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1.
Rev Esp Cir Ortop Traumatol ; 68(2): 97-107, 2024.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36934806

RESUMO

BACKGROUND AND OBJECTIVE: In orthopedic surgery, it is clear that an optimal standardized closure technique has not yet been developed. Locally, there are no objective data describing the standard surgical practice in wound closure. The aim of this study is to analyze the clinical practice of surgical wound closure in orthopedic surgery by means of a survey of a representative local sample and thus obtain information on the context of closure in Spain. METHOD: an ad hoc group of specialists in orthopedic surgery and traumatology was formed. The group of experts, after analyzing the literature, developed a questionnaire of 32 closed multiple-choice questions divided into the following blocks: hemostasis, surgical wound closure (deep, superficial, and cutaneous), and dressings. RESULTS: A total of 471 surgeons responded to the survey completely and with sufficient information to perform the descriptive analysis. 79% believe that ATX can influence the decrease in surgical site infection rate. 96% believe that the type of deep closure at the level of the arthrotomy could influence outcomes and complications after hip and/or knee replacements. 85% believe that the type of shallow closure at the subcutaneous level may influence outcomes and complications after hip and/or knee replacement. 64% of surgeons use single-use incisional negative pressure therapy for the treatment of surgical wound complications (seroma, prolonged drainage, dehiscence). CONCLUSIONS: There is a high level of variability in wound closure in our setting and a low level of training on the subject. The authors recommend that the different scientific societies invest resources to improve training in this field and reduce the percentage of surgeons who are considered inadequately trained, as well as adapting closure techniques to those considered gold standard according to the evidence.

2.
Gene Ther ; 31(1-2): 12-18, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37985879

RESUMO

Glutaric Aciduria type I (GA1) is a rare neurometabolic disorder caused by mutations in the GDCH gene encoding for glutaryl-CoA dehydrogenase (GCDH) in the catabolic pathway of lysine, hydroxylysine and tryptophan. GCDH deficiency leads to increased concentrations of glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body fluids and tissues. These metabolites are the main triggers of brain damage. Mechanistic studies supporting neurotoxicity in mouse models have been conducted. However, the different vulnerability to some stressors between mouse and human brain cells reveals the need to have a reliable human neuronal model to study GA1 pathogenesis. In the present work we generated a GCDH knockout (KO) in the human neuroblastoma cell line SH-SY5Y by CRISPR/Cas9 technology. SH-SY5Y-GCDH KO cells accumulate GA, 3-OHGA, and glutarylcarnitine when exposed to lysine overload. GA or lysine treatment triggered neuronal damage in GCDH deficient cells. SH-SY5Y-GCDH KO cells also displayed features of GA1 pathogenesis such as increased oxidative stress vulnerability. Restoration of the GCDH activity by gene replacement rescued neuronal alterations. Thus, our findings provide a human neuronal cellular model of GA1 to study this disease and show the potential of gene therapy to rescue GCDH deficiency.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Encefalopatias Metabólicas , Lisina , Neuroblastoma , Humanos , Animais , Camundongos , Lisina/genética , Glutaril-CoA Desidrogenase/genética , Glutaril-CoA Desidrogenase/metabolismo , Camundongos Knockout , Terapia Genética
3.
Rev Esp Cir Ortop Traumatol ; 68(2): T97-T107, 2024.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37992859

RESUMO

BACKGROUND AND OBJECTIVE: In orthopaedic surgery, it is clear that an optimal standardised closure technique has not yet been developed. Locally, there are no objective data describing the standard surgical practice in wound closure. The aim of this study is to analyse the clinical practice of surgical wound closure in orthopaedic surgery by means of a survey of a representative local sample and thus obtain information on the context of closure in Spain. MATERIAL AND METHOD: An ad hoc group of specialists in orthopaedic surgery and traumatology was formed. The group of experts, after analyzing the literature, developed a questionnaire of 32 closed multiple-choice questions divided into the following blocks: hemostasis, surgical wound closure (deep, superficial, and cutaneous), and dressings. RESULTS: A total of 471 surgeons responded to the survey completely and with sufficient information to perform the descriptive analysis. 79% believe that ATX can influence the decrease in surgical site infection rate. 96% believe that the type of deep closure at the level of the arthrotomy could influence outcomes and complications after hip and/or knee replacements. 85% believe that the type of shallow closure at the subcutaneous level may influence outcomes and complications after hip and/or knee replacement. 64% of surgeons use single-use incisional negative pressure therapy for the treatment of surgical wound complications (seroma, prolonged drainage, dehiscence). CONCLUSIONS: There is a high level of variability in wound closure in our setting and a low level of training on the subject. The authors recommend that the different scientific societies invest resources to improve training in this field and reduce the percentage of surgeons who are considered inadequately trained, as well as adapting closure techniques to those considered gold standard according to the evidence.

4.
Eur J Haematol ; 112(4): 530-537, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38031389

RESUMO

OBJECTIVES: To compare the efficacy of venetoclax-azacitidine (VEN-AZA) with AZA in the real-life for patients with first relapsed or refractory acute myeloid leukaemia (R/R AML). METHODS: We retrospectively analysed R/R AML patients treated with VEN-AZA at the Institut Paoli Calmettes between September 2020 and February 2022. We compared them to a historical cohort of patients treated with AZA between 2010 and 2021. RESULTS: Thirty-five patients treated with VEN-AZA were compared with 140 patients treated with AZA. There were more favourable cytogenetics (25.7% vs. 8.6%; p = 0.01) and less FLT3-ITD mutated AML (8.8% vs. 25.5%; p = .049) in the VEN-AZA group. The overall 30-day mortality rate was 7.4% and the overall 90-day mortality was 20%, with no difference between the groups. The complete remission rate was 48.6% in the VEN-AZA group versus 15% (p < .0001). The composite complete response rate was 65.7% in the VEN-AZA group versus 23.6% (p < .0001). OS was 12.8 months in the VEN-AZA group versus 7.3 months (p = 0.059). Patients with primary refractory AML, poor-risk cytogenetics, prior hematopoietic stem-cell transplantation (HSCT) and FLT3-ITD mutated AML had lower response and survival rates. CONCLUSION: VEN-AZA was associated with a better response rate and a longer survival than AZA monotherapy in AML patients who relapsed after or were refractory to intensive chemotherapy.


Assuntos
Azacitidina , Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Azacitidina/uso terapêutico , Terapia de Salvação , Estudos Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
ESMO Open ; 8(3): 101213, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37075697

RESUMO

BACKGROUND: Up to 30% of metastatic breast cancer (BC) patients develop brain metastases (BM). Prognosis of patients with BM is poor and long-term survival is rare. Identification of factors associated with long-term survival is important for improving treatment modalities. PATIENTS AND METHODS: A total of 2889 patients of the national registry for BM in BC (BMBC) were available for this analysis. Long-term survival was defined as overall survival (OS) in the upper third of the failure curve resulting in a cut-off of 15 months. A total of 887 patients were categorized as long-term survivors. RESULTS: Long-term survivors compared to other patients were younger at BC and BM diagnosis (median 48 versus 54 years and 53 versus 59 years), more often had HER2-positive tumors (59.1% versus 36.3%), less frequently luminal-like (29.1% versus 35.7%) or triple-negative breast cancer (TNBC) (11.9% versus 28.1%), showed better Eastern Cooperative Oncology Group (ECOG) performance status (PS) at the time of BM diagnosis (ECOG 0-1, 76.9% versus 51.0%), higher pathological complete remission rates after neoadjuvant chemotherapy (21.6% versus 13.7%) and lower number of BM (n = 1, BM 40.9% versus 25.4%; n = 2-3, BM 26.5% versus 26.7%; n ≥4, BM 32.6% versus 47.9%) (P < 0.001). Long-term survivors had leptomeningeal metastases (10.4% versus 17.5%) and extracranial metastases (ECM, 73.6% versus 82.5%) less frequently, and asymptomatic BM more often at the time of BM diagnosis (26.5% versus 20.1%), (P < 0.001). Median OS in long-term survivors was about two times higher than the cut-off of 15 months: 30.9 months [interquartile range (IQR) 30.3] overall, 33.9 months (IQR 37.1) in HER2-positive, 26.9 months (IQR 22.0) in luminal-like and 26.5 months (IQR 18.2) in TNBC patients. CONCLUSIONS: In our analysis, long-term survival of BC patients with BM was associated with better ECOG PS, younger age, HER2-positive subtype, lower number of BM and less extended visceral metastases. Patients with these clinical features might be more eligible for extended local brain and systemic treatment.


Assuntos
Neoplasias Encefálicas , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/secundário , Prognóstico , Encéfalo
6.
Actas Urol Esp (Engl Ed) ; 46(10): 600-605, 2022 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36216763

RESUMO

INTRODUCTION: Papillary renal cell neoplasm with reverse polarity (PRNRP) has recently been recognized as an entity separate from the traditional classification of papillary renal cell carcinomas, due to its specific histopathological, immunophenotypic and molecular characteristics, as well as its indolent behavior. MATERIAL AND METHODS: We provide 6 new cases and a review of the literature published until the present time, which comprises a total number of 104 cases. RESULTS: Our PRNRP cases correspond to 5 men and one woman aged between 47 and 91 years. In 5 of the 6 cases, the PRNRP was an incidental finding in nephrectomy specimens. Nephrectomy had been indicated due to the presence of another renal tumor, except for one case, in which surgical intervention was indicated due to PRNRP. Our cases present mass sizes between 2 and 13 mm, as well as papillary histology with a monolayered lining of eosinophilic cells with low-grade nuclei in apical location. Immunohistochemically, they show a constant positivity for GATA3 and negativity for vimentin. KRAS mutations were identified in 50% of our cases. After a follow-up ranging between one and 60 months, 5 of the cases were still alive without recurrences or metastases, and one died from urothelial carcinoma. CONCLUSIONS: Our cases agree with the clinical and pathological characteristics described in the PRNRP cases published to date. With the present study, we provide the first series of national cases corroborating the existence of well-defined and constant diagnostic criteria that allow PRNRP to be considered as a distinctive entity.


Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias da Bexiga Urinária , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
7.
Ann Oncol ; 33(11): 1149-1158, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35961599

RESUMO

BACKGROUND: Addition of immune checkpoint inhibitors to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pathological complete response (pCR) rate by an absolute 9% (P = 0.287). PATIENTS AND METHODS: Patients with cT1b-cT4a-d triple-negative breast cancer (TNBC) received durvalumab 1.5 g or placebo every 4 weeks added to nab-paclitaxel 125 mg/m2 weekly for 12 weeks, followed by durvalumab/placebo every 4 weeks plus epirubicin/cyclophosphamide every 2 weeks followed by surgery. Durvalumab was not continued after surgery. The primary objective was pCR. Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). RESULTS: A total of 174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab versus 77.2% with placebo [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.97, stratified log-rank P = 0.036]; DDFS 91.7% versus 78.4% (HR 0.31, 95% CI 0.13-0.74, P = 0.005); OS 95.2% versus 83.5% (HR 0.24, 95% CI 0.08-0.72, P = 0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In the non-pCR cohort 3-year iDFS was 76.3% versus 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed a durvalumab effect independent of the pCR effect. No new safety signals occurred. CONCLUSIONS: Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of checkpoint inhibitors in the treatment of early TNBC.


Assuntos
Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida , Intervalo Livre de Doença
8.
J Biol Chem ; 298(8): 102248, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35820485

RESUMO

Protein phosphatase 2A (PP2A) is a major phospho-Ser/Thr phosphatase and a key regulator of cellular signal transduction pathways. While PP2A dysfunction has been linked to human cancer and neurodegenerative disorders such as Alzheimer's disease (AD), PP2A regulation remains relatively poorly understood. It has been reported that the PP2A catalytic subunit (PP2Ac) is inactivated by a single phosphorylation at the Tyr307 residue by tyrosine kinases such as v-Src. However, multiple mass spectrometry studies have revealed the existence of other putative PP2Ac phosphorylation sites in response to activation of Src and Fyn, two major Src family kinases (SFKs). Here, using PP2Ac phosphomutants and novel phosphosite-specific PP2Ac antibodies, we show that cellular pools of PP2Ac are instead phosphorylated on both Tyr127 and Tyr284 upon Src activation, and on Tyr284 following Fyn activation. We found these phosphorylation events enhanced the interaction of PP2Ac with SFKs. In addition, we reveal SFK-mediated phosphorylation of PP2Ac at Y284 promotes dissociation of the regulatory Bα subunit, altering PP2A substrate specificity; the phosphodeficient Y127/284F and Y284F PP2Ac mutants prevented SFK-mediated phosphorylation of Tau at the CP13 (pSer202) epitope, a pathological hallmark of AD, and SFK-dependent activation of ERK, a major growth regulatory kinase upregulated in many cancers. Our findings demonstrate a novel PP2A regulatory mechanism that challenges the existing dogma on the inhibition of PP2A catalytic activity by Tyr307 phosphorylation. We propose dysregulation of SFK signaling in cancer and AD can lead to alterations in PP2A phosphorylation and subsequent deregulation of key PP2A substrates, including ERK and Tau.


Assuntos
Proteína Fosfatase 2 , Proteínas Proto-Oncogênicas c-fyn , Quinases da Família src , Doença de Alzheimer/metabolismo , Humanos , Fosfoproteínas Fosfatases , Fosforilação , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Tirosina/metabolismo , Quinases da Família src/genética , Quinases da Família src/metabolismo , Proteínas tau/metabolismo
9.
ESMO Open ; 7(3): 100495, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35653983

RESUMO

BACKGROUND: Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital. PATIENTS AND METHODS: A total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype. RESULTS: Patients with HER2-positive breast cancer and BMs were-when compared with HER2-negative patients-slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus <60 years: hazard ratio (HR) 1.63, P < 0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P < 0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P < 0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P < 0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups. CONCLUSIONS: We identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Neoplasias Encefálicas/secundário , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/uso terapêutico , Sistema de Registros
10.
Mater Today Bio ; 10: 100098, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33763641

RESUMO

Collagen hydrogels are among â€‹the most well-studied platforms for drug delivery and in situ tissue engineering, thanks to their low cost, low immunogenicity, versatility, biocompatibility, and similarity to the natural extracellular matrix (ECM). Despite collagen being largely responsible for the tensile properties of native connective tissues, collagen hydrogels have relatively low mechanical properties in the absence of covalent cross-linking. This is particularly problematic when attempting to regenerate stiffer and stronger native tissues such as bone. Furthermore, in contrast to hydrogels based on ECM proteins such as fibronectin, collagen hydrogels do not have any growth factor (GF)-specific binding sites and often cannot sequester physiological (small) amounts of the protein. GF binding and in situ presentation are properties that can aid significantly in the tissue regeneration process by dictating cell fate without causing adverse effects such as malignant tumorigenic tissue growth. To alleviate these issues, researchers have developed several strategies to increase the mechanical properties of collagen hydrogels using physical or chemical modifications. This can expand the applicability of collagen hydrogels to tissues subject to a continuous load. GF delivery has also been explored, mathematically and experimentally, through the development of direct loading, chemical cross-linking, electrostatic interaction, and other carrier systems. This comprehensive article explores the ways in which these parameters, mechanical properties and GF delivery, have been optimized in collagen hydrogel systems â€‹and examines their in vitro or in vivo biological effect. This article can, therefore, be a useful tool to streamline future studies in the field, by pointing researchers into the appropriate direction according to their collagen hydrogel design requirements.

11.
Ann Hematol ; 99(4): 773-780, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32088745

RESUMO

Although complete remission (CR) is achieved in 50 to 70% of older fit patients with acute myeloid leukemia (AML), consolidation therapy in this age group remains challenging. In this retrospective study, we aimed to compare outcome in elderly patients treated with different post-remission modalities, including allogenic and autologous hematopoietic stem cell transplantation (HSCT), intensive chemotherapy, and standard-dose chemotherapy (repeated 1 + 5 regimen). We collected data of 441 patients ≥ 60 years in first CR from a single institution. Median age was 67 years. Sixty-one (14%) patients received allo-HSCT, 51 (12%) auto-HSCT, 70 (16%) intensive chemotherapy with intermediate- or high-dose cytarabine (I/HDAC), and 190 (43%) 1 + 5 regimen. Median follow-up was 6.5 years. In multivariate analysis, allo-HSCT, cytogenetics, and PS had a significant impact on OS and LFS. In spite of a more favorable-risk profile, the patients who received I/HDAC had no significantly better LFS as compared with patients treated with 1 + 5 (median LFS 8.8 months vs 10.6 months, p = 0.96). In transplanted patients, median LFS was 13.3 months for auto-HSCT and 25.8 months for allo-HSCT. Pre-transplant chemotherapy with I/HDAC had no effect on the outcome. Toxicity was significantly increased for both transplanted and non-transplanted patients treated with I/HDAC, with more units of blood and platelet transfusion and more time spent in hospitalization, but no higher non-relapse mortality. This study shows that post-remission chemotherapy intensification is not associated with significantly better outcome as compared with standard-dose chemotherapy in elderly patients for whom, overall results remain disappointing.


Assuntos
Quimioterapia de Consolidação , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transfusão de Componentes Sanguíneos , Terapia Combinada , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Daunorrubicina/administração & dosagem , Daunorrubicina/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
12.
Ann Pharm Fr ; 78(1): 70-75, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31810516

RESUMO

The rising of oral anticancer therapies let more and more patients to be cared at home and improve their quality of life. However the toxicities of these drugs and the distance with health professionals imply that the patient needs to be more autonomous with respect to his treatment. Patients through therapeutic education programs allows them to manage side effects, to be more observant and then to subsequently benefit from the treatment. We report here, oncology clinical pharmacists experiences in some health facilities in France, presented at the 1st day of clinical oncology pharmacy (December 2017, Marseille).


Assuntos
Antineoplásicos/uso terapêutico , Oncologia , Neoplasias/tratamento farmacológico , Farmácia , Academias e Institutos , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Institutos de Câncer , França/epidemiologia , Geriatria , Assistência Domiciliar , Humanos , Comunicação Interdisciplinar , Adesão à Medicação , Neoplasias/epidemiologia , Neoplasias/psicologia , Equipe de Assistência ao Paciente , Educação de Pacientes como Assunto/organização & administração , Qualidade de Vida , Encaminhamento e Consulta , Terapias em Estudo
13.
Br J Oral Maxillofac Surg ; 57(10): 1081-1085, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31601435

RESUMO

Peripheral ossifying fibromas are benign mesenchymal lesions that usually arise in the anterior maxilla of young female patients. Histologically they consist of spindle cell proliferation with focal mineralisation. We reviewed 48 specimens from 41 patients and recorded the clinical data, sex, and age of the patients, site and size of the lesions, treatment, and postoperative outcome. Histologically the presence of mature, woven bone, cementum, and calcifications were evaluated and evaluated immunohistochemically. Lesions were more frequent in female patients in the third and fourth decade, and were usually in the lower maxilla and smaller than 2cm. All lesions were conservatively excised, and they relapsed in eight patients. Histopathologically, the lesions were poorly circumscribed, moderately cellular proliferations, with no discernible architectural pattern. All tumours showed some degree of mineralisation, the presence of immature bone being the most common. Immunohistochemical examination showed staining of tumoural cells for smooth muscle actin and CD68. Lesions tended to occur more commonly in female patients, but one decade later than usually reported. We found a higher recurrence rate in lesions that contained cementum-like material but without bone formation, suggesting a lack of maturation in this group. Immunohistochemical results were consistent with myofibroblastic differentiation but they added no information about the behaviour of the lesions.


Assuntos
Calcinose , Fibroma Ossificante , Neoplasias Gengivais , Calcificação Fisiológica , Calcinose/patologia , Feminino , Fibroma Ossificante/patologia , Neoplasias Gengivais/patologia , Humanos , Maxila
14.
J Virol ; 93(6)2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30567992

RESUMO

B lymphocytes are the major cellular reservoir in individuals infected with Kaposi's sarcoma-associated herpesvirus (KSHV), and the virus is etiologically linked to two B cell lymphoproliferative disorders. We previously described the MC116 human B cell line as a KSHV-susceptible model to overcome the paradoxical refractoriness of B cell lines to experimental KSHV infection. Here, using monoclonal antibody inhibition and a deletion mutant virus, we demonstrate that the KSHV virion glycoprotein K8.1A is critical for infection of MC116, as well as tonsillar B cells; in contrast, we confirm previous reports on the dispensability of the glycoprotein for infection of primary endothelial cells and other commonly studied non-B cell targets. Surprisingly, we found that the role of K8.1A in B cell infection is independent of its only known biochemical activity of binding to surface heparan sulfate, suggesting the possible involvement of an additional molecular interaction(s). Our finding that K8.1A is a critical determinant for KSHV B cell tropism parallels the importance of proteins encoded by positionally homologous genes for the cell tropism of other gammaherpesviruses.IMPORTANCE Elucidating the molecular mechanisms by which KSHV infects B lymphocytes is critical for understanding how the virus establishes lifelong persistence in infected people, in whom it can cause life-threatening B cell lymphoproliferative disease. Here, we show that K8.1A, a KSHV-encoded glycoprotein on the surfaces of the virus particles, is critical for infection of B cells. This finding stands in marked contrast to previous studies with non-B lymphoid cell types, for which K8.1A is known to be dispensable. We also show that the required function of K8.1A in B cell infection does not involve its binding to cell surface heparan sulfate, the only known biochemical activity of the glycoprotein. The discovery of this critical role of K8.1A in KSHV B cell tropism opens promising new avenues to unravel the complex mechanisms underlying infection and disease caused by this viral human pathogen.


Assuntos
Linfócitos B/metabolismo , Glicoproteínas/metabolismo , Heparitina Sulfato/metabolismo , Infecções por Herpesviridae/metabolismo , Herpesvirus Humano 8/metabolismo , Tropismo/fisiologia , Proteínas Virais/metabolismo , Animais , Células CHO , Linhagem Celular , Cricetulus , Células Endoteliais/metabolismo , Humanos
15.
J Med Vasc ; 42(5): 255-262, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28964384

RESUMO

BACKGROUND/AIM: Long-term use of low-molecular-weight heparins (LMWH) for the treatment of cancer-associated thrombosis (CAT) has been well-established. Conversely, the use of thromboprophylaxis in patients with cancer remains controversial in the absence of homogeneous guidelines. Our aim was to assess the awareness of treatment guidelines and the management of patients with CAT in daily clinical practice. METHODS: A national survey based on an open questionnaire developed by a panel of health professionals including specialists in vascular medicine, oncology, supportive care and pharmacy, was proposed on line to 2104 specialists experts in the management of CAT with the objective to collect at least 400 answers. Clinical practice assessment included the treatment of lung adenocarcinoma-associated thrombosis, the use of thromboprophylaxis and factors influencing the management of patients with CAT. RESULTS: A total of 401 questionnaires were completed by specialists of vascular medicine (68%), oncology (12%) and other (20%). LMWH was the preferred option for over 90% of the participants for the treatment of recent overt proximal pulmonary embolism or deep-vein thrombosis. Up to 70% of the participants considered treatment duration for 6 months and more than 12 months in case of active malignancy. Patient management in the setting of incidental VTE and thromboprophylaxis were heterogeneous in the absence of clear guidance while VTE risk scores would be used by only 14% of participants. CONCLUSION: Patients with CAT are properly managed based on clear and consistent guidelines. Patient care is heterogeneous regarding treatment duration beyond 6 months and thromboprophylaxis while VTE risk scores are misused. Identification of referent health care professionals for CAT management and more clear guidelines are required.


Assuntos
Heparina de Baixo Peso Molecular/uso terapêutico , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Adenocarcinoma/complicações , Adulto , Cardiologia , Feminino , França , Pesquisas sobre Atenção à Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Neoplasias Pulmonares/complicações , Masculino , Oncologia , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Trombose/etiologia
16.
Rev Esp Cir Ortop Traumatol ; 61(6): 419-426, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28888683

RESUMO

The prevalence of adult spinal deformity has been increasing exponentially over time. Surgery has been credited with good radiological and clinical results. The incidence of complications is high. MIS techniques provide good results with fewer complications. This is a retrospective study of 25 patients with an adult spinal deformity treated by MIS surgery, with a minimum follow-up of 6 months. Radiological improvement was SVA from 5 to 2cm, coronal Cobb angle from 31° to 6°, and lumbar lordosis from 18° to 38°. All of these parameters remained stable over time. We also present the complications that appeared in 4 patients (16%). Only one patient needed reoperation. We describe the technique used and review the references on the subject. We conclude that the MIS technique for treating adult spinal deformity has comparable results to those of the conventional techniques but with fewer complications.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Curvaturas da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Curvaturas da Coluna Vertebral/diagnóstico por imagem , Resultado do Tratamento
17.
Actas Urol Esp ; 41(9): 577-583, 2017 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28461097

RESUMO

OBJECTIVES: The incidental presence of seminal vesicle epithelium in prostate needle biopsies is generally recognisable through routine microscopy. However, the biopsy can sometimes be erroneously interpreted as malignant due to its architectural and cytological characteristics, and immunohistochemistry can be useful for correctly identifying the biopsy. Our objective was to analyse the potential usefulness of GATA-3 as a marker of seminal epithelium. MATERIAL AND METHODS: Through immunohistochemistry with a monoclonal anti-GATA-3 antibody (clone L50-823), we studied seminal vesicle sections from 20 prostatectomy specimens, 12 prostate needle biopsies that contained seminal vesicle tissue and 68 prostate biopsies without seminal vesicle epithelium, 36 of which showed adenocarcinoma. RESULTS: Staining for GATA-3 was intense in the 20 seminal vesicles of the prostatectomy specimens and in the 12 prostate needle biopsies that contained seminal epithelium. In the 60 biopsies without a seminal vesicle, GATA-3 was positive in the prostate basal cells and even in the secretory cells (57 cases), although with less intensity in 55 of the cases. One of the 36 prostatic adenocarcinomas tested positive for GATA-3. CONCLUSIONS: The intense immunohistochemical expression of GATA-3 in the seminal vesicle epithelium can help identify the epithelium in prostate biopsies. This marker is also positive in the basal cells of healthy prostates and, with less intensity, in the secretory cells. Positivity, weak or moderate, is observed on rare occasions in prostatic adenocarcinomas.


Assuntos
Biomarcadores Tumorais/análise , Fator de Transcrição GATA3/análise , Próstata/patologia , Glândulas Seminais/química , Glândulas Seminais/patologia , Biópsia por Agulha , Epitélio/química , Epitélio/patologia , Humanos , Imuno-Histoquímica , Masculino
18.
Rev Esp Cir Ortop Traumatol ; 61(1): 8-18, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27919706

RESUMO

«Minimally invasive¼ techniques have been recently been developed in order to achieve good clinical results with a low incidence of complications. The extralateral interbody fusion or direct transpsoas is a minimally invasive anterior arthrodesis. A total of 97 patients with 138 segments received surgery between May 2012 and May 2015. The follow-up was from 12-44 months. The mean age was 68 years (41-86). The most common cause of intervention was the adjacent segment (30%), deformity (22%), and lumbar disc disease (21%). The interbody cage was implanted as: Single (stand-alone) in 33%, and additional fixation was used in the others: Screws, percutaneous unilateral (11%), bilateral (27%), or with a lateral plate (62%). The mean stay was 3.2 days (2-6). The score on a lumbar visual analogue scale decreased from 9 to 4.1, and dropped to 3 after one year. The improvement in disc height was from 8.4mm to 13.8mm, and a larger increase in the foramen diameter from 10.5 to 13.1mm, which were statistically significant. The early major complications recorded were, three motor femoral nerve injuries and retroperitoneal haematoma (4%), and the early minor were: two fractures (2%). As major late complications there was an abdominal hernia, a mobilization of 10mm and three radiculopathy (5%), and as minor late, three fracture, two mobilisations greater than 10mm, four mobilisations of less than 10mm, and one mobilisation of a screw plate (10%). The extralateral interbody fusion technique is a safe and reliable when performing a lumbar fusion by an alternative minimally invasive route.


Assuntos
Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fusão Vertebral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Placas Ósseas , Parafusos Ósseos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Fusão Vertebral/instrumentação
19.
Dis Esophagus ; 29(2): 185-91, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25515856

RESUMO

Nonerosive reflux disease (NERD) is commonly diagnosed in patients with symptoms of reflux. The aim of the present study was to determine whether high-definition endoscopy (HD) plus equipped with the iScan function or chromoendoscopy with Lugol's solution might permit the differentiation of NERD patients from those without reflux symptoms, proven by targeted biopsies of endoscopic lesions. A total of 100 patients without regular intake of proton pump inhibitors and with a normal conventional upper endoscopy were prospectively divided into NERD patients and controls. A second upper endoscopy was performed using HD+ with additional iScan function and then Lugol's solution was applied. Biopsy specimens were taken from the gastroesophageal junction in all patients. A total of 65 patients with reflux symptoms and 27 controls were included. HD(+) endoscopy with iScan revealed subtle mucosal breaks in 52 patients; the subsequent biopsies confirmed esophagitis in all cases. After Lugol's solution, 58 patients showed mucosal breaks. Sensitivity for the iScan procedure was 82.5%, whereas that for Lugol's solution was 92.06%. Excellent positive predictive values of 100% and 98.3%, respectively, were noted. The present study suggests that the majority of patients with NERD and typical symptoms of reflux disease can be identified by iScan or Lugol's chromoendoscopy as minimal erosive reflux disease (ERD) patients.


Assuntos
Esofagoscopia/métodos , Refluxo Gastroesofágico/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Iodetos , Estudos de Casos e Controles , Diagnóstico Diferencial , Mucosa Esofágica/patologia , Junção Esofagogástrica/patologia , Feminino , Refluxo Gastroesofágico/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Rev Epidemiol Sante Publique ; 63(6): 381-6, 2015 Dec.
Artigo em Francês | MEDLINE | ID: mdl-26525094

RESUMO

AIM: Quality of life of patients suffering from cancer may be influenced by the way healthcare is organized and by patient experiences. Nowadays, chemotherapy is often provided in day care centers. This study aimed to assess patient waiting time and satisfaction in oncology day care centers in Champagne-Ardenne, France. METHODS: This cross-sectional survey involved all patients receiving ambulatory chemotherapy during a one-week period in day care centers of Champagne-Ardenne public and private healthcare institutions participating in the study. Sociodemographic, medical and outpatient data were collected. Patient satisfaction was measured using the Out-Patsat35 questionnaire. RESULTS: Eleven (out of 16) oncology day care centers and 441 patients participated in the study. Most of the patients were women (n=252, 57.1%) and the mean age was 61±12 years. The mean satisfaction score was 82±14 (out of 100) and the mean waiting time between the assigned appointment time and administration of chemotherapy was 97±60 min. CONCLUSION: This study has shown that waiting times are important. However, patients are satisfied with the healthcare organization, especially regarding nursing support. Early preparation of chemotherapy could improve these parameters.


Assuntos
Hospital Dia/estatística & dados numéricos , Serviço Hospitalar de Oncologia/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Listas de Espera , Idoso , Assistência Ambulatorial/estatística & dados numéricos , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
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