteotomies associated with ligament and multiaxial instability including pediatric cases, computer-assisted navigation, external fixation for long bone deformity correction and return to sport after such osteotomies. Altogether, these advances in the experimental and clinical knowledge of complex lower limb osteotomies allow generating improved, adapted therapeutic regimens to treat congenital and acquired lower limb deformities.

12.
Transplantation ; 83(2): 211-9, 2007 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-17264818

RESUMEN

BACKGROUND: Understanding anti-non-gal antibody response is of significance for success in xenotransplantation. Long-term anti-non-gal response in humans was studied in patients transplanted with porcine patellar tendon (PT) lacking alpha-gal epitopes, for replacing ruptured anterior cruciate ligament (ACL). METHODS: Porcine PTs were treated with recombinant alpha-galactosidase to eliminate alpha-gal epitopes and with glutaraldehyde for moderate cross-linking of collagen fibers. The processed pig PTs were implanted to replace ruptured ACL in patients. RESULTS: In five of six evaluable subjects, the xenografts have continued to function for over two years and passed all functional stability assessments. Thus, processed porcine PT seems to be appropriate for replacing ruptured human ACL. Enzyme-linked immunosorbent assay and Western blot studies indicated that all subjects produced anti-non-gal antibodies against multiple pig xenoproteins, but not against human ligament proteins. Production of anti-non-gal antibodies peaked two to six months posttransplantation and disappeared after two years. CONCLUSIONS: These antibodies contribute to a low-level inflammatory process that aids in gradual xenograft replacement by infiltrating host fibroblasts that align with the pig collagen "scaffold" and secrete collagen matrix. The assays monitoring anti-non-gal antibodies will help to determine whether long-term survival of live organ xenografts requires complete suppression of this antibody response.


Asunto(s)
Ligamento Cruzado Anterior/inmunología , Ligamento Cruzado Anterior/trasplante , Formación de Anticuerpos/inmunología , Modelos Inmunológicos , Porcinos , alfa-Galactosidasa/inmunología , Adulto , Animales , Ligamento Cruzado Anterior/patología , Epítopos/genética , Epítopos/inmunología , Epítopos/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Trasplante Heterólogo/inmunología , Resultado del Tratamiento , alfa-Galactosidasa/genética , alfa-Galactosidasa/metabolismo
13.
Arthroscopy ; 23(5): 503-8, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17478281

RESUMEN

PURPOSE: Successful meniscus transplantation may depend on accurate sizing. Meniscal sizing is currently determined by measuring a combination of bony landmarks and soft-tissue insertion points through images obtained radiographically or by magnetic resonance imaging (MRI). The literature widely reports inaccuracy in sizing resulting from radiographic errors in magnification, erroneous identification of bony landmarks, and difficulty in differentiating between the soft-tissue and bone interface. In our meniscus transplantations we have observed that when the height and weight of the recipient matched those of the donor, the meniscal size appeared to be a match at surgical implantation; we designed this study to confirm this observation. METHODS: The MRI-based meniscal sizing of 111 patients (63 male and 38 female patients; mean age, 44 years [range, 15 to 76 years]), totaling 147 menisci (87 lateral and 60 medial), was compared with the height, weight, gender, and body mass index (BMI) of each patient. MRI scans were obtained with a 1.0-Tesla MRI system (ONI Medical Systems, Wilmington, MA). Sizing was performed by an independent musculoskeletal MRI radiologist as established by the literature. Statistical methods include nonparametric Pearson correlation (r) between MRI-based lateral meniscal width, lateral meniscal length, medial meniscal width, medial meniscal length, total tibial plateau width, and patient height, weight, gender, and BMI. Significance at the P = .05 level was used. RESULTS: Height was found to have a linear relationship to total tibial plateau, which has a good predictive correlation with meniscal dimensions of r > 0.7. Female patients generally present with smaller dimensions than male patients. High-BMI groups present with significantly larger meniscal dimensions than low-BMI groups at any given height. CONCLUSIONS: Height, weight, and gender are easily obtained variables and are proportional to meniscal tissue dimensions. These exploratory statistics establish correlations between height, weight, gender, total tibial plateau width, and meniscal size. CLINICAL RELEVANCE: Height, weight, and gender should be considered by both tissue banks and surgeons as fast and cost-effective variables by which to predict meniscal dimensions.


Asunto(s)
Tamaño Corporal , Meniscos Tibiales/anatomía & histología , Meniscos Tibiales/patología , Adolescente , Adulto , Anciano , Estatura , Índice de Masa Corporal , Peso Corporal , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Meniscos Tibiales/trasplante , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores Sexuales , Tibia/patología
14.
Arthroscopy ; 23(4): 411-9, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17418335

RESUMEN

PURPOSE: This study proposes treatment methods to provide a mechanically competent, immunocompatible, and sterile porcine graft for human knee ligament reconstruction. METHODS: The anterior cruciate ligament (ACL) was reconstructed by using treated porcine patellar tendon grafts or controls of untreated porcine grafts or allografts in 20 rhesus monkeys. Animals were stratified into 2-, 6-, and 12-month postreconstruction cohorts. Serologic and histologic assessments were performed to evaluate host immunological and cellular response. Healing and functional integrity of the ACL reconstructions were assessed by tensile biomechanical testing. RESULTS: Untreated porcine grafts were acutely resorbed and rejected, whereas treated porcine grafts and allografts were incorporated by the host as functional grafts. Temporal histologic assessment of treated porcine grafts and rhesus grafts revealed gradual host cellular infiltration and graft collagen remodeling through a similar mechanism of ligamentization. Biomechanical evaluations support graft functional integration with no difference between allograft and treated graft reconstructions. CONCLUSION: Rhesus allograft and treated porcine grafts presented with similar healing profiles in a long-term evaluation of ACL reconstruction. CLINICAL RELEVANCE: Immunochemical modification and sterilization of porcine patellar tendon grafts may improve initial biocompatibility and long-term functionality of xenografts in musculoskeletal applications.


Asunto(s)
Ligamento Cruzado Anterior/cirugía , Ligamento Rotuliano/patología , Ligamento Rotuliano/trasplante , Acondicionamiento Pretrasplante/métodos , Animales , Ligamento Cruzado Anterior/patología , Fenómenos Biomecánicos , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Rechazo de Injerto , Supervivencia de Injerto , Haplorrinos , Ligamento Rotuliano/inmunología , Distribución Aleatoria , Procedimientos de Cirugía Plástica/métodos , Valores de Referencia , Factores de Riesgo , Sensibilidad y Especificidad , Porcinos , Resistencia a la Tracción , Recolección de Tejidos y Órganos , Trasplante Heterólogo , Trasplante Homólogo
15.
Tissue Eng Part B Rev ; 23(4): 412-419, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28068870

RESUMEN

This review describes a novel method developed for processing porcine tendon and other ligament implants that enables in situ remodeling into autologous ligaments in humans. The method differs from methods using extracellular matrices (ECMs) that provide postoperative orthobiological support (i.e., augmentation grafts) for healing of injured ligaments, in that the porcine bone-patellar-tendon-bone itself serves as the graft replacing ruptured anterior cruciate ligament (ACL). The method allows for gradual remodeling of porcine tendon into autologous human ACL while maintaining the biomechanical integrity. The method was first evaluated in a preclinical model of monkeys and subsequently in patients. The method overcomes detrimental effects of the natural anti-Gal antibody and harnesses anti-non-gal antibodies for the remodeling process in two steps: Step 1. Elimination of α-gal epitopes-this epitope that is abundant in pigs (as in other nonprimate mammals) binds the natural anti-Gal antibody, which is the most abundant natural antibody in humans. This interaction, which can induce fast resorption of the porcine implant, is avoided by enzymatic elimination of α-gal epitopes from the implant with recombinant α-galactosidase. Step 2. Partial cross-linking of porcine tendon with glutaraldehyde-this cross-linking generates covalent bonds in the ECM, which slow infiltration of macrophages into the implant. Anti-non-gal antibodies are produced in recipients against the multiple porcine antigenic proteins and proteoglycans because of sequence differences between human and porcine homologous proteins. Anti-non-gal antibodies bind to the implant ECM, recruit macrophages, and induce the implant destruction by directing proteolytic activity of macrophages. Partial cross-linking of the tendon ECM decreases the extent of macrophage infiltration and degradation of the implant and enables concomitant infiltration of fibroblasts that follow the infiltrating macrophages. These fibroblasts align with the implant collagen fibers and secrete their own collagen and other ECM proteins, which gradually remodel the porcine tendon into human ACL. This ligamentization process lasts ∼2 years and the biomechanical integrity of the graft is maintained throughout the whole period. These studies are the first, and so far the only, to demonstrate remodeling of porcine tendon implants into permanently functional autologous ACL in humans.


Asunto(s)
Tendones , Animales , Ligamento Cruzado Anterior , Anticuerpos , Epítopos , Matriz Extracelular , Humanos , Porcinos
16.
Arthroscopy ; 22(5): 469-78, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16651154

RESUMEN

PURPOSE: We present meniscus allograft survival data at least 2 years from surgery for 45 patients (47 allografts) with significant arthrosis to determine if the meniscus can survive in an arthritic joint. TYPE OF STUDY: Prospective, longitudinal survival study. METHODS: Data were collected for 31 men and 14 women, mean age 48 years (range, 14 to 69 years), with preoperative evidence of significant arthrosis and an Outerbridge classification greater than II. Failure is established by previous studies as allograft removal. No patient was lost to follow-up. RESULTS: The success rate was 42 of 47 allografts (89.4%) with a mean failure time of 4.4 years as assessed by Kaplan-Meier survival analysis. Statistical power is greater than 0.9, with alpha = 0.05 and N = 47. There was significant mean improvement in preoperative versus postoperative self-reported measures of pain, activity, and functioning, with P = .001, P = .004, and P = .001, respectively, as assessed by a Wilcoxon rank-sum test with P = .05. CONCLUSIONS: Meniscus allografts can survive in a joint with arthrosis, challenging the contraindications of age and arthrosis severity. These results compare favorably with those in previous reports of meniscus allograft survival in patients without arthrosis. LEVEL OF EVIDENCE: Level IV.


Asunto(s)
Artroplastia , Supervivencia de Injerto , Meniscos Tibiales/trasplante , Osteoartritis de la Rodilla/cirugía , Actividades Cotidianas , Adolescente , Adulto , Anciano , Cartílago Articular/trasplante , Ejercicio Físico , Femenino , Estudios de Seguimiento , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Dimensión del Dolor , Complicaciones Posoperatorias , Radiografía , Reoperación , Análisis de Supervivencia
17.
Arthroscopy ; 22(3): 291-9, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16517314

RESUMEN

PURPOSE: To prospectively assess clinical outcomes and regeneration of osteoarthritic cartilage lesions treated with an articular cartilage paste grafting technique. TYPE OF STUDY: Prospective, longitudinal case series. METHODS: We treated 125 patients (136 procedures; 34% female, 66% male; mean age, 46 years; range, 17 to 73 years) with an Outerbridge classification of grade IV lesions with an articular cartilage paste graft. Clinical data were recorded 2 to 12 years from surgery, with 20 of 145 patients lost to follow-up over 12 years (13.7%). Clinical outcomes were captured annually with validated Western Ontario and McMaster Universities Arthritis Index (WOMAC), International Knee Documentation Committee (IKDC), and Tegner subjective questionnaires. Regenerated cartilage biopsy specimens were obtained at second-look arthroscopy from 66 patients and evaluated as to quality and quantity of defect fill by a blinded, independent histopathology reviewer. RESULTS: Preoperative versus postoperative validated pain, functioning, and activity measures improved significantly (P< .001). Clinically, 18 of the 125 patients were considered failures (14.4%), with 10 patients undergoing subsequent joint arthroplasty and 8 who reported worse pain after surgery. Regional histologic variation occurred. Forty-two of 66 biopsy specimens (63.6%) showed strong and consistent evidence of replacement of their articular surface, and 18 of 66 biopsy specimens (27.3%) showed development of areas of cartilage. CONCLUSIONS: Paste grafting is a low-cost, 1-stage arthroscopic treatment for patients with Outerbridge classification grade IV arthritic chondral lesions. The procedure offers excellent, long-lasting, pain relief, restored functioning, and possibility of tissue regeneration for patients with painful chondral lesions in both arthritic and traumatically injured knees. LEVEL OF EVIDENCE: Level IV, case series.


Asunto(s)
Artroscopía/métodos , Cartílago Articular/cirugía , Osteoartritis de la Rodilla/cirugía , Extractos de Tejidos/uso terapéutico , Adolescente , Adulto , Anciano , Médula Ósea , Cartílago Articular/lesiones , Cartílago Articular/patología , Condrocitos/trasplante , Desbridamiento , Femenino , Fémur/cirugía , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/rehabilitación , Dolor/etiología , Manejo del Dolor , Recuperación de la Función , Regeneración , Reoperación , Método Simple Ciego , Irrigación Terapéutica , Tibia/cirugía , Extractos de Tejidos/administración & dosificación , Trasplante Autólogo , Resultado del Tratamiento , Cicatrización de Heridas
18.
Semin Arthritis Rheum ; 45(4): 379-85, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26522136

RESUMEN

OBJECTIVE: To determine the validity of the hip and knee osteoarthritis guidelines. METHODS: A systematic search of PubMed using a combination of Mesh and text terms with limitations to guidelines was performed to identify hip and knee osteoarthritis guidelines. The study was performed from April 17, 2014 to October 1, 2014. Guidelines were reviewed for graded levels of evidence, methods used to grade the evidence, and disclosures of conflicts of interest. Additionally, guidelines were also assessed for key quality measures using the AGREE II system for assessing the quality of guidelines. RESULTS: A total of 13 guidelines relevant to the diagnosis and/or treatment of hip/knee osteoarthritis was identified. The 180 recommendations reviewed were supported by 231 pieces of evidence. In total, 35% (n = 80; range: 0-26) were supported by level A evidence, 15% (n = 35; range: 0-10) were by level B, and 50% (n = 116; range: 0-62) were by level C. Median age of the guidelines was 4 years (±4.8; range: 0-16) with no comments on planned updates. In total, 31% of the guidelines included patients in the development process. Only one guideline incorporated cost consideration, and only 15% of the guidelines addressed the surgical management of osteoarthritis. Additionally, 46% of guidelines did not comment on conflicts of interest (COI). When present, there was an average 29.8 COI. Notably, 82% of the COI were monetary support/consulting. CONCLUSIONS: In total, 50% of the hip/knee osteoarthritis guideline recommendations are based on lower quality evidence. Nearly half the guidelines fail to disclose relevant COI and when disclosed, multiple potential COI are present. Future hip/knee osteoarthritis guideline development committees should strive to improve the transparency and quality of evidence used to formulate practice guidelines.


Asunto(s)
Conflicto de Intereses , Medicina Basada en la Evidencia/normas , Osteoartritis de la Cadera/terapia , Osteoartritis de la Rodilla/terapia , Guías de Práctica Clínica como Asunto/normas , Revelación , Humanos , Sociedades Médicas
19.
Arthroscopy ; 19(4): 426-30, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12671626

RESUMEN

This technical note describes an improved arthroscopic technique of meniscal transplantation that simplifies the surgical procedure and secures the allograft to the tibia at 3 sites. The technique is useful for both medial and lateral meniscal transplantation and has been used in our clinic for over 60 meniscal transplantation procedures.


Asunto(s)
Artroscopía/métodos , Meniscos Tibiales/trasplante , Trasplante Homólogo , Clavos Ortopédicos , Humanos , Meniscos Tibiales/cirugía , Técnicas de Sutura , Tibia/cirugía
20.
J Gerontol B Psychol Sci Soc Sci ; 69(3): 338-47, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-23531920

RESUMEN

OBJECTIVES: To better understand the effects of misinformation on eyewitnesses of different ages, older and younger adults experienced an event under intentional and incidental learning conditions in a naturalistic experiment using multiple memory tests. METHOD: Following exposure to the event, which was a brief interruption of a group testing session, participants completed several memory tests. For half of the participants, misinformation was embedded in the first cued recall test. On subsequent free recall and cued recall tests, basic scores and misinformation-based memory errors were examined. RESULTS: As expected, younger adults had higher recall scores than older adults. Older and younger adults made the same number of misinformation errors in free recall and in cued recall with intentional learning. However, in the incidental condition, younger adults made more misinformation errors likely due to the information processing strategies they employed after incidental learning. DISCUSSION: Misinformation effects were quite strong, even with a realistic scene and intentional learning. Older adult suggestibility was no worse than that of younger adults. When misinformation was combined with incidental learning, younger adults may have used strategic processing to encode misinformation to their detriment.


Asunto(s)
Envejecimiento/fisiología , Aprendizaje/fisiología , Adulto , Factores de Edad , Anciano , Comunicación , Derecho Penal/normas , Señales (Psicología) , Humanos , Recuerdo Mental/fisiología , Reconocimiento en Psicología/fisiología , Sugestión , Adulto Joven
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