Gildásio Daltro

Tratamento da Osteonecrose da Cabeça Femoral com celulas progenitoras autólogas em anemia falciforme

SUMMARY Purpose: To assess the efficacy and safety of autologous bone- marrow mononuclear cells (BMMC) implantation in necrotic lesions of the femoral head in patients with sickle cell disease. Methods: We studied eight patients with stage-I or -II femoral head osteonecrosis according to the system by Ficat and Arlet. BMMCs were harvested and re-infused into the necrotic zone. The primary endpoints studied were safety, clinical symptoms and disease progression, these being assessed according to the Harris hip score (HHS) and to X-ray studies. Results: After eight months, seven of the eight patients reported improvement from symptoms. There were no complications during anesthetic and surgery procedures. There was a significant postoperative increase in the HHS (98.3 +/- 2.5 points) compared to preop- erative HHS (78.5 +/- 6.2 points) (p< 0.001). X-ray evaluation and cell parameters were found to be favorable. Conclusion: The autologous bone-marrow mononuclear cells implantation seems to be a safe and effective treatment for early stages of femoral head osteonecrosis in patients with sickle cell disease. Although promising, the interpretation of these early results is limited due to the small sample and to the short duration of follow-up. Further studies and advanced cellular assays are required to confirm the results.

Efficacy of autologous stem cell-based therapy for osteonecrosis of the femoral head in sickle cell disease: a five-year follow-up study

IntroductionStem cell therapy with bone marrow-derived mononuclear cells (BMMCs) is an option for improving joint function in osteonecrosis of the femoral head (ONFH). Bone marrow-derived mesenchymal stromal cell (MSC) numbers and their osteogenic differentiation are decreased in patients with ONFH. However, whether this decrease also extends to the early stages of ONFH in sickle cell disease (SCD) is still unclear.MethodsWe conducted a phase I/II, non-controlled study to determine efficacy and safety of BMMC implantation using a minimally invasive technique in SCD patients with ONFH. Eighty-nine patients were recruited and followed up for 60 months after surgery. Clinical and radiographic findings were assessed, and data were completed by in vitro analysis.ResultsAt the final follow-up (60 months) there was a significant improvement in clinical joint symptoms and pain relief as measured by the Harris Hip Score (P = 0.0005). In addition, after the BMMC implantation procedure, radiographic assessment showed disease stabilization and only 3.7 % of the treated patients did not achieve a satisfactory clinical result. The amount of fibroblast colony-forming units was 28.2 ± 13.9 per 1 million BMMCs after concentration. Flow cytometry analysis showed a significantly higher number of hematopoietic stem/endothelial progenitor cell markers in concentrated BMMCs when compared with bone marrow aspirate, indicating an enrichment of these cell types. Isolated MSCs from SCD patients with pre-collapse ONFH maintained the replicative capacity without significant loss of their specific biomolecular characteristics, multi-differentiation potential, and osteogenic differentiation activities. Cytokines and growth factors (interleukin-8, transforming growth factor-beta, stromal cell-derived factor-1alpha and vascular endothelial growth factor) that mediate endogenous bone regeneration were also produced by expanded MSCs from SCD patients.ConclusionThe autologous BMMC implantation with a minimally invasive technique resulted in significant pain relief and halted the progression of early stages of ONFH in SCD patients. MSCs from SCD patients display biological properties that may add to the efficiency of surgical treatment in ONFH. In summary, our results indicate that infusion of BMMCs enriched with stem/progenitor cells is a safe and effective treatment for the early stages of ONFH in SCD patients.Trial registrationClinicalTrials.gov NCT02448121; registered 15 May 2015.

Fixation of the Cemented Stem: Clinical Relevance of the Porosity and Thickness of the Cement Mantle

The aim of this review paper is to define the fixation of the cemented stem. Polymethyl methacrylate, otherwise known as “bone cement”, has been used in the fixation of hip implants since the early 1960s. Sir John Charnley, the pioneer of modern hip replacement, incorporated the use of cement in the development of low frictional torque hip arthroplasty. In this paper, the concepts of femoral stem design and fixation, clinical results, and advances in understanding of the optimal use of cement are reviewed. The purpose of this paper is to help understanding and discussions on the thickness and the porosity of the cement mantle in total hip arthroplasty. Cement does not act as an adhesive, as sometimes thought, but relies on an interlocking fit to provide mechanical stability at the cement–bone interface, while at the prosthesis– cement interface it achieves stability by optimizing the fit of the implant in the cement mantle, such as in a tapered femoral stem.

Osteonecrosis in sickle cell disease patients from Bahia, Brazil: a cross-sectional study

PurposeThe aim of this study was to describe the clinical features of osteonecrosis (ON) in sickle cell disease (SCD) patients in Bahia, a Northeast state with the highest prevalence of the disease in Brazil.MethodsBetween 2006 and 2017, 283 cases of osteonecrosis in SCD patients were enrolled to analyse the age at diagnosis, genotype, gender, pain, distribution of the lesions and disease staging. MRI and radiograph were obtained at the participation.ResultsOf the 283 SCD cases, 120 (42.4%) were haemoglobin SS genotype while 163 (57.6%) were SC genotype. Two hundred and forty-six cases were bilateral and 37 were unilateral, with an average age at diagnosis of 33.7 (range 10–67) years. The most frequent identified ON site not only was the hip (74.6%), but also affected shoulder, knee and ankle. Most cases presented at early stage I (172, 60.8%) disease. No significant differences on the features of osteonecrosis were identified between haemoglobin SS and haemoglobin SC cases.ConclusionsGiven the relatively high prevalence of bilateral osteonecrosis at early stages, painful symptoms and rather late age at diagnosis, SCD patients should have radiological examination of their joints more often in order to prevent severe functional disability and increase patient’s life quality.

Talar Osteonecrosis Related to Adult Sickle Cell Disease: Natural Evolution from Early to Late Stages

BACKGROUND Little is known about the rate of, and factors affecting, progression of talar osteonecrosis related to sickle cell disease. Adult patients with sickle cell disease who presented with hip osteonecrosis were evaluated for talar osteonecrosis with radiographs and magnetic resonance imaging (MRI). Forty-five of them (75 tali) were diagnosed with talar osteonecrosis, and this group was evaluated for factors influencing the progression of the disease. METHODS Forty-five patients with sickle cell disease and osteonecrosis of the talus were identified with radiographs and MRI between 1985 and 1995. Seven of these patients were homozygous for hemoglobin S (S/S genotype), 26 had hemoglobin S/hemoglobin C, and 12 had hemoglobin S/beta-thalassemia. The talar osteonecrosis was graded with radiographs and MRI. The patients were followed with clinical examination and radiographs every 6 months until talar collapse and every year after the collapse. RESULTS The osteonecrosis was unilateral in 15 patients and bilateral in 30 at the time of the initial examination. Forty-five ankles were asymptomatic and 30 were symptomatic at the initial evaluation. MRI performed at the time of the most recent follow-up, and compared with MRI performed at diagnosis, did not show partial or total regression of the osteonecrosis in any of the patients, even those with asymptomatic stage-I osteonecrosis. At the time of the most recent follow-up (mean, 20 years; range, 15 to 25 years), pain and collapse had developed in all except 12 ankles. The stage of the osteonecrosis at the initial visit, pain, the genotype of the sickle cell disease, and the extent and location of the lesion in the talus were risk factors for progression of the disease. CONCLUSIONS In the majority of the patients with sickle cell disease, osteonecrosis of the talus should be expected to show relevant clinical and radiographic evidence of progression over a long period. LEVEL OF EVIDENCE Prospective Level II. See Instructions for Authors for a complete description of levels of evidence.

VISCOSUPPLEMENTATION IN ANKLE OSTEOARTHRITIS: A SYSTEMATIC REVIEW

ABSTRACT To evaluate the efficacy of viscosupplementation in patients with osteoarthritis of the ankle. A systematic review to evaluate the evidence in the literature on the use of viscosupplementation for osteoarthritis of the ankle. For this review, we considered blind randomized prospective studies involving the use of viscosupplementation for osteoarthritis of the ankle. A total of 1,961 articles were identified in various databases. After examining each of the articles, five articles were included in this review. Treatment with intraarticular hyaluronic acid is a safe treatment modality that significantly improves functional scores of patients, with no evidence of superiority in relation to other conservative treatments. Further clinical trials with larger numbers of patients are needed so that we can recommend its use and address unanswered questions. Systematic Review of Randomized Clinical Trials.

Autologous stem cell‐based therapy for sickle cell leg ulcer: a pilot study

Recurrent chronic leg ulcers are among the most severe vasculopathic complications of sickle cell disease (SCD). Their treatment remains a challenge. Stem cell therapy with bone marrow mononuclear cells (BMMC) is a promising new therapeutic option for other forms of chronic ulcers. This prospective pilot study was performed to evaluate safety and feasibility of BMMC implantation in patients with SCD and chronic leg ulcers (SCLU). Ulcer closure, recurrence and local pain were evaluated. BMMC were successfully administered to 23 SCLU patients and no serious adverse events occurred. During the 6‐month follow‐up period, 91·3% of patients had improved ulcer pain compared with baseline and 29·2% of the treated ulcers achieved total healing. The frequency of progenitor stem cells (CD34CD45low and fibroblast colony‐forming units) in BMMC was found to be significantly reduced in SCLU patients and compared to SCD patients without ulcers (P < 0·004 and P < 0·01, respectively). No relationship was observed between treatment outcome and the number of implanted BM progenitor stem cells. In conclusion, BMMC implantation is a feasible and safe procedure, showing favourable outcomes for the treatment of SCLU, and encouraging further controlled clinical trials.

Osteonecrosis in Sickle-Cell Disease

Sickle-cell disease (SCD), an autosomal recessive disorder, is also called sickle-cell anemia (SCA) due to the hemolytic anemia characterized by abnormally shaped (sickled) red blood cells (RBCs), which are removed from the circulation and destroyed at increased rates, leading to anemia. Of greater clinical importance, the sickled RBCs cause vascular occlusion, which leads to tissue ischemia and infarction. The patients who are homozygous for the sickle-cell gene (hemoglobin SS) have a high risk of bone osteonecrosis [1–3] due to microvascular occlusion in relation to the disturbance in the erythrocyte architecture and the polymerization of hemoglobin S (in a deoxygenated state) producing cells that are crescent- or sickle-shaped with decreased deformability; the decreased deformability results in greater risk for clotting in small vessels. The incidence of osteonecrosis is also high in patients with hemoglobin SC (compound heterozygotes for Hb S- and Hb C-producing alleles: SC) and in the various types of sickle-beta-thalassemia (SThal) population. So, patients with sickle-cell disease often present with orthopedic disease manifestations requiring surgical intervention, with the most common indications being osteonecrosis and osteomyelitis. This article based on the experience of the authors treating more than 2,000 patients with SCD reviews the incidence of multifocal osteonecrosis in this disease, the distribution of the joints concerned by multifocal osteonecrosis, and the clinical consequences in the long term (average 15 years of follow-up) of multifocal osteonecrosis in these patients with sickle-cell disease and includes an approach to the medical and surgical management of patients with orthopedic complications related to sickle-cell disease.

Estudo prospectivo e randomizado de pacientes com fraturas expostas da diáfise do fêmur submetidos a osteossíntese com placa e haste intramedular bloqueada a foco aberto

Trata-se de um estudo prospectivo e randomizado de duas tecnicas de osteossintese no tratamento das fraturas expostas diafisarias do femur, realizado entre janeiro de 2002 a abril de 2004. Haste intramedular bloqueada fresada realizada a foco aberto e placa e parafusos foram empregadas no tratamento de 20 pacientes em cada grupo. De acordo com a classificacao de Gustilo, 26 (65%) foram tipo I, 10 (25%) tipo II e 4 (10%) tipo IIIA. Quanto ao mecanismo das fraturas, 21 por trauma contuso e 19 por ferimentos de arma de fogo.Tres pacientes foram excluidos nas avaliacao final. Houve complicacao em 12 (32,4%),sendo 4 no grupo de placas e 8 no grupo das hastes. O grupo de haste bloqueada apresentou 2 (10%) infeccoes profundas, 2 infeccoes superficiais (10%), 1 falha de consolidacao (5%).O grupo de placa e parafusos resultou em 1 infeccao profunda associada a falha de consolidacao (5,8%), 1 infeccao superficial (5,8%). Pela classificacao de resultados de Thorensen obteve-se bons e excelentes resultados em 28 (75,7%) fraturas, 3 (7.5%) casos regulares e 6 (15%) casos ruins. A estabilizacao com placas e parafusos, trouxe menores taxas de complicacoes, quando comparadas com o uso de hastes fresadas a foco aberto,embora sem significado estatistico.

Bacterial cellulose for advanced medical materials

Abstract Bacterial cellulose (BC) has become established as a new biomaterial and can be used in several applied scientific areas, especially for medical devices. In addition, biomedical materials have claimed attention because of the increased interest in tissue engineering materials for wound care and regenerative medicine. The BC bioprocess production can be changed by controlling the fermentation process. It has unique properties that make it an exciting candidate as a medical material: strength, good integration within the host tissue, and flexibility of production in various shapes and sizes. This chapter describes a morphological investigation in human regenerative medicine, stem cell behavior on bacterial cellulose, and recent drug delivery applications for medical applications. It also discusses futures insights and research with bacterial cellulose.