RESUMO
Introducción: Los objetivos de este estudio fueron determinar la incidencia de lesión iatrogénica intraquirúrgica del nervio radial durante la osteosíntesis de la diáfisis y el extremo distal del húmero, distinguir factores de riesgos asociados y reconocer elementos pronósticos que participan de su recuperación. Materiales y Métodos: Se evaluó, en forma retrospectiva, a 82 pacientes con osteosíntesis de húmero entre 2005 y 2021, sin parálisis radial preoperatoria. Se consideraron los sistemas de fijación utilizados, y se compararon las cirugías primarias con las reoperaciones y el tiempo transcurrido entre estas. El diagnóstico de parálisis radial posoperatorio fue clínico. Todos los pacientes fueron tratados con férula en extensión de muñeca, electroestimulación, kinesiología y vitaminas B1, B6, B12. La electromiografía se solicitó a los fines del pronóstico. Resultados: Nueve pacientes tuvieron déficit motor del nervio radial en el posoperatorio inmediato. El sistema de fijación era una placa (7 casos), sistema de cable-placa (1 caso) y clavo endomedular acerrojado anterógrado (1 caso). Siete ocurrieron en cirugías primarias y dos en reoperaciones. El 88% recuperó su función motora completamente antes de los 6 meses después de la parálisis. La electromiografía reveló un nervio radial no excitable en el 22% restante con parálisis definitiva. Conclusiones: El uso de placa de osteosíntesis, la disección intraoperatoria del nervio radial y las reoperaciones aumentan la incidencia de parálisis. Un nervio radial no excitable se relaciona con un peor pronóstico de recuperación espontánea. Nivel de Evidencia: IV
Introduction: The purpose of this study is to determine the incidence of intraoperative iatrogenic radial nerve injury after osteosynthesis of the diaphysis and distal end of the humerus, identify associated risk factors, and determine the prognostic factors involved in its recovery. Materials and Methods: We retrospectively assessed 82 humerus osteosynthesis cases between 2005 and 2021 who had normal radial nerve function before surgery. We evaluated the fixation systems used, the type of surgery (primary versus revision), and the intervals between surgeries. The diagnosis of postoperative radial palsy was made by clinical examination. All patients were treated with wrist extension splint, physiotherapy, and vitamins B1, B6, and B12. Results: After humerus fixation, 9 patients developed motor palsy. Seven cases were fixed with plates, one with a cable-plate system, and one with an anterograde locking intramedullary nail. Seven cases (22%) occurred after primary procedures, while two occurred during revisions. Within 6 months, 88% had regained full motor function. In the remaining 22% of patients with definite palsy, electromyography revealed no excitability of the radial nerve. Conclusions: The use of an osteosynthesis plate, as well as intraoperative dissection and neurolysis of the radial nerve, were identified as risk factors for the development of radial palsy. Reoperations on the humerus, on the other hand, are a risk factor that increases the likelihood of postoperative radial nerve palsy. A radial nerve with no excitability on the postoperative electromyogram has a poor prognosis of spontaneous radial nerve function recovery. Level of Evidence: IV
Assuntos
Braço , Nervo Radial/lesões , Fixação Interna de Fraturas , Fraturas do Úmero , Doença Iatrogênica , Complicações IntraoperatóriasRESUMO
Objetivo: Comunicar los resultados funcionales y radiográficos de pacientes tratados con prótesis reversa por fracturas complejas. El objetivo secundario fue determinar la relación entre rangos de movilidad y puntaje ASES con la evolución radiográfica del troquíter. Materiales y Métodos: Se incluyeron 16 pacientes >65 años, tratados con prótesis reversa y reinserción del troquíter, entre 2013 y 2017, operados antes de las 4 semanas del trauma y con un seguimiento mínimo de 2 años. Se consignaron el puntaje ASES y el rango de movilidad activa. En las radiografías, se evaluaron la posición y la consolidación del troquíter, y se registraron las complicaciones y su tratamiento. Resultados: La media de la edad fue 74.5 años (RIC 66-78.5), 11 (69%) eran mujeres. Once fracturas (69%) eran a 4 fragmentos y 5, luxofracturas a 4 fragmentos. La media entre el trauma y la cirugía fue 9.4 días y el seguimiento, 29.5 meses. En 9 casos (56%), el troquíter presentó consolidación. Rotación interna: 5 pacientes alcanzaron la región glútea con el pulgar; 4, la vértebra T12; 4, la vértebra L3; 3, la T7. Las medianas de rotación externa y flexión anterior fueron 30° (RIC 17,5-40) y 100° (RIC 87,5-160). El puntaje ASES promedio fue 78,3 (RIC 63,3-87,4). No hubo una asociación estadísticamente significativa entre la evolución del troquíter y la flexión anterior y el puntaje (p = 0,24 y 0,52, respectivamente). Conclusión: La prótesis reversa en fracturas agudas con reinserción de las tuberosidades puede llevar a buenos resultados funcionales. No se encontró relación entre la consolidación del troquíter y el puntaje ASES. Nivel de Evidencia: IV
Objective: To report functional and radiologic outcomes of reverse shoulder arthroplasty (RSA) in patients with complex proximal humeral fractures. A second objective was to assess the relation between the greater tuberosity healing and the range of motion (ROM) and the American Shoulder and Elbow Surgeons (ASES) score. Materials and Methods: Sixteen patients treated between 2013 and 2017, older than 65 years old, operated before 4 weeks after the trauma, and with a minimum of 2-year follow-up were included. ASES scores and active ROMs were recorded. Greater tuberosity and the prosthesis position and healing were radiologically evaluated, and the complications and treatment were recorded. Results: The median age was of 74.5 years (IQR 66-78.5), 11 patients were females (69%). According to Neer classification, 11 cases were four-part fractures and 5 were four-part fracture-dislocations. The average time between trauma and surgery was 9.4 days, and the average follow-up was of 29.5 months. The greater tuberosity was healed in 9 cases (56%). Internal rotation: 5 patients (31.25%) were able to reach up with their thumbs to gluteal level, 4 (25%) to T12, 3 (18.75%) to T7, and 4 (25%) to L3. The medians for external rotation and forward flexion were 30° (IQR 17.5°-40°) and 100° (IQR 87.5°-160°). The average ASES score was of 78.3 (IQR 63.3-87.4). There was no significant statistical relation between greater tuberosity healing and forward flexion or ASES score (P=0.24 and P=0.52, respectively). Conclusion: The use of reverse prostheses for complex fractures with greater tuberosity reattachment could lead to good functional outcomes, low complication rates and reoperations. There was no significant statistical relation between ASES score and greater tuberosity healing or failure to heal. Level of Evidence: IV
Assuntos
Idoso , Fraturas do Ombro/cirurgia , Amplitude de Movimento Articular , Resultado do Tratamento , Artroplastia do Ombro , Úmero/lesõesRESUMO
Objetivo: Presentar una nueva técnica quirúrgica y los resultados clínicos comparativos de pacientes con roturas de tenorrafia primaria o lesiones crónicas del flexor profundo en las zonas I y II de Verdan, tratados con avance tendinoso no convencional. Ma-teriales y Métodos: Se incluyó a pacientes >18 años, con antecedente de lesiones en las zonas I y II de Verdan y un seguimiento mínimo de 36 meses. La serie estaba formada por 13 pacientes (edad promedio 29 años) que fueron divididos en dos grupos según el tipo de lesión (7 con roturas de tenorrafia primaria y 6 con lesiones crónicas del flexor profundo) y la técnica quirúrgica utilizada (alargamiento en Z más sutura término-terminal y sutura lateral del tendón alargado a un flexor vecino indemne en la zona V, respectivamente). Se empleó la Clasificación de Strickland para la evaluación. Resultados: El seguimiento promedio fue de 51 meses. El intervalo promedio entre la lesión y la cirugía fue de 11.7 semanas. Según la Clasificación de Strickland, 8 pa-cientes tuvieron resultados excelentes; 4, buenos y uno, pobre. El avance tendinoso promedio fue de 20,5 mm en ambos grupos.Conclusiones: El avance tendinoso no convencional para lesiones en las zonas I y II de Verdan, sea en roturas de tenorrafia primaria o lesiones crónicas del flexor profundo, resultó un tratamiento reproducible y eficaz. Nivel de Evidencia: III
Objective: To report a new surgical technique and the comparative clinical outcomes in patients with primary tenorrhaphy rupture or chronic flexor digitorum profundus (FDP) injuries in Verdan zones I and II, treated with non-conventional tendon advancement. Materials and Methods: The study population consisted of 13 patients over 18 years (averaging 29 years) who had had injuries in Verdan zones I and II and at least a 36-month follow-up. Patients were divided into two groups according to injury type (7 cases of primary tenorrhaphy rupture and 6 cases of chronic FDP injuries) and surgical technique (Z-plasty lengthening plus end-to-end suture or lateral suture to an adjacent undamaged FDP tendon at zone-V level, respectively). The results were evaluated according to Strickland's scoring system. Results: The average follow-up was 51 months. Time period between injury and surgery averaged 11.7 weeks (range, 2-24 weeks). Strickland scoring system results: excellent in 8 patients, good in 4 patients, and poor in 1 patient. Study average tendon advancement was 20.5mm. Conclusions: Non-conventional tendon advancement for primary tenorrhaphy ruptures or chronic FDP injuries in Verdan zones I and II proved to be a reproducible and effective treatment. Level of evidence: III
Assuntos
Traumatismos dos Tendões , MãosRESUMO
Novel bone regeneration approaches aim to obtain immature osteoblasts from somatic stem cells. Umbilical cord Wharton's jelly mesenchymal stem cells (WJ-MSCs) are an ideal source for cell therapy. Hence, the study of mechanisms involved in WJ-MSC osteoblastic differentiation is crucial to exploit their developmental capacity. Here, we have assessed epigenetic control of the Runt-related transcription factor 2 (RUNX2) osteogenic master regulator gene in WJ-MSC. We present evidence indicating that modulation of RUNX2 expression through preventing Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase activity is relevant to enhance WJ-MSC osteoblastic potential. Hence, JARID1B loss of function in WJ-MSC results in increased RUNX2/p57 expression. Our data highlight JARID1B activity as a novel target to modulate WJ-MSC osteoblastic differentiation with potential applications in bone tissue engineering. Stem Cells 2017;35:2430-2441.
Assuntos
Histona Desmetilases com o Domínio Jumonji/metabolismo , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Epigenômica , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Osteoblastos/metabolismo , Cordão Umbilical/citologia , Geleia de Wharton/citologiaRESUMO
Wharton's Jelly mesenchymal stem cells (WJ-MSCs) are an attractive potential source of multipotent stem cells for bone tissue replacement therapies. However, the molecular mechanisms involved in their osteogenic conversion are poorly understood. Particularly, epigenetic control operating at the promoter regions of the two master regulators of the osteogenic program, RUNX2/P57 and SP7 has not yet been described in WJ-MSCs. Via quantitative PCR profiling and chromatin immunoprecipitation (ChIP) studies, here we analyze the ability of WJ-MSCs to engage osteoblast lineage. In undifferentiated WJ-MSCs, RUNX2/P57 P1, and SP7 promoters are found deprived of significant levels of the histone post-translational marks that are normally associated with transcriptionally active genes (H3ac, H3K27ac, and H3K4me3). Moreover, the RUNX2 P1 promoter lacks two relevant histone repressive marks (H3K9me3 and H3K27me3). Importantly, RUNX2 P1 promoter is found highly enriched in the H3K4me1 mark, which has been shown recently to mediate gene repression of key regulatory genes. Upon induction of WJ-MSCs osteogenic differentiation, we found that RUNX2/P57, but not SP7 gene expression is strongly activated, in a process that is accompanied by enrichment of activating histone marks (H3K4me3, H3ac, and H3K27ac) at the P1 promoter region. Histone mark analysis showed that SP7 gene promoter is robustly enriched in epigenetic repressive marks that may explain its poor transcriptional response to osteoblast differentiating media. Together, these results point to critical regulatory steps during epigenetic control of WJ-MSCs osteogenic lineage commitment that are relevant for future applications in regenerative medicine. J. Cell. Physiol. 232: 2519-2527, 2017. © 2016 Wiley Periodicals, Inc.
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Diferenciação Celular , Linhagem da Célula , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Epigênese Genética , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Osteogênese , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Transcriptoma , Geleia de Wharton/metabolismo , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Histonas/metabolismo , Humanos , Metilação , Fenótipo , Fator de Transcrição Sp7 , Fatores de Transcrição/genética , Transcrição Gênica , Ativação Transcricional , Geleia de Wharton/citologiaRESUMO
Skeletal muscle regeneration and long term maintenance is directly link to the balance between self-renewal and differentiation of resident adult stem cells known as satellite cells. In turn, satellite cell fate is influenced by a functional interaction between the transcription factor Pax7 and members of the MyoD family of muscle regulatory factors. Thus, changes in the Pax7-to-MyoD protein ratio may act as a molecular rheostat fine-tuning acquisition of lineage identity while preventing precocious terminal differentiation. Pax7 is expressed in quiescent and proliferating satellite cells, while its levels decrease sharply in differentiating progenitors Pax7 is maintained in cells (re)acquiring quiescence. While the mechanisms regulating Pax7 levels based on differentiation status are not well understood, we have recently described that Pax7 levels are directly regulated by the ubiquitin-ligase Nedd4, thus promoting proteasome-dependent Pax7 degradation in differentiating satellite cells. Here we show that Pax7 levels are maintained in proliferating muscle progenitors by a mechanism involving casein kinase 2-dependent Pax7 phosphorylation at S201. Point mutations preventing S201 phosphorylation or casein kinase 2 inhibition result in decreased Pax7 protein in proliferating muscle progenitors. Accordingly, this correlates directly with increased Pax7 ubiquitination. Finally, Pax7 down regulation induced by casein kinase 2 inhibition results in precocious myogenic induction, indicating early commitment to terminal differentiation. These observations highlight the critical role of post translational regulation of Pax7 as a molecular switch controlling muscle progenitor fate.
Assuntos
Caseína Quinase II/metabolismo , Proliferação de Células/fisiologia , Desenvolvimento Muscular/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Fator de Transcrição PAX7/metabolismo , Fosforilação/fisiologia , Animais , Diferenciação Celular/fisiologia , Linhagem Celular , Regulação para Baixo/fisiologia , Camundongos , Proteína MyoD/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Células Satélites de Músculo Esquelético/fisiologia , Ubiquitinação/fisiologiaRESUMO
PURPOSE: The purpose of this study was to evaluate the aqueous humor bioavailability and clinical efficacy of bromfenac 0.09% vs nepafenac on the presence of cystoid macular edema (CME) after phacoemulsification. MATERIAL AND METHODS: A Phase II, double-blind, masked, active-controlled, multicenter, clinical trial of 139 subjects, randomized to either a bromfenac 0.09% ophthalmic solution (n=69) or nepafenac 0.1% (n=70). Subjects instilled a drop three times a day for a period of 30 days. Follow-up visits were on days 2, 7, 15, 30, and 60. Biomicroscopy, clinical ocular signs, and assessment of posterior segment were performed. The primary efficacy endpoints included the presence of CME evaluated by optical coherence tomography. Safety evaluation included intraocular pressure, transaminase enzymes, lissamine green, and fluorescein stain. RESULTS: The demographic and efficacy variables were similar between groups at baseline. The presence of pain, photophobia, conjunctival hyperemia, chemosis, cellularity, and corneal edema disappeared by day 30 in both groups. The central retinal thickness did not show significant changes after treatment when compared to baseline as follows: in the bromfenac group (247.2±32.9 vs 252.0±24.9 µm; P=0.958) and in nepafenac group (250.8±34 vs 264.0±34.1 µm; P=0.137), respectively. A statistically significant difference was observed between bromfenac and nepafenac group: (252.0±24.9 vs 264.0±34.1 µm; P=0.022), at day 30, respectively; even though there was no clinical relevance in the presentation of CME. There were no significant alterations in intraocular pressure, either lissamine green or fluorescein stains. The adverse events were not related to the interventions. CONCLUSION: Bromfenac 0.09% ophthalmic solution showed similar clinical efficacy to reduce the presentation of CME after phacoemulsification compared to nepafenac 0.01%.
RESUMO
The transcription factor Pax7 regulates skeletal muscle stem cell (satellite cells) specification and maintenance through various mechanisms, including repressing the activity of the muscle regulatory factor MyoD. Hence, Pax7-to-MyoD protein ratios can determine maintenance of the committed-undifferentiated state or activation of the differentiation program. Pax7 expression decreases sharply in differentiating myoblasts but is maintained in cells (re)acquiring quiescence, yet the mechanisms regulating Pax7 levels based on differentiation status are not well understood. Here we show that Pax7 levels are directly regulated by the ubiquitin-ligase Nedd4. Our results indicate that Nedd4 is expressed in quiescent and activated satellite cells, that Nedd4 and Pax7 physically interact during early muscle differentiation-correlating with Pax7 ubiquitination and decline-and that Nedd4 loss of function prevented this effect. Furthermore, even transient nuclear accumulation of Nedd4 induced a drop in Pax7 levels and precocious muscle differentiation. Consequently, we propose that Nedd4 functions as a novel Pax7 regulator, which activity is temporally and spatially controlled to modulate the Pax7 protein levels and therefore satellite cell fate.
Assuntos
Diferenciação Celular/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/biossíntese , Desenvolvimento Muscular , Fator de Transcrição PAX7/biossíntese , Células Satélites de Músculo Esquelético/metabolismo , Ubiquitina-Proteína Ligases/biossíntese , Animais , Proliferação de Células/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Camundongos , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , Proteína MyoD/biossíntese , Ubiquitina-Proteína Ligases Nedd4 , Fator de Transcrição PAX7/genética , Complexo de Endopeptidases do Proteassoma/genética , Células Satélites de Músculo Esquelético/citologia , Ubiquitina-Proteína Ligases/genética , UbiquitinaçãoRESUMO
Dynamic regulation of cell adhesion receptors is required for proper cell migration in embryogenesis, tissue repair, and cancer. Integrins and Syndecan4 (SDC4) are the main cell adhesion receptors involved in focal adhesion formation and are required for cell migration. SDC4 interacts biochemically and functionally with components of the Wnt pathway such as Frizzled7 and Dishevelled. Non-canonical Wnt signaling, particularly components of the planar cell polarity branch, controls cell adhesion and migration in embryogenesis and metastatic events. Here, we evaluate the effect of this pathway on SDC4. We have found that Wnt5a reduces cell surface levels and promotes ubiquitination and degradation of SDC4 in cell lines and dorsal mesodermal cells from Xenopus gastrulae. Gain- and loss-of-function experiments demonstrate that Dsh plays a key role in regulating SDC4 steady-state levels. Moreover, a SDC4 deletion construct that interacts inefficiently with Dsh is resistant to Wnt5a-induced degradation. Non-canonical Wnt signaling promotes monoubiquitination of the variable region of SDC4 cytoplasmic domain. Mutation of these specific residues abrogates ubiquitination and results in increased SDC4 steady-state levels. This is the first example of a cell surface protein ubiquitinated and degraded in a Wnt/Dsh-dependent manner.