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1.
Surgery ; 175(1): 172-179, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37935599

RESUMO

BACKGROUND: The impact of parathyroidectomy on bone mineral density in men with primary hyperparathyroidism is poorly known. This study aimed to evaluate the bone mineral density and bone remodeling biomarker changes in men with primary hyperparathyroidism 1 year after parathyroidectomy. METHODS: Men operated for sporadic primary hyperparathyroidism between 2016 and 2022, enrolled in a monocentric prospective cohort, were analyzed. Patients with follow-up <1 year or missing data were excluded. Bone mineral density (dual X-ray absorptiometry) was measured before and 12 months after parathyroidectomy. Bone mineral density change ≥0.03g/cm2 was deemed significant. Bone remodeling biomarkers were serum cross-linked C-telopeptide, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatases. RESULTS: Forty-five men were included (mean age 58.8 ± 13.1 years). Before surgery, 49% had osteopenia, and 11% had osteoporosis. Mean serum calcium and median serum parathyroid hormone levels decreased significantly after surgery (P < .0001). One year after parathyroidectomy, the mean bone mineral density increased significantly at the lumbar spine (+0.04g/cm2 [0.01;0.70], P = .0054), femoral neck (+0.04g/cm2 [0.03;0.05], P < .0001) and total hip (+0.02g/cm2 [0.01;0.03], P = .0002). Considering significant bone mineral density gain (+1 point) and loss (-1 point) at each site, 29/45 patients (64% [95% CI 49;78]) improved. Bone remodeling biomarker concentrations significantly decreased (P < .001). CONCLUSION: Parathyroidectomy positively affects bone mineral density in men with primary hyperparathyroidism, supporting osteopenia as a surgical indication in these patients.


Assuntos
Doenças Ósseas Metabólicas , Hiperparatireoidismo Primário , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Densidade Óssea , Estudos Prospectivos , Hiperparatireoidismo Primário/cirurgia , Paratireoidectomia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/cirurgia , Biomarcadores , Cálcio
2.
J Clin Endocrinol Metab ; 109(6): 1494-1504, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38152848

RESUMO

CONTEXT: Osteoporosis and/or bone fractures are indications of parathyroidectomy in primary hyperparathyroidism (PHPT), especially in women. However, the benefit of surgery in patients with osteopenia remains unclear. OBJECTIVE: To evaluate bone mineral density (BMD) and bone remodeling biomarkers changes 1 year after parathyroidectomy in women with PHPT. DESIGN: In the prospective, monocentric, observational prospective cohort with primary hyperparathyroidism patients (CoHPT) cohort, women operated for sporadic PHPT since 2016 with ≥1 year follow-up were included. BMD (dual-X ray absorptiometry) and bone remodeling biomarkers [cross-linked C-telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatases] were assessed before and 1 year after parathyroidectomy. SETTING: Referral center. PATIENTS: A total of 177 women with PHPT (62.5 ± 13.3 years, 83.1% menopausal, 43.9% osteopenic, and 45.1% osteoporotic) were included. INTERVENTION: Parathyroidectomy. MAIN OUTCOME MEASURE: BMD change between before and 1 year after parathyroidectomy. RESULTS: Parathyroidectomy resulted in significant increase in BMD and decrease in serum bone remodeling biomarker concentrations. In the 72 patients with baseline osteopenia, mean BMD significantly increased at the lumbar spine [+0.05 g/cm2 (95% confidence interval [CI], 0.03-0.07)], the femoral neck [+0.02 g/cm2 (95% CI 0.00-0.04)], the total hip [+0.02 g/cm2 (95% CI 0.01-0.02)], and the forearm [+0.01 (95% CI 0.00-0.02)], comparable to osteoporotic patients. Among osteopenic patients, those with individual BMD gain (>0.03 g/cm2) at ≥1 site had higher preoperative serum CTX, P1NP, and urine calcium concentrations than those without improvement. CONCLUSION: Parathyroidectomy significantly improved BMD and remodeling biomarkers in women with osteopenia, thereby supporting the benefit of parathyroidectomy in these patients. Preoperative serum CTX and P1NP concentrations could be useful to predict expected BMD gain.


Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas , Hiperparatireoidismo Primário , Paratireoidectomia , Humanos , Feminino , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/complicações , Pessoa de Meia-Idade , Doenças Ósseas Metabólicas/cirurgia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/sangue , Idoso , Estudos Prospectivos , Remodelação Óssea , Biomarcadores/sangue , Absorciometria de Fóton , Seguimentos , Resultado do Tratamento
3.
Pediatr Rheumatol Online J ; 21(1): 95, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670340

RESUMO

BACKGROUND: Although the advent of new therapeutics for juvenile idiopathic arthritis (JIA) patients has considerably lessened the impact of the disease and reduced its sequelae, the outcomes of JIA remain important in their lives. Disease repercussions and side effects of treatments may affect sexual health and cause psychological distress. This aim of the study was to determine the expectations of adolescent JIA patients and the perceptions of their parents regarding knowledge and communication with healthcare providers (HCPs) in the field of sexual health (SH). METHODS: In France, from September 2021 to April 2022, a survey was conducted, using anonymous self-administered questionnaires, among JIA patients (adults (aged 18-45 years) to provide insights from their recollection of their adolescence) and their parents in nine rheumatology centers and three patient associations. RESULTS: The responses to the 76 patient questionnaires and 43 parent questionnaires that were collected were analyzed. Half of the patients thought JIA impacted their romantic relationships, but the results were less clear-cut for their sexual activity; and 58.7% of the patients said they would be comfortable discussing the subject with HCPs, but only 26.3% had done so, mainly regarding biomedical issues. The patients and their parents thought that ideally, the topic should be addressed in an individual patient education session at the hospital (51.3% and 34.9%, respectively), in a regular consultation (47.4% and 53.5%), or in a dedicated consultation requested by the adolescent without the adolescent's parents being informed (38.2% and 20.9%). Most of the respondents thought HCPs should be proactive in SH (77.6% of the patients and 69.8% of their parents). More patients than parents said the following digital information tools must be used: videos (29.0% vs. 9.3%, p = 0.0127) and smartphone applications (25.0% vs. 9.3%, p = 0.0372). CONCLUSION: HCPs should consider addressing the unmet need for SH discussions during their patient encounters. To meet this need, we propose concrete actions in line with the wishes of patients and parents. CLINICAL TRIAL REGISTRATION NUMBER: NCT04791189.


Assuntos
Artrite Juvenil , Saúde Sexual , Adulto , Humanos , Adolescente , Comunicação , Pais , Inquéritos e Questionários
4.
Nutrients ; 14(14)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35889908

RESUMO

Severe forms of anorexia nervosa are responsible for weight loss and life-threatening consequences. Refeeding represents a real psychiatric and somatic challenge. Physical activities are usually not recommended during intensive refeeding in order to avoid energy expenditure. This study assessed the interest in an early return to controlled physical activities, during a hospitalization in a Physical Medicine and Rehabilitation (PMR) department, including continuous nasogastric refeeding and psychiatric care. A total of 37 subjects aged 32 ± 11 years old performed inpatient physical activities during nasogastric refeeding initiated after intensive care. The physical activity program was adapted according to the hyperactivity of the patients. Evaluation parameters were weight, body mass index (BMI), body composition (fat, lean, and bone masses), and function (strength, balance, walking, ventilation). Patient satisfaction, re-hospitalizations, and physical activities continuation were assessed at 12 months of follow-up. Weight, BMI, and body fat increased significantly (+2.7 ± 1.7 kg; +1.0 ± 0.6 kg/m2; +1.7 ± 2.5 kg, respectively). Muscle strength increased even if the lean mass did not. Walking distance, balance, and respiratory function were significantly improved. Weight and fat mass gains did not differ according to the presence or absence of hyperactivity. At 12 months, 46% of the patients continued to be physically active, but 21% of the patients had been re-hospitalized. The early return to controlled physical activities in PMR hospitalization does not compromise the efficiency of intensive refeeding in severe anorexia nervosa patients.


Assuntos
Anorexia Nervosa , Adulto , Composição Corporal , Índice de Massa Corporal , Humanos , Pacientes Internados , Intubação Gastrointestinal , Adulto Jovem
5.
Clin Nucl Med ; 47(2): e197-e198, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35006119

RESUMO

ABSTRACT: A 61-year-old woman presenting with hyperthyroidism received 131I therapy for a toxic adenoma diagnosed by 123I scintigraphy. Six months later, the patient had a relapse of hyperthyroidism, and 123I scintigraphy showed a mirror image of the first scintigraphy: a high and diffuse uptake in the thyroid gland except for the previously treated nodule. Graves disease was confirmed by elevated thyrotropin receptor antibodies. The patient was cured by a second radioiodine therapy. Radioiodine-induced Graves disease may occur within 6 months of 131I treatment of toxic adenoma and can be treated with a second line of 131I.


Assuntos
Adenoma , Doença de Graves , Hipertireoidismo , Feminino , Humanos , Radioisótopos do Iodo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Cintilografia
6.
Nutrients ; 13(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200558

RESUMO

(1) Osteoporosis and sarcopenia are frequent pathologies among the geriatric population. The interlink between these two diseases is supported by their common pathophysiology. The aim is to explore the relationship between bone mineral density (BMD) and body composition in women aged 75 or older. (2) From January 2016 to December 2019, women aged 75 or older of Caucasian ethnicity, who were addressed to perform a biphoton absorptiometry (DXA), were included in this observational study. Femoral neck T-score, lean mass, fat mass, and physical performances were measured. (3) The mean age of 101 patients included was 84.8 (±4.9) years old. Osteoporosis was present in 72% of patients. According to EWGSOP criteria, 37% of patients were sarcopenic. Osteosarcopenia was present in 34% of patients. The femoral neck T-score was significantly associated with fat mass (ß = 0.02, 95% CI (0.01; 0.03), p < 0.05) in multivariable analysis. Osteosarcopenic patients had significantly lower fat mass (16.2 kg (±6.8) vs. 23.1 kg (±10.8), p < 0.001) and body mass index (BMI) (20.7 kg/m2 (±2.8) vs. 26.7 kg/m2 (±5.6), p < 0.001). (4) In postmenopausal women, fat mass is estimated to provide hormonal protection. While osteosarcopenia is described as a lipotoxic disease, fat mass and BMI would appear to protect against the risk of osteosarcopenia. This raises questions about the relevance of BMI and DXA.


Assuntos
Adiposidade/fisiologia , Densidade Óssea/fisiologia , Exercício Físico/fisiologia , Magreza/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Análise Fatorial , Feminino , Colo do Fêmur/fisiopatologia , Humanos , Análise Multivariada , Osteoporose/diagnóstico , Osteoporose/fisiopatologia , Fatores de Risco
7.
Appl Clin Inform ; 12(2): 237-244, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33763845

RESUMO

BACKGROUND: Today, in France, it is estimated that 1 in 850 people aged between 20 and 45 years has been treated for childhood cancer, which equals 40,000 to 50,000 people. As late effects of the cancer and its treatment affect a large number of childhood cancer survivors (CCS) and only 30% of them benefit from an efficient long-term follow-up care for prevention, early detection, and treatment of late effects, health education of CCS represents a challenge of public health. OBJECTIVES: Massive open online courses (MOOCs) are a recent innovative addition to the online learning landscape. This entertaining and practical tool could easily allow a deployment at a national level and make reliable information available for all the CCS in the country, wherever they live. METHODS: The MOOC team brings together a large range of specialists involved in the long-term follow-up care, but also associations of CCS, video producers, a communication consultant, a pedagogical designer, a cartoonist and a musician. We have designed three modules addressing transversal issues (lifestyle, importance of psychological support, risks of fertility problems) and eight modules covering organ-specific problems. Detailed data on childhood cancer treatments received were used to allocate the specific modules to each participant. RESULTS: This paper presents the design of the MOOC entitled "Childhood Cancer, Living Well, After," and how its feasibility and its impact on CCS knowledge will be measured. The MOOC about long-term follow-up after childhood cancer, divided into 11 modules, involved 130 participants in its process, and resulted in a 170-minute film. The feasibility study included 98 CCS (31 males vs. 67 females; p < 0.0001). CONCLUSION: Such personalized, free, and online courses with an online forum and a possible psychologist consultation based on unique characteristics and needs of each survivor population could improve adherence to long-term follow-up without alarming them unnecessarily.


Assuntos
Sobreviventes de Câncer , Educação a Distância , Neoplasias , Adulto , Criança , Comunicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobreviventes , Adulto Jovem
8.
Front Med (Lausanne) ; 8: 817873, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35111788

RESUMO

Noonan syndrome (NS) is an autosomal dominant multisystem disorder caused by the dysregulation of the Rat Sarcoma/Mitogen-activated protein kinase (RAS/MAPK) pathway and characterized by short stature, heart defects, pectus excavatum, webbed neck, learning disabilities, cryptorchidism, and facial dysmorphia. Villonodular synovitis is a joint disorder most common in young adults characterized by an abnormal proliferation of the synovial membrane. Multifocal Villonodular synovitis is a rare disease whose recurrent nature can make its management particularly difficult. Currently, there is no systemic therapy recommended in diffuse and recurrent forms, especially because of the fear of long-term side effects in patients, who are usually young. Yet, tyrosine kinase inhibitors seem promising to reduce the effects of an aberrant colony stimulating factor-1 (CSF-1) production at the origin of the synovial nodule proliferation. We present here the case of a 21-year-old woman with NS associated to diffuse multifocal villonodular synovitis (DMVS). Our clinical case provides therapeutic experience in this very rare association. Indeed, in association with surgery, the patient improved considerably: she had complete daily life autonomy, knee joint amplitudes of 100° in flexion and 0° in extension and was able to walk for 10 min without any technical assistance. To our knowledge, this is the first case of a patient suffering from DMVS associated with a Noonan syndrome treated with Glivec® (oral administration at a dosage of 340 mg/m2 in children, until disease regression) on a long-term basis.

9.
J Med Case Rep ; 14(1): 130, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32792004

RESUMO

BACKGROUND: The rebound effect after stopping treatment with denosumab may be associated with rapid loss of the gains in bone mineral density achieved with treatment, high levels of bone remodeling markers, the occurrence of vertebral fractures, and even hypercalcemia. CASE PRESENTATION: A 64-year-old osteoporotic Caucasian woman suffered from a fracture of her second lumbar vertebra in 2004. From January 2005, she was treated with denosumab for 9 years, with good densitometry results for her hip and lumbar areas, and no fractures over the last 6 years of treatment. Ten months after the treatment with denosumab was stopped, a cascade of vertebral fractures, including some in unusual locations (third thoracic vertebra), and multiple rib fractures in a context of hypercalcemia, suggested possible malignancy. A complete evaluation, including systemic, biological, and biopsy analyses, ruled out this hypothesis. The hypercalcemia was associated with normal plasma phosphate and vitamin D concentrations, and a high parathyroid hormone level, with an abnormal fixation of the lower lobe of the thyroid on sesta-methoxy-isobutyl-isonitrile scintigraphy. Histological analysis of the excised parathyroid tissue revealed hyperplasia. The associated thyroidectomy (goiter) led to the discovery of a thyroid papillary microcarcinoma. CONCLUSIONS: We consider the consequences of this rebound effect, not only in terms of the major loss of bone density (return to basal values within 3 years) and the multiple disabling fracture episodes, but also in terms of the hypercalcemia observed in association with apparently autonomous tertiary hyperparathyroidism. Several cases of spontaneous reversion have been reported in children, but the intervention in our patient precluded any assessment of the possible natural course. The discovery of an associated thyroid neoplasm appears to be fortuitous. Better understanding of the various presentations of the rebound effect after stopping treatment with denosumab would improve diagnostic management of misleading forms, as in this case. Bisphosphonates could partially prevent this rebound effect.


Assuntos
Conservadores da Densidade Óssea , Fraturas Múltiplas , Hipercalcemia , Osteoporose , Densidade Óssea , Conservadores da Densidade Óssea/efeitos adversos , Criança , Denosumab/efeitos adversos , Feminino , Seguimentos , Humanos , Hipercalcemia/tratamento farmacológico , Hiperplasia , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico
10.
Joint Bone Spine ; 87(6): 618-624, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32428690

RESUMO

OBJECTIVES: Patients with acromegaly appear to be at increased risk of vertebral fractures despite normal bone mineral density. We investigated the prevalence of vertebral fractures in a cohort of acromegalic patients under 80 years of age. METHODS: Monocentric cross-sectional study performed at Nantes University Hospital from 1988 to 2018. Fifty patients (18 females, 32 males) with a median age of 52.3 years (range: 27-78) were included. Radiological vertebral fractures were evaluated on conventional lumbar and thoracic spine radiographs using Genant's semiquantitative fracture assessment. We studied qualitative abnormalities of the spine using three criteria: osteophytes, disc-space narrowing and wedge-shaped vertebrae. We analysed bone mineral density and endocrine status. RESULTS: Three patients (6%) had a vertebral fracture: one grade 1 and two grade 2 according to Genant's assessment, with two osteoporotic and one osteopenic patients. They had no unsubstituted pituitary deficiency. Considering the frank deformations (osteophyte or disc narrowing≥grade 2 or wedge-shaped), the thoracic spine was deformed in 22 patients (44%) and the lumbar spine in 21 patients (42%). CONCLUSION: Acromegalic patients had a low prevalence of vertebral fractures but had a significant amount of vertebral deformations. We speculate that this high prevalence of frank deformations could explain the previously reported high prevalence of vertebral fractures.


Assuntos
Acromegalia , Fraturas da Coluna Vertebral , Acromegalia/complicações , Acromegalia/diagnóstico por imagem , Acromegalia/epidemiologia , Adulto , Idoso , Densidade Óssea , Estudos Transversais , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Prevalência , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia
11.
Sci Rep ; 10(1): 4650, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157159

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

12.
Basic Res Cardiol ; 115(3): 26, 2020 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-32146560

RESUMO

Mesenchymal stromal cells (MSCs) exhibit antiapoptotic and proangiogenic functions in models of myocardial infarction which may be mediated by secreted small extracellular vesicles (sEVs). However, MSCs have frequently been harvested from aged or diseased patients, while the isolated sEVs often contain high levels of impurities. Here, we studied the cardioprotective and proangiogenic activities of size-exclusion chromatography-purified sEVs secreted from human foetal amniotic fluid stem cells (SS-hAFSCs), possessing superior functional potential to that of adult MSCs. We demonstrated for the first time that highly pure (up to 1.7 × 1010 particles/µg protein) and thoroughly characterised SS-hAFSC sEVs protect rat hearts from ischaemia-reperfusion injury in vivo when administered intravenously prior to reperfusion (38 ± 9% infarct size reduction, p < 0.05). SS-hAFSC sEVs did not protect isolated primary cardiomyocytes in models of simulated ischaemia-reperfusion injury in vitro, indicative of indirect cardioprotective effects. SS-hAFSC sEVs were not proangiogenic in vitro, although they markedly stimulated endothelial cell migration. Additionally, sEVs were entirely responsible for the promigratory effects of the medium conditioned by SS-hAFSC. Mechanistically, sEV-induced chemotaxis involved phosphatidylinositol 3-kinase (PI3K) signalling, as its pharmacological inhibition in treated endothelial cells reduced migration by 54 ± 7% (p < 0.001). Together, these data indicate that SS-hAFSC sEVs have multifactorial beneficial effects in a myocardial infarction setting.


Assuntos
Líquido Amniótico/citologia , Cardiotônicos/metabolismo , Movimento Celular , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Quimiotaxia , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Ratos , Traumatismo por Reperfusão/patologia
13.
Sci Rep ; 9(1): 8126, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31148575

RESUMO

Expression of OCT4A is one of the hallmarks of pluripotency, defined as a stem cell's ability to differentiate into all the lineages of the three germ layers. Despite being defined as non-tumorigenic cells with high translational potential, human mid-trimester amniotic fluid stem cells (hAFSCs) are often described as sharing features with embryonic stem cells, including the expression of OCT4A, which could hinder their clinical potential. To clarify the OCT4A status of hAFSCs, we first undertook a systematic review of the literature. We then performed extensive gene and protein expression analyses to discover that neither frozen, nor fresh hAFSCs cultivated in multipotent stem cell culture conditions expressed OCT4A, and that the OCT4A positive results from the literature are likely to be attributed to the expression of pseudogenes or other OCT4 variants. To address this issue, we provide a robust protocol for the assessment of OCT4A in other stem cells.


Assuntos
Líquido Amniótico/citologia , Regulação da Expressão Gênica no Desenvolvimento , Fator 3 de Transcrição de Octâmero/genética , Células-Tronco/citologia , Linhagem da Célula , Éxons , Feminino , Perfilação da Expressão Gênica , Variação Genética , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Microscopia de Fluorescência , Células-Tronco Multipotentes/citologia , Gravidez , Segundo Trimestre da Gravidez , Isoformas de Proteínas
14.
Clin Exp Rheumatol ; 37(4): 600-607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30620285

RESUMO

OBJECTIVES: To assess RAPID3 in various rheumatologic conditions, and the impact of pain catastrophising on RAPID3. METHODS: A set of questionnaires, including RAPID3 (0-30) and pain catastrophising score (0-52), was given to all outpatients seen in a one-month period: 518 patients fulfilled the questionnaires, including 127 RA (42% taking biologics), and 135 SpA (58% taking biologics). RESULTS: Mean pain catastrophising was 18.5±12.5, and 19% of patients could be classified as catastrophisers (>30). Higher RAPID3 scores were observed in the 33 osteoarthritis of lower limbs (16.44±5.20), 10 fibromyalgia (15.52±5.53), 47 back-pain (14.88±5.17), 17 osteoarthritis of upper limbs (13.61±7.42), and 38 tendinopathies (12.85±4.38). Lower RAPID3 were observed in the 135 SpA (12.79±6.03), 127 RA (12.18±6.30), 27 miscellaneous disorders (9.83±6.28), 7 entrapment neuropathies (9.81±4.51), 19 systemic connective tissue disorders (8.26±7.04) and 58 osteoporosis (7.85±6.95). Much higher RAPID3 scores were observed in the 19% with high pain catastrophising scores, whatever the conditions, and lower scores in the 15% with disablement benefits. RAPID3 was not associated with age or disease duration, but strongly correlated with daily fatigue, poor sleep, and length of daily pain. CONCLUSIONS: Thanks to progress made in RA and SpA treatment, higher RAPID3 scores were mostly observed in other rheumatic conditions, but co-morbidities and pain catastrophising might contribute to floor effects when assessing rheumatic disorders with RAPID3, hindering the recognition of low disease activity in some RA of SpA patients.


Assuntos
Artrite Reumatoide , Dor/diagnóstico , Artrite Reumatoide/fisiopatologia , Humanos , Dor/epidemiologia , Medição da Dor , Índice de Gravidade de Doença , Inquéritos e Questionários
15.
JBMR Plus ; 2(1): 12-21, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30283887

RESUMO

Genetic determinants contribute to osteoporosis and enhance the risk of fracture. Genomewide association studies of unselected population-based individuals or families have identified polymorphisms in several genes related to low bone density, but not in osteoporotic patients with Z-score < -2.0 SD with fragility fracture(s). The aim of this study was to determine the causal genes of idiopathic osteoporosis in the adulthood. Also, we used next-generation sequencing of candidate genes in a cohort of 123 young or middle-aged adults with idiopathic osteoporosis. All patients were included if they had a low bone mineral density (Z-score < -2 SD), a diagnosis before age 55 years (mean ± SD, 48.4 ± 10.6 years; mean ± SD age at first fracture, 30.4 ± 17.4 years) and fracture or not. We found that 11 patients carried rare or novel variants in COL1A2 (n = 4), PLS3 (n = 2), WNT1 (n = 4), or DKK1 (n = 1). We showed a high prevalence of pathogenic variants in LRP5: 22 patients (17.8%) had the p.Val667Met variant, including three at the homozygous level and 16 (13%) carrying a novel or very rare variant. Functional analysis revealed that the LRP5 missense variants resulted in reduced luciferase activity, which indicates reduced activation of canonical WNT signaling. The clinical phenotype of patients carrying causal gene variants was indistinguishable. In conclusion, molecular screening of young osteoporotic adults revealed several variants and could be useful to characterize susceptibility genes for personalizing treatment, in particular for the new anabolic drugs.© 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

16.
Sci Data ; 5: 180100, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29809174

RESUMO

Micro-computed tomography (micro-CT) is commonly used to assess bone quality and to evaluate the outcome of experimental therapies in animal models of bone diseases. Generating large datasets is however challenging and data are rarely made publicly available through shared repositories. Here we describe a dataset of micro-CT reconstructed scans of the proximal part of 21 tibiae from wild-type mice, osteogenesis imperfecta mice (homozygous oim/oim) and oim/oim mice transplanted with human amniotic fluid stem cells. The dataset contains, for each sample, 991 8-bit Bitmap reconstructed images and a 3D reconstruction of the bone in the PLY format, available at the online repository Figshare. In line with the increasing effort to make scientific datasets open-access, our data can be downloaded and used by other researchers to compare their observations with ours and to directly test scientific questions on osteogenesis imperfecta bones without the need to generate complete datasets.


Assuntos
Osteogênese Imperfeita , Transplante de Células-Tronco , Animais , Humanos , Camundongos , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/patologia , Osteogênese Imperfeita/terapia , Células-Tronco/patologia , Tíbia/diagnóstico por imagem , Microtomografia por Raio-X
17.
Stem Cell Res Ther ; 9(1): 113, 2018 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-29695308

RESUMO

BACKGROUND: Established therapies for managing kidney dysfunction such as kidney dialysis and transplantation are limited due to the shortage of compatible donated organs and high costs. Stem cell-based therapies are currently under investigation as an alternative treatment option. As amniotic fluid is composed of fetal urine harboring mesenchymal stem cells (AF-MSCs), we hypothesized that third-trimester amniotic fluid could be a novel source of renal progenitor and differentiated cells. METHODS: Human third-trimester amniotic fluid cells (AFCs) were isolated and cultured in distinct media. These cells were characterized as renal progenitor cells with respect to cell morphology, cell surface marker expression, transcriptome and differentiation into chondrocytes, osteoblasts and adipocytes. To test for renal function, a comparative albumin endocytosis assay was performed using AF-MSCs and commercially available renal cells derived from kidney biopsies. Comparative transcriptome analyses of first, second and third trimester-derived AF-MSCs were conducted to monitor expression of renal-related genes. RESULTS: Regardless of the media used, AFCs showed expression of pluripotency-associated markers such as SSEA4, TRA-1-60, TRA-1-81 and C-Kit. They also express the mesenchymal marker Vimentin. Immunophenotyping confirmed that third-trimester AFCs are bona fide MSCs. AF-MSCs expressed the master renal progenitor markers SIX2 and CITED1, in addition to typical renal proteins such as PODXL, LHX1, BRN1 and PAX8. Albumin endocytosis assays demonstrated the functionality of AF-MSCs as renal cells. Additionally, upregulated expression of BMP7 and downregulation of WT1, CD133, SIX2 and C-Kit were observed upon activation of WNT signaling by treatment with the GSK-3 inhibitor CHIR99201. Transcriptome analysis and semiquantitative PCR revealed increasing expression levels of renal-specific genes (e.g., SALL1, HNF4B, SIX2) with gestational time. Moreover, AF-MSCs shared more genes with human kidney cells than with native MSCs and gene ontology terms revealed involvement of biological processes associated with kidney morphogenesis. CONCLUSIONS: Third-trimester amniotic fluid contains AF-MSCs of renal origin and this novel source of kidney progenitors may have enormous future potentials for disease modeling, renal repair and drug screening.


Assuntos
Células-Tronco Mesenquimais/metabolismo , Gravidez/fisiologia , Células-Tronco/metabolismo , Líquido Amniótico , Diferenciação Celular , Feminino , Humanos
18.
Stem Cells Transl Med ; 7(5): 439-449, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29489062

RESUMO

Human mesenchymal stem cells (MSCs) have huge potential for regenerative medicine. In particular, the use of pluripotent stem cell-derived mesenchymal stem cells (PSC-MSCs) overcomes the hurdle of replicative senescence associated with the in vitro expansion of primary cells and has increased therapeutic benefits in comparison to the use of various adult sources of MSCs in a wide range of animal disease models. On the other hand, fetal MSCs exhibit faster growth kinetics and possess longer telomeres and a wider differentiation potential than adult MSCs. Here, for the first time, we compare the therapeutic potential of PSC-MSCs (ES-MSCs from embryonic stem cells) to fetal MSCs (AF-MSCs from the amniotic fluid), demonstrating that ES-MSCs have a superior neuroprotective potential over AF-MSCs in the mouse brain following hypoxia-ischemia. Further, we demonstrate that nuclear factor (NF)-κB-stimulated interleukin (IL)-13 production contributes to an increased in vitro anti-inflammatory potential of ES-MSC-conditioned medium (CM) over AF-MSC-CM, thus suggesting a potential mechanism for this observation. Moreover, we show that induced pluripotent stem cell-derived MSCs (iMSCs) exhibit many similarities to ES-MSCs, including enhanced NF-κB signaling and IL-13 production in comparison to AF-MSCs. Future studies should assess whether iMSCs also exhibit similar neuroprotective potential to ES-MSCs, thus presenting a potential strategy to overcome the ethical issues associated with the use of embryonic stem cells and providing a potential source of cells for autologous use against neonatal hypoxic-ischemic encephalopathy in humans. Stem Cells Translational Medicine 2018;7:439-449.


Assuntos
Encéfalo/patologia , Células-Tronco Embrionárias/citologia , Células-Tronco Fetais/citologia , Hipóxia/patologia , Células-Tronco Mesenquimais/citologia , Neuroproteção/fisiologia , Líquido Amniótico/citologia , Animais , Encéfalo/metabolismo , Diferenciação Celular/fisiologia , Células Cultivadas , Meios de Cultivo Condicionados/metabolismo , Células-Tronco Embrionárias/metabolismo , Feminino , Células-Tronco Fetais/metabolismo , Células HEK293 , Humanos , Hipóxia/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Isquemia/metabolismo , Isquemia/patologia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Medicina Regenerativa/métodos , Transdução de Sinais/fisiologia
19.
Sci Rep ; 8(1): 2425, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29402914

RESUMO

Human amniotic fluid contains two morphologically-distinct sub-populations of stem cells with regenerative potential, spindle-shaped (SS-hAFSCs) and round-shaped human amniotic fluid stem cells (RS-hAFSCs). However, it is unclear whether morphological differences correlate with functionality, and this lack of knowledge limits their translational applications. Here, we show that SS-hAFSCs and RS-hAFSCs differ in their neuro-protective ability, demonstrating that a single contralateral injection of SS-hAFSCs into hypoxic-ischemic P7 mice conferred a 47% reduction in hippocampal tissue loss and 43-45% reduction in TUNEL-positive cells in the hippocampus and striatum 48 hours after the insult, decreased microglial activation and TGFß1 levels, and prevented demyelination. On the other hand, RS-hAFSCs failed to show such neuro-protective effects. It is possible that SS-hAFSCs exert their neuroprotection via endoglin-dependent inhibition of TGFß1 signaling in target cells. These findings identify a sub-population of CD117+CD90+CD105+ stem cells as a promising source for the neuro-protection of the developing brain.


Assuntos
Líquido Amniótico/citologia , Isquemia Encefálica/terapia , Doenças Desmielinizantes/prevenção & controle , Hipóxia/prevenção & controle , Neuroproteção/fisiologia , Transplante de Células-Tronco , Células-Tronco/citologia , Líquido Amniótico/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Apoptose , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Linhagem da Célula , Terapia Baseada em Transplante de Células e Tecidos/métodos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Endoglina/genética , Endoglina/metabolismo , Expressão Gênica , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Hipóxia/patologia , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
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