Myelofibrosis-Related Anemia: Current and Emerging Therapeutic Strategies.

Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder characterized by pathological myeloproliferation and aberrant cytokine production resulting in progressive fibrosis, inflammation, and functional compromise of the bone marrow niche. Patients with MF develop splenomegaly (due to extramedullary hematopoiesis), hypercatabolic symptoms (due to overexpression of inflammatory cytokines), and anemia (due to bone marrow failure and splenic sequestration). MF remains curable only with allogeneic hematopoietic stem cell transplantation (ASCT), a therapy that few MF patients are deemed fit to undergo.

Prevalence of Physical Problems Detected by the Distress Thermometer and Problem List in Patients With Myeloproliferative Disorders.

Patients with myeloproliferative neoplasms (MPNs) can have a severe physical symptom burden over an extended disease trajectory that contributes to decreased quality of life. Few studies, however, have characterized which patients most frequently consider physical symptoms a problem. This study describes the physical symptoms of patients with MPNs and the relationship of these symptoms to patient characteristics.

Myeloid/lymphoid neoplasms with FGFR1 rearrangement.

Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare entity. We present a multicenter experience of 17 patients with FISH-confirmed FGFR1 rearrangement. The clinical presentation at diagnosis included myeloproliferative neoplasm (MPN) in 4 (24%) patients, acute leukemia (AL) in 7 (41%), and concomitant MPN with AL in 6 (35%).

The Splicing Factor hnRNPA1 Regulates Alternate Splicing of the MYLK Gene.

Profound lung vascular permeability is a cardinal feature of acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI), two syndromes known to centrally involve the nonmuscle isoform of myosin light chain kinase (nmMLCK) in vascular barrier dysregulation. Two main splice variants, nmMLCK1 and nmMLCK2, are well represented in human lung endothelial cells and encoded by MYLK, and they differ only in the presence of exon 11 in nmMLCK1, which contains critical phosphorylation sites (Y and Y) that influence nmMLCK enzymatic activity, cellular translocation, and localization in response to vascular agonists. We recently demonstrated the functional role of SNPs in altering MYLK splicing, and in the present study we sought to identify the role of splicing factors in the generation of nmMLCK1 and nmMLCK2 spliced variants.

Nematode assemblages associated with the parthenogenetic lizard Ameivula nativo in six restinga areas along the eastern coast of Brazil.

We surveyed the nematode assemblages associated with populations of the parthenogenetic whiptail lizard Ameivula nativo from six coastal restinga areas in eastern Brazil: Setiba, Comboios and Guriri (State of Espirito Santo) and Guaratiba, Prado and Maraú (State of Bahia). A total of five nematode species (Physaloptera retusa, Physalopteroides venancioi, Skrjabinelazia intermedia, Subulura lacertilia and Parapharyngodon sp.) were recorded from the six different populations of A.

Reassessing the safety concerns of utilizing blood donations from patients with hemochromatosis.

Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism that may lead to iron overload. Clinical penetrance is low, however those afflicted may develop cirrhosis, hepatocellular carcinoma, diabetes mellitus, and cardiomyopathy. Treatment of HH involves regular phlebotomy to reduce the systemic iron burden.

Pharmacotherapy of Myelofibrosis.

Myelofibrosis (MF) is a myeloproliferative neoplasm that is pathologically characterized by bone marrow myeloproliferation, reticulin and collagen fibrosis, and extramedullary hematopoiesis. Constitutive activation of the Janus associated kinase (JAK)-signal transducers and activators of transcription signaling pathway with resultant elevation in pro-inflammatory cytokine levels is the pathogenic hallmark of MF. JAK inhibitors, namely ruxolitinib, have been successful in alleviating symptoms and reducing splenomegaly, but therapy-related myelosuppression has led to the further development of highly selective JAK2 inhibitors.

Multicenter phase 2 study of combination therapy with ruxolitinib and danazol in patients with myelofibrosis.

Myelofibrosis is a myeloproliferative neoplasm that is characterized by splenomegaly, profound symptom burden, and cytopenias. JAK inhibitor therapy offers improvements in splenomegaly, symptom burden, and potentially survival; however, cytopenias remain a significant challenge. Danazol has previously demonstrated improvements in myelofibrosis-associated anemia.

High prevalence of norovirus in children with sporadic acute gastroenteritis in Manaus, Amazon Region, northern Brazil.

Background: Norovirus (NoV) is a major cause of acute gastroenteritis (AGE) worldwide, especially in children under five years. Studies involving the detection and molecular characterisation of NoV have been performed in Brazil, demonstrating its importance as an etiological agent of AGE.

Objectives: The objectives of this study were to investigate the frequency of human NoV and to genotype the strains isolated from 0-14-year-old patients of AGE in Manaus, Brazil, over a period of two years.

Norovirus genogroups I and II in environmental water samples from Belém city, Northern Brazil.

This study investigated the presence of norovirus (NoV) GI and GII in environmental samples from the northern region of Brazil. Water samples were collected monthly (November 2008/October 2010) from different sources and sewage and concentrated by the adsorption-elution method. The NoV investigation used molecular methods followed by sequencing reactions.

Programmed cell death-1 pathway inhibition in myeloid malignancies: implications for myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification. Immune checkpoint inhibition, in particular along the programmed cell death protein 1 (PD-1)/B7-H1 (PD-L1) axis, is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies.

Psychological Manifestations of Early Childhood Adversity in the Context of Chronic Hematologic Malignancy.

Background: Myeloproliferative neoplasms (MPNs), a group of chronic hematologic malignancies, carry significant physical and psychological symptom burdens that significantly affect patients' quality of life.

Objectives: We sought to identify the relationship between early childhood adversity (ECA) and psychological distress in patients with MPNs, as ECA may compound symptom burden.

Methods: Patients with MPNs were assessed for ECA (i.

Psychological Symptoms Among Patients With BCR-ABL-Negative Myeloproliferative Neoplasms.

Background: BCR-ABL-negative myeloproliferative neoplasms (MPNs) represent a heterogeneous group of diseases, including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Psychological manifestations among these diseases have not been adequately described.

Methods: Cross-sectional surveys measuring distress, anxiety, and depression were collected from patients with BCR-ABL-negative MPNs from May 2015 to October 2015.

A phase II study of panobinostat in patients with primary myelofibrosis (PMF) and post-polycythemia vera/essential thrombocythemia myelofibrosis (post-PV/ET MF).

Myelofibrosis is a chronic and progressive myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating symptoms and leukemic transformation. Ruxolitinib, an oral JAK1/2 inhibitor, is highly effective in ameliorating systemic symptoms and reducing splenomegaly. Current clinical research is focused on the evaluation of agents based on pre-clinical rationale that can result in disease course modification.

Detection of a novel equine-like G3 rotavirus associated with acute gastroenteritis in Brazil.

Genotype G3P[8] of rotavirus A (RVA) is detected worldwide, usually associated with Wa-like constellation and exhibiting a long RNA migration pattern. More recently, a novel inter-genogroup, G3P[8] reassortant variant with a short electropherotype, has emerged in Asia, Oceania and Europe, denoting an overall potential of unusual rotavirus strains. During a RVA surveillance in Brazil, G3P[8] strains were found displaying a short electropherotype pattern, which had not been detected before in this region.

Should we be treating lower risk myelofibrosis patients with a JAK2 inhibitor?

Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm that is associated with debilitating constitutional symptoms, progressive splenomegaly, and cytopenias. Ruxolitinib, a JAK1/2 inhibitor, is currently the only drug approved for the treatment of patients with intermediate or high risk MF. There is rationale and even limited clinical data supporting the use of ruxolitinib in lower risk patients, although this has not yet been validated in a randomized controlled trial.

Analysis of a genotype G3P[9] rotavirus a strain that shows evidence of multiple reassortment events between animal and human rotaviruses.

The species A rotaviruses (RVA) are important gastroenteric pathogens that infect humans and animals. RVA genotype G3P[9] has been described in human-animal reassortment events, and the complexity of its hosts motivates the genetic investigation of this strain. Therefore, the aim of this study is to analyse a G3P[9] sample that was detected in a child with acute gastroenteritis.

SAPOVIRUSES IN CHILDREN WITH ACUTE GASTROENTERITIS FROM MANAUS , AMAZON REGION, BRAZIL, 2010-2011.

Sapoviruses (SaVs) are responsible for acute gastroenteritis in humans, especially children and the elderly. In Brazil, data on SaVs infections are very limited, especially in Northern Brazil. Here, we investigated the occurrence of SaVs in samples from hospitalized children under ten years old that presented acute gastroenteritis.

Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis.

Combined Janus kinase 1 (JAK1) and JAK2 inhibition therapy effectively reduces splenomegaly and symptom burden related to myelofibrosis but is associated with dose-dependent anemia and thrombocytopenia. In this open-label phase II study, we evaluated the efficacy and safety of three dose levels of INCB039110, a potent and selective oral JAK1 inhibitor, in patients with intermediate- or high-risk myelofibrosis and a platelet count ≥50×10/L. Of 10, 45, and 32 patients enrolled in the 100 mg twice-daily, 200 mg twice-daily, and 600 mg once-daily cohorts, respectively, 50.

Preferences of Patients With Myeloproliferative Neoplasms for Accepting Anxiety or Depression Treatment.

Background: Patients with chronic hematologic malignancies such as myeloproliferative neoplasms suffer from significant physical and psychological symptom burden. This study examined their willingness to accept an antidepressant and their preferences for which provider (mental health professional or hematologist/oncologist) prescribes an antidepressant for the management of anxiety and depression.

Methods: Anxiety and depression treatment preferences were measured with 3 questions assessing: (1) willingness to accept an antidepressant, (2) willingness to have their hematologist/oncologist prescribe the antidepressant, and (3) preference for treatment by a psychiatrist or mental health professional.

Differences in treatment goals and perception of symptom burden between patients with myeloproliferative neoplasms (MPNs) and hematologists/oncologists in the United States: Findings from the MPN Landmark survey.

Background: This analysis of the myeloproliferative neoplasm (MPN) Landmark survey evaluated gaps between patient perceptions of their disease management and physician self-reported practices.

Methods: The survey included 813 patient respondents who had MPNs (myelofibrosis [MF], polycythemia vera [PV], or essential thrombocythemia [ET]) and 457 hematologist/oncologist respondents who treated patients with these conditions.

Results: Greater proportions of physician respondents reported using prognostic risk classifications (MF, 83%; PV, 59%; ET, 77%) compared with patient recollections (MF, 54%; PV, 17%; ET, 31%).

Genetic engineering of CHO cells for viral resistance to minute virus of mice.

Contamination by the parvovirus minute virus of mice (MVM) remains a challenge in Chinese hamster ovary (CHO) biopharmaceutical production processes. Although infrequent, infection of a bioreactor can be catastrophic for a manufacturer, can impact patient drug supply and safety, and can have regulatory implications. We evaluated engineering a CHO parental cell line (CHOZN GS ) to create a new host cell line that is resistant to MVM infection by modifying the major receptors used by the virus to enter cells.

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Chronic and Advanced Phase Myelofibrosis.

Myelofibrosis (MF) is a chronic progressive hematologic malignancy with a median overall survival (OS) of approximately 6 years. Allogeneic hematopoietic stem cell transplantation (HSCT) is the sole treatment approach that offers curative potential. The use of reduced-intensity conditioning regimens has expanded the application of HSCT to patients with MF up to age 70 years.

Preclinical rationale for TGF-β inhibition as a therapeutic target for the treatment of myelofibrosis.

To assess the role of abnormal transforming growth factor-beta (TGF-β) signaling in the pathogenesis of primary myelofibrosis (PMF), the effects of the TGF-β receptor-1 kinase inhibitor SB431542 on ex vivo expansion of hematopoietic cells in cultures from patients with JAK2V617-polycythemia vera (PV) or PMF (JAK2V617F, CALRpQ365f, or unknown) and from normal sources (adult blood, AB, or cord blood, CB) were compared. In cultures of normal sources, SB431542 significantly increased by 2.5-fold the number of progenitor cells generated by days 1-2 (CD34) and 6 (colony-forming cells) (CB) and that of precursor cells, mostly immature erythroblasts, by days 14-17 (AB and CB).