Publications by authors named "Diego Aguiar"

33 Publications

Postmortem coronary artery calcium score in cases of myocardial infarction.

Int J Legal Med 2021 Apr 13. Epub 2021 Apr 13.

University Center of Legal Medicine Lausanne-Geneva, Chemin de la Vulliette 4, CH - 1000, Lausanne 25, Switzerland.

Sudden cardiac death (SCD) related to atherosclerotic coronary artery disease (ACAD) resulting in myocardial infarction is the most prevalent cause of death in western countries. In clinical practice, coronary artery calcium score (CACS) is considered an independent predictor of coronary events, closely related to atherosclerotic burden and is quantified radiologically by the Agatston score being calculated through computed tomography. Postmortem computed tomography (PMCT) allows the visualization and quantification of coronary calcifications before the autopsy. However, it was reported that some patients who died from severe ACAD had a zero CACS in PMCT. In this study, a retrospective evaluation of CACS in adult's myocardial infarction cases related to ACAD, with available CACS and histological slides of coronary arteries, was performed in order to gain a deeper understanding of coronary calcifications and their role in myocardial infarction cases. The CACS was calculated by using the software Smartscore 4.0 after the radiological examination on a 64-row CT unit using a specific cardiac protocol. Thirty-six cases were identified out of 582 autopsies, recorded during a 2-year study period (29 men, 7 women; age 56.3 ± 11.7). CACS was 0-10 in 5 cases (5 men, 44.8 ± 13.7), 11-100 in 8 cases (6 men, 2 women, 53.1 ± 7.7), 101-400 in 13 cases (11 men, 2 women, 57.4 ± 9.6), and > 400 in 10 cases (9 men, 1 woman, 63.1 ± 11.9). Coronary thrombosis was found in 28 cases, histologically identified as plaque erosions in 6 cases and as plaque ruptures in 22 cases. Statistical analyses showed that CACS increases significantly with age (p-value < 0.05) and does not show significant correlation with gender, body weight, body mass index, and heart weight. CACS was significantly higher in plaque ruptures than in plaque erosions (p-value < 0.01). Zero or low CACS on unenhanced PMCT cannot exclude the presence of myocardial infarction related to ACAD. This paradoxical discrepancy between imaging and autopsy findings can be explained considering the histological aspect of fatal coronary plaques.
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http://dx.doi.org/10.1007/s00414-021-02586-zDOI Listing
April 2021

Inside the lungs of COVID-19 disease.

Int J Legal Med 2020 Jul 26;134(4):1271-1274. Epub 2020 May 26.

University Center of Legal Medicine (CURML), Geneva University Hospital, Geneva, Switzerland.

In the setting of the coronavirus disease 2019 (COVID-19) pandemic, only few data regarding lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is available, especially without medical intervention interfering with the natural evolution of the disease. We present here the first case of forensic autopsy of a COVID-19 fatality occurring in a young woman, in the community. Diagnosis was made at necropsy and lung histology showed diffuse alveolar damage, edema, and interstitial pneumonia with a geographically heterogeneous pattern, mostly affecting the central part of the lungs. This death related to COVID-19 pathology highlights the heterogeneity and severity of central lung lesions after natural evolution of the disease.
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http://dx.doi.org/10.1007/s00414-020-02318-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248187PMC
July 2020

Correction to: Clitoral leiomyoma in a premenopausal woman: a case report.

BMC Womens Health 2020 May 20;20(1):110. Epub 2020 May 20.

Department of Obstetrics and Gynaecology, Geneva University Hospitals, 30 Bld de la Cluse, 1211, Geneva, Switzerland.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12905-020-00975-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238590PMC
May 2020

Clitoral leiomyoma in a premenopausal woman: a case report.

BMC Womens Health 2020 05 1;20(1):89. Epub 2020 May 1.

Department of Obstetrics and Gynaecology, Geneva University Hospitals, 30 Bld de la Cluse, 1211, Geneva, Switzerland.

Background: Extrauterine leiomyomata is an uncommon lesion that can lead to several problems of differential diagnosis, especially when localized in the external genitalia. There are few reports in the English literature and a novel association with Alport's syndrome has been investigated since the 1980s.

Case Presentation: Here, we describe the case of a premenopausal woman who presented with an indolent swelling of the right interlabial fossa that resulted in a Bartholin cyst. In addition to this cyst, a benign leiomyoma of the right side of the clitoris was also found and removed. Our patient refused any further examination, although she was informed that genetic counselling could be organized to rule out an association with Alport's syndrome.

Conclusions: Extrauterine leiomyomata localized in the external genitalia is an uncommon lesion arising from smooth muscle cells around vascular epithelium or erectile tissue. Since an association between extrauterine leiomyomata and Alport's syndrome has been described, genetic testing can be proposed to these patients. Upper intestinal tract symptoms such as dysphagia should prompt a gastroenterological evaluation as an association with an esophageal leiomyomatosis has been described.
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http://dx.doi.org/10.1186/s12905-020-00959-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195734PMC
May 2020

Protocol for Harvest, Transport and Storage of Human Osteochondral Tissue.

Rev Bras Ortop (Sao Paulo) 2020 Apr 28;55(2):163-169. Epub 2020 Jan 28.

Divisão de Pesquisa, Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad, Rio de Janeiro, RJ, Brasil.

 To elaborate a protocol for the harvest, transport, and preservation of human osteochondral tissue for use in tissue banks (TBs).  Osteochondral fragments measuring 2 cm of 5 corpse donors aged between 15 and 45 years old were analyzed. The samples were stored in cell preservation medium containing: human albumin, Iscove's and vancomycin preserved at 4°C. The concentration of proteoglycans in the extracellular medium was quantified by the use of Safranin-O, while tissue structural analysis was assessed by histological study with hematoxylin-eosin stained slides. The images obtained were analyzed according to the histological scores of Mankin and the score proposed by the OsteoArthritis Research Society International. The samples were analyzed with 0, 15, 30 and 45 days of preservation.  The osteochondral fragments studied showed a progressive decrease in proteoglycan concentration with increased preservation time. After 30 days of preservation, structural changes were identified with discontinuity of the cartilage surface layer. According to the results obtained by the Mankin score, there was a statistically significant difference between 15 and 30 days of tissue preservation.  The protocol described defined knee transport immersed in Lactated Ringer at a controlled temperature of 10° C until its arrival at the TB. After processing, the preservation solution was composed of Iscove's serum-free cell culture medium supplemented with 10% human albumin and 100 μg/ml vancomycin. The tissue was preserved at a temperature of 4°C until the moment of transplantation characterizing the fresh preservation.
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http://dx.doi.org/10.1055/s-0039-3400522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186072PMC
April 2020

Metal concentrations and biological effects from one of the largest mining disasters in the world (Brumadinho, Minas Gerais, Brazil).

Sci Rep 2020 04 3;10(1):5936. Epub 2020 Apr 3.

Laboratório de Ciências Ambientais, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro. Avenida Alberto Lamego, 2000, Parque Califórnia, Campos dos Goytacazes, Rio de Janeiro, 28013-602, Brasil.

The rupture of the Brumadinho mining tailings dam in Brazil is considered one of the largest mining disasters in the world, resulting in 244 deaths and 26 missing people, in addition to the environmental consequences. The present study aims to evaluate the concentrations of multiple elements and the biological effects on water and sediments of the Paraopeba River after the Brumadinho Dam rupture. The tailings are formed by fine particulate material with large amounts of Fe, Al, Mn, Ti, rare earth metals and toxic metals. In the water, the levels of Fe, Al, Mn, Zn, Cu, Pb, Cd and U were higher than those allowed by Brazilian legislation. In the sediments, Cr, Ni, Cu and Cd levels were higher than the established sediment quality guidelines (TEL-NOAA). The differences in metal concentrations in the water and sediments between the upstream and downstream sides of the dam illustrate the effect of the tailings in the Paraopeba River. Toxicological tests demonstrated that the water and sediments were toxic to different trophic levels, from algae to microcrustaceans and fish. The fish exposed to water and sediments containing mine ore also accumulated metals in muscle tissue. This evaluation emphasizes the necessity of long-term monitoring in the affected area.
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http://dx.doi.org/10.1038/s41598-020-62700-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125165PMC
April 2020

Femoral torsion evaluation by computed tomography in a young Brazilian population with hip pain and femoroacetabular impingement.

J Orthop 2020 Mar-Apr;18:32-35. Epub 2019 Oct 31.

Department of Reserch, National Institute of Traumatology and Orthopaedics Jamil Haddad, Av. Brasil, 500 Caju, Rio de Janeiro, RJ, Brazil.

Introduction: The aim of the study was to evaluate femoral torsion (FT) by computed tomography (CT) in young patients with hip pain and femoroacetabular impingement (FAI) in a Brazilian population. After the diagnosis of impingement, the complete analysis from the hip biomechanics and morphology has become essential.

Methods: Forty-one patients from 18 to 45 years presenting hip pain without arthrosis (Tönnis2) were evaluated by CT scan from February 2017 to February 2018. All patients presented hip pain for at least 3 months and FAI. They have followed the same radiographic protocol and modified Harris Hip Score (mHHS) evaluation. Statistical analyses by software version 3.4.4. with significance p < 0,05.

Results: After exclusion criterias, twenty-six patients (9 bilateral) were included, mostly man (73%). The average age was 35 years for both genders. BMI was 19 kg/m2 for women and 24 kg/m2 for men and the mean modified Harris Hip Score was 67 points. We have found femoral torsion changes in 11 hips with pain (31%) and high variability (60%). The mean FT was 14,5°, ranging from 0 to 39°. Patients with hip pain, CAM impingement and altered FT had no correlation when compared to controls (without pain) (p = 0.234), neither Mixed impingement (p = 0.314). Patients with Pincer impingement and painful hips had higher FT (16,63°) than controls (11,77°) (p = 0.045). : The presence of torsional alterations in almost 1/3 of the patients with FAI and the high variability reveal the importance of measuring FT at this disease.
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http://dx.doi.org/10.1016/j.jor.2019.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068012PMC
October 2019

Viscosupplementation improves pain, function and muscle strength, but not proprioception, in patients with knee osteoarthritis: a prospective randomized trial.

Clinics (Sao Paulo) 2019 25;74:e1207. Epub 2019 Nov 25.

Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad, Rio de Janeiro, RJ, BR.

Objectives: This study aimed to evaluate the clinical outcomes of intra-articular infiltration with hyaluronic acid and dexamethasone alone and in combination in the treatment of knee osteoarthritis (OA).

Method: This prospective randomized trial evaluated 44 patients undergoing treatment for OA. Patients were selected through clinical and radiological analysis using the American College of Rheumatology criteria. We included patients aged between 50 and 70 years who presented with K-L stage ≤2 knee OA and normal limb alignment. Patients with a previous history of knee injury (ligamentous, meniscal or traumatic), infection, patellofemoral OA or chondroprotective drug use in the previous year were excluded. Participants were randomized into 3 groups and underwent treatment with viscosupplementation (VS, n=16), viscosupplementation plus dexamethasone (VD, n=16) or dexamethasone (DX, n=12). All patients were evaluated before and 6 weeks, 3 months and 6 months after infiltration. Analysis included a physical examination, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire (total score and domain subscores) and an evaluation of knee extensor and flexor strength and proprioception using an isokinetic dynamometer.

Results: VS significantly improved the WOMAC total score and subscores for pain, stiffness and function for up to 6 months after infiltration. It also improved knee extensor and flexor strength during the same period. Proprioception was not affected by any of the treatments.

Conclusions: VS alone improved pain, stiffness and function according to the WOMAC total score and subscores and improved knee extensor and flexor strength, but not proprioception, for up to six months after infiltration. These findings suggest that VS has a positive effect on quadriceps arthrogenic inhibition.
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http://dx.doi.org/10.6061/clinics/2019/e1207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844143PMC
March 2020

Osteoarthritic Synovial Fluid Modulates Cell Phenotype and Metabolic Behavior .

Stem Cells Int 2019 15;2019:8169172. Epub 2019 Jan 15.

Research Division, National Institute of Traumatology and Orthopedics Jamil Haddad, Rio de Janeiro, RJ, Brazil.

Synovial fluid holds a population of mesenchymal stem cells (MSC) that could be used for clinical treatment. Our goal was to characterize the inflammatory and metabolomic profile of the synovial fluid from osteoarthritic patients and to identify its modulatory effect on synovial fluid cells. Synovial fluid was collected from non-OA and OA patients, which was centrifuged to isolate cells. Cells were cultured for 21 days, characterized with specific markers for MSC, and exposed to a specific cocktail to induce chondrogenic, osteogenic, and adipogenic differentiation. Then, we performed a MTT assay exposing SF cells from non-OA and OA patients to a medium containing non-OA and OA synovial fluid. Synovial fluid from non-OA and OA patients was submitted to ELISA to evaluate BMP-2, BMP-4, IL-6, IL-10, TNF-, and TGF-1 concentrations and to a metabolomic evaluation using H-NMR. Synovial fluid cells presented spindle-shaped morphology . Samples from OA patients formed a higher number of colonies than the ones from non-OA patients. After 21 days, the colony-forming cells from OA patients differentiated into the three mesenchymal cell lineages, under the appropriated induction protocols. Synovial fluid cells increased its metabolic activity after being exposed to the OA synovial fluid. ELISA assay showed that OA synovial fluid samples presented higher concentration of IL-10 and TGF-1 than the non-OA, while the NMR showed that OA synovial fluid presents higher concentrations of glucose and glycerol. In conclusion, SFC activity is modulated by OA synovial fluid, which presents higher concentration of IL-10, TGF-, glycerol, and glucose.
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http://dx.doi.org/10.1155/2019/8169172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350599PMC
January 2019

Osteoarthritic Synovial Fluid Modulates Cell Phenotype and Metabolic Behavior .

Stem Cells Int 2019 15;2019:8169172. Epub 2019 Jan 15.

Research Division, National Institute of Traumatology and Orthopedics Jamil Haddad, Rio de Janeiro, RJ, Brazil.

Synovial fluid holds a population of mesenchymal stem cells (MSC) that could be used for clinical treatment. Our goal was to characterize the inflammatory and metabolomic profile of the synovial fluid from osteoarthritic patients and to identify its modulatory effect on synovial fluid cells. Synovial fluid was collected from non-OA and OA patients, which was centrifuged to isolate cells. Cells were cultured for 21 days, characterized with specific markers for MSC, and exposed to a specific cocktail to induce chondrogenic, osteogenic, and adipogenic differentiation. Then, we performed a MTT assay exposing SF cells from non-OA and OA patients to a medium containing non-OA and OA synovial fluid. Synovial fluid from non-OA and OA patients was submitted to ELISA to evaluate BMP-2, BMP-4, IL-6, IL-10, TNF-, and TGF-1 concentrations and to a metabolomic evaluation using H-NMR. Synovial fluid cells presented spindle-shaped morphology . Samples from OA patients formed a higher number of colonies than the ones from non-OA patients. After 21 days, the colony-forming cells from OA patients differentiated into the three mesenchymal cell lineages, under the appropriated induction protocols. Synovial fluid cells increased its metabolic activity after being exposed to the OA synovial fluid. ELISA assay showed that OA synovial fluid samples presented higher concentration of IL-10 and TGF-1 than the non-OA, while the NMR showed that OA synovial fluid presents higher concentrations of glucose and glycerol. In conclusion, SFC activity is modulated by OA synovial fluid, which presents higher concentration of IL-10, TGF-, glycerol, and glucose.
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http://dx.doi.org/10.1155/2019/8169172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350599PMC
January 2019

Chronic Periodontitis and RANKL/OPG Ratio in Peri-Implant Mucosae Inflammation.

Braz Dent J 2018 Jan-Feb;29(1):14-22

Postgraduate Program in Dentistry, UFF - Universidade Federal Fluminense, Niterói, RJ, Brazil.

tHistory of chronic periodontitis (CP) is a risk factor for oseointegration failure. The osteoclastogenesis system (RANK, RANKL and OPG) is critical for bone homeostatic control. We investigated the levels of OPG and RANKL in peri-implant tissues from volunteers with and without a history of CP and their association with mucosae inflammation. This is a single-blind case-contro study. Diagnosis of a history of CP and peri-implant examination was performed on 46 volunteers, divided into control (without history of CP, n=26) and CP group (with history of CP, n=20). Gingival biopsies were harvested during implant exposure. Quantitative PCR evaluated OPG/RANKL mRNA expressions. OPG and RANKL proteins were analyzed by western blot and immunohistochemistry assay. The chi-square test analyzed the significance of nominal variables between groups while continuous variables were analyzed by T-test or Mann-Whitney test, after Shapiro-Wilk test evaluation. The 2-ΔΔCT Livak method calculation evaluated the gene expression. Values of p<0.05 were considered statistically significant. Volunteers with CP history had 23 times higher chance of developing mucosae inflammation. High mucosae levels of RANKL (p=0.04) and RANKL/OPG (p=0.001) mRNA expressions were observed in CP group. CP volunteers showed increased RANKL protein levels in opposition to decreased OPG expression. Even without active periodontitis, volunteers with a history of CP had elevated gingival levels of RANKL/OPG and higher correlation with peri-implant mucosae inflammation and implant loss.
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http://dx.doi.org/10.1590/0103-6440201801241DOI Listing
July 2018

Vertical femoral neck fractures in young adults: a closed fixation strategy using a transverse cancellous lag screw.

Injury 2017 Oct;48 Suppl 4:S10-S16

Research Division, National Institute of Traumatology and Orthopedics.

Vertical femoral neck fractures (Pauwels type III classification) in young adults generally occur as a consequence of high-energy trauma and are frequently seen in association with multiple injuries. Considering the controversies regarding the optimal fixation for this fracture, our aim was to evaluate the clinical outcome of a closed fixation strategy for vertical femoral neck fractures in young adults using two parallel and one transverse cancellous lag screws. This was a single-surgeon, prospective study including 20 young adults with average age of 38.75 years (range 18-59 years) with a high-energy Pauwels III femoral neck fracture. Closed reduction and internal fixation with three cancellous lag screws were performed. The first screw was inserted crosswise to avoid further shear forces. Second and third parallel screws were placed above the lesser trochanter and centrally on the greater trochanter, respectively. Clinical outcomes were assessed by comparing postoperative and final follow-up radiographs 24 months post-injury. Eleven patients had an isolated vertical femoral neck fracture. Of these, five had further femoral neck comminution. Nine patients had an associated ipsilateral femoral shaft fracture. All fractures were displaced at the time of the first radiological evaluation. Closed reduction quality was considered excellent or good in 15 patients. After 24 months, bone union was achieved in 16 cases. Osteonecrosis of the femoral head developed in association with two fractures, and a nonunion developed in association with two fractures. We conclude that vertical high-energy femoral neck fractures can be treated successfully with internal fixation with two parallel cancellous lag screws positioned above the lesser trochanter and a third screw inserted centrally on the greater trochanter at an angle perpendicular to the fracture line.
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http://dx.doi.org/10.1016/S0020-1383(17)30769-6DOI Listing
October 2017

First report of clinical responses to immunotherapy in 3 relapsing cases of chordoma after failure of standard therapies.

Oncoimmunology 2017;6(8):e1338235. Epub 2017 Jun 21.

Department of Oncology, Geneva University Hospital, Geneva, Switzerland.

Chordoma is a rare tumor of notochordal origin, currently principally treated by surgery and/or irradiation. Here, we describe the clinical outcome of 3 consecutive patients with metastatic and locally advanced chordoma, treated with different immunotherapeutic approaches. All patients presented fast growing tumors and failure of standard therapies. One was treated with a tumor-based vaccine, the 2 others with anti-PD1 antibodies, all with impressive clinical and radiological responses. We therefore propose that chordoma is an immunogenic tumor and thus that translational and clinical research is necessary to develop rationally designed immunotherapy approaches.
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http://dx.doi.org/10.1080/2162402X.2017.1338235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593713PMC
June 2017

Real-World Multicenter Experience of Immunosuppression Minimization Among 661 Liver Transplant Recipients.

Ann Transplant 2017 May 2;22:265-275. Epub 2017 May 2.

Liver Unit, University Clinic of Navarra, Pamplona, Spain.

BACKGROUND Long-term morbidity and mortality in liver transplant recipients is frequently secondary to immunosuppression toxicity. However, data are scarce regarding immunosuppression minimization in clinical practice. MATERIAL AND METHODS In this cross-sectional, multicenter study, we reviewed the indications of immunosuppression minimization (defined as tacrolimus levels below 5 ng/mL or cyclosporine levels below 50 ng/mL) among 661 liver transplant recipients, as well as associated factors and the effect on renal function. RESULTS Fifty-three percent of the patients received minimized immunosuppression. The median time from transplantation to minimization was 32 months. The most frequent indications were renal insufficiency (49%), cardiovascular risk (19%), de novo malignancy (8%), and cardiovascular disease (7%). The factors associated with minimization were older age at transplantation, longer post-transplant follow-up, pre-transplant diabetes mellitus and renal dysfunction, and the hospital where the patients were being followed. The patients who were minimized because of renal insufficiency had a significant improvement in renal function (decrease of the median serum creatinine level, from 1.50 to 1.34 mg/dL; P=0.004). Renal function significantly improved in patients minimized for other indications, too. In the long term, glomerular filtration rate significantly decreased in non-minimized patients and remained stable in minimized patients. CONCLUSIONS Immunosuppression minimization is frequently undertaken in long-term liver transplant recipients, mainly for renal insufficiency. Substantial variability exists regarding the use of IS minimization among centers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248177PMC
http://dx.doi.org/10.12659/aot.902523DOI Listing
May 2017

Conversion from Calcineurin Inhibitor-Based Immunosuppression to Mycophenolate Mofetil in Monotherapy Reduces Risk of De Novo Malignancies After Liver Transplantation.

Ann Transplant 2017 Mar 17;22:141-147. Epub 2017 Mar 17.

Liver Unit, Clinica Universidad de Navarra, Pamplona, Navarra, Spain.

BACKGROUND Immunosuppression increases the risk of malignancy in liver transplant recipients. The potential impact of mycophenolate mofetil monotherapy on this risk has not been studied. MATERIAL AND METHODS The incidence and risk factors for de novo malignancies of 392 liver transplant recipients with a survival higher than 3 months and a mean follow-up of 8.5 years were studied. RESULTS De novo malignancies were diagnosed in 126 patients (32.1%) (64 non-melanoma skin cancer and 81 other malignancies). Sixty-nine patients (18.1%) stopped receiving calcineurin inhibitors and were maintained on mycophenolate mofetil monotherapy. The proportion of time on mycophenolate mofetil monotherapy (obtained after dividing the time on monotherapy by the time until diagnosis of neoplasia/last follow-up) was independently associated with a lower risk of de novo malignancy (HR: 0.16, 95% CI: 0.05-0.48; P=0.001), non-melanoma skin cancer (HR: 0.17, 95% CI: 0.03-0.79; P=0.024), and other malignancies (HR: 0.23, 95% CI: 0.07-0.77; P=0.017). Older age and male sex were also associated with a higher risk of malignancy, and transplantation for hepatocellular carcinoma increased the risk of non-melanoma skin cancer. CONCLUSIONS Mycophenolate mofetil monotherapy is associated with a lower risk of cancer in liver transplant recipients compared with maintenance immunosuppression with calcineurin inhibitors.
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http://dx.doi.org/10.12659/aot.901556DOI Listing
March 2017

Vascular Endothelial Growth Factor Receptor-2 Polymorphisms Have Protective Effect against the Development of Tendinopathy in Volleyball Athletes.

PLoS One 2016 8;11(12):e0167717. Epub 2016 Dec 8.

Divisão de Pesquisa, Instituto Nacional de Traumatologia e Ortopedia, Rio de Janeiro, Brasil.

The aim of the study was to investigate whether genetic variants in VEGF and KDR genes can be correlated with susceptibility of tendinopathy in volleyball athletes. This study was conducted at the Brazilian Volleyball Federation, and comprised 179 volleyball athletes: 88 had a confirmed diagnosis of tendinopathy (cases), whereas 91 had no evidence of the disease (controls). The VEGF (-2578C>A, -460T>C and +936C>T) and KDR (-604C>T, 1192G>A and 1719T>A) polymorphisms were determined by TaqMan real-time polymerase chain reaction. The odds ratio (OR) with their 95% confidence intervals (CI) were calculated using an unconditional logistic regression model. The evaluation of demographic and clinical characteristics revealed the athlete age (P < 0.001), years of practice in volleyball (P < 0.001) and presence of pain (P = 0.001) were risk factors for tendinopathy. KDR 1192 GA and GA + AA genotypes were associated with lower risk of tendinopathy (OR: 0.41, 95% CI: 0.19-0.88 and OR: 0.47, 95% CI: 0.23-0.98, respectively). The KDR (-604C>T, 1192G>A and 1719T>A) haplotypes CGA and CAT were associated with decreased tendinopathy risk (OR: 0.46, 95% CI: 0.21-0.99 and OR: 0.23, 95% CI: 0.07-0.76, respectively). With regards to pain, traumatic lesion and away from training due to injury, VEGF and KDR polymorphisms were not associated with clinical symptoms complaints. The present results provide evidence that the KDR polymorphisms were associated with development of tendinopathy, and can contribute to identify new therapeutic targets or personalized training programs to avoid tendinopathy development in athletes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167717PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5145183PMC
July 2017

Liposclerosing myxofibrous tumor: A series of 9 cases and review of the literature.

J Orthop 2016 Sep 26;13(3):136-9. Epub 2016 Mar 26.

Research Division, National Institute of Orthopedics and Traumatology/MS, Rio de Janeiro, RJ, Brazil.

Background: Liposclerosing myxofibrous primary bone tumor is a rare benign bone lesion that was characterized by complex mixture of various histological elements.

Methods: We have studied the radiological, clinical and pathological features of nine patients with this disorder. Pain and limping were the main symptoms.

Results: Radiographic images typically showed a geographic lytic lesion with thick sclerotic margin, reflecting a pattern of slow growth. Histological sections revealed a polymorphic neoplasia characterized by predominant proliferation of stellate and fusiform cells aimed the myxoid matrix.

Conclusions: These features suggest that the lesion may represent a variant of fibrous dysplasia with a high risk of malignant transformation.
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http://dx.doi.org/10.1016/j.jor.2016.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821442PMC
September 2016

Mesenchymal stromal cells from bone marrow treated with bovine tendon extract acquire the phenotype of mature tenocytes.

Rev Bras Ortop 2016 Jan-Feb;51(1):70-4. Epub 2016 Jan 6.

Instituto Nacional de Traumatologia e Ortopedia, Rio de Janeiro, RJ, Brazil.

Objective: This study evaluated in vitro differentiation of mesenchymal stromal cells isolated from bone marrow, in tenocytes after treatment with bovine tendon extract.

Methods: Bovine tendons were used for preparation of the extract and were stored at -80 °C. Mesenchymal stromal cells from the bone marrow of three donors were used for cytotoxicity tests by means of MTT and cell differentiation by means of qPCR.

Results: The data showed that mesenchymal stromal cells from bone marrow treated for up to 21 days in the presence of bovine tendon extract diluted at diminishing concentrations (1:10, 1:50 and 1:250) promoted activation of biglycan, collagen type I and fibromodulin expression.

Conclusion: Our results show that bovine tendon extract is capable of promoting differentiation of bone marrow stromal cells in tenocytes.
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http://dx.doi.org/10.1016/j.rboe.2015.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767843PMC
March 2016

A Vascular Malformation Invading the Medial Plantar Nerve.

Int J Surg Pathol 2016 Jun 22;24(4):332-3. Epub 2016 Jan 22.

Geneva University Hospitals, Geneva, Switzerland

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http://dx.doi.org/10.1177/1066896915627487DOI Listing
June 2016

Adapting anatomy teaching to surgical trends: a combination of classical dissection, medical imaging, and 3D-printing technologies.

Surg Radiol Anat 2016 Apr 9;38(3):361-7. Epub 2015 Nov 9.

Department of Radiology, Geneva University Hospitals, Geneva, Switzerland.

Purpose: Many regions worldwide report difficulties in recruiting applicants to surgery. One strategy proposed to reverse this trend consists of early exposure of medical students to the field. Against this backdrop, the present study presents an innovative approach for anatomy teaching, integrating a surgically relevant trend: 3D printing.

Methods: Whole-body computed tomography (CT) was made of two cadavers. Twelve students performed measurements and 3D reconstructions of selected anatomical structures (Osirix, Mimics). 3D printed (3DP) models were obtained (ZPrinter 310 Plus), and the students completed the analogous measurements on these replicas. Finally, classical anatomical dissection was performed and the same parameters were measured. The differences between the values obtained by the three modalities were submitted to standard statistical analysis (Wilcoxon two-tail paired test).

Results: Qualitative comparison of the digital 3D reconstructions based on the students' manual CT segmentation and the anatomical reality showed excellent correlation. Quantitatively, the values measured on the CT images and the physical models created by 3D printing differed from those measured on the cadavers by less than 2 mm. Students were highly appreciative of the approach (CT, 3DP, cadaver). Their average satisfaction score was 5.8 on a 1-6 scale.

Conclusions: This study shows that the approach proposed can be achieved. The results obtained also show that CT-based 3D printed models are close to the authentic anatomic reality. The program allows early and interactive exposure of medical students to a surgically relevant trend-in this case 3D printing.
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http://dx.doi.org/10.1007/s00276-015-1588-3DOI Listing
April 2016

Different contribution of BRINP3 gene in chronic periodontitis and peri-implantitis: a cross-sectional study.

BMC Oral Health 2015 Mar 11;15:33. Epub 2015 Mar 11.

Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Peri-implantitis is a chronic inflammation, resulting in loss of supporting bone around implants. Chronic periodontitis is a risk indicator for implant failure. Both diseases have a common etiology regarding inflammatory destructive response. BRINP3 gene is associated with aggressive periodontitis. However, is still unclear if chronic periodontitis and peri-implantitis have the same genetic background. The aim of this work was to investigate the association between BRINP3 genetic variation (rs1342913 and rs1935881) and expression and susceptibility to both diseases.

Methods: Periodontal and peri-implant examinations were performed in 215 subjects, divided into: healthy (without chronic periodontitis and peri-implantitis, n = 93); diseased (with chronic periodontitis and peri-implantitis, n = 52); chronic periodontitis only (n = 36), and peri-implantitis only (n = 34). A replication sample of 92 subjects who lost implants and 185 subjects successfully treated with implants were tested. DNA was extracted from buccal cells. Two genetic markers of BRINP3 (rs1342913 and rs1935881) were genotyped using TaqMan chemistry. Chi-square (p < 0.05) compared genotype and allele frequency between groups. A subset of subjects (n = 31) had gingival biopsies harvested. The BRINP3 mRNA levels were studied by CT method (2(ΔΔCT)). Mann-Whitney test correlated the levels of BRINP3 in each group (p < 0.05).

Results: Statistically significant association between BRINP3 rs1342913 and peri-implantitis was found in both studied groups (p = 0.04). The levels of BRINP3 mRNA were significantly higher in diseased subjects compared to healthy individuals (p = 0.01).

Conclusion: This study provides evidence that the BRINP3 polymorphic variant rs1342913 and low level of BRINP3 expression are associated with peri-implantitis, independently from the presence of chronic periodontitis.
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http://dx.doi.org/10.1186/s12903-015-0018-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367924PMC
March 2015

The enteric glia: identity and functions.

Glia 2015 Jun 20;63(6):921-35. Epub 2015 Feb 20.

Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria de Estado de Saúde do Rio de Janeiro - SES/RJ, Rio de Janeiro, Brazil; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Enteric glial cells were first described at the end of the 19th century, but they attracted more interest from researchers only in the last decades of the 20th. Although, they have a different embryological origin, the enteric GLIA share many characteristics with astrocytes, the main glial cell type of the central nervous system (CNS), such as in their expression of the same markers and in their functions. Here we review the construction of the enteric nervous system (ENS), with a focus on enteric glia, and also the main studies that have revealed the action of enteric glia in different aspects of gastrointestinal tract homeostasis, such as in the intestinal barrier, in communications with neurons, and in their action as progenitor cells. We also discuss recent discoveries about the roles of enteric glia in different disorders that affect the ENS, such as degenerative pathologies including Parkinson's and prion diseases, and in cases of intestinal diseases and injury.
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http://dx.doi.org/10.1002/glia.22795DOI Listing
June 2015

Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and therapeutic perspectives.

Stem Cell Res Ther 2014 Oct 3;5(5):112. Epub 2014 Oct 3.

Mesenchymal stem cells (MSCs) have the ability to differentiate into osteoblasts, chondroblasts, adipocytes, and even myoblasts. Most studies have focused on finding MSCs in different parts of the body for medical treatment. Every joint structure, including bone, joint fat, articular cartilage, and synovium, potentially contains resident MSCs. Recently, a progenitor cell population has been found in synovial fluid and showed similarities with both bone marrow and synovial membrane MSCs. Synovial fluid MSCs have been studied in healthy persons and osteoarthritic patients in order to explore its potential for treatment of some orthopedic disorders. Here, we briefly review the current knowledge on synovial fluid MSCs, their origin, relation to some orthopedic diseases, and future applications.
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http://dx.doi.org/10.1186/scrt501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339206PMC
October 2014

Approaches to preserve human osteochondral allografts.

Cell Tissue Bank 2015 Sep 6;16(3):425-31. Epub 2014 Dec 6.

Research Division, National Institute of Traumatology and Orthopaedics, Avenida Brasil, 500 - 5° Andar, Rio de Janeiro, RJ, 20940-070, Brazil,

Osteochondral defects may progress to osteoarthritis. Many attempts have been developed to overcome this issue, including osteochondral autografts and allografts. The goal of this study was to develop a new protocol for storage of human osteochondral allografts. Osteochondral plugs were randomly allocated in the following groups: control, immediate freezing up to -70 °C, cooling at 4 °C, and storage at 37 °C. Samples from the cooling at 4 °C and storage at 37 °C groups were stored in tubes containing medium plus human albumin and analyzed after 1, 3, and 14 days. The frozen groups' samples were cryopreserved for 1 year in cryotubes containing medium only (FM), medium plus human albumin (FA), and medium plus human albumin and glucose (FG) and were then analyzed. Analysis involved histological study with hematoxylin-eosin and Safranin O and a modified Live/Dead assay. In samples stored both at 37 and 4 °C, analysis showed statistically significant higher cellular mortality at 14 days compared to 1 and 3 days, but mortality in the 4 °C group was lower. In the freezing protocols, the FA group showed less cellular mortality than the FM and FG groups. Cooling at 4 °C offers better preservation capacity than storage at 37 °C, but both offer the capacity for preservation for 14 days. Adding human albumin to the storage medium is useful in reducing cellular mortality in samples frozen for 1 year.
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http://dx.doi.org/10.1007/s10561-014-9486-1DOI Listing
September 2015

New strategy to control cell migration and metastasis regulated by CCN2/CTGF.

Cancer Cell Int 2014 12;14:61. Epub 2014 Jul 12.

Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Connective tissue growth factor (CTGF)/CCN family member 2 (CCN2) is a CCN family member of matricellular signaling modulators. It has been shown that CCN2/CTGF mediates cell adhesion, aggregation and migration in a large variety of cell types, including vascular endothelial cells, fibroblasts, epithelial cells, aortic smooth muscle and also pluripotent stem cells. Others matricellular proteins are capable of interacting with CCN2/CTGF to mediate its function. Cell migration is a key feature for tumor cell invasion and metastasis. CCN2/CTGF seems to be a prognostic marker for cancer. In addition, here we intend to discuss recent discoveries and a new strategy to develop therapies against CCN2/CTGF, in order to treat cancer metastasis.
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http://dx.doi.org/10.1186/1475-2867-14-61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130434PMC
August 2014

The facial neural crest controls fore- and midbrain patterning by regulating Foxg1 expression through Smad1 activity.

Development 2014 Jun;141(12):2494-505

Institut de Neurobiologie, Laboratoire de Neurobiologie et Développement, Avenue de la Terrasse, Gif-sur-Yvette 91198, France

The facial neural crest (FNC), a pluripotent embryonic structure forming craniofacial structures, controls the activity of brain organisers and stimulates cerebrum growth. To understand how the FNC conveys its trophic effect, we have studied the role of Smad1, which encodes an intracellular transducer, to which multiple signalling pathways converge, in the regulation of Foxg1. Foxg1 is a transcription factor essential for telencephalic specification, the mutation of which leads to microcephaly and mental retardation. Smad1 silencing, based on RNA interference (RNAi), was performed in pre-migratory FNC cells. Soon after electroporation of RNAi molecules, Smad1 inactivation abolished the expression of Foxg1 in the chick telencephalon, resulting in dramatic microcephaly and partial holoprosencephaly. In addition, the depletion of Foxg1 activity altered the expression Otx2 and Foxa2 in di/mesencephalic neuroepithelium. However, when mutated forms of Smad1 mediating Fgf and Wnt signalling were transfected into FNC cells, these defects were overcome. We also show that, downstream of Smad1 activity, Dkk1, a Wnt antagonist produced by the FNC, initiated the specification of the telencephalon by regulating Foxg1 activity. Additionally, the activity of Cerberus in FNC-derived mesenchyme synergised with Dkk1 to control Foxg1 expression and maintain the balance between Otx2 and Foxa2.
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http://dx.doi.org/10.1242/dev.101790DOI Listing
June 2014

BMP4 and FGF3 haplotypes increase the risk of tendinopathy in volleyball athletes.

J Sci Med Sport 2015 Mar 1;18(2):150-5. Epub 2014 Mar 1.

Research Division, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil. Electronic address:

Objectives: To investigate whether genetic variants can be correlated with tendinopathy in elite male volleyball athletes.

Design: Case-control study.

Methods: Fifteen single nucleotide polymorphisms within BMP4, FGF3, FGF10, FGFR1 genes were investigated in 138 elite volleyball athletes, aged between 18 and 35 years, who undergo 4-5h of training per day: 52 with tendinopathy and 86 with no history of pain suggestive of tendinopathy in patellar, Achilles, shoulder, and hip abductors tendons. The clinical diagnostic criterion was progressive pain during training, confirmed by magnetic resonance image. Genomic DNA was obtained from saliva samples. Genetic markers were genotyped using TaqMan real-time PCR. Chi-square test compared genotypes and haplotype differences between groups. Multivariate logistic regression analyzed the significance of covariates and incidence of tendinopathy.

Results: Statistical analysis revealed participant age (p=0.005) and years of practice (p=0.004) were risk factors for tendinopathy. A significant association between BMP4 rs2761884 (p=0.03) and tendinopathy was observed. Athletes with a polymorphic genotype have 2.4 times more susceptibility to tendinopathy (OR=2.39; 95%CI=1.10-5.19). Also, association between disease and haplotype TTGGA in BMP4 (p=0.01) was observed. The FGF3 TGGTA haplotype showed a tendency of association with tendinopathy (p=0.05), and so did FGF10 rs900379. FGFR1 showed no association with disease.

Conclusions: These findings indicate that haplotypes in BMP4 and FGF3 genes may contribute to the tendon disease process in elite volleyball athletes.
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http://dx.doi.org/10.1016/j.jsams.2014.02.011DOI Listing
March 2015

Cubilin, a high affinity receptor for fibroblast growth factor 8, is required for cell survival in the developing vertebrate head.

J Biol Chem 2013 Jun 16;288(23):16655-16670. Epub 2013 Apr 16.

Institut de la Vision, INSERM U968, CNRS UMR7210, Université Pierre et Marie Curie UMRS968, 17 Rue Moreau, F-75012 Paris, France. Electronic address:

Cubilin (Cubn) is a multiligand endocytic receptor critical for the intestinal absorption of vitamin B12 and renal protein reabsorption. During mouse development, Cubn is expressed in both embryonic and extra-embryonic tissues, and Cubn gene inactivation results in early embryo lethality most likely due to the impairment of the function of extra-embryonic Cubn. Here, we focus on the developmental role of Cubn expressed in the embryonic head. We report that Cubn is a novel, interspecies-conserved Fgf receptor. Epiblast-specific inactivation of Cubn in the mouse embryo as well as Cubn silencing in the anterior head of frog or the cephalic neural crest of chick embryos show that Cubn is required during early somite stages to convey survival signals in the developing vertebrate head. Surface plasmon resonance analysis reveals that fibroblast growth factor 8 (Fgf8), a key mediator of cell survival, migration, proliferation, and patterning in the developing head, is a high affinity ligand for Cubn. Cell uptake studies show that binding to Cubn is necessary for the phosphorylation of the Fgf signaling mediators MAPK and Smad1. Although Cubn may not form stable ternary complexes with Fgf receptors (FgfRs), it acts together with and/or is necessary for optimal FgfR activity. We propose that plasma membrane binding of Fgf8, and most likely of the Fgf8 family members Fgf17 and Fgf18, to Cubn improves Fgf ligand endocytosis and availability to FgfRs, thus modulating Fgf signaling activity.
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http://dx.doi.org/10.1074/jbc.M113.451070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675600PMC
June 2013

Evaluation of mechanical properties of five cements for orthodontic band cementation.

Braz Oral Res 2013 Mar-Apr;27(2):136-41. Epub 2013 Mar 1.

Univ Federal de Santa Catarina - UFSC, Programa de Pós-Graduação em Odontologia, Florianópolis, SC, Brazil.

The aim of this in vitro study was to compare the flexural, compressive and diametral tensile strengths of five cements used in orthodontics for band cementation. Twelve specimens of each cement were tested: 1 - GC Fuji Ortho Band (FJ), GC America Inc.; 2 - Meron (MR), Voco; 3 - Multi-Cure Glass Ionomer Band Cement (MC), 3M Unitek; 4 - Band-Lok (BL), Reliance Orthodontic Products; and 5 - Ketac Cem (KC), 3M ESPE. The results (mean) for diametral tensile strength were: 10.51 MPa (FJ), 9.60 MPa (MR), 20.04 MPa (MC), 42.80 MPa (BL), and 4.08 MPa (KC). The results for compressive strength were (in the same order): 64.50 MPa, 77.71 MPa, 94.21 MPa, 193.88 MPa, and 81.93 MPa. The results for flexural strength were (in the same order): 20.72 MPa, 25.84 MPa, 53.41 MPa, 137.41 MPa, and 20.50 MPa. The statistical analysis was performed by two-way ANOVA and Tukey tests with p-value £ 0.05. In terms of diametral tensile strength, BL showed the highest strength statistically, and MC, the second highest. In terms of compressive tensile strength, BL showed the highest strength statistically, and FJ did not attain the minimum recommended strength. In terms of flexural tensile strength, BL cement was superior to MC, and MR, FJ and KC were equivalent and inferior to BL and MC.
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http://dx.doi.org/10.1590/S1806-83242013005000002DOI Listing
June 2013