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A dearth of Mesozoic-aged, three-dimensional fossils hinders understanding of the origin of the distinctive skull and brain of modern (crown) birds1. Here we report Navaornis hestiaegen. et sp. nov., an exquisitely preserved fossil species from the Late Cretaceous of Brazil. The skull of Navaornisis toothless and large-eyed, with a vaulted cranium closely resembling the condition in crown birds; however, phylogenetic analyses recover Navaornisin Enantiornithes, a highly diverse clade of Mesozoic stem birds. Despite an overall geometry quantitatively indistinguishable from crown birds, the skull of Navaornisretains numerous plesiomorphies including a maxilla-dominated rostrum, an akinetic palate, a diapsid temporal configuration, a small cerebellum and a weakly expanded telencephalon. These archaic neurocranial traits are combined with a crown bird-like degree of brain flexion and a bony labyrinth comparable in shape to those of many crown birds but substantially larger. Altogether, the emergent cranial geometry of Navaornisshows an unprecedented degree of similarity between crown birds and enantiornithines, groups last sharing a common ancestor more than 130 million years ago2. Navaornisprovides long-sought insight into the detailed cranial and endocranial morphology of stem birds phylogenetically crownward of Archaeopteryx, clarifying the pattern and timing by which the distinctive neuroanatomy of living birds was assembled.

Introduction:Chronic lymphocytic leukemia (CLL) exhibits diverse treatment requirements, with some patients receiving immediate treatment while others remain under observation. In 2008, the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) established criteria for treatment indications, widely adopted in clinical practice and trials. The Brazilian Group of CLL (BGCLL) has been evaluating a more conservative approach to treatment indication performed in multiple centers, which avoids predefined cutoff levels for cytopenias and refrains from considering progressive lymphocytosis, extranodal involvement, or disease-related symptoms as isolated criteria. However, the safety and potential different outcomes of this conservative approach compared to the strict IWCLL criteria remain uncertain. Objective: This study aims to compare the outcomes of CLL patients without indication for treatment according to the BGCLL criteria, who were either treated or not based on the center's decision.

Background- The treatment of multiple myeloma has evolved significantly in the last decade and combinations of the new drugs have allowed better responses and significant gain in survival. Studies comparing different chemotherapy combinations before transplant suggest that the triple combo is superior to double. The use of bortezomib as backbone in these combos has been identified as superior to other drugs. Unfortunately bortezomib is not part of the drugs available for use in the Brazilian public health system to myeloma treatment and the only available drug is thalidomide. Comparisons between different triple combinations are rare in the literature. In the present study we compared two different triple combinations composed of bortezomib + cyclophosphamide + dexamethasone (VCD) versus thalidomide + cyclophosphamide + dexamethasone (CTD) in order to identify which of the two combinations lead to the best response after 4 cycles before bone marrow transplantation for eligible new diagnose patients with multiple myeloma.

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No relevant conflicts of interest to declare.

Rule: Gilead: Research Funding; Celgene: Consultancy, Other: Travel reimbursement; J&J: Consultancy, Other: Travel reimbursement, Research Funding; Roche: Consultancy, Other: Travel reimbursement. Rusconi:Roche: Honoraria. Joao:Celgene, Novartis: Consultancy; Janssen, Roche: Membership on an entity's Board of Directors or advisory committees. Witzens-Harig:Pfizer: Honoraria, Research Funding; Roche: Honoraria. Hess:Pfizer, Janssen, Roche, Mundipharma: Honoraria, Research Funding; Janssen, Roche, , Celgene, Novartis: Consultancy. Balasubramanian:Janssen: Employment, Equity Ownership; Pharmacyclics LLC, an AbbVie Company: Equity Ownership. Bandyopadhyay:Janssen: Employment. Sun:Janssen/J&J: Employment, Equity Ownership. Goldberg:Janssen: Employment. Bothos:Janssen: Employment. Traina:Janssen: Employment. Enny:Janssen: Employment. Rizo:Janssen: Employment. Vermeulen:Janssen: Employment.

Introduction

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No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Nowadays, the best evidence for symptomatic patients with Multiple Myeloma (MM) is initial induction therapy with more than two drugs that contains bortezomib. If patients are eligible it is established the use of high dose chemotherapy and autologous stem cell transplantation (ASCT). We do not have to prescribe in Brazilian public health service, due to economic reasons, new drugs such as: bortezomib and lenalidomide. On the other hand, it is known that Cyclophosphamide, thalidomide and dexamethasone (CTD) regimen is an effective primary therapy for MM and it is widely used in some countries such as United Kingdom. We have been prescribing for first line therapy CTD regimen in our clinical practice for approximately 4 years. Thus, we performed a retrospective analysis of patients with MM treated with CTD regimen in the Instituto do Câncer do Estado de São Paulo. Here we present response rate, reduction dose rate, toxicity rate and progression free survival (PFS) and overall survival (OS).

Acute Myeloid Leukemia (AML) widely affects elderly patients, with disappointing survival rates with increasing age. Although chronological age is an independent prognostic risk, it is really important to understand that this group is heterogeneous, so a geriatric assessment may be helpful before making decisions regarding therapy. We describe a 91 year-old patient with AML treated with decitabine, achieving a complete response and good quality of life for 10 months.In May 2012, a 91 year-old woman with myelodysplastic syndrome was admitted at the emergency department presenting asthenia, pallor, pain and edema of the left inferior limb. Her blood count showed: hemoglobin 10.7g/dL, leukocytes 81.800/mm³ with 95% blast cells, and platelets 45.000/mm³. In addition, a Doppler ultrasound evidenced deep venous thrombosis in her left leg. A bone marrow aspirate confirmed AML with myelodysplasia-related alterations, with 95% blast cells, with positive expression of CD45, CD33, MPO, and CD117 (CD45+; CD33+; MPO+; CD117+). Her karyotype was 46,XX [20 cells analyzed]. She was first treated with hydroxyurea. Afterwards, as her performance status improved and in spite of her age, we decided to treat her with Decitabine 20mg/m²/day for 5 days, because she had no severe comorbidity or any severe impairment of every-day-life instrumental activities. After a first cycle with grade 4 neutropenia and thrombocytopenia, she was discharged. After 40 days, complete hematologic recovery was observed. She received seven treatment cycles, and the most important symptom of toxicity was febrile grade 3 neutropenia in the 3rd cycle, with the only inpatient treatment. After this intercurrence, the doses were reduced by 25%. The patient achieved complete remission, spent eleven months without needing blood transfusions and with an acceptable quality of life, but then she relapsed, presenting persistent neutropenia and 44% of blasts in a bone marrow aspirate (05/27/2013). She died on 07/02/2013 due to the progression of the disease.This case shows that, despite her advanced chronological age, our patient, affected by a fatal disease, lived approximately 13 months with optimal response to treatment (with Decitabine) and enjoying an acceptable quality of life for ten months. Considering this patient profile, could we conclude that this outcome is the best our treatment can aim to achieve?No relevant conflicts of interest to declare.

Chronic Myeloid Leukemia (CML) is the most well described disease result of t(9;22)(q34,q11.2). This chromosomal rearrangement leads to well-know BCR-ABL fusion that promotes tyrosine kinase activity. There are others oncogenic BCR fusion found such as PDGFRA (4q12), FGFR1(8p12) that causes myeloproliferative disorders (MD).JAK2 gene is one of the 4 genes members of JAK family. The JAK2 V617F mutation which results from a G –>T transversion at nucleotide 1849 in exon 14 of the JAK2 gene, the consequence of which is substitution of valine by phenylalanine at codon 617 is associated with MD and it is a major diagnosis criterion for Primary Myeloficrosis, Polycythaemia vera and Essential thrombocytemia. There are described a lot chromosomal translocations involving the JAK2 locus.We report an extremely rare case with BCR-JAK2 fusion gene as the result of t(9;22)(p24,q11.2) for the first time in Brazilian people, and it is the 6thcase all of the world.In April 2010, a 54 years old male patient presented fatigue, abdominal pain and splenomegaly. A blood count revealed leukocytosis 93.380/mm3 with a predominance of neutrophils and left shift. Conventional cytogenetic analysis was performed and it was evidenced 46,XY, t(9;22)(p24;q11.2) in 90% metaphases examined, due to expected association it was promoted BCR-ABL1 fusion gene and it was not detected by using RT-PCR. He was treated with imatinib 400mg/day because the involvement of BCR gene. After three months he presented weight loss, progressive splenomegaly without hematologic response and it was modified to Dasatinib 150mg/day plus hydroxyureia 3g/day. In August 2011, due to not hematologic response, it was stopped Dasatinib treatment and nowadays patient has been treating with hydroxyureia 1.5g/day. His last follow up in May 2012, blood count was abnormal Hb 16.8g/dl leukocytes 7730/mm3 and low platelets count 32.000/mm3. The differential count showed 65.3% segmented granulocytes, 13.6% eosinophlis, 1.6% basophil, 2.6% monocytes, 16.9% lymphocytes.It was repeated conventional Karyotyping and it was evidenced 46,XY, t(9;22)(p24;q11.2) in all of metaphases examined. The presence of BCR-ABL rearrangement was excluded by using the fluorescence in situ hybridization (FISH) using a BCR-ABL probe. In addition, it was not evidenced FIP1L1-PDGFRa fusion gene and JAK2 V617F mutation by using RT-PCR.We have described a male patient with MD with t(9;22)(p24;q11.2) wich leads to the BCR-JAK2 fusion and it was not evidenced BCR-ABL1, FIP1L1-PDGFRa fusion genes and JAK2 V617F mutation by using RT-PCR. Moreover, patient has not been achieved hematologic response with tyrosine kinase inhibitors: imatinib and dasatinib. In the five cases reported three presented MD, one Acute Myeloid Leukemia and one Acute Lymphoblastic Leukemia. Only in one case report it was prescribed imatinib and the patient lost the follow up (Table1). The BCR-JAK2 fusion protein contain the coiled-coil dimerization domain of BCR and the protein tyrosine Kinase domain (JH1) of JAK2. It was not possible to define what would be the best therapy, because tyrosine kinase inhibitors may not be effective to the BCR-JAK2 fusion. Maybe in MD presentation, we could return to pre- tyrosine kinase inhibitors era based on treatments with hydroxyureia, subcutaneous cytarabine and interferon for patients that were not potential candidates for allogeneic transplant.No relevant conflicts of interest to declare.

Background: The identification of occult micrometastatic disease is potentially important in management of breast cancer (BC) patients. Therefore, detection of cytokeratin 19 (CK-19) and others molecular markers using reverse transcriptase polymerase chain reaction (RT-PCR)-based techniques to detect micrometastases could have significant implications in prevention, early detection and treatment of breast cancer. Objective: To assess the diagnostic specificity and sensitivity of detection of CK-19 in the peripheral blood (PB) of BC patients as well as to assess its relation to prognostic factors and implication on survival. Methods: We conducted a systematic review/meta-analysis of all studies that analyzed CK-19 in the PB of BC patients. We searched MEDLINE, LILACS and Cochrane Database of Systematic Reviews (last search June 2004). Studies that had at least 10 BC patients and controls and evaluated the presence of CK-19 in PB using RT-PCR were included in this review. Diagnostic sensitivity was defined as the percentage of detection of CK-19 in patients with histological proven diagnosis of breast cancer. The specificity was defined as the percentage of negative tests for CK-19 in the control group (healthy individuals or non breast cancer patients). Results: Out of 1842 relevant studies that were identified, 26 met our inclusion criteria, enrolling 2398 patients (1176 treatment and 1222 controls). Results showed that PCR had an overall diagnostic sensitivity of 0.39 (95% CI: 0.36–0.42) and diagnostic specificity of 0.83 (95% CI: 0.76–0.87) regardless of the breast cancer stage. Six studies researched the association between CK-19 and well established prognostic factors (i.e. positive axillary lymph nodes, hormonal receptors, tumor size); however data were not available for quantitative synthesis. Survival was poorly reported making impossible to generate any conclusion about the implication of detection of CK-19 on prognosis. When studies were critically appraised, we also identified many methodological weaknesses in the design, conduct and the analysis of these studies (e.g. use of multiple control arms, use of non-consecutive patients, different timing of sample collection, inclusion of all stages of breast cancer and differential work-up in the study & control groups) hence resulting in biased findings due to selection, verification, detection and spectrum bias. Conclusion: The existing body of evidence regarding the assessment and prognostic value of CK-19 using RT-PCR techniques is poor and needs ample improvement before the initiation of its clinical application.