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1.
N Engl J Med ; 384(21): 1991-2001, 2021 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-34042388

RESUMEN

BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.).


Asunto(s)
Antibacterianos/administración & dosificación , Prótesis de Cadera/efectos adversos , Prótesis de la Rodilla/efectos adversos , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Anciano , Antibacterianos/efectos adversos , Terapia Combinada , Esquema de Medicación , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/cirugía , Insuficiencia del Tratamiento
2.
Epidemiol Infect ; 149: e227, 2021 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-34612186

RESUMEN

Vertebral osteomyelitis (VO) represents 4-10% of bone and joint infections. In Western countries, its incidence seems to increase, simultaneously with an increasing number of comorbidities among an ageing population. This study aimed to assess the evolution of VO epidemiology in France over the 2010-2019 decade. A nationwide cross-sectional study was conducted using the French hospital discharge data collected through the French diagnosis-related groups 'Programme de Médicalisation des Systèmes d'Information'. VOs were detected with a previously validated case definition using International Classification of Diseases 10 (ICD-10) codes, implemented with the French current procedural terminology codes. The study population included all patients hospitalised in France during the 2010-2019 decade, aged 15 years old and more. Patient and hospital stay characteristics and their evolutions were described. During the study period, 42 105 patients were hospitalised for VO in France involving 60 878 hospital stays. The mean VO incidence was 7.8/100 000 over the study period, increasing from 6.1/100 000 in 2010 to 11.3/100 000 in 2019. The mean age was 64.8 years old and the sex ratio was 1.56. There were 31 341 (74.4%) patients with at least one comorbidity and 3059 (7.3%) deceased during their hospital stay. Even if rare, device-associated VOs (4450 hospital stays, 7.3%) highly increased over the period. The reliability of the method, based upon an exhaustive database and a validated case definition, provided an effective tool to compare data over time in real-life conditions to regularly update the epidemiology of VO.


Asunto(s)
Hospitalización/estadística & datos numéricos , Osteomielitis/epidemiología , Enfermedades de la Columna Vertebral/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/aislamiento & purificación , Comorbilidad , Estudios Transversales , Femenino , Francia/epidemiología , Mortalidad Hospitalaria , Humanos , Incidencia , Tiempo de Internación , Masculino , Persona de Mediana Edad , Osteomielitis/microbiología , Prótesis e Implantes/efectos adversos , Infecciones Relacionadas con Prótesis/epidemiología , Enfermedades de la Columna Vertebral/microbiología
3.
Int J Cancer ; 145(8): 2135-2143, 2019 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-30924137

RESUMEN

Soft tissue sarcomas (STS) are rare tumors accounting for less than 1% of human cancers. While the highest incidence of sarcomas is observed in elderly, this population is often excluded or poorly represented in clinical trials. The present study reports on clinicopathological presentation, and outcome of sarcoma patients over 90 recorded in the Netsarc.org French national database. NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor board (MDTB), funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB, second pathological review, and collection of sarcoma patient characteristics and follow-up are collected in a database Information of patients registered from January 1, 2010, to December 31, 2016, in NETSARC were collected, analyzed and compared to the younger population. Patients with sarcomas aged >90 have almost exclusively sarcomas with complex genomics (92.0% vs. 66.3%), are less frequently metastatic (5.3% vs. 14·7%) at diagnosis, have more often superficial tumors (39.8% vs. 14.7%), as well as limbs and head and neck sites (75.2% vs. 38.7%) (all p < 0.001). Optimal diagnostic procedures and surgery were less frequently performed in patients over 90 (p < 0.001). These patients were less frequently operated in NETSARC centers, as compared to those of younger age groups including aged 80-90. However, local relapse-free survival, metastatic relapse-free survival and relapse-free survival were not significantly different from those of younger patients, in the whole cohort, as well as in the subgroup of operated patients. As expected overall survival was worse in patients over 90 (p < 0.001). Patients over 90 who were not operated had worse overall survival than younger patients (9.9 vs. 27.3 months, p < 0.001). Patients with STS diagnosed after 90 have distinct clinicopathological features, but comparable relapse-free survival, unless clinical practice guidelines recommendations are not applied. Standard management should be proposed to these patients if oncogeriatric status allows.


Asunto(s)
Bases de Datos Factuales/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Francia/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Sarcoma/diagnóstico , Sarcoma/epidemiología , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/epidemiología , Adulto Joven
4.
Ann Surg Oncol ; 26(11): 3526-3534, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31338771

RESUMEN

BACKGROUND: The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown. OBJECTIVE: The aim of this study was to evaluate the impact of delayed RE versus systematic RE after UE on overall survival (OS), metastatic relapse-free survival (MRFS), local relapse-free survival (LRFS), and rate of amputation. METHODS: Patients who underwent complete UE, without metastasis or residual disease, for primary extremity or superficial STS between 2007 and 2013 were analyzed. The amputation rate, LRFS, MRFS, and OS were assessed in cases of systematic RE in sarcoma referral centers (Group A), systematic RE outside of community centers (Group B), or without RE (Group C). RESULTS: Groups A, B, and C included 300 (48.2%), 71 (11.4%), and 251 (40.4%) patients, respectively. Median follow-up was 61 months and 5-year OS was 88.4%, 87.3%, and 88% in Groups A, B, and C, respectively (p = 0.22), while 5-year MFRS was 85.4%, 86.2%, and 84.9%, respectively (p = 0.938); RE (p = 0.55) did not influence MRFS. The 5-year LRFS was 83%, 73.5%, and 63.8% in Groups A, B and C, respectively (p = 0.00001). Of the 123 local recurrences observed, 0/28, 1/15, and 5/80 patients in Groups A, B, and C, respectively, required amputation (p = 0.41). Factors influencing LRFS were adjuvant radiotherapy [hazard ratio (HR) 0.21; p = 0.0001], initial R0 resection (HR 0.24, p = 0.0001), and Group A (HR 0.44; p = 0.01). CONCLUSION: Systematic RE in sarcoma centers offers best local control but does not impact OS. Delayed RE at the time of local relapse, if any, could be an option.


Asunto(s)
Amputación Quirúrgica/estadística & datos numéricos , Extremidades/cirugía , Recurrencia Local de Neoplasia/mortalidad , Neoplasia Residual/mortalidad , Reoperación/estadística & datos numéricos , Sarcoma/mortalidad , Extremidades/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasia Residual/patología , Neoplasia Residual/cirugía , Pronóstico , Estudios Retrospectivos , Sarcoma/patología , Sarcoma/cirugía , Tasa de Supervivencia
5.
Cytotherapy ; 21(8): 870-885, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31272868

RESUMEN

BACKGROUND: Safety and feasibility of a regenerative strategy based on the use of culture-expanded mesenchymal stromal cells (MSCs) have been investigated in phase 2 trials for the treatment of nonunion and osteonecrosis of the femoral head (ONFH). As part of the clinical study, we aimed to evaluate if bone turnover markers (BTMs) could be useful for predicting the regenerative ability of the cell therapy product. MATERIALS AND METHODS: The bone defects of 39 patients (nonunion: n = 26; ONFH: n = 13) were treated with bone marrow-derived MSCs, expanded using a clinical-grade protocol and combined with biphasic calcium phosphate before implantation. Bone formation markers, bone-resorption markers and osteoclast regulatory proteins were measured before treatment (baseline) and after 12 and 24 weeks from surgery. At the same time-points, clinical and radiological controls were performed to evaluate the bone-healing progression. RESULTS: We found that C-Propeptide of Type I Procollagen (CICP) and C-terminal telopeptide of type-I collagen (CTX) varied significantly, not only over time, but also according to clinical results. In patients with a good outcome, CICP increased and CTX decreased, and this trend was observed in both nonunion and ONFH. Moreover, collagen biomarkers were able to discriminate healed patients from non-responsive patients with a good diagnostic accuracy. DISCUSSION: CICP and CTX could be valuable biomarkers for monitoring and predicting the regenerative ability of cell products used to stimulate the repair of refractory bone diseases. To be translated in a clinical setting, these results are under validation in a currently ongoing phase 3 clinical trial.


Asunto(s)
Biomarcadores/sangre , Regeneración Ósea/fisiología , Necrosis de la Cabeza Femoral/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Adulto , Biomarcadores/metabolismo , Células de la Médula Ósea , Resorción Ósea/metabolismo , Colágeno Tipo I/sangre , Colágeno Tipo I/metabolismo , Femenino , Necrosis de la Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/patología , Humanos , Hidroxiapatitas/uso terapéutico , Masculino , Células Madre Mesenquimatosas/citología , Persona de Mediana Edad , Osteoclastos/fisiología , Fragmentos de Péptidos/sangre , Fragmentos de Péptidos/metabolismo , Péptidos/sangre , Péptidos/metabolismo , Procolágeno/sangre , Procolágeno/metabolismo
6.
J Surg Oncol ; 119(4): 479-488, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30609044

RESUMEN

BACKGROUND AND OBJECTIVES: Soft tissue sarcoma localization in distal extremities (DESTS) of the limbs (hand/fingers, and foot/toes) is unusual. The literature is scarce about their behavior and this study was designed to assess their epidemiological characteristics, outcomes, and prognosis compared to other limb localizations (OLSTS). METHODS: From 1980 to 2010, adult DESTS and OLSTS in 22 centers were included. Demographics, tumor type, treatment modalities, and latest follow-up status were collected. Primary endpoints were overall survival and local/metastatic recurrence incidences. RESULTS: Two hundred five DESTS and 3001 OLSTS were included. The patients were younger, with more female and smaller tumors in DESTS. There were more clear cell/epithelioid sarcomas, synovial sarcomas, and myxoid liposarcomas vs more dedifferentiated liposarcomas in OLSTS. DESTS tumors were less irradiated and more often amputated (24.3% vs 3.4%). The five-year survival rate was 78.2% compared to 68.6% in OLSTS and after multivariate analysis, STS localization did not impact survival or local/metastatic recurrence. CONCLUSION: Though rare and smaller than other limb localizations, DESTS are to be considered as aggressive. Despite a higher amputation rate, the prognosis remains the same as in OLSTS. Limb sparing vs amputation should be carefully assessed in DESTS, especially if grade 3 or of a poor prognosis histological subtype.


Asunto(s)
Extremidades , Sarcoma/terapia , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Sarcoma/mortalidad , Sarcoma/patología
7.
BMC Infect Dis ; 18(1): 665, 2018 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-30558553

RESUMEN

BACKGROUND: Intra-osseous (IO) access is recommended in cases of pre-hospital emergency or resuscitation when intravascular (IV) route is difficult or impossible. Despite recent improvement in IO devices and increasing indications, it remains rarely used in practice. Various complications have been reported but are uncommon. CASE PRESENTATION: We report a case of massive acute tibial osteomyelitis in an adult male three months after an IO catheter insertion for emergency drug infusion. We review the literature on association between IO access and acute osteomyelitis in children and adults. CONCLUSIONS: Emergency-care givers and radiologists should be informed about this infrequent complication in order to make early diagnosis and initiate adequate antibiotic therapy.


Asunto(s)
Infecciones Relacionadas con Catéteres/etiología , Sobredosis de Droga/terapia , Infusiones Intraóseas/efectos adversos , Osteomielitis/etiología , Resucitación , Tibia/microbiología , Enfermedad Aguda , Adulto , Infecciones Relacionadas con Catéteres/microbiología , Infecciones Relacionadas con Catéteres/patología , Servicios Médicos de Urgencia , Humanos , Enfermedad Iatrogénica , Masculino , Osteomielitis/microbiología , Osteomielitis/patología , Resucitación/efectos adversos , Resucitación/métodos , Infecciones Estafilocócicas/etiología , Infecciones Estafilocócicas/patología , Staphylococcus aureus/aislamiento & purificación , Tibia/patología
8.
Int J Mol Sci ; 19(3)2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29494553

RESUMEN

Osteosarcoma (OS) is suspected to originate from dysfunctional mesenchymal stromal/stem cells (MSC). We sought to identify OS-derived cells (OSDC) with potential cancer stem cell (CSC) properties by comparing OSDC to MSC derived from bone marrow of patients. This study included in vitro characterization with sphere forming assays, differentiation assays, cytogenetic analysis, and in vivo investigations of their tumorigenicity and tumor supportive capacities. Primary cell lines were isolated from nine high-grade OS samples. All primary cell lines demonstrated stromal cell characteristics. Compared to MSC, OSDC presented a higher ability to form sphere clones, indicating a potential CSC phenotype, and were more efficient at differentiation towards osteoblasts. None of the OSDC displayed the complex chromosome rearrangements typical of high grade OS and none of them induced tumors in immunodeficient mice. However, two OSDC demonstrated focused genomic abnormalities. Three out of seven, and six out of seven OSDC showed a supportive role on local tumor development, and on metastatic progression to the lungs, respectively, when co-injected with OS cells in nude mice. The observation of OS-associated stromal cells with rare genetic abnormalities and with the capacity to sustain tumor progression may have implications for future tumor treatments.


Asunto(s)
Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Células Madre Mesenquimatosas/metabolismo , Células Madre Neoplásicas/metabolismo , Osteosarcoma/metabolismo , Osteosarcoma/patología , Microambiente Tumoral , Adolescente , Adulto , Biomarcadores , Médula Ósea/patología , Línea Celular Tumoral , Células Cultivadas , Técnicas de Cocultivo , Femenino , Humanos , Inmunofenotipificación , Cariotipo , Masculino , Células Madre Mesenquimatosas/patología , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Células Madre Neoplásicas/patología , Adulto Joven
9.
J Cell Mol Med ; 20(4): 655-65, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26773707

RESUMEN

Similar to other adult tissue stem/progenitor cells, bone marrow mesenchymal stem/stromal cells (BM MSCs) exhibit heterogeneity at the phenotypic level and in terms of proliferation and differentiation potential. In this study such a heterogeneity was reflected by the CD200 protein. We thus characterized CD200(pos) cells sorted from whole BM MSC cultures and we investigated the molecular mechanisms regulating CD200 expression. After sorting, measurement of lineage markers showed that the osteoblastic genes RUNX2 and DLX5 were up-regulated in CD200(pos) cells compared to CD200(neg) fraction. At the functional level, CD200(pos) cells were prone to mineralize the extra-cellular matrix in vitro after sole addition of phosphates. In addition, osteogenic cues generated by bone morphogenetic protein 4 (BMP4) or BMP7 strongly induced CD200 expression. These data suggest that CD200 expression is related to commitment/differentiation towards the osteoblastic lineage. Immunohistochemistry of trephine bone marrow biopsies further corroborates the osteoblastic fate of CD200(pos) cells. However, when dexamethasone was used to direct osteogenic differentiation in vitro, CD200 was consistently down-regulated. As dexamethasone has anti-inflammatory properties, we assessed the effects of different immunological stimuli on CD200 expression. The pro-inflammatory cytokines interleukin-1ß and tumour necrosis factor-α increased CD200 membrane expression but down-regulated osteoblastic gene expression suggesting an additional regulatory pathway of CD200 expression. Surprisingly, whatever the context, i.e. pro-inflammatory or pro-osteogenic, CD200 expression was down-regulated when nuclear-factor (NF)-κB was inhibited by chemical or adenoviral agents. In conclusion, CD200 expression by cultured BM MSCs can be induced by both osteogenic and pro-inflammatory cytokines through the same pathway: NF-κB.


Asunto(s)
Antígenos CD/genética , Células de la Médula Ósea/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , FN-kappa B/genética , Osteoblastos/efectos de los fármacos , Adulto , Antígenos CD/metabolismo , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Proteína Morfogenética Ósea 4/farmacología , Proteína Morfogenética Ósea 7/farmacología , Diferenciación Celular/efectos de los fármacos , Linaje de la Célula/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Dexametasona/farmacología , Matriz Extracelular/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Interleucina-1beta/farmacología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , FN-kappa B/metabolismo , Osteoblastos/citología , Osteoblastos/metabolismo , Fosfatos/farmacología , Cultivo Primario de Células , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factor de Necrosis Tumoral alfa/farmacología
10.
Clin Sci (Lond) ; 127(5): 277-93, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24827940

RESUMEN

Aseptic loosening as a result of wear debris is considered to be the main cause of long-term implant failure in orthopaedic surgery and improved biomaterials for bearing surfaces decreases significantly the release of micrometric wear particles. Increasingly, in-depth knowledge of osteoimmunology highlights the role of nanoparticles and ions released from some of these new bearing couples, opening up a new era in the comprehension of aseptic loosening. Mouse models have been essential in the progress made in the early comprehension of pathophysiology and in testing new therapeutic agents for particle-induced osteolysis. However, despite this encouraging progress, there is still no valid clinical alternative to revision surgery. The present review provides an update of the most commonly used bearing couples, the current concepts regarding particle-cell interactions and the approaches used to study the biology of periprosthetic osteolysis. It also discusses the contribution and future challenges of mouse models for successful translation of the preclinical progress into clinical applications.


Asunto(s)
Artroplastia de Reemplazo/efectos adversos , Macrófagos/fisiología , Osteólisis/etiología , Animales , Fenómenos Biomecánicos , Cerámica/efectos adversos , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Falla de Equipo , Humanos , Inflamación/fisiopatología , Ratones , Nanopartículas/efectos adversos , Osteólisis/fisiopatología , Tamaño de la Partícula , Polietilenos/efectos adversos , Polietilenos/química , Polimetil Metacrilato/efectos adversos , Reoperación , Investigación Biomédica Traslacional
11.
FASEB J ; 27(8): 2977-87, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23592762

RESUMEN

Bone-marrow mesenchymal stem cells (MSCs) are the origin of bone-forming cells with immunomodulation potential. HLA-G5 is among the generated immunosuppressive molecules. HLA-G proteins play a crucial role in promoting the acceptance of allografts. However, the mechanisms regulating the expression of HLA-G5 in human MSCs are unknown. We induced differentiation of MSCs and found that HLA-G5 was greatly up-regulated only in osteoblastic cells (+63% for mRNA). Growth plates and bone callus postfracture in adults showed that only bone-lining cells and mesenchymal progenitors were positive for HLA-G5. Use of gene silencing and dominant-negative factors revealed that HLA-G5 depends on the expression and function of the skeletogenesis master genes RUNX2 and DLX5. In addition, HLA-G5 could directly inhibit osteoclastogenesis by acting on monocytes through SHP1. However, in mature osteoblasts, the expression of HLA-G5 protein was greatly suppressed whereas the proosteoclastogenic factor, RANKL, was concomitantly increased. Down-regulation of HLA-G5 expression during the maturation of osteoblasts was due to binding of the repressor GLI3, a signal transducer of the Hedgehog pathway, to the GLI binding element within the HLA-G promoter. Our findings show that mesenchymal progenitors and osteoblastic cells specifically express HLA-G5 during osteogenesis, with a key role in bone homeostasis.


Asunto(s)
Huesos/metabolismo , Antígenos HLA-G/genética , Células Madre Mesenquimatosas/metabolismo , Osteoblastos/metabolismo , Osteogénesis/genética , Adulto , Huesos/citología , Línea Celular Tumoral , Linaje de la Célula/genética , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Regulación de la Expresión Génica , Antígenos HLA-G/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Homeostasis/genética , Humanos , Inmunohistoquímica , Microscopía Fluorescente , Modelos Genéticos , Osteoblastos/citología , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
12.
Int Orthop ; 38(9): 1845-53, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24728310

RESUMEN

PURPOSE: Tibial fractures are the most common lower limb fractures. Some criteria such as open fractures and increasing open stage are known to be associated with high delayed union and pseudarthrosis rate. In cases of delayed or nonunion, classical treatment is autologous cancelous bone graft which is associated with high morbidity rate. The ideal treatment would be a percutaneous harvesting and grafting technique. As bone marrow autologous concentrate (BMAC) presents both advantages, we evaluated this technique from 2002 to 2007. METHODS: This was a retrospective study of 43 cases of open tibial fractures with initial surgical treatment. The criteria of inclusion were open fracture and nonunion, delayed union or suspicion of delayed union. RESULTS: In 23 cases (53.5 %) BMAC was successful. The success group had received significantly more CFU-F than the failure group (469 vs 153.10(3), p = 0.013). A threshold of 360.10(3) CFU-F grafted could be established over which there was 100 % success. BMAC done before 110 days after fracture had 47 % success and BMAC done since 110 days after fracture had 73 % success. BMAC success rate decreased with increasing initial fracture skin open stage. There was no BMAC success in cases of a fracture with a remaining gap of more than 4 mm. We had no complications with the technique at the iliac harvesting zone and tibia injection point. CONCLUSION: BMAC is a technique that should be considered as one of the different alternatives for management of long-bone delayed and nonunion because of its effectiveness, low complication rate, preservation of bone stock and low cost.


Asunto(s)
Trasplante de Médula Ósea/métodos , Trasplante Óseo/métodos , Fracturas Mal Unidas/cirugía , Fracturas de la Tibia/cirugía , Administración Cutánea , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Ilion/citología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
13.
J Orthop ; 58: 40-45, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39040137

RESUMEN

Introduction: Granuloma formation following total hip arthroplasty (THA) can occur regardless of the bearing surface. In very rare cases, extensive granulomas mimicking tumors may develop which are known as pseudotumors. The aim of this study is to report on these rare yet complex situations to stimulate reflection in diagnostic and therapeutic approaches. Methods: A retrospective case series study of 5 patients (2 females, 3 males) of aggressive granulomatous lesions on primary prostheses and 4 revision prostheses for aseptic loosening, implanted at a mean age of 74.8 years (range 64-83). A clinical, functional, radiographic, and anatomopathological analysis were conducted. Results: Four patients underwent revision surgery, while one died before intervention. Functional impairment was significant with a mean pre-reintervention Postel-Merle d'Aubigné (PMA) score of 8.2 (range 4-11). Femoral involvement was constant, associated with acetabular involvement in only one case. bony involvement was major, with a minimum of 5 Gruen zones affected, showing complete cortical lysis. Histopathological analysis consistently revealed multinucleated giant cells and macrophages, predominantly with metallic wear particles. In 2 cases, vascular involvement was suspected without a clearly delineated tumor. Two cases required femoral resection prostheses, one necessitated inter-ilio-abdominal amputation due to extensive soft tissue involvement, one underwent implant removal which failed to prevent progression, and one patient died before reoperation. Conclusion: The volume of lesions in these 5 cases appears markedly larger than reported cases.Extensive pseudo-tumoral granulomatous lesions following THA are rare but carry poor functional prognosis. Evaluation to rule out infection and neoplastic pathology is imperative. Surgical management often resembling tumor treatment should be considered. Early diagnosis is crucial to allow intervention before reaching the stage of massive prosthetic replacement. Level of evidence: IV retrospective study.

14.
Stud Health Technol Inform ; 316: 1979-1983, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39176881

RESUMEN

Electronic health data concerning implantable medical devices (IMD) opens opportunities for dynamic real-world monitoring to assess associated risks related to implanted materials. Due to population ageing and expanding demands, total hip, knee, and shoulder arthroplasties are increasing. Automating the collection and analysis of orthopedic device features could benefit physicians and public health policies enabling early issue detection, IMD monitoring and patient safety assessment. A machine learning tool using natural language processing (NLP) was developed for the automated extraction of operation information from medical reports in orthopedics. A corpus of 959 orthopaedic operative reports from 5 centres was manually annotated using the Prodigy software® with a strong inter-annotator agreement of 0.80. Data to extract concerned key clinical and procedure information (n= 9) selected by a multidisciplinary group based on the French health authority checklist. Performances parameters of the NLP model estimated an overall strong precision and recall of respectively 97.0 and 96.0 with a F1-score 96.3. Systematic monitoring of orthopedic devices could be ensured by an automated tool, leveraging clinical data warehouses. Traceability of medical devices with implantation modalities will allow detection of implant factors leading to complications. The evidence from real-world data could provide concrete and dynamic insights to surgeons and infectious disease specialists concerning implant follow-up, guiding therapeutic decision-making, and informing public health policymakers. The tool will be applied on clinical data warehouses to automate information extraction and presentation, providing feedback on mandatory information completion and contents of operative reports to support improvements, and thereafter implant research projects.


Asunto(s)
Registros Electrónicos de Salud , Aprendizaje Automático , Procesamiento de Lenguaje Natural , Francia , Humanos , Procedimientos Ortopédicos
15.
Mod Pathol ; 26(7): 911-21, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23370769

RESUMEN

GNAS (guanine nucleotide-binding protein/α-subunit) mutations that induce the activation of G-protein α-subunit participate in the pathogenesis of fibrous dysplasia. The aim of this study was to evaluate the sensitivity and specificity of GNAS mutations in fibrous dysplasia and other fibro-osseous lesions, to assess the value of investigating this mutation in the diagnosis of fibro-osseous lesions. We studied 91 cases of fibrous dysplasia. The quality and/or quantity of genomic DNA were suitable for molecular analysis for 51 cases of fibrous dysplasia. GNAS mutations were investigated by three techniques: high-resolution melting (exon 8), allele-specific PCR (exons 8 and 9) and/or direct DNA sequencing (exons 8 and 9). Fibrous dysplasia samples were classified blind to the GNAS mutation status into six histological subtypes as conventional, fibro-involutive, osteosclerosing, cementifying, osteocartilaginous and with prominent aneurysmal cystic changes. We also studied 14 cases of low-grade osteosarcoma, 21 cases of ossifying fibroma, 3 cases of osteofibrous dysplasia, 1 case of osseous dysplasia of the jawbone and 1 post-traumatic lesion of the ribs. Twenty-three cases of fibrous dysplasia (45%) showed mutations of codon 201 (exon 8, p.R201H or p.R201C). No mutation was found on codon 227 (exon 9). GNAS mutations in conventional fibrous dysplasia were detected in the same proportion (47%) as in the other histological subtypes (47%, P=0.96), regardless of sex (P=0.44), age (P=0.90) and location (P=1). GNAS mutations were not detected in any other fibro-osseous lesions. The GNAS mutation was thus specific to fibrous dysplasia in the context of fibro-osseous lesions. The particular mosaicism of mutant and non-mutant cells within the lesion or the existence of other mutations not already described could explain the lack of GNAS mutation in cases of fibrous dysplasia. Investigating this mutation may constitute a valuable complementary diagnostic tool, despite its low sensitivity, particularly in unconventional morphologically different subtypes of fibrous dysplasia.


Asunto(s)
Biomarcadores/análisis , Enfermedades del Desarrollo Óseo/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Mutación , Adolescente , Adulto , Neoplasias Óseas/genética , Niño , Cromograninas , Análisis Mutacional de ADN , Femenino , Fibroma Osificante/genética , Humanos , Masculino , Persona de Mediana Edad , Osteosarcoma/genética , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Adulto Joven
16.
Orthop Traumatol Surg Res ; 109(7): 103661, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37474020

RESUMEN

BACKGROUND: Trochanteric fractures are a public health issue due to the aging of the population. Treatment aims to reduce their related morbidity and mortality and to allow an early return to independence. Postoperative anemia is associated with poorer functional recovery and an increased mortality rate. The aim of this study was to assess whether minimally invasive side plate fixation (Minimal Invasive Screw System, MISS™) resulted in reduced perioperative bleeding compared with conventional fixation (Pertrochanteric Hip Screw, PHS™). HYPOTHESIS: We hypothesized that minimally invasive side plate fixation (MISS) would result in reduced perioperative bleeding compared with conventional fixation (PHS). PATIENTS AND METHODS: We conducted an open randomized controlled trial with blinded assessment of the primary outcome. Inclusion criteria were patients aged over 65 years with isolated reducible trochanteric fracture. The 2 surgical implants were of the same shape, the only difference between them being the locking mode of the femoral neck screw on the plate of the MISS device, allowing a percutaneous approach. Primary outcome was perioperative bleeding evaluated with Mercuriali's formula. Secondary outcomes included operating time, scar length, length of hospital stay, radiological criteria such as quality of fracture reduction, implant positioning, bone healing, complications and functional recovery compared between the 2 groups. RESULTS: One hundred and eight patients met the inclusion criteria and were randomized to receive either PHS (n=54) or MISS (n=54). Osteosynthesis with MISS significatively reduced perioperative bleeding (median 243mL, interquartile range [152-410] vs. 334mL [247-430] [p=0.0299]), operating time (65min [57-73] vs. 79min [66-89] [p=0.0002]) and scar length after 45 days (7cm [5-8] vs. 14cm [12-15] [p<0.0001]). There was no statistically significant difference between groups in postoperative complications, revision surgery or serious adverse events. CONCLUSION: Compared with PHS, MISS reduced operating time, perioperative bleeding and scar length with no observed functional difference. LEVEL OF EVIDENCE: I.


Asunto(s)
Cicatriz , Fracturas de Cadera , Humanos , Anciano , Resultado del Tratamiento , Fijación Interna de Fracturas/métodos , Tornillos Óseos , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Hemorragia , Placas Óseas
17.
Orthop Traumatol Surg Res ; : 103748, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37923176

RESUMEN

INTRODUCTION: Soft tissue sarcomas (STS) are often treated with wide excision in combination with adjuvant or neoadjuvant radiotherapy. This is currently the gold standard procedure for the treatment of STS that arise in the extremities. Wound healing complications frequently occur and negatively affect the prognosis. One of the options is to use a buried de-epithelialized flap as it can increase the lymphatic flow, fill the dead space, and cover neurovascular structures and implants. This aim of this retrospective study were two-fold. 1) Describe the surgical technique for this buried de-epithelialized flap after STS removal in the thigh. 2)Evaluate the efficacy of the buried de-epithelialized flap for decreasing wound complications based on a small case series and compare it with previous publications. HYPOTHESIS: We hypothesized that the complication rate of this flap is not higher than the published complication rate for traditional flaps. MATERIALS AND METHODS: Twelve patients (7 women and 5 men) with a mean age of 62±12years (38-76), who underwent surgical removal of an STS in the thigh with coverage by a buried de-epithelialized flap were reviewed at a mean follow-up of 15.8months (range 8-24). RESULTS: Two patients presented with a postoperative wound infection (17%): one superficial and one deep at the surgical site. Neither required an additional plastic surgery procedure. Another patient had a dislocation of their total hip arthroplasty that was managed by closed reduction. One patient died from metastatic progression. There was no skin necrosis of the superficial skin edges, no hematoma or seroma in the other 10 patients. The flap was still visible on cross-sectional imaging at 1 month postoperative with no fluid between the tissue planes or signs of necrosis. The rate of wound healing complications that required surgical treatment was 17% in our case series, versus 16 to 56% in previous publications reporting the results of suture closure only. CONCLUSION: A buried de-epithelialized flap reduces the risk of skin complications by filling dead space, improving lymphatic flow and covering critical structures. It is a reliable and reproducible option after wide local excision of STS in the thigh, with no additional morbidity. LEVEL OF EVIDENCE: IV, retrospective study.

18.
Orthop Traumatol Surg Res ; 108(1S): 103162, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34863958

RESUMEN

Adipose tumors of the limbs are the most common soft tissue lesions and are essentially benign (lipomas). However, in some cases, they can be considered as tumors with intermediate malignancy (atypical lipomatous tumor [ALT]) or sarcoma lineage (liposarcoma [LS]). The essential work-up for a potential adipose tumor consists of a clinical examination and initial ultrasound imaging to determine the size (more or less than 5 cm), the location (over or under the fascia) and any potential atypical vascularization. As needed, MRI will complete the assessment and validate the ultrasound results and confirm the fatty nature of the lesion. Percutaneous biopsy will be done when a deep fatty lesion is larger than 5 cm (long axis), with detection by amplification of the MDM2 gene that guides the diagnosis towards ALT or dedifferentiated LS. Superficial lesions without atypia are not challenging from a surgical point of view. However, large ALT can be more difficult to manage. Their local malignancy does not justify sacrificing any critical structures. As for true LS, their treatment is well defined, with tumor excision addressed at a center belonging to the Network of Sarcomas Reference Centers in France (NETSARC+) and for potential (neo)adjuvant treatment if needed. Inappropriate treatment of a malignant tumor can have serious consequences (loss of chance to survive or to be cured) for the patient. Furthermore, treatment at a specialized cancer center has been proven to be effective as it improves overall survival and reduces local recurrences.


Asunto(s)
Lipoma , Liposarcoma , Neoplasias de los Tejidos Blandos , Biopsia , Diagnóstico Diferencial , Humanos , Lipoma/diagnóstico , Lipoma/patología , Lipoma/cirugía , Liposarcoma/diagnóstico , Liposarcoma/patología , Liposarcoma/cirugía , Proteínas Proto-Oncogénicas c-mdm2/genética , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/cirugía
19.
Orthop Traumatol Surg Res ; 108(6): 103233, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35124250

RESUMEN

INTRODUCTION: Modular locking revision total hip arthroplasty femoral implants have been little assessed over the long term. We therefore conducted a retrospective assessment of the Renaissance™ fully hydroxyapatite-coated distal locking cementless femoral modular revision implant at a minimum 10 years' follow-up, analyzing: 1) survivorship, 2) complications, 3) radiologic and functional results, and 4) prevalence of thigh pain. HYPOTHESIS: This implant shows more than 90% 10-year survival. MATERIAL AND METHOD: Between December 2002 and December 2008, 213 implant exchanges were performed in 206 patients, including 97 Renaissance™ stems in 93 patients. Three patients were excluded for missing data. Survival was analyzed for 94 stems in 90 patients at a mean 11.2±3 years' follow-up; radiographic and clinical assessment was performed for 48 stems in 45 patients. The survival criterion was implant fracture and/or femoral stem removal. RESULTS: Survival was 93.5% at 10 years (95% CI: 86-97) and 91.3% at 15 years (95% CI: 82.9-96). Eight stems (8.5%) were exchanged or removed by last follow-up: 5 for infection (5.3%) and 3 for implant breakage (3.2%). The complications rate was 18.1% (N=17, including the 8 stem revisions): 3 stem exchanges for breakage (3.2%), 9 stem infections (9.6%), 3 dislocations (3.2%), and 2 traumatic greater trochanter fractures (2.1%). For the 45 patients with long-term clinical assessment, the mean Postel Merle d'Aubigné and Harris Hip scores were respectively 15±3 and 80 ±19 at last follow-up. Metaphysis reconstruction was satisfactory in 36/48 cases (75.0%). Seven of the 48 stems (14.6%) assessed at longest follow-up, in 45 patients, were causing thigh pain, unrelated to stress-shielding, distal locking screws or metaphyseal filling index. DISCUSSION: The Renaissance™ fully hydroxyapatite-coated modular locking stem with curved nail showed 90% 10-year survival, with satisfactory functional results and little thigh pain. LEVEL OF EVIDENCE: IV; case study without control group.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Artroplastia de Reemplazo de Cadera/métodos , Durapatita , Fémur/cirugía , Estudios de Seguimiento , Humanos , Dolor/cirugía , Diseño de Prótesis , Falla de Prótesis , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento
20.
Orthop Traumatol Surg Res ; 108(4): 103158, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34856405

RESUMEN

INTRODUCTION: Soft tissue sarcomas (STS) are rare malignant tumors that require regimented treatment at designated cancer centers. The surgical care of groin tumors is difficult because of frequent local complications. Few studies have been done on prognostic factors and complications. This led us to conduct a retrospective study to: (1) identify factors associated with local postoperative complications during the surgical care of primary groin STS; (2) identify the factors associated with delayed adjuvant radiation therapy; (3) define the optimal surgical treatment strategy to allow adjuvant treatments to start as early as possible, if applicable. HYPOTHESIS: We hypothesized that certain patients presenting with an STS of the groin or inguinal area are at higher risk of complications. MATERIALS AND METHODS: This retrospective single-center study included all the patients admitted to our referral sarcoma center between 1995 and 2016 for the resection of a primary STS of the groin. Major complications were defined as surgical revision, an invasive procedure, or prolonged dressing use. RESULTS: Of the 55 included patients, 13 suffered major complications (24%) of which 10 were surgical revisions, two were repeated aspirations and one was prolonged dressing use. Among the 10 surgical revisions, there were two pedicled salvage flaps. The patients who suffered major complications were significantly more likely to be smokers than the patients who did not have major complications (31% vs 2% (p=0.002)). Obesity and surgical bone exposure were most often associated with complications but not significantly (23% vs 5%, p=0.053 and 38% vs 14% (p=0.057), respectively). Of the 39 patients (71%) who needed postoperative radiation therapy, 5 patients (13%) had it delayed, and 3 patients (8%) did not receive any at all due to major complications. CONCLUSION: In our study, smoking was associated with the occurrence of major complications after groin STS resection and there was a strong trend for obesity and surgical bone exposure. Major complications were associated with a delay in starting postoperative radiation therapy. Thus, we recommend flap coverage after tumor resection in patients who have factors known to contribute to complications. LEVEL OF EVIDENCE: IV, Retrospective study.


Asunto(s)
Procedimientos de Cirugía Plástica , Sarcoma , Neoplasias de los Tejidos Blandos , Ingle/patología , Ingle/cirugía , Humanos , Obesidad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Sarcoma/radioterapia , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/cirugía
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