Advances in ex vivo expansion of hematopoietic stem and progenitor cells for clinical applications.

As caretakers of the hematopoietic system, hematopoietic stem cells assure a lifelong supply of differentiated populations that are responsible for critical bodily functions, including oxygen transport, immunological protection and coagulation. Due to the far-reaching influence of the hematopoietic system, hematological disorders typically have a significant impact on the lives of individuals, even becoming fatal. Hematopoietic cell transplantation was the first effective therapeutic avenue to treat such hematological diseases. Since then, key use and manipulation of hematopoietic stem cells for treatments has been aspired to fully take advantage of such an important cell population. Limited knowledge on hematopoietic stem cell behavior has motivated in-depth research into their biology. Efforts were able to uncover their native environment and characteristics during development and adult stages. Several signaling pathways at a cellular level have been mapped, providing insight into their machinery. Important dynamics of hematopoietic stem cell maintenance were begun to be understood with improved comprehension of their metabolism and progressive aging. These advances have provided a solid platform for the development of innovative strategies for the manipulation of hematopoietic stem cells. Specifically, expansion of the hematopoietic stem cell pool has triggered immense interest, gaining momentum. A wide range of approaches have sprouted, leading to a variety of expansion systems, from simpler small molecule-based strategies to complex biomimetic scaffolds. The recent approval of Omisirge, the first expanded hematopoietic stem and progenitor cell product, whose expansion platform is one of the earliest, is predictive of further successes that might arise soon. In order to guarantee the quality of these ex vivo manipulated cells, robust assays that measure cell function or potency need to be developed. Whether targeting hematopoietic engraftment, immunological differentiation potential or malignancy clearance, hematopoietic stem cells and their derivatives need efficient scaling of their therapeutic potency. In this review, we comprehensively view hematopoietic stem cells as therapeutic assets, going from fundamental to translational.

Evaluation of the theranostic potential of [64Cu]CuCl2 in glioblastoma spheroids.

BACKGROUND: Glioblastoma is an extremely aggressive malignant tumor with a very poor prognosis. Due to the increased proliferation rate of glioblastoma, there is the development of hypoxic regions, characterized by an increased concentration of copper (Cu). Considering this, 64Cu has attracted attention as a possible theranostic radionuclide for glioblastoma. In particular, [64Cu]CuCl2 accumulates in glioblastoma, being considered a suitable agent for positron emission tomography. Here, we explore further the theranostic potential of [64Cu]CuCl2, by studying its therapeutic effects in advanced three-dimensional glioblastoma cellular models. First, we established spheroids from three glioblastoma (T98G, U373, and U87) and a non-tumoral astrocytic cell line. Then, we evaluated the therapeutic responses of spheroids to [64Cu]CuCl2 exposure by analyzing spheroids' growth, viability, and cells' proliferative capacity. Afterward, we studied possible mechanisms responsible for the therapeutic outcomes, including the uptake of 64Cu, the expression levels of a copper transporter (CTR1), the presence of a cancer stem cell population, and the production of reactive oxygen species (ROS). RESULTS: Results revealed that [64Cu]CuCl2 is able to significantly reduce spheroids' growth and viability, while also affecting cells' proliferation capacity. The uptake of 64Cu, the presence of cancer stem-like cells and the production of ROS were in accordance with the therapeutic response. However, expression levels of CTR1 were not in agreement with uptake levels, revealing that other mechanisms could be involved in the uptake of 64Cu. CONCLUSIONS: Overall, our results further support [64Cu]CuCl2 potential as a theranostic agent for glioblastoma, unveiling potential mechanisms that could be involved in the therapeutic response.

Hypothermic Preservation of Adipose-Derived Mesenchymal Stromal Cells as a Viable Solution for the Storage and Distribution of Cell Therapy Products.

Cell and gene therapies (CGT) have reached new therapeutic targets but have noticeably high prices. Solutions to reduce production costs might be found in CGT storage and transportation since they typically involve cryopreservation, which is a heavily burdened process. Encapsulation at hypothermic temperatures (e.g., 2-8 °C) could be a feasible alternative. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)) expanded using fetal bovine serum (FBS)- (MSC-FBS) or human platelet lysate (HPL)-supplemented mediums (MSC-HPL) were encapsulated in alginate beads for 30 min, 5 days, and 12 days. After bead release, cell recovery and viability were determined to assess encapsulation performance. MSC identity was verified by flow cytometry, and a set of assays was performed to evaluate functionality. MSC(AT) were able to survive encapsulated for a standard transportation period of 5 days, with recovery values of 56 ± 5% for MSC-FBS and 77 ± 6% for MSC-HPL (which is a negligible drop compared to earlier timepoints). Importantly, MSC function did not suffer from encapsulation, with recovered cells showing robust differentiation potential, expression of immunomodulatory molecules, and hematopoietic support capacity. MSC(AT) encapsulation was proven possible for a remarkable 12 day period. There is currently no solution to completely replace cryopreservation in CGT logistics and supply chain, although encapsulation has shown potential to act as a serious competitor.

Influence of the mesenchymal stromal cell source on the hematopoietic supportive capacity of umbilical cord blood-derived CD34+-enriched cells.

BACKGROUND: Umbilical cord blood (UCB) is a clinically relevant alternative source of hematopoietic stem/progenitor cells (HSPC). To overcome the low cell number per UCB unit, ex vivo expansion of UCB HSPC in co-culture with mesenchymal stromal cells (MSC) has been established. Bone marrow (BM)-derived MSC have been the standard choice, but the use of MSC from alternative sources, less invasive and discardable, could ease clinical translation of an expanded CD34+ cell product. Here, we compare the capacity of BM-, umbilical cord matrix (UCM)-, and adipose tissue (AT)-derived MSC, expanded with/without xenogeneic components, to expand/maintain UCB CD34+-enriched cells ex vivo. METHODS: UCB CD34+-enriched cells were isolated from cryopreserved mononuclear cells and cultured for 7 days over an established feeder layer (FL) of BM-, UCM-, or AT-derived MSC, previously expanded using fetal bovine serum (FBS) or fibrinogen-depleted human platelet lysate (HPL) supplemented medium. UCB cells were cultured in serum-free medium supplemented with SCF/TPO/FLT3-L/bFGF. Fold increase in total nucleated cells (TNC) as well as immunophenotype and clonogenic potential (cobblestone area-forming cells and colony-forming unit assays) of the expanded hematopoietic cells were assessed. RESULTS: MSC from all sources effectively supported UCB HSPC expansion/maintenance ex vivo, with expansion factors (in TNC) superior to 50x, 70x, and 80x in UCM-, BM-, and AT-derived MSC co-cultures, respectively. Specifically, AT-derived MSC co-culture resulted in expanded cells with similar phenotypic profile compared to BM-derived MSC, but resulting in higher total cell numbers. Importantly, a subpopulation of more primitive cells (CD34+CD90+) was maintained in all co-cultures. In addition, the presence of a MSC FL was essential to maintain and expand a subpopulation of progenitor T cells (CD34+CD7+). The use of HPL to expand MSC prior to co-culture establishment did not influence the expansion potential of UCB cells. CONCLUSIONS: AT represents a promising alternative to BM as a source of MSC for co-culture protocols to expand/maintain HSPC ex vivo. On the other hand, UCM-derived MSC demonstrated inferior hematopoietic supportive capacity compared to MSC from adult tissues. Despite HPL being considered an alternative to FBS for clinical-scale manufacturing of MSC, further studies are needed to determine its impact on the hematopoietic supportive capacity of these cells.

Tailored Cytokine Optimization for ex vivo Culture Platforms Targeting the Expansion of Human Hematopoietic Stem/Progenitor Cells.

Umbilical cord blood (UCB) has been established as an alternative source for hematopoietic stem/progenitor cells (HSPC) for cell and gene therapies. Limited cell yields of UCB units have been tackled with the development of cytokine-based ex vivo expansion platforms. To improve the effectiveness of these platforms, namely targeting clinical approval, in this study, we optimized the cytokine cocktails in two clinically relevant expansion platforms for HSPC, a liquid suspension culture system (CS_HSPC) and a co-culture system with bone marrow derived mesenchymal stromal cells (BM MSC) (CS_HSPC/MSC). Using a methodology based on experimental design, three different cytokines [stem cell factor (SCF), fms-like tyrosine kinase 3 ligand (Flt-3L), and thrombopoietin (TPO)] were studied in both systems during a 7-day culture under serum-free conditions. Proliferation and colony-forming unit assays, as well as immunophenotypic analysis were performed. Five experimental outputs [fold increase (FI) of total nucleated cells (FI TNC), FI of CD34+ cells, FI of erythroid burst-forming unit (BFU-E), FI of colony-forming unit granulocyte-monocyte (CFU-GM), and FI of multilineage colony-forming unit (CFU-Mix)] were followed as target outputs of the optimization model. The novel optimized cocktails determined herein comprised concentrations of 64, 61, and 80 ng/mL (CS_HSPC) and 90, 82, and 77 ng/mL (CS_HSPC/MSC) for SCF, Flt-3L, and TPO, respectively. After cytokine optimization, CS_HSPC and CS_HSPC/MSC were directly compared as platforms. CS_HSPC/MSC outperformed the feeder-free system in 6 of 8 tested experimental measures, displaying superior capability toward increasing the number of hematopoietic cells while maintaining the expression of HSPC markers (i.e., CD34+ and CD34+CD90+) and multilineage differentiation potential. A tailored approach toward optimization has made it possible to individually maximize cytokine contribution in both studied platforms. Consequently, cocktail optimization has successfully led to an increase in the expansion platform performance, while allowing a rational side-by-side comparison among different platforms and enhancing our knowledge on the impact of cytokine supplementation on the HSPC expansion process.

Addressing the Manufacturing Challenges of Cell-Based Therapies.

Exciting developments in the cell therapy field over the last decades have led to an increasing number of clinical trials and the first cell products receiving marketing authorization. In spite of substantial progress in the field, manufacturing of cell-based therapies presents multiple challenges that need to be addressed in order to assure the development of safe, efficacious, and cost-effective cell therapies.The manufacturing process of cell-based therapies generally requires tissue collection, cell isolation, culture and expansion (upstream processing), cell harvest, separation and purification (downstream processing), and, finally, product formulation and storage. Each one of these stages presents significant challenges that have been the focus of study over the years, leading to innovative and groundbreaking technological advances, as discussed throughout this chapter.Delivery of cell-based therapies relies on defining product targets while controlling process variable impact on cellular features. Moreover, commercial viability is a critical issue that has had damaging consequences for some therapies. Implementation of cost-effectiveness measures facilitates healthy process development, potentially being able to influence end product pricing.Although cell-based therapies represent a new level in bioprocessing complexity in every manufacturing stage, they also show unprecedented levels of therapeutic potential, already radically changing the landscape of medical care.

Retrospective study to assess the impact of ranibizumab 0. 5mg in the visual acuity of patients with macular diseases in a real life context / Estudo retrospectivo para avaliar o impacto de ranibizumab 0, 5mg na acuidade visual de pacientes com doenças maculares num contexto de vida real

Abstract Objective: The primary objective of the study is to evaluate, in a population in the state of Bahia, Brazil, the impact of ranibizumab in best-corrected visual acuity of patients with macular disease and macular edema. Methods: This study did a retrospective and observational assessment visual acuity of the group of patients followed at the Professor Edgard Santos University Hospital and Oftalmodiagnose Eye Hospital in 2011 and 2012 in a real life context. Results: The impact on sample patientes post-treatment demonstrated favorable outcome with an increase in visual acuity of 32%, which means improvement of more than one line in the snellem chart. Conclusion: Improvement in visual acuity of this group was observed from baseline to the end of follow up in a real-life context.

Resumo Objetivo: O objetivo principal do estudo é avaliar, em uma população no estado da Bahia, o impacto do ranibizumab na acuidade visual melhor corrigida de pacientes com doença macular e edema macular. Métodos: Para isso, fizemos uma avaliação retrospectiva e observacional da acuidade visual do grupo de pacientes seguidos no Hospital Universitário Professor Edgard Santos e Oftalmodiagnose Hospital de Olhos em 2011 e 2012 em um contexto de vida real. Resultados: O estudo demonstrou desfecho favorável com aumento da acuidade visual de 32%, o que significa melhora de mais de uma linha no quadro snellem. Conclusão: A melhora da acuidade visual desse grupo foi observada desde o início até o final do seguimento em um contexto da vida real.

Blocking negative effects of senescence in human skin fibroblasts with a plant extract.

There is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life- and healthspan of mice. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). Here we identified an extract from the plant Solidago virgaurea subsp. alpestris, which exhibited weak senolytic activity, delayed the acquisition of a senescent phenotype and induced a papillary phenotype with improved functionality in human dermal fibroblasts. When administered to stress-induced premature senescent fibroblasts, this extract changed their global mRNA expression profile and particularly reduced the expression of various SASP components, thereby ameliorating the negative influence on nearby cells. Thus, the investigated plant extract represents a promising possibility to block age-related loss of tissue functionality.

Optic neuritis and chorioretinitis as ocular manifestations of borreliosis in Brazil: three cases reported / Neurite óptica e coriorretinite como manifestações oculares da borreliose no Brasil: três casos relatados

Abstract Lyme disease is a systemic infection caused by a tick bite and transmission of the Borrelia burgdorferi spirochete. Species of tick vectors of the disease infest mainly wild or rural animals and rodents that may be asymptomatic reservoirs of the bacteria. Characteristic of the northern hemisphere, Lyme disease in Brazil takes on different characteristics, complicating diagnosis. This paper aims to describe three cases of Lyme-like disease in a city in the state of Bahia, Brazil, with ophthalmologic findings.

Resumo A doença de Lyme é uma infecção sistêmica causada pela picada do carrapato e transmissão da espiroqueta Borrelia burgdorferi. As espécies de carrapatos vetores da doença infestam, principalmente, animais silvestres, rurais e roedores que podem ser reservatórios assintomáticos da bactéria. Característica do hemisfério norte, a doença de Lyme no Brasil assume características distintas, dificultando seu diagnóstico. Esse trabalho tem por objetivo, descrever três casos da doença Lyme símile do Brasil, com achados oftalmológicos, em município do Estado da Bahia.

Multicenter, Randomized Clinical Trial to Assess the Effectiveness of Intravitreal Injections of Bevacizumab, Triamcinolone, or Their Combination in the Treatment of Diabetic Macular Edema.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of combined bevacizumab-triamcinolone intravitreal injection in the treatment of diabetic macular edema (DME) compared to monotherapy. PATIENTS AND METHODS: At eight clinical sites, 111 patients with DME were randomly assigned to receive an intravitreal injection of bevacizumab (Avastin; Genentech, South San Francisco, CA), triamcinolone (Ophthalmos Pharmaceutical Industry, São Paulo-SP, Brazil), or their combination. The primary outcome was visual acuity (VA) at 6 months' follow-up. RESULTS: The average number of injections was 3.2 in the bevacizumab group, 2.4 in the combined group, and 2.1 in the triamcinolone group. All groups presented with improvements in VA (P < .001); however, no differences between groups were observed (P = .436). Mean reduction in central retinal thickness was statistically different only between the triamcinolone and bevacizumab groups (P < .015). CONCLUSION: Mono- or combination therapy was effective for DME treatment. No synergistic effects were observed; however, triamcinolone alone or a drug combination may reduce the number of injections required when compared to bevacizumab alone. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:734-740.].

Bloqueio ilioinguinal e ílio-hipogástrico em anestesia pediátrica: comparação da analgesia entre as técnicas de visualização direta e a guiada por ultrassom / Ilioinguinal and iliohypogastric nerve block in pediatric anesthesia: a comparison of analgesia between direct and ultrasound-guided visualization techniques

Introdução: Comparar o grau de dor em pacientes pediátricos que foram submetidos a bloqueio dos nervos ilioinguinal e ílio-hipogástrico, através das técnicas de visualização direta e guiada por ultrassom em cirurgias de herniorrafia e orquidopexia em intervalos de 30 minutos, 3 e 6 horas após a saída da sala cirúrgica. Métodos: Foi realizado um ensaio clínico, randomizado, com 38 pacientes submetidos às cirurgias propostas, divididos em 2 grupos através de sorteio aleatório: grupo 1 bloqueio por visualização direta e grupo 2 por ultrassom. Os pacientes foram avaliados em 3 fases, nos intervalos aventados pelo estudo com a utilização das escalas FLACC e Comfort-Behavior, aplicadas de maneira observacional. Para a associação entre as variáveis de interesse, foram utilizados o teste de qui-quadrado de Pearson e o teste t de Student para a comparação entre médias. Os dados foram inseridos no Epi InfoT 3.5.4 e SPSS 18.0. Para verificar as variáveis de interesse, foram utilizados os testes de qui-quadrado e teste t de Student, sendo considerado nível de significância de 5%. Resultados: Participaram do estudo 38 pacientes, com média de 3,44 anos de idade. A cirurgia mais realizada foi a de hérnia inguinal bilateral em 17 (44,7%) dos pacientes. 52,5% dos pacientes utilizaram analgésico, sendo que desses, 19 fizeram uso somente uma vez, desses, 8 necessitaram de analgesia 30 minutos após a saída da sala cirúrgica. Conclusão: O trabalho evidenciou superioridade na técnica de visualização direta na redução da dor no pós-operatório em relação à técnica por ultrassom (AU)

Introduction: To compare the degree of pain in pediatric patients who underwent ilioinguinal and iliohypogastric nerve block through direct and ultrasound-guided visualization techniques in herniorrhaphy and orchidopexy surgeries at 30-minute intervals, 3 and 6 hours after leaving the operating room. Methods: A randomized clinical trial was conducted with 38 patients submitted to the proposed surgeries, divided randomly into 2 groups, group 1 block by direct visualization and group 2 by ultrasound. The patients were evaluated in 3 phases, at the intervals proposed by the study, using the FLACC and Comfort-Behavior scales applied observationally. For the association between the variables of interest, the Pearson chi-square test and Student's t-test were used to compare the means. The data was entered into Epi InfoT 3.5.4 and SPSS 18.0. Chi-square and Student's t-tests were used to verify the variables of interest. A level of significance of 5% was considered. Results: Thirty-eight patients with a mean of 3.44 years of age participated in the study. The most commonly performed surgery was for bilateral inguinal hernia in 17 (44.7%) of the patients. Analgesics were used by 52.5% of the patients, of whom 19 used them only once, and of these, 8 required analgesia 30 minutes after leaving the operating room. Conclusion: The work showed superiority of the technique of direct visualization in reducing postoperative pain as compared to the ultrasound technique (AU)

Perfil epidemiológico das crianças internadas por queimaduras em hospital do sul do Brasil, de 1998 a 2008 / Epidemiological profile of children inmate by burns in a hospital in the south of Brazil from 1998 to 2008

Objetivo: Descrever o perfil epidemiológico de pacientes vítimas de queimaduras, verificar a prevalência desse trauma, os fatores associados e sua relação com diversas variáveis. Método: Estudo transversal, conduzidono Hospital Nossa Senhora da Conceição, em Tubarão, Santa Catarina,no período compreendido entre janeiro de 1998 a dezembro de 2008, cuja amostra final constituiu-se de 111 crianças e adolescentes. Os dados foram analisados por meio dos testes de qui-quadrado e t de Student, com nível de significância de 95%. Resultados: Observou-se maior prevalência de crianças com idade entre 0 e 3 anos, com predominância do gênero masculino (p< 0,001). O agente etiológico mais frequente foi a escaldadura (p< 0,001), seguido por fogo (chamas ou explosão) e contatocom superfícies quentes. Crianças mais novas tiveram maior relação com queimadura por escaldadura (p = 0,01), enquanto pacientes com maioridade queimaram-se com fogo. O tempo médio de internação foi de uma semana e as áreas corporais mais acometidas foram face, tórax e membros superiores. Não houve qualquer relação entre queimaduras e sazonalidade. Conclusões: As queimaduras foram mais comuns em menores de 3 anos do sexo masculino. O mecanismo mais prevalente foi a escaldadura.

Objective: To describe the epidemiological profile of burned patients, to verify the prevalence of this trauma, the associated factors and their relation to diverse variables. Methods: Cross-sectional study conducted at Nossa Senhora da Conceição Hospital in Tubarão, Santa Catarina, from January 1998 through December 1998, which final sample was constituted of 111 children and adolescents. The data was analyzed through tests of chi-square and t-student with a level of significance of 95%. Results: It was observed a greater prevalence of children between 0 and 3 years of age, with a predominance of the male gender (p< 0.001). The etiologic agent more frequent was the scald (p< 0.001), followed by fire (flames or explosion) and contact with hot surfaces. Younger children were more related to scald burns (p = 0.01), while the older ones were burned by fire. The approximate internment time was of a week and the body areas more affected were the face, chest and superior members. There was no relation between burns and seasons. Conclusions: The burns were more common in male children between 0 and 3 years of age. The predominant mechanism was the scald.

[Management of congenital nasolacrimal duct obstruction]. / Tratamento das obstruções congênitas do ducto nasolacrimal.

PURPOSE: To present the success rate in treating congenital nasolacrimal duct obstruction with hydrostatic pressure (Crigler method). METHODS: Clinical data from 186 children aged up to 32 months treated from 1990 until 2005 were reviewed retrospectively. The procedure was repeated up to 3 times at a one week interval. Using EPI INFO version 6.04 software for analysis, data were tabulated and statistical significance was evaluated by applying chi-square and Kruskal-Wallis tests. RESULTS: Leading age group was 1 to 5 months old (56.4%) for males and females. Affection was bilateral in 36.3%, 34.1% on right side and 29.6% on the left side. All cases had epiphora and 56.5% presented mucopurulent discharge. Cure was achieved with one massage for 43.6%, 23.3% with two, 17.4% with three and, with 4 and 5+ sessions in respectively 5.8% and 9.0%. Those 14 cases who did not respond to massage were treated with probing. CONCLUSION: The Crigler method was effective in managing congenital nasolacrimal duct obstruction cases.

Tratamento das obstruções congênitas do ducto nasolacrimal / Management of congenital nasolacrimal duct obstruction

OBJETIVO: Apresentar os resultados do tratamento da obstrução nasolacrimal congênita com a massagem hidrostática de Crigler. MÉTODOS: Cento e oitenta e seis crianças com idade de até 32 meses com obstrução nasolacrimal congênita foram estudadas retrospectivamente de 1990 a 2005. O procedimento foi repetido três vezes em cada sessão, com intervalo de uma semana entre as sessões. A análise foi realizada com o programa informatizado EPI INFO versão 6.04. A significância estatística foi avaliada pela aplicação dos testes do qui-quadrado e Kruskal-Wallis. RESULTADOS: A faixa de idade predominante nos dois sexos foi de 1 a 5 meses (56,4 por cento), a localização foi bilateral em 36,3 por cento, do lado direito em 34,1 por cento e do lado esquerdo em 29,6 por cento. A epífora estava presente em 100 por cento dos casos e secreção em 56,5 por cento. Curaram com uma sessão 43,6 por cento dos casos, com duas 23,3 por cento, com três 17,4 por cento e com 4 e 5 ou mais sessões 5,8 por cento e 9,0 por cento dos pacientes, respectivamente. Os 14 pacientes que não responderam a massagem foram tratados com sondagem. CONCLUSÃO: A massagem hidrostática de Crigler é efetiva para a obstrução nasolacrimal congênita.

PURPOSE: To present the success rate in treating congenital nasolacrimal duct obstruction with hydrostatic pressure (Crigler method). METHODS: Clinical data from 186 children aged up to 32 months treated from 1990 until 2005 were reviewed retrospectively. The procedure was repeated up to 3 times at a one week interval. Using EPI INFO version 6.04 software for analysis, data were tabulated and statistical significance was evaluated by applying chi-square and Kruskal-Wallis tests. RESULTS: Leading age group was 1 to 5 months old (56.4 percent) for males and females. Affection was bilateral in 36.3 percent, 34.1 percent on right side and 29.6 percent on the left side. All cases had epiphora and 56.5 percent presented mucopurulent discharge. Cure was achieved with one massage for 43.6 percent, 23.3 percent with two, 17.4 percent with three and, with 4 and 5+ sessions in respectively 5.8 percent and 9.0 percent. Those 14 cases who did not respond to massage were treated with probing. CONCLUSION: The Crigler method was effective in managing congenital nasolacrimal duct obstruction cases.

Controle de danos após trauma torácico contuso com lesão cardíaca em criança - relato de caso / damage control after abdominal trauma

O objetivo é descrever o caso de um traumatismo torácico contuso que cursou com grave lesão da artériapulmonar, tipo laceração, que conduziu o paciente ao choque hipovolêmico refratário às medidas de suporte,sendo adotado o controle de danos torácicos. A cirurgia de controle de danos tem sido muito difundida na literatura que aborda trauma, especialmente quando se trata detrauma abdominal. Entretanto, esse relato pretende demonstrar que também é possível adotar a cirurgia de controle de danos quando se aborda um traumatismo torácico grave em pacientes com pouca reserva fisiológica.

The objective is to describe a case of blunt chest trauma causing severe laceration-type injury in the pulmonary artery, which led the patient to developrefractory hypovolemic shock to the support measures, with the adoption of chest damage control. Damage control surgery has been quite spread in the literature on trauma, especially when dealing with abdominal trauma.Nevertheless, this report is aimed to demonstrate that it is also possible to adopt damage control surgery whentreating severe chest trauma in patients with reduced physiological reserve.

[Ophthalmic manifestations of neuroendocrine carcinoma: case report]. / Manifestações oftalmológicas de carcinoma neuroendócrino: relato de caso.

Ophthalmic manifestations of neuroendocrine carcinoma. This case report describes the clinical presentation, diagnosis and treatment of a case of neuroendocrine carcinoma. A 43-year-old man presented with ocular manifestation due to orbital and brain metastasis of neuroendocrine carcinoma. The histopathologic and immunohistochemical analysis suggested the diagnosis. Partial and temporary remission of the symptoms occurred after the first chemotherapy cycle. We discuss the importance of creating treatment guidelines for this type of neoplasm, that can be very aggressive and fatal.

Manifestações oftalmológicas de carcinoma neuroendócrino: relato de caso / Ophthalmic manifestations of neuroendocrine carcinoma: case report

Relatar o caso de um paciente de 43 anos com metástase de carcinoma neuroendócrino intracraniana e intra-orbitária, cujas primeiras manifestações foram oftalmológicas. Relato de caso. Remissão temporária do quadro clínico após um ciclo de quimioterapia. A análise histopatológica e a imuno-histoquímica foram sugestivas de carcinoma neuroendócrino. A regressão das manifestações clínicas após quimioterapia e o óbito posterior aos ciclos de quimioterapia nos faz pensar na necessidade da criação de protocolos de tratamento para essa forma de neoplasia, levando em consideração, fatores locais e/ou sistêmicos.

Endoftalmite pós-cirurgia de estrabismo / Endophthalmitis after strabismus surgery

Ratificamos a importância do exame biomicroscópico e oftalmoscópio em pacientes submetidos à cirurgia de correção do estrabismo, para identificação de endoftalmite. Descrição de uma paciente que evoluiu com endoftalmite no pós-operatório de correção de estrabismo, descrevendo os achados pós-operatórios, resultados da avaliação laboratorial e terapêutica realizada. Paciente de 28 anos, negra, atendida no ambulatório de oftalmologia do Hospital Universitário Professor Edgard Santos, apresentava acuidade visual de 20/20 em ambos os olhos e esotropia. Paciente foi submetida a recuo de 5mm dos retos mediais e evoluiu a partir do 3º dia de pós-operatório com hipópio e que após início do tratamento com amicacina e vancomicina intravítrea e colírios de cefalotina e gentamicina fortificados, evolui com melhora da acuidade visual. Mesmo rara, a endoftalmite pós-cirurgica de estrabismo deve ser motivo de preocupação dos oftalmologistas.

Clinicopathologic study after submacular removal of choroidal neovascular membranes treated with verteporfin ocular photodynamic therapy.

PURPOSE: To report the clinicopathologic findings after submacular removal of choroidal neovascular membranes (CNV) treated with verteporfin ocular photodynamic therapy. DESIGN: Interventional case series. METHODS: Retrospective review of eight eyes of eight patients who underwent submacular surgery for CNV after having previously received verteporfin ocular photodynamic therapy for presumed ocular histoplasmosis (one patient), age-related macular degeneration ([AMD] three patients) pathologic myopia (two patients), punctate inner choroiditis (one patient), and idiopathic CNV (one patient). All cases had undergone ocular photodynamic therapy with verteporfin using standard protocols. Six of eight patients suffered a submacular hemorrhage after ocular photodynamic therapy, and two of eight patients refused further ocular photodynamic therapy. All patients subsequently had submacular surgery with removal of the CNV. One membrane was routinely processed, sectioned, and stained with hematoxylin and eosin. Five membranes were stained with toluidine blue for light microscopic examination. Semithin (1.0 microm) sections were cut and stained with uranyl acetate-lead citrate for transmission electron microscopy. RESULTS: Choroidal neovascular membranes were removed at 3 days (presumed ocular histoplasmosis), 29 days (punctate inner choroiditis), 63 days (AMD, pathologic myopia), 66 days (AMD), 107 days (pathologic myopia), 116 days (AMD), and 152 days (idiopathic) after verteporfin ocular photodynamic therapy. Histopathologic and ultrastructural examination showed areas of vascular occlusion at 3 days that were not seen at later time points. All specimens had patent CNV. There were signs of vascular damage with extravasated erythrocytes and fibrin, pigment clumping in cells, and inflammatory cells in all but the 3-day specimen. CONCLUSIONS: This case series presents data only from patients who refused repeat treatment with ocular photodynamic therapy or who developed submacular hemorrhage after initial photodynamic therapy. Histopathologic evaluation of CNV 3 days after verteporfin ocular photodynamic therapy showed partial vascular occlusion that was not present in later specimens. These later specimens demonstrated evidence of vascular damage. Verteporfin ocular photodynamic therapy does not appear to lead to permanent and complete occlusion of the CNV. Thus, treatments that lead to permanent closure of CNV without damage to the retinal pigment epithelium and sensory retina are still needed.

Vasculopatia polipoidal idiopática da coróide / Idiopathic polypoidalchoroidal vasculopathy

Objetivo: Descrever os achados da tomografia de coerência óptica, angiofluoresceinografia e indocianinografia na vasculopatia polipoidal idiopática da coróide. Métodos: Realizou-se análise criteriosa dos exames complementares de angiofluoresceinografia e indocianinografia, comumente utilizados para o diagnóstico, assim como da tomografia de coerência óptica, em quatro olhos de uma série de três pacientes com vasculopatia polipoidal idiopática da coróide. Resultados: Os quatro olhos motraram lesöes subretinianas vermelho-alaranjadas, sendo que dois casos apresentaram descolamento hemorrágico do epitélio pigmentado da retina, além de manifestaçöes exsudativas e hemorrágicas associadas. A angiofluoresceinografia revelou dilataçöes aneurismáticas em ramificaçöes anormais de vasos da coróide em apenas 1 caso, ao contrário da indocianinografia que claramente demonstrou as lesöes em todos os casos. A tomografia de coerência óptica confirmou o descolamento hemorrágico espontâneo do epitélio pigmentado da retina em 2 casos. Conclusäo: A indocianinografia é o exame de escolha no diagnóstico da vasculopatia polipoidal da coróide, mas em alguns casos a associaçäo com a tomografia de coerência óptica e angiofluoresc einografia pode ser útil no diagnóstico e seguimento.