MISP Is Overexpressed in Intestinal Metaplasia and Gastric Cancer.

Gastric cancer is the fifth most common cancer and the fourth cause of global cancer mortality. The identification of new biomarkers and drug targets is crucial to allow the better prognosis and treatment of patients. The mitotic spindle positioning (MISP) protein has the function of correcting mitotic spindle positioning and centrosome clustering and has been implicated in the cytokinesis and migration of cancer cells. The goal of this work was to evaluate the expression and clinical relevance of MISP in gastric cancer. MISP expression was evaluated by immunohistochemistry in a single hospital series (n = 286) of gastric adenocarcinomas and compared with normal gastric mucosa and intestinal metaplasia, a preneoplastic lesion. MISP was detected on the membrane in 83% of the cases, being overexpressed in gastric cancer compared to normal gastric mucosa (n = 10). Its expression was negatively associated with diffuse and poorly cohesive types. On the other hand, it was strongly expressed in intestinal metaplasia where it was associated with MUC2 and CDX2 expression. Furthermore, when we silenced MISP in vitro, a significant decrease in the viability of gastric carcinoma cells was observed. In conclusion, MISP is overexpressed in gastric cancer, being associated with an intestinal phenotype in gastric carcinogenesis and having a role in cellular proliferation.

Recent advances in boron removal in aqueous media. An approach to the adsorption process and process optimization.

The numerous oxidation states of the element boron bring great challenges in containing its contamination in receptor bodies. This scenario increases significantly due to the widespread use of boron compounds in various industries in recent years. For this reason, the removal of this contaminant is receiving worldwide attention. Although adsorption is a promising method in boron removal, finding suitable adsorbents, that is, those with high efficiency, and feasible remains a constant challenge. Hence, this review presents the boron removal methods in comparison to costs of adsorbents, reaction mechanisms, economic viability, continuous bed application, and regeneration capacity. In addition, the approach of multivariate algorithms in the solution of multiobjective problems can enable the optimized conditions of dosage of adsorbents and coagulants, pH, and initial concentration of boron. Therefore, this review sought to comprehensively and critically demonstrate strategic issues that may guide the choice of method and adsorbent or coagulant material in future research for bench and industrial scale boron removal.

High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells.

Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP reporter system embedded in gastric non-CSCs (SORE6-), we performed a high-throughput image-based drug screen with 1200 small molecules to identify compounds capable of converting SORE6- to SORE6+ (CSCs). Here, we report that the antifungal agent ciclopirox olamine (CPX), a potential candidate for drug repurposing in cancer treatment, is able to reprogram gastric non-CSCs into cancer stem-like cells via activation of SOX2 expression and increased expression of C-MYC, HIF-1α, KLF4, and HMGA1. This reprogramming depends on the CPX concentration and treatment duration. CPX can also induce cellular senescence and the metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. We also disclose that the mechanism underlying the cellular reprogramming is similar to that of cobalt chloride (CoCl2), a hypoxia-mimetic agent.

Use of brewer's residual yeast for production of bacterial nanocellulose with Gluconacetobacter hansenii.

Bacterial nanocellulose (BNC) has attained elevated interest due to its versatile structure and high resistance characteristics. Accordingly, efforts have been made in order to reduce its production costs, such as the employment of its by-products as a nutrient broth to yield the microorganism. Residual brewer's yeast is an excellent recourse, due to its high nutritional value and availability. Therefore, research which aimed to contribute to the development of a low cost, efficient and biosustainable technology for BNC production with Gluconacetobacter hansenii was carried out. BNC was obtained from residual brewer's yeast hydrolysate at pH 7.0 and five days of incubation at 30 °C in static culture. The hydrolysate was characterized by the amount of sugars, fatty acids, total proteins and ash content. Subsequently, BNC obtained was characterized in terms of yield, carbon conversion ratio, hydrodynamic size, crystallinity, morphology, Fourier-transform infrared spectroscopy, and surface analysis. Residual brewer's yeast hydrolysate proved to be efficient in BNC production via gluconeogenesis with consumption of alanine, threonine and glycerol, obtaining 1.9 times the yield of the chemically defined broth adopted as standard. Additionally, properties observed in the obtained BNC were equal to those obtained from conventional chemical medium. The research contributed to bacterial nanocellulose production using by-products from the brewing industry.

Untargeted metabolomic profile of recovered bioactive compounds by subcritical water extraction of acerola (Malpighia emarginata DC.) pomace.

The untargeted metabolomics approach was used to compare the chemical profiles of acerola (Malpighia emarginata DC.) pomace extracts. The effect of drying the raw material before subcritical water extraction (SWE) at different temperatures on the yield, phenolic content, and in vitro antioxidant activity was evaluated. The results were compared with those obtained via Soxhlet and the findings suggest that SWE saves time (15 min) and solvent for extracting valuable components as compared to Soxhlet (6 h). An increase in temperature significantly improved the extraction yield (23.9 to 33.4 %), phenolic content (119.1 to 362 mgGAEg-1), and antioxidant activity, and higher values were obtained with SWE as compared to Soxhlet. The most abundant compounds detected by UPLC-ESI-QTOF-MS were ascorbic acid, kaempferol, quercetin, and isorhamnetin. The investigation of different moisture contents in the SWE showed promising results for eliminating the drying operation, saving time and energy, and obtaining highly concentrated phenolic-rich by-products.

Inhibition of CXCR2 plays a pivotal role in re-sensitizing ovarian cancer to cisplatin treatment.

cDNA microarray data conducted by our group revealed overexpression of CXCL2 and CXCL8 in ovarian cancer (OC) microenvironment. Herein, we have proven that the chemokine receptor, CXCR2, is a pivotal molecule in re-sensitizing OC to cisplatin, and its inhibition decreases cell proliferation, viability, tumor size in cisplatin-resistant cells, as well as reversed the overexpression of mesenchymal epithelium transition markers. Altogether, our study indicates a central effect of CXCR2 in preventing tumor progression, due to acquisition of cisplatin chemoresistant phenotype by tumor cells, and patients' high lethality rate. We found that the overexpression of CXCR2 by OC cells is persistent and anomalously confined to the cellular nuclei, thus pointing to an urge in developing highly lipophilic molecules that promptly permeate cells, bind to and inhibit nuclear CXCR2 to fight OC, instead of relying on the high-cost genetic engineered cells.

Prognostic significance of MUC2, CDX2 and SOX2 in stage II colorectal cancer patients.

BACKGROUND: Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. METHODS: For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. RESULTS: In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. CONCLUSION: In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.

HMGA1 Has Predictive Value in Response to Chemotherapy in Gastric Cancer.

Gastric cancer is a serious health problem worldwide. Although its incidence is decreasing, the five-year survival rate remains low. Thus, it is essential to identify new biomarkers that could promote better diagnosis and treatment of patients with gastric cancer. High-mobility group AT-hook 1 (HMGA1) is a non-histone, chromatin-binding protein that has been found overexpressed in several tumor types. It has been correlated with invasion, metastasis, and drug resistance, leading to worse patient survival. The aim of this work was to evaluate the clinical value of HMGA1 in gastric cancer. HMGA1 expression was analyzed by immunohistochemistry in a single hospital series (n = 323) of gastric adenocarcinoma cases (stages I to IV) with clinicopathological and treatment data. In this series, HMGA1 expression showed no significant relevance as a prognostic biomarker. Nevertheless, a significantly better overall survival was observed in cases with high levels of HMGA1 when they were treated with chemotherapy, compared to the nontreated ones, implying that they can benefit more from treatment than patients with low expression of HMGA1. We thereby show for the first time that HMGA1 expression has a substantial value as a biomarker of response to chemotherapy in gastric cancer.

Intensified green-based extraction process as a circular economy approach to recover bioactive compounds from soursop seeds (Annona muricata L.).

Soursop (Annona muricata L.) seeds, which is a residue obtained from juice agro-industries, were subjected to supercritical fluid extraction (SFE) and subcritical water extraction (SWE) in single or combined mode to extract the potential value-added compounds. Different extraction methods were evaluated in terms of the extraction yield, phenolics content, antioxidant activity (DPPH, ABTS, and FRAP), and Maillard reaction products. The extracts were analyzed using SEM, GC-MS, and LC-MS/MS techniques. The temperature and a combination of high-pressure techniques positively affected the overall results (SFE + SWE), affording nonpolar and polar extracts rich in phenolics and antioxidant compounds. SEM analysis showed that the use of SFE caused modifications in the cell wall, and the oil fraction was rich in fatty acids. Twenty-nine compounds associated with soursop seed extracts were detected for the first time using LC-MS/MS, showing the potential of the raw material as well as promoting resource re-utilization in circular economy.

The Relevance of Transcription Factors in Gastric and Colorectal Cancer Stem Cells Identification and Eradication.

Gastric and colorectal cancers have a high incidence and mortality worldwide. The presence of cancer stem cells (CSCs) within the tumor mass has been indicated as the main reason for tumor relapse, metastasis and therapy resistance, leading to poor overall survival. Thus, the elimination of CSCs became a crucial goal for cancer treatment. The identification of these cells has been performed by using cell-surface markers, a reliable approach, however it lacks specificity and usually differs among tumor type and in some cases even within the same type. In theory, the ideal CSC markers are those that are required to maintain their stemness features. The knowledge that CSCs exhibit characteristics comparable to normal stem cells that could be associated with the expression of similar transcription factors (TFs) including SOX2, OCT4, NANOG, KLF4 and c-Myc, and signaling pathways such as the Wnt/ß-catenin, Hedgehog (Hh), Notch and PI3K/AKT/mTOR directed the attention to the use of these similarities to identify and target CSCs in different tumor types. Several studies have demonstrated that the abnormal expression of some TFs and the dysregulation of signaling pathways are associated with tumorigenesis and CSC phenotype. The disclosure of common and appropriate biomarkers for CSCs will provide an incredible tool for cancer prognosis and treatment. Therefore, this review aims to gather the new insights in gastric and colorectal CSC identification specially by using TFs as biomarkers and divulge promising drugs that have been found and tested for targeting these cells.

A panel of intestinal differentiation markers (CDX2, GPA33, and LI-cadherin) identifies gastric cancer patients with favourable prognosis.

BACKGROUND: Gastric cancer is the fifth most common cancer and the third cause of global cancer mortality. CDX2 is an intestinal differentiation marker with prognostic value in gastric cancer and transcriptionally regulates the expression of glycoprotein A33 (GPA33) and liver intestine cadherin (LI-cadherin). METHODS: This study evaluated the clinical significance of the combined expression of CDX2 and its targets GPA33 and LI-cadherin in gastric cancer by fluorescence-based multiplex immunohistochemistry together with digital image analysis and chromogenic immunohistochemistry in 329 gastric cancer samples arranged in tissue microarrays. Additionally, publicly available RNA-seq expression data from 354 gastric cancer samples from the TCGA database were used to validate the immunohistochemistry results. RESULTS: Expression of the three markers (CDX2, GPA33, and LI-cadherin) was strongly correlated, defining an intestinal differentiation panel. Low or negative protein expression of the intestinal differentiation panel identified patients with particularly poor overall survival, irrespective of the methodology used, and was validated in the independent series at the RNA-seq level. CONCLUSIONS: Expression of the intestinal differentiation panel (CDX2, GPA33, and LI-cadherin) defines a set of biomarkers with a strong biological rationale and favourable impact for prognostication of gastric cancer patients.

A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin.

Gastric cancer remains a serious health burden with few therapeutic options. Therefore, the recognition of cancer stem cells (CSCs) as seeds of the tumorigenic process makes them a prime therapeutic target. Knowing that the transcription factors SOX2 and OCT4 promote stemness, our approach was to isolate stem-like cells in human gastric cancer cell lines using a traceable reporter system based on SOX2/OCT4 activity (SORE6-GFP). Cells transduced with the SORE6-GFP reporter system were sorted into SORE6+ and SORE6- cell populations, and their biological behavior characterized. SORE6+ cells were enriched for SOX2 and exhibited CSC features, including a greater ability to proliferate and form gastrospheres in non-adherent conditions, a larger in vivo tumor initiating capability, and increased resistance to 5-fluorouracil (5-FU) treatment. The overexpression and knockdown of SOX2 revealed a crucial role of SOX2 in cell proliferation and drug resistance. By combining the reporter system with a high-throughput screening of pharmacologically active small molecules we identified monensin, an ionophore antibiotic, displaying selective toxicity to SORE6+ cells. The ability of SORE6-GFP reporter system to recognize cancer stem-like cells facilitates our understanding of gastric CSC biology and serves as a platform for the identification of powerful therapeutics for targeting gastric CSCs.

Expression and Clinical Relevance of SOX9 in Gastric Cancer.

Gastric cancer is one of the most frequent tumours and the third leading cause of cancer-related death worldwide. The investigation of new biomarkers that can predict patient outcome more accurately and allow better treatment and follow-up decisions is of crucial importance. SOX9 (sex-determining region Y (SRY)-box 9) is a regulator of cell fate decisions in embryogenesis and adulthood. Here, we sought to ascertain the relevance of SOX9 transcription factor as a prognostic marker in gastric cancer. SOX9 expression was analyzed by immunohistochemistry in 333 gastric adenocarcinoma cases, and its association with clinicopathological and follow-up data was evaluated. SOX9 nuclear expression was absent in 17% of gastric cancer cases and predicted worse disease-free survival (P = 0.03). SOX9 expression was associated with lower risk of relapse in Cox univariable analysis (HR = 0.58; 95% CI = 0.35-0.97; P = 0.04). The prognostic value of SOX9 was more pronounced in tumours with expansive growth (P = 0.01) or with venous invasion (P = 0.02). Two validation cohorts from the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) confirmed that low SOX9 expression was significantly associated with poor patient outcome. In conclusion, we have identified SOX9 as a biomarker of disease relapse in gastric cancer patients. Further experiments are needed to elucidate its biological relevance at the cellular level.

Fixed-bed study for bone char adsorptive removal of refractory organics from electrodialysis concentrate produced by petroleum refinery.

Water reuse in industrial processes has been an increasing need encouraged in recent years. However, as the streams are recycled, solutes accumulate, thus requiring purification techniques. Membrane processes (reverse osmosis and electrodialysis) have been implemented and in order to increase the reuse of water at its highest level, crystallization has been evaluated to remove salts from the concentrate produced and get a feasible disposal. Nevertheless, contaminants affect the crystallization performance, thus making the removal of residual organics important for both the efficiency of crystallization and the increase of water reuse. In this context, aiming at establishing a sustainable virtuous circle, bone char (0.5-1.4 mm particle size, mesoporous structure) was used to remove refractory organics from an electrodialysis concentrate effluent (C-EDR) from a Brazilian petroleum refinery, at a lab-scale, in a fixed-bed adsorption column. Bone char selectively and partially removed the refractory organics, a complex mixture of long-chain hydrocarbons, aromatic compounds, carboxylic acids, amines and amides. The maximum adsorption capacity increased with the increase in bed depth and reduction in flow rate. A maximum removal of 35.60 mg g-1 was achieved for the highest bed depth evaluated (12.9 cm). The breakthrough curves indicated that bone char could adsorb part of the organic compounds from the C-EDR. The scaling up was possible for the C/C0 ratios of 0.55, 0.60 and 0.65, providing a service time at about 16 days for 45% removal efficiency for typical real operational conditions used in the refinery.

Evaluation of coronary calcium score in patients with normocalcemic primary hyperparathyroidism.

RATIONALE: Given that the diagnosis of primary hyperparathyroidism (PHPT) is given at an increasingly less-symptomatic phase, and the literature data on the cardiovascular risk of patients with normocalcemic primary hyperparathyroidism (NPHPT) are controversial, the coronary calcium score (CCS), which is correlated with coronary artery disease, may be useful for clarifying the association between cardiovascular risk and NPHPT. OBJECTIVE: This research aims to describe the CCS and the clinical and laboratory variables of patients with NPHPT compared with a control group and to verify the presence of an association between NPHPT and CCS. STUDY POPULATION AND METHODS: A questionnaire on anthropometric data (weight, height, waist circumference, and blood pressure) was used, laboratory examinations (estimations of glucose, glycated hemoglobin [HbA1c], total cholesterol [TC] and its fractions, triglycerides, creatinine, calcium, parathyroid hormone, and 25-OH vitamin D) were conducted, and computerized tomography was carried out to measure the CCS in 13 patients diagnosed with NPHPT and 16 controls. RESULTS: There was no association between NPHPT and altered CCS (odds ratio [OR]: 0.27; 95% confidence interval [CI]: 0.05-1.26; p=0.095). Differences between the case and control groups were found in terms of body mass index (BMI) (26.97 kg/m2 vs 31.53 kg/m2, respectively; p=0.044), HbA1c (5.59% vs 6.62%; p=0.000), and TC (188.07 mg/dL vs 220.64 mg/dL; p=0.088). After adjustment for potential confounders, no statistical significance was observed for the association between changes in CCS and presence of NPHPT (adjusted OR: 1.64; 95% CI: 0.1-26.43; p=0.726). CONCLUSION: No association was found between the CCS and the presence of NPHPT.

The effects of intermittent vitamin D3 supplementation on muscle strength and metabolic parameters in postmenopausal women with type 2 diabetes: a randomized controlled study.

BACKGROUND: The aim of this study was to evaluate the effect of weekly vitamin D3 supplementation on metabolic parameters and muscle strength of postmenopausal women with type 2 diabetes. METHODS: A total of 38 patients with serum 25-hydroxy vitamin D [25(OH)D] below 30 ng/ml and hand strength below 20 kg were randomly assigned to oral vitamin D3 (6600 IU/week in 2 cc oil preparation) or 2 cc olive oil weekly for 3 months. RESULTS: There were nonsignificant increases in serum 25(OH)D in the intervention group to 22.98 ± 4.23 ng/ml and nonsignificant decreases in the control group to 22.84 ± 3.88 (26% of the intervention and 48% of the control groups had 25(OH)D < 20 ng/ml). Handgrip strength improved significantly in the intervention group (right arm 17.4 ± 2.68 to 19.9 ± 3.53 kg, p = 0.002; left arm 16.31 ± 2.6 to 18.46 ± 3.2 kg, p < 0.001) but not in the control group (right arm 16.87 ± 3.99 to 17.93 ± 4.91 kg, p = 0.1; left arm 16.13 ± 4.29 to 16.86 ± 4.79 kg, p < 0.2). More patients in the control group became obese at the end of the study period (p = 0.014). There were no significant changes in mean fasting glucose, glycated haemoglobin (HbA1c), serum triglycerides and blood pressure with vitamin D supplementation. Systolic blood pressure increased significantly in the control group from 136.6 ± 18.6 to 141.4 ± 17.6 mmHg, p = 0.04). CONCLUSIONS: Vitamin D3 supplementation in doses equivalent to 942 IU/day improved isometric handgrip strength, but had no effect on glycaemic control in postmenopausal women with longstanding type 2 diabetes.

Prevalence of Orthostatic Hypertension in Elderly Patients with Type 2 Diabetes.

Background. The aim of the present study was to determine the prevalence of orthostatic hypertension (OHT) in elderly patients with type 2 diabetes and its relation to metabolic and echocardiographic parameters. Methods. This was an analytical cross-sectional study in 97 patients normotensive or hypertensive. OHT was defined as a ≥10 mmHg increase in systolic blood pressure after four minutes in the standing position. Results. The prevalence of OHT was 20.6%. The mean body mass index was significantly higher in patients with OHT than in those without it (29.80 ± 4.10 versus 27.51 ± 3.98 kg/m(2); P = 0.026). There were no statistically significant differences between the two groups for other metabolic parameters. Among the 68 patients who had an echocardiographic examination 27% of those with OHT had an increase in their left atrial volume index (LAVi) compared with 75% of those who did not have OHT (P = 0.004). The mean LAVi of patients with OHT was significantly lower than that of those without OHT (26.27 ± 6.37 versus 32.65 ± 7.54, resp.; P = 0.011). Conclusion. We found a high prevalence of orthostatic hypertension and a lower left atrial volume indexed in the patients with orthostatic hypertension.

CDX2 homeoprotein is involved in the regulation of ST6GalNAc-I gene in intestinal metaplasia.

De novo expression of Sialyl-Tn (STn) antigen is one of the most common features of intestinal metaplasia (IM) and gastric carcinomas, and its biosynthesis has been mostly attributed to ST6GalNAc-I activity. However, the regulation of this glycosyltransferase expression is not elucidated. In IM lesions and in the intestine, CDX2 homeobox transcription factor is co-expressed with STn and ST6GalNAc-I. We therefore hypothesized that CDX2 might induce STn expression by positive regulation of ST6GalNAc-I. We showed that ST6GalNAc-I transcript levels and CDX2 have a coordinated expression upon Caco-2 in vitro differentiation, and overexpression of CDX2 in MKN45 gastric cells increases ST6GalNAc-I transcript levels. Nine putative CDX-binding sites in the ST6GalNAc-I-regulatory sequence were identified and analyzed by chromatin immunoprecipitation in Caco-2 cells and in IM. The results showed that CDX2 protein is recruited to all regions, being the most proximal sites preferentially occupied in vivo. Luciferase assays demonstrated that CDX2 is able to transactivate ST6GalNac-I-regulatory region. The induction was stronger for the regions mapped in the neighbourhood of ATG start codon and site-directed mutagenesis of these sites confirmed their importance. In conclusion, we show that CDX2 transcriptionally regulates ST6GalNAc-I gene expression, specifically in the preneoplastic IM lesion.

Diagnosis and management of Paget's disease of bone.

OBJECTIVE: To conduct a literature review on the diagnosis and management of Paget's disease of bone. MATERIALS AND METHODS: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society of Endocrinology and Metabolism (SBEM) as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including "D", are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. CONCLUSION: We present a scientific statement on Paget's disease of bone providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment.

Diagnosis and management of Paget?s disease of bone / Diagnóstico e tratamento da doença de Paget óssea

Objective: To conduct a literature review on the diagnosis and management of Paget’s disease of bone. Materials and methods: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society of Endocrinology and Metabolism (SBEM) as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including “D”, are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. Conclusion: We present a scientific statement on Paget’s disease of bone providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment. Arq Bras Endocrinol Metab. 2014;58(6):587-99 .

Objetivo: Conduzir uma atualização das últimas evidências científicas a respeito da apresentação, diagnóstico e manejo clínico da doença de Paget óssea. Materiais e métodos: Este documento foi concebido pelo Departamento de Metabolismo Ósseo da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) a partir daquele oriundo do Programa de Diretrizes da Associação Médica Brasileira (AMB). Realizamos uma revisão dos artigos mais relevantes obtidos nos bancos de dados PubMed e Cochrane, além de abstracts apresentados nos encontros anuais da Endocrine Society, Sociedade Brasileira de Endocrinologia e da American Society for Bone and Mineral Research dos últimos cinco anos e classificamos as evidências em níveis de recomendações de acordo com a força científica por tipo de estudo, adaptando o primeiro relato do “Oxford Centre for Evidence-based Medicine”. Todos os graus de recomendação, incluindo-se o “D”, foram baseados em evidência científica, sendo as diferenças entre o A, B, C e D devidas exclusivamente ao desenho empregado na geração da evidência. Conclusão: Apresentamos uma atualização científica a respeito da doença de Paget óssea, classificando e graduando em níveis de recomendações as principais evidências científicas sobre as suas causas, as variadas formas de apresentação, seu diagnóstico e tratamento. .