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    Clozapine-induced myocarditis.
    Oxf Med Case Reports 2018 Jan 9;2018(1):omx080. Epub 2018 Jan 9.
    Division of Cardiology, Department of Internal Medicine, The George Washington University, Washington, DC 20037, USA.
    Approved in 1989 for the management of treatment-resistant schizophrenia, Clozapine is a last-line atypical antipsychotic drug used with increasing frequency. In addition to its well-known side effect of agranulocytosis, this drug also carries with it rare but serious adverse cardiovascular risk of myocarditis. We present a patient on Clozapine who was admitted to the cardiology service with chest pain, ST segment elevations and elevated troponin concerning for acute myocardial infarction. Read More

    HLA Association with Drug-Induced Adverse Reactions.
    J Immunol Res 2017 23;2017:3186328. Epub 2017 Nov 23.
    Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
    Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. Read More

    Type 1 autoimmune hepatitis presenting with severe autoimmune neutropenia.
    Ann Gastroenterol 2018 Jan-Feb;31(1):123-126. Epub 2017 Aug 4.
    4 Department of Internal Medicine, Hippokration General Hospital, Medical School Aristotle University of Thessaloniki (Petros Doumtsis, Evangelos Cholongitas, Theodora Oikonomou, Ioannis Goulis), Greece.
    Autoimmune hepatitis (AIH) is a progressive, chronic liver disease characterized by unresolving hepatocellular inflammation of autoimmune origin. The clinical spectrum may vary from asymptomatic presentation, to non-specific symptoms such as fatigue, arthralgias, nausea and abdominal pain, to acute severe liver disease. AIH is characterized by the presence of interface hepatitis and portal plasma cell infiltration on histological examination, hypergammaglobulinemia, and positive autoantibodies. Read More

    Cost-effectiveness of HLA-DQB1/HLA-B pharmacogenetic-guided treatment and blood monitoring in US patients taking clozapine.
    Pharmacogenomics J 2018 Jan 3. Epub 2018 Jan 3.
    Division of Nephrology, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
    Less than 1% of adult patients with schizophrenia taking clozapine develop agranulocytosis, and most of these cases occur within the first weeks of treatment. The human leukocyte antigen (HLA) region has been associated with genetic susceptibility to clozapine-induced agranulocytosis (single amino acid changes in HLA-DQB1 (126Q) and HLA-B (158T)). The current study aimed to evaluate the cost-effectiveness, from a healthcare provider's perspective, of an HLA genotype-guided approach in patients with treatment-resistant schizophrenia who were taking clozapine and to compare the results with the current absolute neutrophil count monitoring (ANCM) schemes used in the USA. Read More


    Two-year observational study of deferiprone in superficial siderosis.
    CNS Neurosci Ther 2017 Dec 28. Epub 2017 Dec 28.
    Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
    Introduction: Superficial siderosis is a rare, neurodegenerative disease caused by toxic accumulation of hemosiderin on the surface of the brain and the spinal cord, most commonly from chronic subarachnoid hemorrhage.

    Aims: The aim of this study was to assess the clinical and radiological outcomes of superficial siderosis patients using deferiprone, a cell permeant iron chelator. Subjects obtained pre- and post-treatment brain MRIs and weekly laboratory tests. Read More

    Reduction and Scavenging of Chemically Reactive Drug Metabolites by NAD(P)H:Quinone Oxidoreductase 1 and NRH:Quinone Oxidoreductase 2 and Variability in Hepatic Concentrations.
    Chem Res Toxicol 2018 Jan 11. Epub 2018 Jan 11.
    AIMMS-Division of Molecular Toxicology, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit , De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.
    Detoxicating enzymes NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) catalyze the two-electron reduction of quinone-like compounds. The protective role of the polymorphic NQO1 and NQO2 enzymes is especially of interest in the liver as the major site of drug bioactivation to chemically reactive drug metabolites. In the current study, we quantified the concentrations of NQO1 and NQO2 in 20 human liver donors and NQO1 and NQO2 activities with quinone-like drug metabolites. Read More

    Recent advances in understanding the pathogenesis and management of reticular dysgenesis.
    Br J Haematol 2017 Dec 21. Epub 2017 Dec 21.
    Institute for Transfusion Medicine, University of Ulm, Ulm, Germany.
    Reticular Dysgenesis is a rare immunodeficiency which is clinically characterized by the combination of Severe Combined Immunodeficiency (SCID) with agranulocytosis and sensorineural deafness. Mutations in the gene encoding adenylate kinase 2 (AK2) were identified to cause this phenotype. In this review, we will demonstrate important clinical differences between reticular dysgenesis and other SCID entities and summarize recent concepts in the understanding of the pathophysiology of the disease and the management strategies for this difficult condition. Read More

    Decreased miR-17-92 cluster expression level in serum and granulocytes preceding onset of antithyroid drug-induced agranulocytosis.
    Endocrine 2018 Jan 18;59(1):218-225. Epub 2017 Dec 18.
    Department of Metabolism & Endocrinology, the First Affiliated Hospital of University of South China, 69 Chuanshan Road, Hengyang, 421001, China.
    Purpose: We aimed to determine changes in miR-17-92 cluster expression in serum and granulocytes from patients with antithyroid drug (ATD)-induced agranulocytosis.

    Methods: In this study, real-time polymerase chain reaction (PCR) was used to detect serum miR-17-92 expression levels in 20 ATD-induced agranulocytosis and 16 control patients. Importantly, dynamic changes in neutrophil counts from granulocytopenia to agranulocytosis were observed in 6 of the 20 patients. Read More

    Clozapine and Gastrointestinal Hypomotility.
    CNS Drugs 2017 Dec;31(12):1083-1091
    Mental Health Organization North-Holland North, Stationsplein 138, 1703 WC, Heerhugowaard, The Netherlands.
    Gastrointestinal hypomotility (GIH) is an under-reported but highly prevalent and potentially dangerous side effect of clozapine. In a comprehensive meta-analysis of clozapine-treated patients, the prevalence of GIH was 32%. In general, GIH has consistently been reported to have a negative impact on quality of life, and there is no reason to believe this will be different in clozapine-treated patients with therapy-resistant schizophrenia. Read More

    Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.
    N Engl J Med 2017 12 10;377(26):2531-2544. Epub 2017 Dec 10.
    From the University of Texas M.D. Anderson Cancer Center, Houston (S.S.N., J.R.W.); H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (F.L.L., J.C.C.); Washington University and Siteman Cancer Center, St. Louis (N.L.B., A. Ghobadi); University of Miami, Miami (L.J.L., K.V.K.); Stanford University, Stanford (D.B.M., R.L.), City of Hope National Medical Center, Duarte (T.S.), University of California at Los Angeles, Los Angeles (J.M.T.), University of California at San Diego, San Diego (J.E.C.), and Kite Pharma, Santa Monica (A.B., J.R., L.N., Y.J., J.A., M.E., D.C., J.W., W.Y.G.) - all in California; Dana-Farber Cancer Institute, Boston (C.A.J., E.D.J.); Montefiore Medical Center, Bronx (I.B.), and the University of Rochester School of Medicine, Rochester (J.W.F., P.R.) - both in New York; Vanderbilt University Medical Center (O.O.O.) and the Sarah Cannon Research Institute and Tennessee Oncology (I.W.F.), Nashville; Mayo Clinic, Rochester, MN (Y.L., T.E.W.); Loyola University Medical Center, Maywood, IL (P.J.S.); John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ (A. Goy); Cleveland Clinic, Cleveland (B.T.H., M.R.S.); Karmanos Cancer Center, Wayne State University, Detroit (A.D.); University of Iowa Carver College of Medicine, Iowa City (U.F.); Colorado Blood Cancer Institute, Denver (P.M.S.); Banner M.D. Anderson Cancer Center, Gilbert, AZ (J.M.); and Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (I.A.).
    Background: In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.

    Methods: In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. Read More

    [Incidence of blood stream infections of 1265 patients with hematopoietic stem cell transplantation and analysis of pathogenic bacteria].
    Zhonghua Xue Ye Xue Za Zhi 2017 Nov;38(11):930-933
    Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Jiangsu Clinical Medicine Center, Suzhou 215006, China.
    Objective: To analyze the incidence and microbiological features of blood stream infections (BSI) of patients with hematopoietic stem cell transplantation (HSCT) and to provide laboratory data for empirical use of antibiotic for the HSCT patients with BSI. Methods: The incidence of bloodstream infection, the positive rate of blood culture, bacterial spectrum and drug resistance were analyzed in 1 265 HSCT recipients during 2013 and 2015 were retrospectively studied. Results: Of 1265 patients undergoing HSCT, 1 422 cases of suspected BSI occurred in 784 patients (61. Read More

    Non-chemotherapy drug-induced neutropenia: key points to manage the challenges.
    Hematology Am Soc Hematol Educ Program 2017 Dec;2017(1):187-193
    Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI.
    Non-chemotherapy idiosyncratic drug-induced neutropenia (IDIN) is a relatively rare but potentially fatal disorder that occurs in susceptible individuals, with an incidence of 2.4 to 15.4 cases per million population. Read More

    Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity.
    Curr Opin Hematol 2018 Jan;25(1):29-36
    aDepartment of Pathology, Oregon Health and Science University, Portland, OregonbDepartment of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, California, USA.
    Purpose Of Review: Levamisole was previously used for its immunomodulatory properties to treat rheumatoid arthritis and some cancers. However, because of serious side-effects, it was taken off the market in the United States. Recently, levamisole has reemerged as a popular cocaine adulterant. Read More

    Methamphetamine Use With Subsequent Thyrotoxicosis/Thyroid Storm, Agranulocytosis, and Modified Total Thyroidectomy: A Case Report.
    Clin Med Insights Ear Nose Throat 2017 17;10:1179550617741293. Epub 2017 Nov 17.
    Division of Otolaryngology, Department of Surgery, St. Joseph's Medical Hospital and Medical Center, Phoenix, AZ, USA.
    Thyroid storm is a rare, potentially lethal condition involving collapse of the hypothalamic-pituitary-thyroid feedback loop. Thyroid storm carries a significant mortality rate, thus requiring prompt identification and treatment. A 47-year-old woman presented to the emergency department complaining of palpitations, shortness of breath, and emesis for 24 hours after using methamphetamine. Read More

    FOLFOX as First-line Therapy for Gastric Cancer with Severe Peritoneal Metastasis.
    Anticancer Res 2017 12;37(12):7037-7042
    Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
    Background/aim: Severe peritoneal metastasis (PM) from advanced gastric cancer (AGC) causes massive ascites and inadequate oral intake. Because patients with severe PM are often not included in clinical trials, little is known regarding the efficacy and safety of oxaliplatin with l-leucovorin and bolus/continuous infusion of 5-fluorouracil (FOLFOX) for them.

    Patients And Methods: We retrospectively studied AGC patients with massive ascites and/or inadequate oral intake due to severe PM treated with FOLFOX as the first-line treatment. Read More

    Graves' Disease Thyrotoxicosis and Propylthiouracil Related Agranulocytosis Successfully Treated with Therapeutic Plasma Exchange and G-CSF Followed by Total Thyroidectomy.
    Mediterr J Hematol Infect Dis 2017 16;9(1):e2017058. Epub 2017 Oct 16.
    Division of Hematology, University Hospital-Santa Maria Misericordia, Udine, Italy.
    Antithyroid drugs can be a rare cause of agranulocytosis (0.5% of treated patients). Suspension of these drugs is mandatory in these patients and may result in worsening hyperthyroidism. Read More

    Correlation study between osteoporosis and hematopoiesis in the context of adjuvant chemotherapy for breast cancer.
    Ann Hematol 2018 Feb 23;97(2):309-317. Epub 2017 Nov 23.
    Laboratory of Regenerative Hematopoiesis, Swiss Institute for Experimental Cancer Research (ISREC) & Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
    This retrospective study attempts to establish if a correlation exists between osteoporosis and hematopoiesis before and after adjuvant chemotherapy in the context of non-metastatic breast cancer. Osteoporosis is interpreted both as a direct marker of osteoblastic decline and as an indirect marker of increased bone marrow adiposity within the hematopoietic microenvironment. Patients from the "Centre du Sein" at CHUV (Centre Hospitalier Universitaire Vaudois) undergoing adjuvant chemotherapy were included in this study. Read More

    [Guidelines for standardizedmanagement of neutropenia induced by chemotherapy and radiotherapy].
    • Authors:
    Zhonghua Zhong Liu Za Zhi 2017 Nov;39(11):868-878
    Neutropenia is the most common hematologic toxicity of myelosuppressive chemotherapy and radiotherapy. The degree and duration of neutropenia are directly related to the risk of infection and even death, which can also affect the relative dose intensity of chemotherapy and the prognosis of patients. At present, clinicians tend to underestimate the harm of neutropenia, and are in lack of knowledge on granulocyte colony-stimulating factor(G-CSF), especially on prevention and treatment of neutropenia. Read More

    FACTORS ASSOCIATED WITH TREATMENT OUTCOME OF PEDIATRIC CANCERPATIENTS ADMITTED WITH FEBRILE NEUTROPENIA IN TIKURANBESSA SPECIALIZED TEACHING HOSPITAL, ADDIS ABABA, ETHIOPIA.
    Ethiop Med J 2017 Jan;55(1):43-7
    Background: Cancer treatment is associated with variable degrees of myelosupression. Infection is often a life-threatening complication of chemotherapy-induced neutropenia, and it is also considered an oncologic emergency. Febrile neutropenia is a common, costly and potentially fatal complication in oncology. Read More

    [Leukopenia - A Diagnostic Guideline for the Clinical Routine].
    Dtsch Med Wochenschr 2017 Nov 16;142(23):1744-1749. Epub 2017 Nov 16.
    Reasons for leukopenia can be numerous. To get close to the diagnosis it's always useful to check previous blood counts of the patient to get a feeling for the dynamic development of the leukopenia. Furthermore, it's important to check the red blood cell count and platelet count as well; a bi- or a pancytopenia usually implies an insufficient production in the bone marrow. Read More

    Risk of adverse events with the addition of targeted agents to endocrine therapy in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis.
    Cancer Treat Rev 2018 Jan 3;62:123-132. Epub 2017 Nov 3.
    Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B), Brussels, Belgium; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B), Brussels, Belgium. Electronic address:
    Background: Combining targeted agents and endocrine therapy (ET) improves outcomes in hormone receptor-positive metastatic breast cancer patients but increases the risk of adverse events (AEs). This meta-analysis aims to estimate the comparative risk of AEs with ET in addition to targeted agents in this setting.

    Methods: A systematic literature search of MEDLINE, EMBASE, Cochrane Library and conference proceedings up to July 17th 2017 was conducted to identify randomized controlled trials investigating ET with or without CDK4/6, mTOR, PI3K inhibitors and anti-HER2 agents. Read More

    Eruption of lymphocyte recovery with atypical lymphocytes mimicking a primary cutaneous T-cell lymphoma: a series of 12 patients.
    Hum Pathol 2018 Jan 28;71:100-108. Epub 2017 Oct 28.
    Department of Pathology and INSERM U955 team 9, AP-HP, Henri-Mondor Hospital, 94220 Créteil, France. Electronic address:
    Eruption of lymphocyte recovery (ELR) may occur during bone marrow aplasia after chemotherapies. We reviewed the clinical and pathologic features of 12 patients (male-female ratio, 7:5; median age, 61 years) with an atypical ELR histologically mimicking a primary cutaneous T-cell lymphoma such as Sézary syndrome or CD30+ T-cell lymphoproliferative disorder. All the patients displayed an erythematous maculopapular eruption on the trunk and the limbs associated with fever. Read More

    An Unexpected Circumstance: Acute Dystonic Reaction in the Setting of Clozapine Administration.
    J Pharm Pract 2017 Jan 1:897190017737696. Epub 2017 Jan 1.
    1 Department of Behavior Health, Tripler Army Medical Center, Honolulu, HI, USA.
    Clozapine is a second-generation antipsychotic typically reserved for refractory psychotic disorders due to its high-risk side effect profile to include agranulocytosis, with its attendant need for regular blood draws. While reports of extrapyramidal symptoms (EPS), including acute dystonic reactions, are exceedingly rare, we present the case of a 44-year-old male with a long-standing history of treatment-resistant schizoaffective disorder and no history of EPS who experienced an acute buccal dystonic reaction in the setting of clozapine initiation and discontinuation of depot and oral risperidone. This case report presents one of the few documented episodes of acute dystonic reactions occurring in the setting of clozapine administration. Read More

    Neutropenic Fever.
    Hematol Oncol Clin North Am 2017 Dec;31(6):981-993
    Department of Emergency Medicine, MedStar Georgetown University Hospital, Washington, DC, USA.
    Fever is a common presenting complaint among adult or pediatric patients in the emergency department setting. Although fever in healthy individuals does not necessarily indicate severe illness, fever in patients with neutropenia may herald a life-threatening infection. Therefore, prompt recognition of patients with neutropenic fever is imperative. Read More

    Neutropenia with Multiple Antipsychotics Including Dose Dependent Neutropenia with Lurasidone.
    Clin Psychopharmacol Neurosci 2017 Nov;15(4):413-415
    Maricopa Integrated Health System/District Medical Group, University of Arizona School of Medicine, Phoenix, AZ, USA.
    Antipsychotic-induced agranulocytosis is a significant side effect that is known to occur with most of the antipsychotic medications. It usually resolves once the medications are stopped and patients are able to be switched over to another antipsychotic medication. Lurasidone has not been reported to cause leukopenia and neutropenia. Read More

    How I treat warts, hypogammaglobulinemia, infections, and myelokathexis syndrome.
    Blood 2017 12 24;130(23):2491-2498. Epub 2017 Oct 24.
    Service d'Hémato-Oncologie Pédiatrique Registre des neutropénies congénitales, Hôpital Trousseau, Assistance Publique Hôpitaux de Paris, Paris, France.
    Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a genetic disease characterized by neutropenia, lymphopenia, susceptibility to infections, and myelokathexis, which describes degenerative changes of mature neutrophils and hyperplasia of bone marrow myeloid cells. Some patients present with hypogammaglobulinemia and/or refractory warts of skin and genitalia. Congenital cardiac defects constitute uncommon manifestations of the disease. Read More

    Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients.
    Br J Cancer 2017 Oct 24;117(9):1269-1277. Epub 2017 Aug 24.
    Department of Biomolecular Sciences, Università degli Studi di Urbino 'Carlo Bo', Urbino 61032, Italy.
    Background: Dihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients' risk of fluoropyrimidine-related severe toxicity. Read More

    Intravenous Zanamivir in Hospitalized Patients With Influenza.
    Pediatrics 2017 Nov;140(5)
    GlaxoSmithKline, Boston, Massachusetts.
    Background: Children with severe influenza infection may require parenteral therapy if oral or inhaled therapies are ineffective or cannot be administered. Results from a study investigating intravenous (IV) zanamivir for the treatment of hospitalized infants and children with influenza are presented.

    Methods: This phase II, open-label, multicenter, single-arm study assessed the safety of investigational IV zanamivir in hospitalized children with influenza. Read More

    The Prevalence and Investigation of Risk Factors of Oral Mucositis in a Pediatric Oncology Inpatient Population; a Prospective Study.
    J Pediatr Hematol Oncol 2018 Jan;40(1):15-21
    Departments of Paediatric Dentistry.
    Background: Oral mucositis can be a frequent and severe complication of chemotherapy in children. It can result in pain, infection, depression, prolonged admission, treatment delays, increase in patient morbidity, and increased costs.

    Aim: To record the prevalence and severity of oral mucositis among inpatients and explore the relationship of risks factors and the development of oral mucositis. Read More

    Use of granulocyte colony-stimulating factor in the treatment of methimazole-induced agranulocytosis: a case report.
    Clin Case Rep 2017 Oct 8;5(10):1701-1705. Epub 2017 Sep 8.
    College of PharmacyOregon State UniversityOregon Health & Science University2730 SW Moody Ave.PortlandOregon97201USA.
    A comparison of this case to previously published reports suggests that granulocyte colony-stimulating factor may be associated with improved prognosis in severe antithyroid drug-induced neutropenia, and that weight-based doses could be an appropriate strategy. Read More

    The use of dipyrone (metamizol) as an analgesic in children: What is the evidence? A review.
    Paediatr Anaesth 2017 Dec 12;27(12):1193-1201. Epub 2017 Oct 12.
    Department of Pediatric Intensive Care and Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
    Dipyrone has analgesic, spasmolytic, and antipyretic effects and is used to treat pain. Due to a possible risk of agranulocytosis with the use of dipyrone, it has been banned in a number of countries. The most commonly used data for the use of dipyrone are related to adults. Read More

    [Nasal phaeohyphomycosis by Curvularia spicifera in pediatric patient with neutropenia and acute myeloid leukemia].
    Rev Chilena Infectol 2017 Jun;34(3):280-286
    Departamento de Enfermedades Infecciosas e Inmunología Pediátricas, Pontificia Universidad Católica de Chile, Santiago, Chile,
    There are very few reports of pediatric patients with infections by dematiaceous filamentous fungi. In this publication we report a case of invasive fungal infection of the nasal septum by Curvularia spicifera in a pediatric patient with acute myeloid leukemia. The patient presented with a painful scabby wound in the nasal vestibule. Read More

    Bis-choline tetrathiomolybdate in patients with Wilson's disease: an open-label, multicentre, phase 2 study.
    Lancet Gastroenterol Hepatol 2017 Dec 5;2(12):869-876. Epub 2017 Oct 5.
    Department of Medicine and Surgery, Yale University Medical Center, New Haven, CT, USA. Electronic address:
    Background: Wilson's disease is a genetic disorder in which copper accumulates in the liver, brain, and other tissues. Therapies are limited by efficacy, safety concerns, and multiple daily dosing. Bis-choline tetrathiomolybdate (WTX101) is an oral first-in-class copper-protein-binding molecule that targets hepatic intracellular copper and reduces plasma non-ceruloplasmin-bound copper (NCC) by forming tripartite complexes with albumin and increasing biliary copper excretion. Read More

    Clozapine-induced agranulocytosis/granulocytopenia: mechanisms and monitoring.
    Curr Opin Hematol 2018 Jan;25(1):22-28
    Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.
    Purpose Of Review: Clozapine-induced agranulocytosis/granulocytopenia (CIAG) is an uncommon condition, but potentially fatal in consequences. The pathogenesis, despite multiple experiments, is not fully elucidated. The current theory suggests reactive oxygen species - nitrenium ion as the most important factor of CIAG. Read More

    Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.
    J Clin Invest 2017 Nov 3;127(11):4090-4103. Epub 2017 Oct 3.
    Laboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR - S1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
    Shwachman-Diamond syndrome (SDS) (OMIM #260400) is a rare inherited bone marrow failure syndrome (IBMFS) that is primarily characterized by neutropenia and exocrine pancreatic insufficiency. Seventy-five to ninety percent of patients have compound heterozygous loss-of-function mutations in the Shwachman-Bodian-Diamond syndrome (sbds) gene. Using trio whole-exome sequencing (WES) in an sbds-negative SDS family and candidate gene sequencing in additional SBDS-negative SDS cases or molecularly undiagnosed IBMFS cases, we identified 3 independent patients, each of whom carried a de novo missense variant in srp54 (encoding signal recognition particle 54 kDa). Read More

    Venetoclax for the treatment of chronic lymphocytic leukemia.
    Expert Opin Investig Drugs 2017 Nov 9;26(11):1307-1316. Epub 2017 Oct 9.
    b Department of Hemato-Oncology , Unità di Ricerca Biotecnologica (URB) , Aprigliano , Italy.
    Introduction: Venetoclax, an orally bioavailable inhibitor of BCL-2, was approved in 2016 by the United States Food and Drug Administration (FDA) for the treatment of chronic lymphocytic leukemia (CLL) patients with 17p deletion [del(17p)], who have received at least one prior therapy. Areas covered: We focus on the mechanism of action of venetoclax and on the clinical trial data that led to the approval of venetoclax for CLL patients. We also review the studies in which this drug has being explored in combination with other anti-CLL drugs. Read More

    Cabazitaxel-conjugated nanoparticles for docetaxel-resistant and bone metastatic prostate cancer.
    Cancer Lett 2017 Dec 28;410:169-179. Epub 2017 Sep 28.
    Drug Delivery and Formulation, Drug Discovery Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada. Electronic address:
    Effective treatment of metastatic castration resistant prostate cancer (mCRPC) remains an unmet challenge. Cabazitaxel (CBZ) is approved for mCRPC after docetaxel (DTX) failure, but the improvement in survival is only moderate (∼2 months) and patients suffer from significant side effects. Here, we report the development of a polymer based delivery system for CBZ to improve its safety and efficacy against DTX-resistant mCRPC. Read More

    History and Outcome of Febrile Neutropenia Outside the Oncology Setting: A Retrospective Study of 76 Cases Related to Non-Chemotherapy Drugs.
    J Clin Med 2017 Sep 26;6(10). Epub 2017 Sep 26.
    Departments of Onco-hematology, Strasbourg University Hospitals, Strasbourg 67000, France.
    Background: Despite major advances in its prevention and treatment, febrile neutropenia remains a most concerning complication of cancer chemotherapy. Outside the oncology setting, however, only few data are currently available on febrile neutropenia related to non-chemotherapy drugs. We report here data on 76 patients with febrile neutropenia related to non-chemotherapy drugs, followed up in a referral center within a university hospital. Read More

    SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting.
    Br J Cancer 2017 Sep 24;117(7):938-946. Epub 2017 Aug 24.
    The Christie Hospital NHS Foundation Trust, Manchester, UK.
    Background: We investigated selumetinib (AZD6244, ARRY-142886), an oral, potent, and highly selective, allosteric MEK1/2 inhibitor, plus platinum-doublet chemotherapy for patients with advanced/metastatic non-small cell lung cancer.

    Methods: In this Phase I, open-label study (NCT01809210), treatment-naïve patients received selumetinib (50, 75, 100 mg BID PO) plus standard doses of gemcitabine or pemetrexed plus cisplatin or carboplatin. Primary objectives were safety, tolerability, and determination of recommended Phase II doses. Read More

    Correlation Between Serum Concentrations of N-Desmethylclozapine and Granulocyte Levels in Patients with Schizophrenia: A Retrospective Observational Study.
    CNS Drugs 2017 Nov;31(11):991-997
    Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
    Background: Clozapine is restricted to use in patients with treatment-refractory schizophrenia due to the risk of a serious drop in absolute neutrophil granulocyte count (ANC). The formation of reactive, unstable metabolites (adducts) has been suggested as a mechanism of clozapine-induced granulocyte decline. These adducts are not detectable in vivo, but stable clozapine metabolites could potentially be indirect pharmacokinetic measures of adduct formation. Read More

    Recurrent desmoplastic small round cell tumor responding to an mTOR inhibitor containing regimen.
    Pediatr Blood Cancer 2018 Jan 22;65(1). Epub 2017 Sep 22.
    Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas.
    Desmoplastic small round cell tumor (DSRCT) is a rare mesenchymal tumor that typically presents with multiple abdominal masses. Initial treatment is multimodal in nature. Patients with relapsed DSRCT have a poor prognosis, and there are no standard therapies. Read More

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