Revista Brasileira De Research Articles

Therapeutic drug monitoring of imatinib

Therapeutic drug monitoring of imatinib

Secondary myeloid neoplasias

Secondary myeloid neoplasias are a heterogeneous group of diseases characterized by the proliferation of myeloid cells; they were recently recognized by the World Health Organization (WHO) as an entity. The wide use of chemotherapy and better diagnosis of hematological malignancies has caused a growth in the number of secondary malignancies. Most of them are myeloid: a) myelodysplastic syndromes (MDS), a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and dysplastic changes in bone marrow and peripheral blood with the risk of transformation to acute myeloid leukemia (AML) or b) sometimes the previous disease directly evolves to an overt AML. Usually the prognosis of patients with a secondary myeloid neoplasia is poor, especially when the previous disease is a MDS. However, patients may achieve a complete response. In this situation, progenitor stem cell transplantation is the best therapy. Cytogenetic analysis still plays a pivotal role in the diagnosis of hematological diseases. Cytogenetics and mutational analysis are the main prognostic tools in both AML and MDS. For this reason, cytogenetic studies are critical in the correct management of these diseases. There are several cytogenetic abnormalities associated with better prognosis, such as translocations involving core binding factors in AML patients, and losses in 20q, 5q or chromosome Y in MDS. In contrast, many others abnormalities are associated with dismal prognoses, such as the presence of a complex karyotype, abnormalities of either chromosome 3 or chromosome 7 and, in case of AML, the loss of the long arm of chromosome 5. All of these abnormalities are included in the new staging system for MDS (IPSS-2). Recently new data regarding the presence of abnormalities in chromosome 7 in primary MDS showed that the presence of a partial deletion of the long arm of this chromosome (7q-) is associated with a better prognosis than monosomy 7.(1) This abnormality is a common event in secondary MDS and AML and the potential value of this observation in secondary MDS should be addressed. In this issue of the Revista Brasileira de Hematologia e Hemoterapia a new observation highlighted the importance of performing cytogenetic studies in secondary MDS.(2) Over recent years, the wide use of microarrays and, more recently, the possibility of sequencing the human genome have provided new insights into knowledge of the molecular mechanisms involved in MDS and AML. Analysis of the gene expression profile by means of microarray technology demonstrated the presence of new pathways involved in the pathogenesis of these disorders, although studies focusing on secondary myeloid diseases are lacking.(3) Since the sequencing of the entire genome of the first hematological malignancy, a patient with AML,(4) several papers have shown the interest of the detection of new genes involved in these diseases.(5) Some of these papers have also described the involvement of new functions involved in myeloid diseases such as the spliceosome mechanism that could play an essential role in the genesis of both MDS and AML.(6) Therefore, near future investigations should provide more information of the genes involved in secondary myeloid diseases. The challenges will be to understand these genes which are thought to be drivers in the genesis of secondary myeloid neoplasias and, more importantly, to identify new therapeutic targets.

The Langerhans cell histiocytosis

The Langerhans cell histiocytosis

Titers of ABO antibodies in group O blood donors

Overt hemolysis from the transfusion of ABO incompatible plasma containing high titer anti-A or anti-B is a rare event. Plasma from group O donors and the transfusion of single donor platelets are most often associated with these reactions when transfused to group A or AB recipients. Several studies over the years have evaluated donor ABO antibody class, titer, and subclass in an effort to understand the breadth of the problem and reduce or eliminate this potentially serious immune complication of transfusion. In this regard, de Franca et al.(1) in this issue of the Revista Brasileira de Hematologia e Hemoterapia underscore the lack of a national standard of practice to guide the transfusion of incompatible ABO plasma transfusions. They point out that seminal work, started more than 2 decades ago, has yet to set policy and safety guidelines with the use of plasma that potentially contain life-threatening levels of anti-A or anti-B.(2) de Franca et al. examined over 5% of their blood donors included males and females across all age groups in an effort to understand which donors pose the biggest risk for the transfusion of high-titer anti-A or anti-B. Not surprising they found that ABO antibody titers decrease with age, with older males having the lowest titers by age 50. Cumulatively, nearly 1 in 10 plasma contain anti-A titers ≥ 128. Their work suggests that targeting ABO incompatible plasma and platelets from older males would lower the risk, if one assumes titers over 64 by the doublingdilution method (generally titers = 100 are regarded as critical) pose significant risk of hemolysis. However, there is still a 1:20 (5.3%) chance that plasma from males over 50 will contain a titer ≥ 128. Thus, targeting sex and specific age groups as surrogate markers for the transfusion of ABO incompatible platelets could hardly be considered safe practice, although it would be a step in the right direction. The lack of a standardized test and the impact on blood product availability is having an effect on the ability to drive policy and develop meaningful guidelines. Methodology appears to be a major issue. de Franca et al. used direct agglutination, however, other studies have used a test tube indirect antiglobulin test (IAT), gel microcolumn agglutination in an IAT, and flow cytometry to measure the amount of anti-A,B, anti-A and anti-B. The measurement of anti-A,B does not appear to provide any additional information on titers when compared to anti-A (de Franca et al.(1) Table 1). One problem with defining a standard may be the lack of studies necessary to correlation these methods and thus an agreement on the critical titer for which non-ABO matched platelet transfusions should be avoided. European blood centers have addressed the issue of titers and have identified low-risk titers for ABO incompatible plasma transfusions. It is important to establish critical ABO antibody titers by population (national), using the most clinically relevant method, since it appears that diet and ethnicity may result in significant differences in titers.(3,4) Performing population estimates for anti-A and anti-B levels across blood donors determines the frequency of high titers and help estimate the cost of implementing a nationalized testing policy. de Franca et al. have made a significant contribution in this regard. However, the challenge remains to quantify the impact that such a policy will have on the provision of plasma containing platelet products to recipients.(5)

The journal's performance in 2011

At the close of the year and of Volume 33 of the Revista Brasileira de Hematologia e Hemoterapia (RBHH) several significant changes deserve reflection and considerations. The first change this year was that the journal was printed in English. There was almost unanimous agreement about this decision. Even so, one or two colleagues contacted me and said they believed that this measure was inapt and even unpatriotic. This theme has been debated for some time, even among journal editors at events of the Associacao Brasileira de Editores Cientificos (ABEC). Since 2002, in its instructions for authors, the RBHH has stated that it is a bilingual journal; papers in Portuguese or English would be published and so the choice of language has always depended on the author. The times have changed and in recent years the country changed with greater participation in the global scientific market as was reported in previous issues.(1) Concurrently the academic pressure for authors' visibility has increased and the Qualis scientific journal classification system of the Coordenacao de Apoio aos Profissionais do Ensino Superior (CAPES) implanted four years ago was a fatal blow for many national journals and authors, alike.(2,3) Editorial staff felt that their work was devalued and the authors were discouraged because their contributions were given low scores with a direct impact on the productivity factor of professors and researchers. Since then the quest for visibility has become a mantra of all editors and the pursuit of the internationalization of journals has become a national goal. At this point ABEC and the Associacao Medica Brasileira (AMB) issued clear signals that it is essential to implement changes. Among which is the internationalization of the editorial board, with the participation of foreign experts in journals; this is one of the main demands for journals to become indexed to the Institute for Scientific Information Web of Knowledge/Journal Citation Reports (ISI/JCR) and PubMed/Medline electronic databases. And at this time both printed and electronic journals need to be edited in English. Thus, recent publications and events such as those of the Fundacao de Amparo a Pesquisas do Estado de Sao Paulo (FAPESP) and of the Scientific Electronic Library Online (SciELO) have been stimulating journals to publish in English on the grounds that English should be considered technical, frank and the most important or even the only international language. FAPESP recommends, albeit inexplicitly, that English be used for national publications if the objective is to reach international audiences. Publish, be read and cited or perish. This is the key. So today, on filling out disclosure documents, such as requests for financial support for the journal there is always the question of whether the journal is published in English. So the RBHH started to be printed in English, and because of this it was indexed in PubMed Central (PMC) of the National Institutes of Health, an auspicious achievement in 2011. Volume 33 will be indexed in PMC in full thereby providing international visibility to all authors. Another accomplishment this year was a 20% increase in submissions, a fact that comforts us as it shows that the changes have been accepted not only in respect to our attempts at internationalization but also in respect to measures implemented on the quality of print and the scientific rigor used in the evaluation of submissions. So, in line with policies of the Associacao Brasileira de Hematologia e Hemoterapia (ABHH) and affiliated societies [Sociedade Brasileira de Transplante de Medula Ossea (SBTMO), Associacao Italo-Brasileira de Hematologia (AIBE) and Sociedade Brasileira de Oncologia Pediatrica (SOBOPE)] the RBHH is becoming internationalized and fulfilling its role as representative of the Brazilian hematology community with the aim of becoming an alternative for the international scientific communities.

A new era, a new journal

Recently we completed 30 years of hematopoietic stem cell transplantation in Brazil. We have over 50 transplant centers, totaling approximately 320 beds and more than 20,000 transplants have been performed. We have the third largest bone marrow donor registry in the world, with around two million donors registered. Over the years, the 'Boletim da Sociedade Brasileira de Hematologia e Hemoterapia', which began in 1973, has accompanied all these changes. It became a journal with scientific articles in 1984 (ISSN) and changed in 1999 to 'Revista Brasileira de Hematologia e Hemoterapia' (RBHH). In 2000 the journal was indexed by SciELO, in 2008 by Scopus and now in 2011 we will have the first issue published in English, thus improving international visibility of our Brazilian works. Moreover, this is the official publication of the Brazilian Society of Bone Marrow Transplantation, where many transplant groups have published their clinical and laboratory studies. We are very fortunate that Professor Milton Artur Ruiz set his body and mind during long years of his life improving this journal to where today we are proud to publish works related to our area. It was not without help that the journal has evolved because many other doctors have helped by sending their articles, giving suggestions and supporting the RBHH. The RBHH, in 2010, edited a special issue in which the Brazilian guidelines for hematopoietic stem cell transplantation were published. This important publication counted on the participation of all transplant centers across the country. Finally, I would like to congratulate the President of the Associacao Brasileira de Hematologia e Hemoterapia, Professor Carmino Antonio de Souza, who with his friendship and understanding always encouraged the development of the RBHH. The Sociedade Brasileira de Transplante de Medula Ossea fully supports the initiative to internationalize the journal with the objective of promoting and improving Brazilian transfusion medicine. Congratulations to all!

The evolution of the "Revista Brasileira de Hematologia e Hemoterapia" to meet the challenges of a new era

The evolution of the "Revista Brasileira de Hematologia e Hemoterapia" to meet the challenges of a new era

The AIBE and the new phase of the RBHH

The Associacao Italo-Brasileira de Hematologia (Italian-Brazilian Association of Hematology - AIBE) was founded on 04/02/2004 in the city of Genoa, Italy. The primary objectives of the AIBE are to promote the integration of the hematology service of both countries through an exchange of healthcare professionals and the development of research of common interest. Since its inception, the AIBE chose the Revista Brasileira de Hematologia e Hemoterapia (RBHH) as its official vehicle for the publication of scientific articles. For us, it is a great pleasure to participate in this new phase of the journal, its internationalization. The AIBE can be a powerful tool in this process, as publishing the journal in English and its future indexing by Pubmed will increase, without any doubt whatsoever, the interest of colleagues and Italian researchers in publishing their articles in the journal. It is important to note that at present Italy is ranked second in the world in the number of scientific publications in the field of hematology. The Italian members, who helped found the AIBE are also in the leadership and participate in several cooperative groups that develop highly important research protocols. Today, cooperation and multicenter studies are of fundamental importance in the development of medical science and Italy has a long tradition and has advanced greatly in recent years in the development of these studies. The AIBE and the RBHH are partners in this process and we believe that there will be a great synergy in actions that undoubtedly will lead to great steps forward for both.

The Revista Brasileira de Hematologia e Hemoterapia now and discussion on the new classification of brazilian journals

The Revista Brasileira de Hematologia e Hemoterapia (RBHH) is now the official organ of the Sociedade Brasileira de Oncologia Pediatrica (Brazilian Society of Pediatric Oncology - SOBOPE). With this, SOBOPE will assist us to achieve our objectives to develop and internationalize the journal. The question regarding the Qualis classification of CAPES remains a matter of widespread debate and controversy. A recent event of FAPESP/SciELO, highlighted the progress of Brazil in respect to global scientific production as we had already discussed in issue no 3 of the RBHH this year.(1) In an atmosphere of jingoism, several editors presented measures they adopted for their journals to be included in the Thomson Reuters/ISI/JCR database, the most prestigious among all existing databases and the one responsible for calculating the famous Impact Factor. The measures used are all basically the same and already known to most participants. They include professionalization of the journal, publishing in English to increase international visibility and massive investment to improve the quality of content, in addition to trivial details, such as care with the frequency and quality of printing. With this, in few years, Brazil now has 89 scientific journals in all fields of the Thomson Reuters/ISI/JCR database. Several aspects were mentioned and a presentation by the representative of the University of Granada, Spain responsible for SCImago, emphasized the importance of Brazil and suggested adopting different approaches within the editorial market such as partnerships especially between scientific groups in Brazil and other countries in order to produce material with greater appeal and international impact. Examples of the influence of international publishers as well as criticism of the current Qualis classification were presented by another speaker(2-4) (Table 1). Table 1 Qualis classification of scientific journals With the approach of the publication of the new Qualis classification, representatives of SciELO and FAPESP suggested that some journals will be reclassified in higher positions than the old classification; those chosen would receive good financial support over a fiveyear period but this was not explained well. They mentioned that three journals from each of the three medical categories (Medicine 1, 2 and 3) would be indicated. Others suggested that it would only be two in each area. The criteria would be the existing parameters such as the impact factor, possibly using SCImago and the inclusion in SciELO which are criteria of the old classification system. Thus, the discussion is on the agenda. For this reason the Brazilian Medical Association met with all medical journal editors to discuss the new classification and the parameters that will be employed. Without much information, one of the area coordinators reported that Capes had asked him to indicate three journals, pure and simply. He also informed us that the nominees may even be promoted to classification A1 even with an impact factor lower than that stipulated by the old classification. At this point the meeting came to an end as the discussion became general with different opinions on various aspects; one conclusion was reached that if this measure were adopted there would be major discouragement for all the excluded journals. The RBHH, since the new classification was established, has been feeling the impact and thus has been trying to adapt to the new situation with much effort to improve.(5) The journal has invested in human resources and professionalism, which can be seen from the first edition of this volume. At this moment the RBHH advocates a comprehensive policy to stimulate national journals and does not agree with the support by sector for a few journals. However, we also know of the distinctive position of the RBHH in the world in relation to the other journals of this specialty and of course with evolution, our journal will become an even stronger representative of South America and of Latin countries as an alternative for developing countries to publish their scientific production.

The importance of cytogenetics in polycythemia vera, primary myelofibrosis and essential thrombocythemia

The importance of cytogenetics in polycythemia vera, primary myelofibrosis and essential thrombocythemia

Progress in chronic graft-versus-host disease

The National Institute of Health (NIH) consensus conference on criteria for clinical trials in chronic graft-versus-host disease (GvHD) brought fresh attention to a problem that is all too familiar to clinicians involved in hematopoietic stem cell transplantation. The series of 6 papers published in 2005 proposed new diagnostic criteria for the disease, summarized information regarding biomarkers and pathologic features associated with the disease, and offered recommendations for supportive care, measurement of response to treatment and the conduct of clinical trials.(1-6) Subsequent publications have focused on efforts to validate the diagnostic criteria through retrospective studies and some additional work has been done to elucidate the significance of biomarkers, especially those indicating a possible role for B cells in the pathogenesis of the disease. In the United States, Dr. Stephanie Lee organized a consortium of investigators in multiple centers to collect prospective data from a large cohort of incident and prevalent cases. These data are now being used to address several important questions, including the optimal methods for measuring ocular and oral involvement, the association of disease severity with quality of life and risk of mortality, and the prognostic significance of acute GvHD manifestations including cutaneous erythema and gastrointestinal and hepatic involvement. Ultimately, the results of these studies will be used to refine and validate recommendations that emerged from the NIH consensus conference, which were mostly based on expert opinion. In this issue of the Revista Brasileira de Hematologica e Hemoterapia, Vigorito and colleagues describe the initial results of work by a group of Brazilian investigators to develop a platform for collaboration in clinical trials related to chronic GvHD.(7) These investigators translated the US prospective data forms into Portuguese and then tested their use in five Brazilian centers. To date, the study has enrolled 34 patients with chronic GvHD. The Brazilian group and their colleagues in the US are to be congratulated for this first demonstration that international collaborations in the field of chronic GvHD are feasible in an academic setting. Much work lies ahead. The authors emphasize the theme that the Brazilian consortium is intended to serve as a platform for future collaboration in clinical trials. Better insight into the pathogenesis of chronic GvHD is needed in order to select treatments that are most likely to be effective and safe. Further discussion is needed in order to standardize eligibility criteria, organ and overall response criteria, and assessment time points in studies of secondary treatment for chronic GvHD. The shared language emerging from this standardization will facilitate informative comparisons of results between different studies. Even more importantly, benchmarks of success should be established from both retrospective and prospective cohorts so that adequately powered, rigorous phase II studies can be conducted with one-sample statistical methods to identify the most promising agents for testing in future phase III trials. The case-report forms used by the US and Brazilian consortiums will benefit from further refinement, since their current length and complexity is likely to discourage physicians from enrolling patients in clinical trials. The analysis of data from the forms will help to identify the most reliable and useful items that should be retained in shorter and less complex report forms to be used for future clinical trials. Members of the Brazilian consortium are in a good position to suggest how the forms can be improved since they were not involved in the design. As a more important contribution, however, the current members should celebrate the success illustrated in this report as a way of recruiting additional Brazilian colleagues to join in this new international effort to improve the treatment of patients with chronic GvHD.

Brazilian Society of Pediatric Oncology - SOBOPE

The history of pediatric oncology in Brazil is strongly linked to the history of the Sociedade Brasileira de Oncologia Pediatrica (SOBOPE). In the seventies two of our most prestigious pediatric oncologists, Waldir Veiga Pereira and Vicente Odone Filho, decided to go to Memphis, USA to learn about the most recent advances in pediatric hematology and Oncology. It was there they met Rhomes Joao Amim Aur. Rhomes Aur is a pioneer in pediatric hematology and oncology; the most important award in Brazilian pediatric oncology is named after him. Saint Jude Children's Hospital has a strong connection with Brazil. Since he moved to Memphis, Raul Ribeiro has continuously provided opportunities by helping Brazilian pediatric oncologists and institutions. Silvia Brandalise also visited Dr. Odone in Saint Jude. There they talked about acute lymphoblastic leukemia and a few years later in 1980, she met Milton Ruiz, Celso Carlos Campos Guerra and Rhomes Aur in Santos to discuss the first Brazilian protocol for acute lymphoblastic leukemia. The Brazilian society of pediatric oncology was founded in 1981 by a group of physicians led by Virgilio Carvalho Pinto. The founders were committed to change the dismal prognosis of children and adolescents with cancer. At that time diagnosis was practically a death sentence; few hospitals could offer a proper treatment. At the same time Beatriz de Camargo started the Wilms' tumor study group.(1) Alois Bianchi, the first head of the Pediatric Oncology Department at the A C Camargo Hospital, was the second president of SOBOPE. With Nubia Mendonca, one of the founders and most active pediatric oncologists in Brazil, the meetings of SOBOPE became routine. She officially established the Brazilian cooperative groups. After Nubia, Waldir Pereira, Silvia Brandalise, Fernando Werneck and Jose Roberto Resende contributed to the growth of SOBOPE making it a more prestigious Society. Ten years ago, with effort of one of our former presidents, Sidnei Epelman, SOBOPE started a data management center, a Computerized Data Center. This center and the cooperative groups continued to develop with Sonia Vianna. Renato Melaragno, another former President, created a strong partnership with the Instituto Ronald Mc Donald. All these collaborative studies resulted in National and International publications. The osteosarcoma study by Dr Petrilli demonstrated the Brazilian reality as opposed to the reality of other countries in respect to the size of tumors and metastasis.(2) The Ewing Sarcoma Study, led by Brunetto(3) highlighted a new combination of drugs. More recent projects are using an efficient on-line data collection system. With this quicker and more efficient system, data analysis will correct protocols in relation to toxicity. The Ewing Sarcoma protocol, like the osteosarcoma study, was developed in partnership with GALOP (the Latin American Group of Pediatric Oncology), showing that it is possible to work in harmony with other countries. The last Brazilian study of acute lymphoblastic leukemia showed new maintenance therapy.(4) The cooperative group of germ cell tumors by Luiz Fernando Lopes also published their results;(5) This group has a strong partnership with other international institutions that present data at international meetings. The Brazilian Committee of Pediatric Bone Marrow Transplantation, in a joint effort between SOBOPE and theSociedade Brasileira de Transplante de Medula Ossea (SBTMO), also published a consensus.(6) This consensus, organized by the SBTMO, was developed not only with international data, but with our local experience and publications. We cannot forget Celia Gianotti, who is internationally recognized because of her important work with the campaign for early diagnosis of retinoblastoma in Brazil.(7,8) The National Cancer Institute is making every effort to know about the reality of pediatric cancer in Brazil.(9) We should not need to use data from other countries to infer the situation here in Brazil; a few years ago, we had no idea about the numbers of new cases. SOBOPE is happy about this opportunity to join the Revista Brasileira de Hematologia e Hemoterapia (RBHH). We are very thankful to ABHH who kindly opened this door to us. This partnership will certainly further improve the quality of the RBHH. It is important to remember that the RBHH is the only scientific journal in the area of hematology in the southern hemisphere. SOBOPE is now one of the few societies of pediatric oncology that has the honor of participating in an official journal.

Enrichment of iron and folic acid

Enrichment of iron and folic acid

Countries emerging as major scientific powers

The last issue emphasized the changes taking place in the Revista Brasileira de Hematologia e Hemoterapia (RBHH) and discussed the reasons that the Associacao Brasileira de Hematologia e Hemoterapia (ABHH) and her two sister societies decided to internationalize the journal.(1-3) It was pointed out that one of the primary reasons for this was the new Qualis classification by the Brazilian further education council (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Capes). In several articles, editors of many Brazilian journals voiced their unanimous disagreement at the use of just the Thomson-Reuters impact factor in the preparation of this new classification.(4,5) The impact factor has long been used inappropriately to assess the productivity of individual researchers and professors and consequently in academic decisions related to promotion. Thus, several reports exorcise the Thomson-Reuters impact factor and recommend that other indices, such as those of SCImago and SciELO, should also be used in the classification of scientific journals.(6,7) This is justified and so the objective of the Brazilian editors was to valorize national production and Brazilian journals. In June, Crossref Quarterly, the e-letter of one of the institutions that attribute Digital Object Identifiers (DOIs) to scientific publications on the internet, reported on the Brazilian evolution over the last two years in respect to the number of requests for DOIs.(8) Crossref cites Brazil because of the recent increase in membership; the RBHH is one of these new members. Another article from the Royal Society entitled Knowledge, Networks and Nations: Global scientific collaboration in the 21st century identifies the new emerging countries of great scientific power led by China and including Brazil and also throws light on the growing scientific production of countries that are not normally mentioned such as Iran, Turkey and Tunisia.(9) China is now the second highest producer of scholarship articles worldwide and the fourth in medicine.(10) Eleven years ago it was the nineteenth in the ranking of SCImago in medicine, that is, behind Brazil which was the seventeenth (Table 1). China's contribution has accompanied its intense economic progress that has been observed over the last fifteen years. Table 1 Scientific publications in medicine - 1996 to 2010(10) Albeit not so evident, a similar evolution has happened number giving a larger slice of the share in these years (Figure 1). Today, both in general publications and in medicine, we are in the thirteenth position according to the SCImago Journal Rank (SJR - Table 1). Figure 1 Evolution of scientific production in Brazil between 1996 and 2010(10) And how is the production of Hematology? Table 2 is the cumulated publications from 1996 to 2010. In 2009 and 2010 there was intense and comparable production in Italy, the UK and Germany; these countries produced the highest number of articles after the USA. Between 1999 and 2009 China climbed from the twenty-fifth place to the seventh place giving it an aggregate position of thirteenth in 2010 (Table 2). Table 2 Scientific publications in hematology – 1996 to 2010(10) In the same period, Brazil moved from twenty-fourth to fourteenth position and its aggregate position for 1996 to 2010 is eighteenth. This is important but it is even more significant if we look at the production of Brazil in 2010 when it is in the twelfth position and not so far behind countries such as Australia and Spain (Table 3). Table 3 Scientific publications in hematology – 2010(10) However we can improve as is clear on comparing the percentage of production in hematology in respect to the overall production of documents in Medicine. Table 4 is a simple comparison of evolution of randomly chosen years of the countries that lead aggregate ranking in Hematology as well as China and Brazil. What is observed is that every year the percentage contribution of the USA and Italy in the field of hematology compared to its overall scientific production in medicine is higher than China and Brazil which shows we can and should improve. Table 4 Percentage of publications in hematology compared to the overall scientific publications in medicine of each country in 1999, 2004, 2009, cumulative of 2006 and 2009 and the year of highest productivity(10) At this point we should emphasize that the RBHH has an important role in the evolution of hematology in Brazil; it is publishing most of the citable and cited documents which make up the score of the ranking of the SJR. These data can be challenged or considered irrelevant, but should be viewed as a stimulus; an encouragement to continue with changes to transform the Revista Brasileira de Hematologia e Hemoterapia.

Results and goals

Results and goals

Perforin and hematological cancer

Perforin (PRF) is a soluble cytotoxic pore-forming glycoprotein that is a crucial component of the cocktail of cytotoxic granules harbored by cytotoxic T lymphocytes (CTL) and natural killer cells (NK), collectively known as cytotoxic lymphocytes (CLs). CLs are able to detect virus-infected or transformed cells and destroy them through perforindependent mechanisms and death receptor-dependent pathways. The cell lytic pathway also involves the interaction of perforin and other granule toxins, particularly those of the granzyme family of cytotoxins.(1) Perforin is encoded by the PRF1 gene located in chromosome 10q22 in humans. PRF1 gene is approximately 6 kb long and is composed of three exons and a promoter region of 1409 bp.(2) Deficiency of PRF results in severe immunodeficiency in both mice and humans. PRFdeficient mice are pathologically susceptible to many viruses and develop B cell lymphomas.(3) Deficiency of PRF in human infants leads to an aggressive immunoregulatory disorder called familial hemophagocytic lymphohistiocytosis (FHL) that appears within the first few months of life. FHL is fatal unless treated with cytotoxic drugs followed by bone marrow transplantation. Partial deficiency of PRF leads to a late-onset form of FHL characterized by the appearance of various forms of hematological malignancies, including B and T-cell lymphomas, and acute and chronic leukemias.(1) These data strongly suggest that deficiency of CL function due to PRF deficiency has a critical role in the increased incidence of cancer. Sixteen allelic variants of the PRF1 gene, which result in perforin deficiency, have been described (OMIN # 170280). These variants are determined by point mutations and base deletions in the coding region of the PRF1 gene. In homozygosis these variants result in reduced expression or in the synthesis of a truncated protein. Three variants (W374T, N252S and A91V) are clearly linked to the development of hematologic cancers. The A91V allele is the most prevalent variant in the Caucasian population with a reported frequency of between 3 and 17%. The A91V frequency is very low in African-Americans and there are no reported cases of this polymorphism in Japanese subjects. The A91V polymorphism has also been proposed to predispose patients to B and T-cell lymphoma, acute lymphoblastic leukemia, anaplastic large cell lymphoma, and Dianzani autoimmune lymphoproliferative disease. In a large epidemiological study, an increased incidence of the A91V mutation was found in BCR-ABL positive ALL patients indicating the necessity to investigate the effect of the presence of the A91V allele in a large cohort of cancer patients. The importance of the association of PRF function and the predisposition to hematological cancer was recently emphasized by Chia et al. who conducted a study in a cohort of patients with atypical or delayed FHL type 2.(4) The authors found a frequency of hematological cancer of over 100 times higher than that reported in the general population and argue in favor of the important role of PRF in the immune surveillance of cancer. PRF deficiency occurs not only with allelic variants characterized by mutations in the coding region of the gene. McIlroy et al. reported that the occurrence of a C/T polymorphism at position -398 of the proximal promoter region of the PRF1 gene was associated with decreased quantities of PRF in CTLs in HIV infected patients. A decrease of about 50% of control PRF levels was observed in heterozygous patients but no patients homozygous for -398T/T mutations were studied.(5) In this issue of the Revista Brasileira de Hematologia e Hemoterapia, Garcia et al.(6) present an analysis of the frequency of the C398T polymorphism in a cohort of 62 patients with hematological cancers that had no allelic disequilibrium when compared to control populations matched by inferred ascendency. However, they describe an excess of the C398T polymorphism in the patients taken as whole group compared with the controls. This discrepancy could be attributed to the small number of patients studied or to the criteria used to define the control population. It is worth mentioning that all patients, except for one, were heterozygous (C398T). The only homozygous patient has myelodysplastic syndrome, but unfortunately the corresponding clinical and epidemiological data were not included in the paper. Overall, the paper raises a number of important questions related to the role of PRF in hematological cancer and some points should be addressed in future studies: 1. Is the level of PRF reduced in the cancer patients studied as observed in HIV infected patients? 2. Is the CTL response of the lymphocytes of patients with the allelic variants normal when compared to patients with wild type and normal individuals? 3. What is the prevalence of the coding allelic variants in this group of patients? To clarify these important points it is necessary to increase the population enrolled and perform the entire PRF1 gene sequencing of patients and matched controls. A multicenter study would be welcome.

O tratamento cartográfico da informação em saúde do trabalhador

Geographic studies and spatial analyses have been recognized in Brazilian public health papers. It is still, however, very little explored by researchers. In a survey of the leading scientific journals covering issues related to Brazilian worker's health, we found the predominant use of charts and tables as a way to organize and present results with a small number of maps. This survey was conducted by examining all papers published in four journals, covering the period from 1967 to 2009 (Revista de Saúde Pública, Cadernos de Saúde Pública, Revista Saúde e Sociedade, and Revista Brasileira de Epidemiologia). After analyzing the set of papers selected for the study, the papers that used maps were given special attention. The tools of geoprocessing and geostatistics with GIS support, although little used, open new possibilities to use thematic cartography in the field of workers' health. However, it is recommended that editors of scientific journals have detailed technical standards as well as specific reports for the publication of cartographic figures aimed at facilitating the modifications necessary for the improvement of the visual quality of maps and of the spatial correlations through cartography.

RANDOMIZED CONTROLLED TRIALS IN ORTHOPEDICS AND TRAUMATOLOGY: SYSTEMATIC ANALYSIS ON THE NATIONAL EVIDENCE

Objective: To assess whether there has been any improvement in the quality and quantity of randomized controlled trials (RCTs) in nationally published journals through the application of standardized and validated scores. Methods: We electronically selected all RCTs published in the two indexed Brazilian journals that focus on orthopedics, over the period 2000-2009: Acta Ortopédica Brasileira (AOB) and Revista Brasileira de Ortopedia (RBO). These RCTs were identified and scored by two independent researchers in accordance with the Jadad scale and the Cochrane Bone, Joint and Muscle Trauma Group score. The studies selected were grouped as follows: 1) publication period (2000-2004 or 2004-2009); 2) journal of publication (AOB or RBO). Results: Twenty-two papers were selected: 10 from AOB and 12 from RBO. No statistically significant differences were found between the proportions (nRCT/nTotal of published papers) of RCTs published in the two journals (p = 0.458), or in the Jadad score (p = 0.722) and Cochrane score (p = 0.630). Conclusion: The relative quality and quantity of RCTs in the journals analyzed were similar. There was a trend towards improvement of quality, but there was no increase in the number of RCTs between the two periods analyzed.

Is there a ‘gender gap’ in authorship of the main Brazilian psychiatric journals at the beginning of the 21st century?

The aim of this study was to investigate the existence of a "gender gap" in the authorship of the four most important peer-reviewed psychiatric journals in Brazil and to quantify its magnitude. In addition, we examined the patterns of change in this gap during the period extending from 2001 to 2008 and variations according to the total number of authors, the type of article (original vs. non-original studies), and the journals themselves. A total of 1,036 articles were analyzed. We found that the proportion of female overall participation has increased from 2001 to 2008. Nevertheless, the incremental rate was accounted mostly by the growth of the participation in non-original articles. While the average annual increment for original articles was virtually null (.01%), for the non-original articles the corresponding figure was 3.7%. We also found that the chance of a woman being first author was about three times greater in original papers as compared to non-original ones at the beginning of the study period; this differential declined by 11% per year during this period. A different pattern emerged from the analysis of female last authorship. Year of publication and type of study were still associated with the chance of a woman being the last author but without interaction. Further, the journals themselves were found to be related with female last authorship: the chance of a woman being the last author in an article published in the Revista Brasileira de Psiquiatria was significantly smaller than in the other three journals. Our findings indicate clearly that some progress in being achieved in eliminating the gender gap also in field of Psychiatry and highlight the need for further research in this area.

Frequency of the Adequate Use of Statistical Tests of Hypothesis in Original Articles Published in the Revista Brasileira de Anestesiologia between January 2008 and December 2009

Statistical analysis is necessary for adequate evaluation of the original article by the reader allowing him/her to better visualize and comprehend the results. The objective of the present study was to determine the frequency of the adequate use of statistical tests in original articles published in the Revista Brasileira de Anestesiologia from January 2008 to December 2009. Original articles published in the Revista Brasileira de Anestesiologia between January 2008 and December 2009 were selected. The use of statistical tests was deemed appropriate when the selection of the tests was adequate for continuous and categorical variables and for parametric and non-parametric tests, the correction factor was described when the use of multiple comparisons was reported, and the specific use of a statistical test for analysis of one variable was mentioned. Seventy-six original articles from a total of 179 statistical tests were selected. The frequency of the statistical tests used more often was: Chi-square 20.11%, Student t test 19.55%, ANOVA 10.05%, and Fisher exact test 9.49%. The frequency of the adequate use of statistical tests was 56.42% (95% CI 49.16% to 63.68%), erroneous use in 13.41% (95% CI 8.42% to 18.40%), and an inconclusive result in 30.16% (95% CI 23.44% to 36.88%). The frequency of inadequate use of statistical tests in the articles published by the Revista Brasileira de Anestesiologia between January 2008 and December 2009 was 56.42%.