Comparison of mastocytosis with onset in children and adults

OBJECTIVE: To compare the incidence, symptomatology and course of mastocytosis with onset in childhood and in adults. DESIGN: Retrospective study of 101 patients with mastocytosis who were referred from 1980 to 1998. PATIENTS: Medical records of 65 cases of mastocytosis with onset in childhood and 36 in adulthood were analysed. The clinical course was assessed in a subgroup consisting of 33 subjects with childhood onset who were followed up until at least adolescence and 12 subjects with adult onset who were followed up for at least 10 years. RESULTS: The onset of the disease occurred before the age of 2 years in 50% and between the ages of 2 and 15 years in 14% of cases (childhood onset). In 36% of patients onset occurred at the age of 16 years and older (adult onset). An incidence peak of 60% was noted in the first year of life. Mast cell-mediated symptoms were not experienced by 21 of 36 adult onset mastocytosis patients nor by 27 of 65 childhood onset mastocytosis patients. Complete resolution was observed in five of 33 children. The majority of childhood onset cases (21 of 33) showed some improvement. Complete resolution was achieved in three of 12 adults. The majority of the remaining adults (eight of 12) showed no improvement. CONCLUSIONS: We confirm the incidence of onset of mastocytosis previously reported in the literature. We conclude that childhood onset mastocytosis is much less transitory than generally is assumed, although improvement occurs in the majority of cases. Symptomatology and clinical course of adult onset mastocytosis is less severe than suggested in the literature.     

Aromatic polyethers with oxadiazole units – synthesis and application in organic light emitting diodes

Detailed synthetic aspects of new aromatic polyethers containing oxadiazole units are described. They are obtained by the nucleophilic displacement reaction of 2,2-bis(4-hydroxyphenyl)hexafluoropropane with 2,5-bis(4-fluorophenyl)-1,3,4-oxadiazole and 2,5-bis(4-fluoronaphthyl)-1,3,4-oxadiazole. The purity of the polyethers strongly depends on the reaction solvent. Best results were achieved with Ph₂SO₂ as compared to N-methyl-2-pyrrolidone (NMP) and 1,3-dimethyltetrahydro-2(1H)-pyrimidinone (DMPU) in the temperature range from 190–200°C. All polyethers are fully soluble in common organic solvents and excellent films are obtained by spin-coating. High molecular weight polyethers without oligomers were only achieved, when Ph₂SO₂ was used as solvent. All polyethers are characterized by high thermal stability and high glass transition temperatures. The substitution of bisphenyloxadiazole by bisnaphthyloxadiazole units in the polyethers leads to a bathochromic shift of the absorption from 299 nm to 345 nm. Polyethers with bisnaphthyloxadiazole units show a blue fluorescence with a maximum at 427 nm. The application of these novel polyethers as efficient electron transport and injection layer in bilayer light emitting diodes based on poly(1,4-phenylenevinylene) is shown. The best results were obtained with oxadiazole polyethers containing bisnaphthyloxadiazole units.     

Effect of rifampicin in the treatment of pruritus in hepatic cholestasis

Pruritus in hepatic cholestasis has been suggested to be secondary to a high concentration of serum bile acids. Rifampicin, which inhibits the uptake of bile acids by hepatocytes, has been used to treat pruritus. To determine the efficacy of rifampicin as a treatment for refractory pruritus, the medical records of 33 children (median age 25 months, range 4-135; 19 boys) with chronic cholestasis liver disease (21 with Alagille's syndrome, eight with progressive intrahepatic cholestasis, one with extrahepatic biliary atresia, one with an inborn error of bile acid metabolism, and one with cryptogenic cirrhosis) were reviewed retrospectively. The median dose of rifampicin was 5(4-10) mg/kg/day. The median duration of intake was 36(4-120) weeks. Complete relief of pruritus was noted in five (15%) patients and a partial response in 12 (36%). Overall, no significant difference was noted in the laboratory parameters before and after treatment with rifampicin. In the 21 patients with Alagille's syndrome, however, a significant decrease in alkaline phosphatase was seen before and after one and six months of starting treatment. No adverse side effects were seen. Rifampicin appears to be effective in the treatment of refractory pruritus. A prospective study is warranted to assess further the effect of rifampicin treatment in children with hepatic cholestasis.     

Emerging treatment using tubulin inhibitors in advanced non-small cell lung cancer

Introduction: Tubulin inhibitors including taxanes and vinca alkaloids are important components of chemotherapy regimens used in advanced non-small cell lung cancer (NSCLC). Despite a treatment paradigm shift due to molecularly-targeted therapies and immunotherapy, a majority of patients will receive chemotherapy during their treatment course. Either used alone or in combination, tubulin inhibitors have demonstrated clinical benefits in different settings of lung cancer management.

Areas covered: This review first discusses FDA-approved tubulin inhibitors for NSCLC, such as paclitaxel, docetaxel, vinorelbine, and nab-paclitaxel. The article then provides a summary of novel tubulin inhibitors, including cabazitaxel, eribulin, ixabepilone, patupilone, plinabulin, new colchicine analogues and others. It also discusses new tubulin inhibitor combinations with immunotherapy (PD-1/PD-L1 inhibitors) and molecularly-targeted therapies (e.g. anti-angiogenic agents, mTOR inhibitors, heat shock protein 90 inhibitors, MEK inhibitors, and anti-HER3 agents). Lastly, emerging data on potential resistance mechanisms and predictive biomarkers for tubulin inhibitors are explored.

Expert opinion: Tubulin inhibitors will likely continue to play important roles in NSCLC management due to the advent of novel agents and combinations. Through further understanding of tumor biology, investigation of drug resistance, and development of predictive biomarkers, we will be better positioned to incorporate microtubule inhibition into patient specific treatment strategies.     

Analysis of vancomycin use and associated risk factors in a university teaching hospital: a prospective cohort study

Background  

Vancomycin use is considered inappropriate in most hospitals. A particular concern is the recent emergence of S. aureus with decreased susceptibility to vancomycin, making it important to reduce overall exposure to vancomycin to minimize the incidence of VRE (vancomycin-resistant enterococci). The aim of this work was to analyze the use of vancomycin and the risk factors associated with inappropriate treatment.     

Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission

Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.     

Characterization of novel Mycobacterium tuberculosis pncA gene mutations in clinical isolates from the Ukraine

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis cases in the Ukraine are increasing. Pyrazinamide (PZA) is critically important for first- and second-line tuberculosis (TB) treatment regimes. However, PZA drug susceptibility testing is time consuming and technically challenging. The present study utilized Next-generation sequencing (NGS) to identify mutations in the pncA gene from clinical isolates and to assess the prevalence of pncA gene mutations in MDR/XDR-TB patients. Clinical isolates were inactivated in molecular transport media and shipped from Kharkiv, Ukraine, to San Antonio, TX. Whole-genome and targeted pncA gene sequencing was carried out using Illumina MiSeq instrumentation. Mutations were noted in 67 of 91 (74%) clinical isolates comprising substitutions, insertions, and deletions in the pncA coding and upstream promoter region. Of 45 mutation types, there were 11 novel, i.e., to date unknown, pncA mutations identified of which 3 were confirmed PZA resistant. Seven isolates contained mixed base mutations, whereas 4 harbored doubled mutations. Data reported here further support use of NGS for pncA gene characterization and may contribute in significant fashion to PZA therapy, especially in MDR- and XDR-TB patients.