Administration of recombinant erythropoietin alone does not improve the phenotype in iron refractory iron deficiency anemia patients.

Mutations in transmembrane protease, serine 6 (TMPRSS6) cause iron refractory iron deficiency anemia (IRIDA). Parenteral iron administration may slightly improve hemoglobin level but is troublesome for patients. Optimal treatment has yet to be determined. We identified five patients from four independent families displaying the IRIDA picture with truncating biallelic mutations in TMPRSS6, one of which is novel. Liver iron determined by superconducting quantum interference device biosusceptometry ranged from 390 to 720 µg Fe/g wet weight (normal range 100-500; n = 3). Intestinal iron absorption (12 and 32 %, normal range 10-50; n = 2) and 59Fe erythrocyte incorporation after ingestion of 59Fe (57 and 38 %, normal range 70-90; n = 2) were inadequately low for iron-deficient anemic individuals. Baseline serum erythropoietin was elevated or borderline high in four patients. Administration of recombinant human erythropoietin (rhEPO) at up to 273 and 188 U/kg body weight/week alone did not improve anemia or result in a decrease of urinary hepcidin in two individuals. In conclusion, the ability of exogenous rhEPO to increase hemoglobin level appears to be impaired in IRIDA.

Oxaliplatin, irinotecan, and gemcitabine: a novel combination in the therapy of progressed, relapsed, or refractory tumors in children.

Therapeutic options for unresectable neuroendocrine carcinomas and relapsed or refractory solid tumors are still limited in pediatric patients. We present a retrospective review of 12 children (3 to 16 y) in a case series treated with a novel combination of oxaliplatin, irinotecan, and gemcitabine (triple therapy). We defined its feasibility in a mainly outpatient setting and assessed its toxicity and effectiveness. Three patients with unresectable neuroendocrine carcinomas received triple therapy as first-line treatment; 9 children with relapsed or refractory solid tumors of different entities were assigned after failure of standard treatment protocols. The treatment schedule comprised oxaliplatin (85 mg/m²), irinotecan (175 mg/m²), and gemcitabine (1,000 mg/m²), the latter to be repeated on day 8. A median of 7 cycles was applied. Nine of 12 patients showed hematotoxicity 0-III degrees. Gastrointestinal toxicity I-II degrees were handled satisfactorily by supportive drugs. Tumor response was defined as partial response in 1 of 12 children, stable disease in 8 of 12 children, and progressive disease in 3 of 12 children with a median time of disease control of 7 months. We regard triple therapy as a well-tolerated outpatient treatment option offering children a high quality of life and showing considerable effectiveness in delaying tumor progress.

A Muslim Chaplaincy for Asylum Seekers? Results from an Evaluation Research Study.

Due to the high number of Muslim applicants in the Swiss asylum system, in recent years there have been calls for an introduction of a Muslim chaplaincy service into Switzerland's asylum centers. Acknowledging this need, the Swiss federal government ran a Muslim chaplaincy pilot service in Zurich's Juch Asylum Center between July 2016 and June 2017, with a view to its possible roll-out across Switzerland's federal asylum centers. This paper links methodological reflection with a presentation of key results in the evaluation of this project. Applying a mixed-method design based on the fourth-generation evaluation research, the study investigates the perspectives of the main stakeholder groups on the pilot project. The interaction with Muslim chaplains mostly led to a high degree of satisfaction among asylum seekers. The study shows there were difficulties and obstacles integrating Muslim chaplaincy into the center's inter-professional setting, although the interfaith cooperation with Christian chaplains nonetheless developed intensively. The study's methodological limitations, primarily caused by the setting of the study, are also discussed, as well as the impact the evaluation itself had on the asylum center setting.

That's Cool. Computational Sociolinguistic Methods for Investigating Individual Lexico-grammatical Variation.

The present study deals with variation in the use of lexico-grammatical patterns and emphasizes the need to embrace individual variation. Targeting the pattern that's adj (as in that's right, that's nice or that's okay) as a case study, we use a tailor-made Python script to systematically retrieve grammatical and semantic information about all instances of this construction in BNC2014 as well as sociolinguistic information enabling us to study social and individual lexico-grammatical variation among speakers who have used this pattern. The dataset amounts to 4,394 tokens produced by 445 speakers using 159 adjective types in 931 conversations. Using detailed descriptive statistics and mixed-effects regression models, we show that while the choice of some adjectives is partly determined by social variables, situational and especially individual variation is rampant overall. Adopting a cognitive-linguistic perspective and relying on the notion of entrenchment, we interpret these findings as reflecting individual speakers' routines. We argue that computational sociolinguistics is in an ideal position to contribute to the data-driven investigation of individual lexico-grammatical variation and encourage computational sociolinguists to grab this opportunity. For the routines of individual speakers ultimately both underlie and compromise systematic social variation and trigger and steer well-known types of language change including grammaticalization, pragmaticalization and change by invited inference.

Improved survival after gross total resection of malignant gliomas in pediatric patients from the HIT-GBM studies.

The present study was performed to investigate the prognostic impact of tumor resection on survival in children and adolescents with malignant gliomas. From the HIT-GBM data base of the Gesellschaft für Paediatrische Onkologie und Haematologie (GPOH), 85 pediatric patients with malignant non-pontine gliomas were analyzed. Histological diagnosis and extent of tumor resection had been confirmed by central neuropathological review and post-surgical imaging. The extent of tumor resection represented the most prominent prognostic factor for overall (OS) and event-free survival (EFS) in univariate and Cox regression analyses. Four-year survival after gross total tumor resection was 48.0 +/- 12.0% (OS) and 14.1 +/- 8.9% (EFS), after non-total resection 13.2 +/- 6.1% and 2.9 +/- 2.8%, respectively. From several clinical parameters, only histological grading displayed a similar statistical significance in Cox regression analysis. In conclusion, gross total tumor resection improves survival in pediatric patients with malignant gliomas and should always be attempted when possible.

Effect of a single dose of rituximab in chronic immune thrombocytopenic purpura in childhood.

Twenty-two children with immune thrombocytopenic purpura (ITP) with long-lasting thrombocytopenia, adversely affecting their quality of life, were treated with a reduced rituximab regimen in order to eliminate B cells producing anti-platelet antibody. A single dose of rituximab resulted in a response rate similar to that reported for cases in which 4 doses of rituximab were used.

High-dose methotrexate prior to simultaneous radiochemotherapy in children with malignant high-grade gliomas.

BACKGROUND: Preradiation chemotherapy including methotrexate (MTX) was effective in children with completely resected high-grade gliomas (HGG). The specific role of MTX remains uncertain. PATIENTS AND METHODS: Children with newly diagnosed HGG and diffuse intrinsic pontine gliomas (DIPG) were enrolled. Two cycles of HD-MTX (5 mg/m2) were given prior to simultaneous radiochemotherapy (SRCT). Response was evaluated two weeks after SRCT. RESULTS: Of 26 children (17 males, median age: 10.3 years) tumor grading was WHO IV (n=9), III (n=10), II/I (n=4, DIPG), unknown (n=3, DIPG). Fourteen tumors were resected. III/IV toxicity after SRCT was: 10/19 anemia, 15/19 leukocytopenia, 12/19 thrombocytopenia, 8/18 infection. No IV infection, gastrointestinal, hepatic or dermal toxicity or toxic death was seen. Stable disease or better was seen in 95.3% (CCR:2, CR:1, PR:8, SD:9, PD:1, unknown:5). CONCLUSION: HD-MTX prior to SRCT is well tolerated and feasible. A randomized trial evaluating the effect of HD-MTX on survival is justified.

Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis.

Atypical teratoid/rhabdoid tumors are malignant embryonal tumors characterized by the presence of rhabdoid cells, genetic alterations affecting the SMARCB1 gene (hSNF5/INI1), and a poor prognosis. Whether INI1 plays a role in the pathogenesis of other central nervous system tumors is uncertain. We report on cases of 2 young children with unusual intracranial nonrhabdoid neuroectodermal tumors within and around the third or fourth ventricle that are characterized by cribriform strands and trabeculae and well-defined epithelial membrane antigen-immunopositive surfaces and show INI1 protein loss. Histological and immunohistochemical features did not correspond to established tumor types, including atypical teratoid/rhabdoid tumors, medulloepithelioma, choroid plexus carcinoma, and ependymoma. Fluorescence in situ hybridization analyses failed to identify chromosomal alterations affecting the SMARCB1 locus, but sequencing revealed a homozygous 4-bp duplication in exon 4 (492duplCCTT) in one of the tumors. Both children responded well to conventional adjuvant therapy protocols and are alive and in complete remission longer than 5 years postoperatively. We suggest that cribriform neuroepithelial tumor (CRINET) is a nonrhabdoid ventricular tumor that shows loss of tumoral INI1 protein and has a relatively favorable prognosis.

G-CSF mobilised granulocyte transfusions in 32 paediatric patients with neutropenic sepsis.

INTRODUCTION: In this retrospective, uncontrolled, observational study, the effect of granulocyte colony-stimulating factor (G-CSF)-stimulated granulocyte transfusions (GTX) in neutropenic paediatric patients with sepsis was evaluated. PATIENTS AND METHODS: Granulocytes were collected from unrelated, ABO group-matched and cytomegalic-antibody compatible donors. For neutrophil mobilization, donors received a single subcutaneous dose of glycosylated G-CSF (Lenograstim, Chugai Pharma, Japan) plus oral dexamethasone (8 mg). In total, 168 (range 1-19 per patient) GTX were transfused in 32 children with a median age of 7.4 (0.25 to 16) years. RESULTS: The underlying diseases comprised predominantly haematooncological malignancies (31 children). In 15 of 32 patients, neutropenia was related to allogeneic stem cell transplantation. All children suffered from sepsis based on international criteria (fever, tachycardia, respiratory rate >2 SD above normal in the context of a suspected or proven infection). In ten children bacteria were isolated, in six children a fungal infection was diagnosed and four sepsis episodes were caused by viral infections. GTX contained a median neutrophil number of 6.3 (range 1.9-13.9)x10(10) per transfusion and obtained a sustained haematological response after GTX. Nineteen out of 32 children survived the neutropenic sepsis, particularly nine out of 11 patients with bacterial sepsis. DISCUSSION: In contrast to the non-survivors, we observed a significant decrease in the C-reactive protein levels shortly after initiation of the GTX treatment in the surviving patients. A clear-cut benefit of GTX for children with neutropenic sepsis cannot be concluded from these data, but in children with (severe) bacterial sepsis refractory to antibiotic treatment, GTX were feasible, safe and could reduce mortality rates in this subgroup of patients.