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1.
Nature ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693268

RESUMO

The liver has a unique ability to regenerate1,2; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option3-5. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2+ migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. Four-dimensional intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 reduces hepatocyte growth factor-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation that mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut-liver barrier may advance new areas of therapeutic discovery in regenerative medicine.

2.
Nature ; 575(7783): 512-518, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31597160

RESUMO

Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2+CD9+ subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1+ and PLVAP+ endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.


Assuntos
Células Endoteliais/patologia , Cirrose Hepática/patologia , Fígado/patologia , Macrófagos/patologia , Análise de Célula Única , Animais , Estudos de Casos e Controles , Linhagem da Célula , Sistema do Grupo Sanguíneo Duffy/metabolismo , Células Endoteliais/metabolismo , Feminino , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatócitos/citologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/citologia , Cirrose Hepática/genética , Macrófagos/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Fenótipo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores Imunológicos/metabolismo , Tetraspanina 29/metabolismo , Transcriptoma , Migração Transendotelial e Transepitelial
3.
Diagn Interv Imaging ; 100(7-8): 437-444, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30853414

RESUMO

PURPOSE: The purpose of this study was to determine the performance of CT arthrography for the diagnosis of intra-articular long head of biceps (LHB) tendon intrinsic lesions using arthroscopy findings as standard of reference. MATERIAL AND METHODS: CT arthrography studies of 98 patients (55 men, 43 women; mean age 54.8±12.7 [SD] years [range: 16-77 years]) were retrospectively evaluated by two radiologists independently. Per operative arthroscopic images and surgical reports were retrospectively reviewed by a shoulder-specialist surgeon. Based on the analysis of arthroscopic images and the surgical reports, the LHB tendon was classified as normal (continuous with uniform tendon thickness), tendinopathy/partial rupture (focal change in tendon thickness and contour irregularities) and total rupture (total loss in tendon continuity). Imaging results were compared to those of surgery that served as standard of reference. Interobserver agreement was assessed. RESULTS: At arthroscopy, the LHB tendon was classified as normal in 38/98 (38.8%) patients, tendinopathic in 51/52 (52%) and totally ruptured in 9/98 (9.2%). The sensitivity and specificity of CT arthrography for the diagnosis of LHB tendinopathy were respectively 74% (95%CI: 60%-85%) and 93% (95%CI: 80%-99%) for reader 1 and 79% (95% CI: 67%-89%) and 95% (95% CI: 83%-99%) for reader 2. The sensitivity and specificity for the diagnosis of LHB tendon total ruptures were 100% (95%CI: 66%-100%) and 93% (95%CI: 86%-98%) for both readers. Interobserver agreements for the identification of the LHB tendon tendinopathy and total ruptures were excellent (kappa values of 0.94 and 0.96, respectively). CONCLUSION: CT arthrography demonstrates good sensitivity and excellent specificity for the detection of intra-articular LHB tendinopathy and tear.


Assuntos
Artrografia , Articulação do Ombro/diagnóstico por imagem , Tendinopatia/diagnóstico por imagem , Traumatismos dos Tendões/diagnóstico por imagem , Tendões/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Artroscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ruptura , Sensibilidade e Especificidade , Adulto Jovem
4.
Orthop Traumatol Surg Res ; 104(3): 317-323, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29474948

RESUMO

INTRODUCTION: The PFMR® proximal femoral modular reconstruction implant (Protek, Sulzer Orthopedics, Switzerland) is a straight modular stem in sanded titanium with press-fit anchorage, intended to achieve spontaneous bone reconstruction following Wagner's principle. The aim of the present study was to analyze long-term clinical and radiological outcome. MATERIAL AND METHOD: A single-center retrospective study included 48 PFMR stems implanted in 47 patients between 1998 and 2002. Results in this series were previously reported at 7 years' follow-up. Clinical assessment used PMA and Harris scores. Radiologic assessment focused on stem stability and osseointegration, and bone stock following Le Béguec. RESULTS: Twenty-three patients were seen at a mean 14.5 years' follow-up (13 deceased, 11 lost to follow-up), including 1 with bilateral implants, i.e., 24 stems. PMA and Harris scores, stem stability and osseointegration and bone stock were stable with respect to the 7-year findings. Radiology found 7 stem fractures in the Morse taper, i.e., in 29% of implants. Two of these cases required femoral implant replacement; 5 were asymptomatic. DISCUSSION AND CONCLUSION: Long-term outcome for PFMR stems was clinically and radiologically satisfactory for the 16 patients free of mechanical complications. The Morse taper fracture rate was high, and higher than reported elsewhere. The usual risk factors for implant fracture were not found in the present series. The modular design of the press-fit revision implant is its weak point; monoblock implants should be used in patients with good life-expectancy. LEVEL OF EVIDENCE: IV (retrospective study).


Assuntos
Artroplastia de Quadril/instrumentação , Fêmur/diagnóstico por imagem , Prótese de Quadril , Osseointegração , Desenho de Prótese , Falha de Prótese , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Prótese de Quadril/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Reoperação , Estudos Retrospectivos
5.
Diagn Interv Imaging ; 97(7-8): 735-47, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27452630

RESUMO

BACKGROUND: Several imaging modalities can be used to diagnose complications of hip prosthesis placement. Despite progress in these imaging techniques, there are, as yet, no guidelines as to their respective indications. METHODS: We formed a panel of experts in fields related to prosthesis imaging (radiology, nuclear medicine, orthopedic surgery) and conducted a review of the literature to determine the value of each modality for diagnosing complications following hip replacement. RESULTS: Few recent studies have investigated the benefits related to the use of the latest technical developments, and studies comparing different methods are extremely rare. CONCLUSIONS: We have developed a diagnostic tree based on the characteristics of each imaging technique and recommend its use. Computed topography was found to be the most versatile and cost-effective imaging solution and therefore a key tool for diagnosing the complications of hip replacement surgery.


Assuntos
Artroplastia de Quadril , Diagnóstico por Imagem/métodos , Prótese de Quadril , Algoritmos , Artefatos , Humanos , Imagem Multimodal , Fraturas Periprotéticas/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Infecções Relacionadas à Prótese/diagnóstico por imagem
6.
Orthop Traumatol Surg Res ; 102(5): 651-6, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27185332

RESUMO

BACKGROUND: Ankle arthrodesis is a treatment of choice for advanced tibio-talar disease unresponsive to conservative treatment. Using arthroscopy to perform this procedure minimises soft-tissue trauma while providing similar outcomes to those of open surgery. Union rates have ranged across studies from 85% to 100%. The objective of this study was to assess the potential influence on union of the number of screws used for arthrodesis fixation. HYPOTHESIS: The working hypothesis was that using three screws for arthrodesis produced a higher union rate than did using only two screws. MATERIAL AND METHODS: This single-centre retrospective comparative study included 111 cases of arthroscopic ankle arthrodesis (in 108 patients) carried out between February 1994 and October 2012. The number of screws was two in 75 cases and three in 36 cases. Union was assessed on radiographs taken 2, 6, and 12months postoperatively. RESULTS: Mean age at surgery was 55.8years. After 12months, union was achieved in 87.4% cases overall. The non-union rate was 16% with two screws and 5.6% with three screws. Three-screw fixation was associated with a significantly higher rate of union of the medial gutter after 6months and of the lateral gutter after 12months. DISCUSSION: Our findings support the use of three screws for fixation of arthroscopic tibio-talar arthrodesis. Adding a third screw seems associated with a lower risk of non-union and a shorter time to union. These effects can be ascribed to greater stability of the construct. LEVEL OF EVIDENCE: Level IV, retrospective study.


Assuntos
Articulação do Tornozelo/cirurgia , Artrodese/instrumentação , Parafusos Ósseos , Osseointegração , Articulação do Tornozelo/diagnóstico por imagem , Artrodese/métodos , Artroscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/cirurgia , Estudos Retrospectivos
7.
Cell Death Dis ; 7: e2197, 2016 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-27077813

RESUMO

Kynurenine 3-monooxygenase (KMO) is a critical regulator of inflammation. The preferred KMO substrate, kynurenine, is converted to 3-hydroxykynurenine (3HK), and this product exhibits cytotoxicity through mechanisms that culminate in apoptosis. Here, we report that overexpression of human KMO with orthotopic localisation to mitochondria creates a metabolic environment during which the cell exhibits increased tolerance for exogenous 3HK-mediated cellular injury. Using the selective KMO inhibitor Ro61-8048, we show that KMO enzyme function is essential for cellular protection. Pan-caspase inhibition with Z-VAD-FMK confirmed apoptosis as the mode of cell death. By defining expression of pathway components upstream and downstream of KMO, we observed alterations in other key kynurenine pathway components, particularly tryptophan-2,3-dioxygenase upregulation, through bidirectional nonlinear feedback. KMO overexpression also increased expression of inducible nitric oxide synthase (iNOS). These changes in gene expression are functionally relevant, because siRNA knockdown of the pathway components kynureninase and quinolinate phosphoribosyl transferase caused cells to revert to a state of susceptibility to 3HK-mediated apoptosis. In summary, KMO overexpression, and importantly KMO activity, have metabolic repercussions that fundamentally affect resistance to cell stress.


Assuntos
Apoptose/efeitos dos fármacos , Quinurenina 3-Mono-Oxigenase/metabolismo , Cinurenina/análogos & derivados , Clorometilcetonas de Aminoácidos/farmacologia , Inibidores Enzimáticos/farmacologia , Células HEK293 , Humanos , Cinurenina/toxicidade , Quinurenina 3-Mono-Oxigenase/antagonistas & inibidores , Quinurenina 3-Mono-Oxigenase/genética , Microscopia Confocal , Mitocôndrias/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Pentosiltransferases/antagonistas & inibidores , Pentosiltransferases/genética , Pentosiltransferases/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Imagem com Lapso de Tempo , Transfecção
8.
Orthop Traumatol Surg Res ; 102(4): 517-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27052938

RESUMO

Hip prosthesis implantation requires a stable pelvic foundation, which may be lacking in patients with complex pelvic abnormalities (e.g., arthrodesis conversion, tumour excision, or revision with large bony defects). Many reconstructive options exist for these situations, but their outcomes vary with the initial amount of bone loss and with the technique used. We describe a two-stage arthroplasty technique (acetabular cup first, then femoral stem) and report its use in a case of arthrodesis conversion with concomitant treatment of pelvic and acetabular non-union. Clinical and radiological outcomes after 5 years are reported. This procedure can be adapted to the most complex cases of pelvic reconstruction.


Assuntos
Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Articulação do Quadril/cirurgia , Ossos Pélvicos/cirurgia , Acetábulo/diagnóstico por imagem , Adolescente , Artrodese , Doenças Ósseas Metabólicas/cirurgia , Feminino , Articulação do Quadril/diagnóstico por imagem , Prótese de Quadril , Humanos , Ossos Pélvicos/diagnóstico por imagem , Procedimentos de Cirurgia Plástica/métodos , Reoperação
10.
Oncogene ; 34(34): 4546, 2015 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-26289678

RESUMO

Correction to: Oncogene (2015) 34, 4482­4490; doi:10.1038/onc.2014.378; published online 24 November 2014. Following the online publication of this article, the authors have noticed a misspelt surname: S Hider should read S Haider. There is also an addition to the acknowledgements to read 'This study makes use of data generated by the Molecular Taxonomy of Breast Cancer International Consortium, which was funded by Cancer Research UK and the British Columbia Cancer Agency Branch'. The corrected article appears in this issue. The authors would like to apologise for any inconvenience this may cause.

11.
Oncogene ; 34(34): 4482-90, 2015 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-25417700

RESUMO

Activation of cellular transcriptional responses, mediated by hypoxia-inducible factor (HIF), is common in many types of cancer, and generally confers a poor prognosis. Known to induce many hundreds of protein-coding genes, HIF has also recently been shown to be a key regulator of the non-coding transcriptional response. Here, we show that NEAT1 long non-coding RNA (lncRNA) is a direct transcriptional target of HIF in many breast cancer cell lines and in solid tumors. Unlike previously described lncRNAs, NEAT1 is regulated principally by HIF-2 rather than by HIF-1. NEAT1 is a nuclear lncRNA that is an essential structural component of paraspeckles and the hypoxic induction of NEAT1 induces paraspeckle formation in a manner that is dependent upon both NEAT1 and on HIF-2. Paraspeckles are multifunction nuclear structures that sequester transcriptionally active proteins as well as RNA transcripts that have been subjected to adenosine-to-inosine (A-to-I) editing. We show that the nuclear retention of one such transcript, F11R (also known as junctional adhesion molecule 1, JAM1), in hypoxia is dependent upon the hypoxic increase in NEAT1, thereby conferring a novel mechanism of HIF-dependent gene regulation. Induction of NEAT1 in hypoxia also leads to accelerated cellular proliferation, improved clonogenic survival and reduced apoptosis, all of which are hallmarks of increased tumorigenesis. Furthermore, in patients with breast cancer, high tumor NEAT1 expression correlates with poor survival. Taken together, these results indicate a new role for HIF transcriptional pathways in the regulation of nuclear structure and that this contributes to the pro-tumorigenic hypoxia-phenotype in breast cancer.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Neoplasias da Mama/patologia , Hipóxia Celular , RNA Longo não Codificante/fisiologia , Ativação Transcricional , Animais , Apoptose , Neoplasias da Mama/metabolismo , Moléculas de Adesão Celular/genética , Proliferação de Células , Sobrevivência Celular , Feminino , Humanos , Camundongos , Receptores de Superfície Celular/genética
12.
Orthop Traumatol Surg Res ; 100(6 Suppl): S333-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25155203

RESUMO

BACKGROUND: The objective of this randomised trial was to compare surgical rotator cuff repair to simple decompression by acromioplasty and biceps tenotomy in patients older than 60 years of age with a mean follow-up of 4 years. HYPOTHESIS: Tendon repair produces better functional outcomes than simple decompression and prevents progression towards cuff tear arthropathy in the longer term. PATIENTS AND METHOD: Of 130 initially included patients older than 60 years of age and having rotator cuff tears deemed amenable to surgical repair, 103 (79%) were evaluated after a mean of 4 years. These patients had been randomly allocated to acromioplasty and tenotomy (AT group, n=49) or to acromioplasty, tenotomy, and tendon suture (CR group, n=54). The tear was distal in 41 patients, intermediate in 40, and retracted in 22. At last follow-up, the evaluation included the clinical Constant's Score, radiographs and, in the CR group, ultrasonography. RESULTS: The complication rate was 4%. The mean Constant Score was 44 preoperatively; values after 4 years were 76 overall (P=0.01), 78 in the CR group, and 73 in the AT group (P=0.01). The tendon-healing rate as assessed using ultrasonography was 63%. The Constant Score was significantly better when tendon healing was achieved (82/73, P<0.001). In the AT group, the acromio-humeral distance was significantly shorter (6.9 mm/7.8mm, P=0.03) and eccentric humeral head position was more common (44%/26%, P=0.01). DISCUSSION: Arthroscopic rotator cuff repair provides better functional outcomes than does simple decompression in patients older than 60 years and prevents cuff tear arthropathy with eccentric humeral head position in the medium term. Tendon healing is the main determinant of outcomes after rotator cuff repair. LEVEL OF EVIDENCE: II, randomised trial.


Assuntos
Artroplastia/métodos , Artroscopia/métodos , Lesões do Manguito Rotador , Manguito Rotador/cirurgia , Tenotomia/métodos , Articulação Acromioclavicular/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Manguito Rotador/diagnóstico por imagem , Tendões/diagnóstico por imagem , Tendões/cirurgia , Resultado do Tratamento , Ultrassonografia
13.
Orthop Traumatol Surg Res ; 100(3): 265-70, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24679371

RESUMO

INTRODUCTION: Intramedullary fixation of displaced surgical neck fractures of the humerus can be performed either by retrograde pinning or anterograde nailing. The goal of the current study was to compare the postoperative reduction and stability obtained with these two techniques. HYPOTHESIS: Intramedullary nailing will provide the best reduction and stabilization of these fractures. PATIENTS AND METHODS: This was a multicenter retrospective study that included patients with sub-tuberosity fractures with or without greater tuberosity fragment. These patients were treated either by retrograde Hackethal type pinning (group 1) or Telegraph anterograde nailing (group 2). To be included, patients needed to have A/P and lateral X-rays that had been taken before the surgery, immediately post-operative, between four and six weeks post-operative, and at the last follow-up. The outcomes were head angulation, translation and greater tuberosity position. RESULTS: One hundred and five patients (40 retrograde pinning and 65 anterograde nailing) with an average age of 69 years (18-97 years) were included. The pre-operative fracture displacement was similar between the two groups. After the surgery, the A/P head angulation had been corrected in 72.5% of patients in group 1 and 84% in group 2 (no significant difference). Translation was still present in 17.5% of patients in group 1 and 1.5% in group 2 (P<0.05). At the last follow-up, union was achieved without residual angulation on lateral X-rays in 71% of patients in group 1 and 88% in group 2 (P<0.05). The fractures had healed with residual translation is 19.5% of patients in group 1 and 3% in group 2 (P<0.05). DISCUSSION AND CONCLUSION: In cases of displaced surgical neck fractures with or without a greater tuberosity fragment, anterograde nailing provides better reduction and stability than retrograde pinning. However, fixation of the greater tuberosity fragment must be improved. LEVEL OF EVIDENCE: IV (retrospective comparative study).


Assuntos
Pinos Ortopédicos , Fixação Intramedular de Fraturas/métodos , Fraturas do Úmero/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fraturas do Úmero/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Radiografia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Protein Expr Purif ; 95: 96-103, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24316190

RESUMO

Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington's disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification.


Assuntos
Quinurenina 3-Mono-Oxigenase/isolamento & purificação , Quinurenina 3-Mono-Oxigenase/metabolismo , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Escherichia coli/genética , Histidina , Humanos , Cinética , Quinurenina 3-Mono-Oxigenase/química , Quinurenina 3-Mono-Oxigenase/genética , Redes e Vias Metabólicas , Oligopeptídeos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Solubilidade
15.
Orthop Traumatol Surg Res ; 100(1): 113-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24370486

RESUMO

INTRODUCTION: Traumatic sequelae of the elbow are difficult to manage because of bone deformities, changes in joint congruency and bone defects. MATERIALS AND METHODS: Total elbow arthroplasty is a therapeutic option when the joint space has disappeared. Nineteen patients underwent semi-constrained Coonrad-Morrey(®) total elbow arthroplasty in 12 cases for post-traumatic elbow arthritis (group 1) and in seven cases for 7 non-union of the distal humerus (group 2). The mean age at surgery was 60 years old (56 in group 1 and 67 in group 2). The mean delay between the initial trauma and arthroplasty was 16 years (group 1) and 22 months (group 2). RESULTS: At a mean follow-up of 5.5 years (24-156 months) in group 1, the Quick-DASH score was 34 points with outcomes that were considered to be good to excellent in 75% of the cases according to the Mayo Elbow Performance Score (MEPS). A progressive radiolucency was identified on X-ray in 33% of the cases, and moderate wear of the polyethylene insert in 17%. There were 7 complications (58%) requiring revision in 3 cases (25%). At a mean follow-up of 4.6 years (24-108 months) in group 2, the Quick-DASH score was 39 points with good and excellent results in 86% according to the MEPS. A radiolucency was noted in 28% and moderate wear of the inserts in 14%. There were 2 complications (28%) requiring revision in 1 case (14%). CONCLUSION: Semi-constrained total elbow arthroplasties provide recovery of functional range of motion with a stable and pain-free elbow for post-traumatic conditions. The age at surgery is a risk factor for complications. The indication for total elbow arthroplasty in patients under 60 should be carefully considered in relation to alternative treatment options. LEVEL OF EVIDENCE: Level IV Retrospective study.


Assuntos
Artroplastia de Substituição do Cotovelo , Lesões no Cotovelo , Articulação do Cotovelo/cirurgia , Idoso , Artroplastia de Substituição do Cotovelo/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
16.
Orthop Traumatol Surg Res ; 99(4): 465-72, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23644030

RESUMO

INTRODUCTION: Os acromiale is a failure of fusion of the acromial process. It is usually asymptomatic and discovered by chance. When it is painful a differential diagnosis must be made in relation to the subacromial impingement syndrome. HYPOTHESIS: Unstable os acromiale is the cause of atypical scapulalgias. Stabilization by tension band wiring and an embedded slot shaped graft achieves union and relieves pain. PATIENTS ET METHODS: This series includes 10 patients mean age 43 years old presenting with shoulder pain resistant to a mean 15 months of conservative treatment. Pain followed trauma in three cases. Three patients had a history of acromioplasty, which had not relieved pain. All had pain during palpation of the superior aspect of the acromion. The diagnosis was confirmed in eight patients by positive results to local injection of the os acromiale. The mean preoperative Constant score was 53.4. The procedure included open reduction and fixation of the acromion by tension band wiring and pinning associated with an embedded iliac crest graft without acromioplasty. RESULTS: The mean follow-up was 48 months. Pain was relieved in seven cases and all patients had improved and were satisfied. Union of os acromiale was confirmed on CT scan in all patients. The mean Constant score was 82.2. DISCUSSION: The role of os acromiale in the origination of pain is confirmed by the efficacy of preoperative injection of the os acromiale and pain relief after achieving union. Moreover, our technique is reliable and always resulted in union of the os acromiale. Internal fixation by tension banding favors minimal upward migration of the os acromiale and union. In case of subacromial impingement syndrome an os acromiale should be looked for, as this condition could deteriorate with simple acromioplasty. LEVEL OF EVIDENCE: Level IV retrospective observational study.


Assuntos
Acrômio/lesões , Transplante Ósseo/métodos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/complicações , Ílio/transplante , Dor de Ombro/etiologia , Acrômio/diagnóstico por imagem , Acrômio/cirurgia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Dor de Ombro/diagnóstico por imagem , Dor de Ombro/cirurgia , Resultado do Tratamento , Adulto Jovem
17.
Br J Cancer ; 108(5): 1133-42, 2013 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-23449350

RESUMO

BACKGROUND: Clear cell renal cancer frequently harbours von Hippel-Lindau (VHL) gene mutations, leading to stabilisation of the hypoxia-inducible factors (HIFs) and expression of their target genes. We investigated HIF-1 and HIF-2 in the regulation of microRNA-210 (miR-210), and its clinical relevance in renal tumours. METHODS: RCC4 and 786-O renal cancer cell lines transfected with either an empty vector or functional VHL and incubated in normoxia or hypoxia were examined for miR-210 expression. Hypoxia-inducible factor siRNAs were used to examine their regulation of miR-210. Seventy-one clear cell renal tumours were sequenced for VHL mutations. Expression of miR-210, VHL, CA9, ISCU and Ki-67 were determined by immunohistochemistry and qRT-PCR. RESULTS: In addition to HIF-1 regulating miR-210 in renal cancer, HIF-2 can regulate this microRNA in the absence of HIF-1. MicroRNA-210 is upregulated in renal cancer compared with normal renal cortex tissue. MicroRNA-210 correlates negatively with its gene target ISCU at the protein and mRNA level. MicroRNA-210 correlated with positive outcome variables and negatively with Ki-67. CONCLUSION: We provide further evidence of miR-210 activity in vivo, and show that high miR-210 expression is associated with better clinico-pathological prognostic factors.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Neoplasias Renais/genética , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Regulação para Cima , Proteína Supressora de Tumor Von Hippel-Lindau/genética
18.
Orthop Traumatol Surg Res ; 98(6 Suppl): S124-30, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22926294

RESUMO

BACKGROUND: This study originated from a symposium held by the French Hip and Knee Society (Société française de la hanche et du genou [SFHG]) and was carried out to better assess the distribution of causes of unicompartmental knee arthroplasty (UKA) failures, as well as cause-specific delay to onset. HYPOTHESIS: Our working hypothesis was that most failures were traceable to wear occurring over a period of many years. MATERIALS AND METHODS: A multicentre retrospective study (25 centres) was conducted in 418 failed UKAs performed between 1978 and 2009. We determined the prevalence and time to onset of the main reasons for revision surgery based upon available preoperative findings. Additional intraoperative findings were analysed. The results were compared to those of nation wide registries to evaluate the representativeness of our study population. RESULTS: Times to revision surgery were short: 19% of revisions occurred within the first year and 48.5% within the first 5 years. Loosening was the main reason for failure (45%), followed by osteoarthritis progression (15%) and, finally, by wear (12%). Other reasons were technical problems in 11.5% of cases, unexplained pain in 5.5%, and failure of the supporting bone in 3.6%. The infection rate was 1.9%. Our results were consistent with those of Swedish and Australian registries. DISCUSSION: Our hypothesis was not confirmed. The short time to failure in most cases suggests a major role for surgical technique issues. Morbidity related to the implant per se may be seen as moderate and not greater than with total knee prostheses. The good agreement between our data and those of nationwide registries indicates that our population was representative. A finer analysis is needed, indicating that the establishment of a French registry would be of interest.


Assuntos
Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Prótese do Joelho , Desenho de Prótese/métodos , Falha de Prótese/tendências , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Estudos de Coortes , Feminino , Seguimentos , França , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Reoperação/métodos , Estudos Retrospectivos , Medição de Risco , Suécia , Fatores de Tempo , Resultado do Tratamento
19.
Orthop Traumatol Surg Res ; 98(3): 296-300, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22463868

RESUMO

INTRODUCTION: Displaced fractures of the femoral neck in the elderly are best treated with arthroplasty. The type of arthroplasty to be used, either hemi- or total hip arthroplasty, remains controversial as total hip replacements potentially have a higher rate of dislocation. HYPOTHESIS: Dual mobility cups have a low dislocation rate when used to manage acute fractures of the femoral neck. PATIENTS AND METHODS: In a multicenter prospective study conducted in France over an inclusion time of 3 months, all displaced fractures of the femoral neck treated with arthroplasty were operated on with insertion of a dual mobility cup. Patients had clinical and radiological assessment at 3, 6, and 9 months postoperative. RESULTS: Two hundred and fourteen hips in 214 patients with a mean age of 83 years (range, 70-103 years) were included. None of the patients was lost to follow-up. The mortality rate after 9 months was 19%. Two patients (1%) had early postoperative infection successfully treated with lavage and antibiotics. Three patients (1.4%), operated through a posterior approach, presented one postoperative dislocation, all of which were posterior. Reduction was performed through closed external manipulation under general anesthesia. There was no recurrence of dislocation. DISCUSSION: This low rate of dislocation after acute total hip replacement using dual mobility design cups favorably compares with hemiarthroplasties. Dual mobility cups might therefore be considered a valuable option to prevent postoperative dislocation when treating displaced intracapsular fractures of the proximal femur in elderly patients if a total hip replacement is recommended. Further study is needed before extending the indications for total hip arthroplasty following a fracture of the femoral neck, to assess the potential cost and complications of a longer procedure with its potential acetabular complication, and weigh them against the potential benefits.


Assuntos
Artroplastia de Quadril/métodos , Fraturas do Colo Femoral/cirurgia , Luxação do Quadril/cirurgia , Prótese de Quadril , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Colo Femoral/complicações , Fraturas do Colo Femoral/epidemiologia , Seguimentos , França/epidemiologia , Luxação do Quadril/epidemiologia , Luxação do Quadril/etiologia , Articulação do Quadril/fisiopatologia , Humanos , Incidência , Masculino , Prognóstico , Estudos Prospectivos , Desenho de Prótese , Falha de Prótese , Amplitude de Movimento Articular , Reoperação , Taxa de Sobrevida/tendências
20.
Orthop Traumatol Surg Res ; 98(2): 129-37, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22349206

RESUMO

INTRODUCTION: Treatment of acetabular loosening and accompanying bone defects requires that the bone stock be rebuilt, the primary stability ensured, and the hip center of rotation restored to its anatomical location. HYPOTHESIS: Acetabular reconstruction using morselized allograft and a reinforcement ring will meet these requirements and ensure medium-term survival. PATIENTS AND METHODS: A retrospective study was performed on 95 acetabular revision cases (95 patients) performed between 1987 and 1995. The average age at revision was 69.5 years (42 to 86 years). Among these acetabular loosening cases, 12 cases had a type II Paprosky acetabular bone defect and 83 cases had a type III defect. RESULTS: The average follow-up was 8 years (5 to 13 years). There were seven post-operative dislocations, three deep infections, and two cases of repeated acetabular loosening. The cumulative survival rate at 14 years was 77.9% (95% CI: 61.96% to 93.84%). The average Postel Merle d'Aubigné (PMA) score improved from 8 (range 6-11) preoperatively to 14.8 (range 8-18) at follow-up; the Harris score improved from 35.3 (range 11-52) to 71.1 (range 40-94) (P<0.001). Based on the parameters outlined by Ranawat, the optimal centre of rotation was restored in 45% of cases. Graft integration was found to be good in 60% of cases. The reinforcement ring had migrated in five cases, including two cases of acetabular loosening that required an additional revision. The functional result was better when the hip center of rotation was restored (P<0.05). Conversely, the position of the hip center of rotation had no effect on graft integration or acetabular fixation. DISCUSSION: This series confirmed that acetabular reconstruction using morselized allograft and a reinforcement ring is effective in the medium term as a treatment for acetabular loosening with severe bone deficiency. It also revealed that restoring the hip center of rotation can improve functional results. LEVEL OF EVIDENCE: Level IV, retrospective study.


Assuntos
Acetábulo/cirurgia , Artroplastia de Quadril , Reabsorção Óssea/cirurgia , Cabeça do Fêmur/transplante , Sobrevivência de Enxerto , Procedimentos de Cirurgia Plástica/métodos , Reoperação/métodos , Adulto , Idoso de 80 Anos ou mais , Reabsorção Óssea/diagnóstico por imagem , Reabsorção Óssea/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/cirurgia , Falha de Prótese , Radiografia , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento
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