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Hideki Sano, Kazuhiro Mochizuki, Mitsuko Akaihata, Shogo Kobayashi, Hitoshi Ohto, Atsushi Kikuta
Intensive chemotherapy with tyrosine kinase inhibitor (TKI) improves the prognosis of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). However, the prognosis of cases of relapsed or refractory Ph-ALL remains poor. Here, we aimed to assess the efficacy of T-cell-rich HLA-haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) in eight patients with relapsed or refractory pediatric Ph-ALL. Transplant-related mortality was observed in two patients. All patients discontinued TKI after receiving TCR-haplo-HSCT...
October 26, 2016: Pediatric Blood & Cancer
Gregory F Guzauskas, Kathleen F Villa, Geertrui F Vanhove, Vicki L Fisher, David L Veenstra
PURPOSE: To estimate the risk-benefit trade-off of a pediatric-inspired regimen versus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) for first-line treatment of adolescents/young adult (AYA; ages 16-39 years) patients with Philadelphia-negative acute lymphoblastic leukemia. METHODS: Patient outcomes were simulated using a 6-state Markov model, including complete response (CR), no CR, first relapse, second CR, second relapse, and death...
October 25, 2016: Journal of Adolescent and Young Adult Oncology
Sarah K Tasian, David T Teachey, Yong Li, Feng Shen, Richard C Harvey, I-Ming Chen, Theresa Ryan, Tiffaney L Vincent, Cheryl L Willman, Alexander E Perl, Stephen P Hunger, Mignon L Loh, Martin Carroll, Stephan A Grupp
Philadelphia chromosome-like B-cell lymphoblastic leukemia (BCR-ABL1-like or Ph-like ALL) is associated with activated JAK/STAT, SRC/ABL, and/or PI3K/Akt/mTOR signaling and poor clinical outcomes. Inhibitors of PI3K pathway signaling (PI3Ki) have been minimally investigated in Ph-like ALL to date. We hypothesized that targeted inhibition of PI3Kα, PI3Kδ, PI3K/mTOR, or TORC1/TORC2 would decrease leukemia proliferation and abrogate aberrant kinase signaling. We further hypothesized that combined PI3K pathway and JAK inhibition or PI3K pathway and SRC/ABL inhibition would have superior efficacy compared to inhibitor monotherapy...
October 24, 2016: Blood
Prithviraj Bose, Srdan Verstovsek
INTRODUCTION: Primary myelofibrosis (PMF) is the least common but the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms. Survival is much shorter in PMF than in polycythemia vera (PV) or essential thrombocythemia (ET). Post-PV/ET myelofibrosis (MF) is clinically indistinguishable from PMF and approached similarly. AREAS COVERED: Current pharmacologic therapy of MF revolves around the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib, which dramatically improves constitutional symptoms and splenomegaly in the majority of patients, and improves overall survival (OS)...
October 22, 2016: Expert Opinion on Pharmacotherapy
Lasse Kjær, Sabrina Cordua, Morten O Holmström, Mads Thomassen, Torben A Kruse, Niels Pallisgaard, Thomas S Larsen, Karin de Stricker, Vibe Skov, Hans C Hasselbalch
Discovery of somatic mutations in the calreticulin gene (CALR) has identified a subgroup of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) with separate haematological characteristics and prognosis. CALR mutations serve as novel markers both of diagnostic value and as targets for monitoring molecular responses during therapy. Interferon-α (IFN) selectively targets the malignant clone in a subset of MPN patients and can induce both haematological and molecular remissions in CALR mutated essential thrombocythemia (ET) patients...
2016: PloS One
Elizabeth J Bhoj, Zhenming Yu, Qiaoning Guan, Rebecca Ahrens-Nicklas, Kajia Cao, Minjie Luo, Tanya Tischler, Matthew A Deardorff, Elaine Zackai, Avni B Santani
INTRODUCTION: RASopathies include disorders generally characterized by developmental delay, specific heart defects, short stature, cardiac hypertrophy, and facial dysmorphisms. Next-generation sequencing (NGS)-based panels have widespread acceptance as a diagnostic tool for RASopathies. MATERIALS AND METHODS: The first 126 patients evaluated by clinical examination and the NGS RASopathy panel at the Children's Hospital of Philadelphia were enrolled. We calculated diagnosis rate, correlated reported clinical findings with positive or negative test results, and identified final molecular diagnoses in 28/96 patients who tested negative for RASopathies...
October 20, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Joseph Gibbons, Michael S Barton
There exists controversy as to the impact gentrification of cities has on the well-being of minorities. Some accuse gentrification of causing health disparities for disadvantaged minority populations residing in neighborhoods that are changing as a result of these socioeconomic shifts. Past scholarship has suggested that fears of displacement and social isolation associated with gentrification lead to poorer minority health. However, there is a lack of research that directly links gentrification to minority health outcomes...
October 19, 2016: Journal of Urban Health: Bulletin of the New York Academy of Medicine
Surjit Singh, Pramod Kumar Sharma
Here, we present a case of chronic myeloid leukemia for which imatinib therapy was initated. Triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone was normal, and thyroid microsomal autoantibodies (TMA) were positive and patient was diagnosed as thyroiditis treated with corticosteroids for 1½ months which lead to resolution.
July 2016: Indian Journal of Pharmacology
Prithviraj Bose, Srdan Verstovsek
The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) mainly comprise polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF, primary or post-PV/ET). Therapy in PV and ET focuses on minimizing thrombosis and bleeding risk, while in MF, prolongation of survival is an important goal. Different cytoreductive agents are employed in high risk PV and ET, while the JAK inhibtior ruxolitinib is the cornerstone of therapy in MF. Histone deacetylase inhibitors (HDACi) are pleiotropic agents with diverse epigenetic and non-epigenetic actions, selectively in transformed cells...
October 18, 2016: Expert Opinion on Investigational Drugs
L Germine, E B Robinson, J W Smoller, M E Calkins, T M Moore, H Hakonarson, M J Daly, P H Lee, A J Holmes, R L Buckner, R C Gur, R E Gur
Breakthroughs in genomics have begun to unravel the genetic architecture of schizophrenia risk, providing methods for quantifying schizophrenia polygenic risk based on common genetic variants. Our objective in the current study was to understand the relationship between schizophrenia genetic risk variants and neurocognitive development in healthy individuals. We first used combined genomic and neurocognitive data from the Philadelphia Neurodevelopmental Cohort (4303 participants ages 8-21 years) to screen 26 neurocognitive phenotypes for their association with schizophrenia polygenic risk...
October 18, 2016: Translational Psychiatry
Asuka Desroches, Yuichiro Morishita, Itaru Yugue, Takeshi Maeda, Charles-Henri Flouzat-Lachaniette, Philippe Hernigou, Keiichiro Shiba
STUDY DESIGN: A retrospective evaluation of sagittal angular motion from cervical spinal flexion to extension. OBJECTIVE: To evaluate the kinematic effects of cervical laminoplasty for cervical spondylotic myelopathy (CSM) on the occipitoatlantoaxial junction. SUMMARY OF BACKGROUND DATA: The kinematic effects of cervical laminoplasty for CSM on the occipitoatlantoaxial junction remain controversial. METHODS: A total of 65 CSM patients who were treated with cervical laminoplasty ranging from the C3 to C7 vertebrae were included in the study...
October 6, 2016: Clinical Spine Surgery
Diva D De Leon, Charles A Stanley
Hypoglycemia continues to be an important cause of morbidity in neonates and children. Prompt diagnosis and management of the underlying hypoglycemia disorder is critical for preventing brain damage and improving outcomes. Congenital hyperinsulinism (HI) is the most common and severe cause of persistent hypoglycemia in neonates and children. Recent discoveries of the genetic causes of HI have improved our understanding of the pathophysiology, but its management is complex and requires the integration of clinical, biochemical, molecular, and imaging findings to establish the appropriate treatment according to the subtype...
October 18, 2016: Pediatric Diabetes
Yusuf Ransome, Ichiro Kawachi, Lorraine T Dean
High neighborhood social capital could facilitate earlier diagnosis of HIV and higher rates of linkage and HIV care engagement. Multivariate analysis was used to examine whether social capital (social cohesion, social participation, and collective engagement) in 2004/2006 was associated with lower 5-year average (2007-2011) prevalence of (a) late HIV diagnosis, (b) linked to HIV care, and (c) engaged in HIV care within Philadelphia, PA, United States. Census tracts (N = 332). Higher average neighborhood social participation was associated with higher prevalence of late HIV diagnosis (b = 1...
October 17, 2016: AIDS and Behavior
S Rajashree Nandagopalan, Nivedita Kuila, Sutapa Biswas, Naresh Chandra Pattnayak, Gyanashyam Biswas, Soumen Chakraborty
BACKGROUND & OBJECTIVES: Chronic myeloid leukaemia is (CML) characterized by the presence of a hallmark chromosomal translocation, the Philadelphia chromosome. Although there are many reports available regarding the different variants of BCR-ABL in CML, we studied the co-expression of e13a2 and e14a2 transcripts and a few polymorphisms in CML patients. METHODS: Molecular genetics approach was adapted to screen for polymorphisms, mutation and translocation in BCR, ABL kinase domain and BCR-ABL breakpoint region in 73 CML patients...
May 2016: Indian Journal of Medical Research
Govind Babu Kanakasetty, Lakshmaiah Kuntejowdahalli, Aditi Harsh Thanky, Lokanatha Dasappa, Linu Abraham Jacob, Suresh Babu Mallekavu, Prasanna Kumari
INTRODUCTION: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by Philadelphia (Ph) chromosome with classical t(9;22)(q34;q11) seen in up to 90% of cases. However 5% to 10% of patients who present with variant Ph translocations (vPh) have been an area of research for their significance in predicting response to various therapies including tyrosine kinase inhibitors as well as prognosticating survival outcomes for many years involving varied patient populations, with conflicting results...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
Mark E Kunik, A Lynn Snow, Nancy Wilson, Amber B Amspoker, Shubhada Sansgiry, Robert O Morgan, Jun Ying, Gayle Hersch, Melinda A Stanley
OBJECTIVES: To compare the efficacy of Preventing Aggression in Veterans with Dementia (PAVeD) with that of usual care in decreasing incidence of aggression (primary outcome) and pain and improving depression, pleasant events, caregiver burden, and patient-caregiver relationship quality (secondary outcomes). DESIGN: Randomized controlled trial with assessments at baseline and 3, 6, 9, and 12 months SETTING: Houston, TX. PARTICIPANTS: A total of 203 community-dwelling veterans with pain and dementia and their caregivers...
April 27, 2016: American Journal of Geriatric Psychiatry
David Gómez-Almaguer, Edson René Marcos-Ramírez, Efreen Horacio Montaño-Figueroa, Guillermo J Ruiz-Argüelles, Carlos Roberto Best-Aguilera, María Del Carmen López-Sánchez, Esperanza Barrera-Chairez, José Luis López-Arrollo, Christian Omar Ramos-Peñafiel, Andrés León-Peña, Elías Eugenio González-López, Perla Edith Rivas-García, Carlos Alberto Tellez-Hinojosa, Andrés Gómez-De León, José Carlos Jaime-Pérez
BACKGROUND: The incidence of acute leukemia (AL) has increased. Its prognosis is variable and depends on several baseline characteristics with a highly heterogeneous presentation. In Mexico, large-scale descriptive studies have not yet been published; the objective of this study was to analyze the initial basic characteristics of patients diagnosed with AL in our population. PATIENTS AND METHODS: In this multicenter, retrospective study, 1018 patients ≥ 16 years of age and diagnosed with AL between 2009 and 2014, were included...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
Christopher N Morrison, Beidi Dong, Charles C Branas, Therese S Richmond, Douglas J Wiebe
AIMS: This study estimated, with high spatial and temporal specificity, individuals' risk of being assaulted relative to their momentary proximity to alcohol outlets during daily activities. DESIGN: Case-control study. SETTING: Philadelphia, Pennsylvania, USA. PARTICIPANTS: Cases were 194 non-gun assault victims and 135 gun assault victims aged between 10 and 24 years. Age-matched controls (n = 274) were selected using random-digit dialing...
October 14, 2016: Addiction
Charles C Branas, Michelle C Kondo, Sean M Murphy, Eugenia C South, Daniel Polsky, John M MacDonald
OBJECTIVES: To determine if blight remediation of abandoned buildings and vacant lots can be a cost-beneficial solution to firearm violence in US cities. METHODS: We performed quasi-experimental analyses of the impacts and economic returns on investment of urban blight remediation programs involving 5112 abandoned buildings and vacant lots on the occurrence of firearm and nonfirearm violence in Philadelphia, Pennsylvania, from 1999 to 2013. We adjusted before-after percent changes and returns on investment in treated versus control groups for sociodemographic factors...
October 13, 2016: American Journal of Public Health
Pooja K Mehta, Marcus A Bachhuber, Roy Hoffman, Sindhu K Srinivas
OBJECTIVES: To understand the effect of unintentional injuries (e.g., drug overdose), suicide, and homicide on pregnancy-associated death (death during or within 1 year of pregnancy). METHODS: We analyzed all cases of pregnancy-associated death among Philadelphia, Pennsylvania, residents from 2010 to 2014, examining cause of death, contributing factors, and history of health care use. RESULTS: Approximately half (49%; 42 of 85) of pregnancy-associated deaths were from unintentional injuries (n = 31), homicide (n = 8), or suicide (n = 3); drug overdose was the leading cause (n = 18)...
October 13, 2016: American Journal of Public Health
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