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Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%, P = 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%, P

© The Author(s) 2020., Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide toward the relevant classification panel and final diagnosis. In this study, we designed and validated an algorithm for automated (database-supported) gating and identification (AGI tool) of cell subsets within samples stained with ALOT. A reference database of normal peripheral blood (PB, n = 41) and bone marrow (BM; n = 45) samples analyzed with the ALOT was constructed, and served as a reference for the AGI tool to automatically identify normal cells. Populations not unequivocally identified as normal cells were labeled as checks and were classified by an expert. Additional normal BM (n = 25) and PB (n = 43) and leukemic samples (n = 109), analyzed in parallel by experts and the AGI tool, were used to evaluate the AGI tool. Analysis of normal PB and BM samples showed low percentages of checks ( 0.95 for all cell types in PB and r2 > 0.75 in BM) and resulted in highly concordant classification of leukemic cells by our previously published automated database-guided expert-supervised orientation tool for immunophenotypic diagnosis and classification of acute leukemia (Compass tool). Similar data were obtained using alternative, commercially available tubes, confirming the robustness of the developed tools. The AGI tool represents an innovative step in minimizing human intervention and requirements in expertise, toward a “sample-in and result-out” approach which may result in more objective and reproducible data analysis and diagnostics. The AGI tool may improve quality of immunophenotyping in individual laboratories, since high percentages of checks in normal samples are an alert on the quality of the internal procedures., The EuroFlow Consortium received support from the FP6- 2004-LIFESCIHEALTH-5 program of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP). The Prague team received support from the grant number NV18-03-00343. The Salamanca team received support from the Instituto de Salud Carlos III (ISCIII) (PI16/00787-FEDER) and from Agencia Estatal de Investigación (RTC-2016-4865-1-FEDER), Ministerio de Economía y Competitividad, Madrid, Spain. AHD is supported from the program DI-17-09591 from Agencia Estatal de Investigación, Ministerio de Ciencia, Innovación y Universidades, Madrid, Spain. SB is supported from the program PTQ16-08364 from Agencia Estatal de Investigación, Ministerio de Ciencia, Innovación y Universidades, Madrid, Spain. Medical University of Silesia in Katowice team was supported by the Strategmed III PersonALL grant [No. 304586/5/NCBR/2017] from the Polish National Center of Research and Development. The EuroFlow Consortium is part of the European Scientific Foundation for Hemato-Oncology (ESLHO), a Scientific Working Group (SWG) of the European Hematology Association (EHA).

Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%, P = 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%, P 0.01), while there was no significant difference regarding OS or transformation. With the limitations of a retrospective analysis, these results suggest a benefit for R-CHOP over R-B in FL3A or FL1-2-3A. Confirmatory data from prospective clinical trials are needed.

Context.Following a multi-year minimum of solar activity, a solar energetic particle event on 2020 Nov. 29 was observed by multiple spacecraft covering a wide range of solar longitudes including ACE, the Solar Terrestrial Relations Observatory-A, and the recently launched Parker Solar Probe and Solar Orbiter.Aims.Multi-point observations of a solar particle event, combined with remote-sensing imaging of flaring, shocks, and coronal mass ejections allows for a global picture of the event to be synthesized, and made available to the modeling community to test, constrain, and refine models of particle acceleration and transport according to such parameters as shock geometries and particle mass-to-charge ratios.Methods.Detailed measurements of heavy ion intensities, time dependence, fluences, and spectral slopes provided the required test data for this study.Results.The heavy ion abundances, timing, and spectral forms for this event fall well within the range found in prior surveys at 1 au. The spectra were well fitted by broken power law shapes; the Fe/O ratio was somewhat lower than the average of other events. In addition,3He/4He was very low, with only the upper limits established here.

Context. The Solar Orbiter spacecraft cruised in the inner heliosphere during Feb. 2020 – Jan. 2021, moving between ∼0.5–1.0 au radial distance. The Energetic Particle Detector suite operated continuously during this period. Aims. The Suprathermal Ion Spectrograph and High Energy Telescope observations made during intervals in between transient intensity increases were used to determine the low energy ion spectra and composition during quiet times. Methods. Energetic particle spectra and major ion components, including 3He, were measured over the range ∼0.1–100 MeV nucleon−1. The radial dependence of 4.4 MeV nucleon−1 4He and O was measured. A short interval of extremely low intensities (“super-quiet”) was also studied. Results. Spectra measured during the quiet period showed transitions, including galactic cosmic rays (> 50 MeV nucleon−1), anomalous cosmic rays (a few to ∼50 MeV nucleon−1), and a steeply rising “turn-up” spectrum below a few MeV nucleon−1 whose composition resembled impulsive, 3He-rich solar energetic particle events. The radial dependence had large uncertainties but was consistent with a small gradient. During the super-quiet interval, the higher energy components remained similar to the quiet period, while the approximately flat low energy 4He spectrum extended downward, reaching ∼300 keV nucleon−1 before transitioning to a steeply rising spectrum.

Viral meningitis is mainly caused by non-polio enteroviruses (NPEV). Large-scale data on the clinical characteristics between different outbreaks within the same region are lacking. This study aimed to analyse a possible influence of the circulating NPEV genotype on the disease outcome of affected children. A retrospective cohort study analysing two major outbreaks of NPEV meningitis in Germany in 2008 and 2013 was conducted in cooperation with the National Reference Centre for Poliomyelitis and Enteroviruses (NRC PE) and five German children's hospitals. A total of 196 patients with laboratory-confirmed NPEV meningitis were enrolled. In 2008, children with NPEV meningitis had significantly higher fever and showed more behavioural changes and less back pain. To better define typical findings in echovirus 30 (E-30) meningitis, patients were split into the following three groups: E-30 positive patients, patients with "Non E-30" infection and patients with "Untyped" NPEV infection. E-30 positive patients were significantly older and their disease course was more acute, with early admission to but also early discharge from hospital. E-30 positive patients showed a significantly higher rate of headache and meningism, and a lower rate of diarrhoea and clinically defined septicaemia when compared to the others. Regarding laboratory testing, E-30 positive patients presented with significantly elevated peripheral blood neutrophil counts when compared to patients with "Non E-30" or "Untyped" NPEV infection. In conclusion, E-30 meningitis in children shows a characteristic pattern of clinical features. To further characterise NPEV strains worldwide, continuous surveillance and typing of NPEV strains causing central nervous system disease is warranted.

Frequent evolution of copy number alterations in CLL following first-line treatment with FC(R) is enriched with TP53 alterations: results from the CLL8 trial

The aim of the present study was to evaluate the off-flavour masking potential of pea dextrin (PD) in emulsions rich in ω-3 and ω-6-fatty acids in comparison with maltodextrin (MD) and 2-hydroxypropyl-β-cyclodextrin (HPBCD). After optimisation of the homogenisation procedure, stable emulsions were prepared and stored for up to eight weeks. The development of six secondary lipid oxidation products: propanal, 1-penten-3-one, 1-penten-3-ol, hexanal, (E,E)-2,4-heptadienal and (E,Z)-2,6-nonadienal, was monitored via headspace gas chromatography after solid-phase microextraction. Sensory evaluation of the emulsions was performed by a trained panel. PD already showed masking properties for propanal, 1-penten-3-one, hexanal and (E,E)-2,4-heptadienal during validation of the gas chromatographic analysis, but not for 1-penten-3-ol or (E,Z)-2,6-nonadienal. During storage, the course of lipid oxidation was similar in all emulsions as concluded from the hydroperoxide value. Results from the sensory evaluation confirmed a masking of rancid off-flavour. In conclusion, pea dextrin is suitable for masking off-flavour resulting from early stages of lipid oxidation.

Ziel: Zugangswege zur Zielgruppe in den Projekten des Forderschwerpunktes Praventionsforschung des Bundesministeriums fur Bildung und Forschung wurden untersucht. Methodik: Eine schriftliche Projektbefragung wurde durchgefuhrt. Gefragt wurde nach den genutzten Zugangs- und Kommunikationswegen, den eingesetzten Teilnahmeanreizen, dem Erreichungsgrad der Zielgruppe sowie nach Strategien, die sich bei der Zugangsgestaltung als erfolgreich bzw. hinderlich erwiesen haben. Ergebnisse: 38 von 60 angeschriebenen Projekten schickten einen ausgefullten Fragebogen zuruck. Der Zugang zu den Zielgruppen erfolgte am haufigsten uber Institutionen (z. B. Kitas, Schulen, Betriebe). Die Projekte nutzten multiple Kommunikationskanale und Anreize; am haufigsten erfolgte eine schriftliche Ansprache und es wurden monetare Anreize vor allem fur die Teilnahme an der Evaluation geboten. Nur wenige Projekte gaben den Erreichungsgrad der Zielgruppe an; erfolgte der Zugang uber Institutionen, war der Erreichungsgrad besonders hoch. Ein aktives Zugehen durch personliche Kommunikation mit der Zielgruppe und den Multiplikatoren erwiesen sich aus der Sicht der Befragten als erfolgreiche Strategien. Schlussfolgerung: Der Beitrag bietet einen Uberblick zu Zugangstrategien in aktuellen Praventionsprojekten. Mehr systematische Forschung zum Erreichungsgrad ist notwendig.

Persistent polyclonal B-cell lymphocytosis: extensively proliferated CD27+IgM+IgD+ memory B cells with a distinctive immunophenotype

Chemoimmunotherapies like the combination of fludarabine, cyclophosphamide, and rituximab (FCR) achieve response rates as high as 95% in patients with previously untreated chronic lymphocytic leukemia (CLL).1 Further improvements in clinical outcome will therefore mainly depend on attaining more durable remissions in those responders who suffer an early relapse. In general, progression of disease within 24 months after intensive chemoimmunotherapy is regarded as unsatisfactory2 and might be associated with a shortened overall survival (OS).3

Bei der Nachresektion nach T1-Blasentumoren kann eine exakte Relokalisation des ehemaligen infiltrativen Tumorareals wegen reaktiver Veranderungen, multipler Narben oder wechselnder Operateure erschwert sein. In unserer Untersuchung haben wir die Bedeutung der exakten Tumordokumentation und die Lokalisation und Rate der Residualtumore analysiert. Von Juli 2007 bis Februar 2012 sind an unserer Klinik 167 Nachresektionen nach einem T1 high grade-Blasentumor durchgefuhrt worden. Neben der Residualtumorrate und klinischen Parametern wurde die Lokalisation der Residualtumore untersucht, die anhand unserer standardisierten Blasentumordokumentation evaluiert wurde. Es zeigte sich eine Residualtumorrate von 58,1 % (97 von 167 Patienten). In 85,6 % (83 von 97 Patienten) der Falle war das Residuum im Bereich des ehemaligen Tumorareals: davon 41,2 % (n = 40) ausschlieslich im Areal des ehemaligen Tumors, 44,3 % (n = 43) multifokal im ehemaligen Areal und zusatzlich an neuen Arealen. Bei 11 Patienten (11,3 %) lag ein Residualtumor im Bereich des ehemaligen Tumorareals vor, welches endoskopisch vom Operateur als unauffallig eingeschatzt und erst histologisch bestatigt wurde. T1 high grade-Blasentumore zeigten eine relevante Rate von Residualtumoren in der Nachresektion, was nach unseren Ergebnissen die leitliniengerechte obligate Nachresektion rechtfertigt. In den meisten Fallen ist das ehemalige Tumorareal betroffen. Eine exakte Nachresektion des ehemaligen Tumorareals ist durch die vorgestellte Blasentumordokumentation auch bei multiplen Narben, reaktiven Veranderungen und wechselnden Operateuren gezielt moglich.

In einer urologischen Ausbildungsklinik findet ein relevanter Teil der TURB als „teaching“-Eingriff statt. Ist der Ausbildungsstand des Operateurs fur das onkologische Ergebnis bei der TURB von Bedeutung? Von Juli 2007 bis Februar 2012 sind an unserer Klinik insgesamt 254 Nachresektionen nach Ta high grade- und T1 high grade-Blasentumoren durchgefuhrt worden. Die Operateure der Primar-TURB wurden aufgeteilt je nach klinischem Ausbildungsstand in „junge Assistenten“ (1. und 2. Ausbildungsjahr), „erfahrene ­Assistenten“ (3.–5. Jahr), Facharzte, Oberarzte und Chefarzt. Wir haben die Rezidivrate der Nachresektionen mit dem jeweiligen Operateur bei Primarresektion verglichen. Initial lag ein Ta high grade-Blasentumor bei 87 Patienten (34,3%) und ein T1 high-grade Blasentumor bei 167 (67,7%) vor. Die meisten TURB wurden von „erfahrenen Assistenten“ (3.–5. Jahr) und vom Chefarzt durchgefuhrt. Der Anteil von „teaching-TURBs“ war 36,6% (n=93). Die Rezidivrate bei Nachresektion war insgesamt 52,4%. Einen signifikanten Einfluss auf die Rezidivrate hatten die Anzahl der Primartumoren, die Tumorgrose und das T-Stadium. Die jeweiligen Operateure unterschieden sich nicht signifikant in ihren Rezidivraten. Zwischen den Operateuren zeigte die Detrusorrate, als Hinweis auf eine ausreichend tiefe Resektion, keine signifikanten Unterschiede. Ein Bias, dass „jungere“ Operateure gunstigere Tumoren (solitar, kleiner als 3 cm) operiert haben, konnten wir ausschliesen. Unsere Daten zeigten keine signifikant unterschiedlichen Rezidiv-und Detrusorraten fur den jeweiligen Ausbildungsstand des Operateurs. Aus onkologischer Sicht ist eine „teaching-TURB“ unter entsprechender Anleitung mit ungestorter Kommunikation und einer personlichen Supervision sicher und einer facharztlichen TURB nicht unterlegen.

Wir haben die Wertigkeit der TURB-Nachresektion nach T1-Blasentumoren an unserer Klinik uber einen Zeitraum von 4,5 Jahren untersucht. Von Juli 2007 bis Februar 2012 sind an unserer Klinik 2172 TURB durchgefuhrt worden. Von diesen waren 1 130 Initialresektionen bei einem Erstbefund oder Rezidivtumor der Blase. Bei 258 Patienten zeigte sich ein T1-Blasentumor. Es wurden sowohl der Tumorbefund der Initial-TURB und das Ergebnis der Nachresektion evaluiert. Die Inzidenz von T1 high grade-­Tumoren war in unseren Patienten 22,8% (N=258). Von 167 Patienten, die eine Nachresektion nach T1-Blasentumor erhielten, zeigte sich ein Rezidivtumoren in 58,1% (97 Patienten). Die Rezidivtumoren waren meist multifokal (61,9%) und kleiner als 3 cm (69,1%). Die Histologie der Nachresektion zeigte Ta-Tumoren in 24,6% (41 von 167 Patienten), Persistenz von T1 high grade in 19,8% (33 von 167 Patienten) und ein Upstaging auf T2 und mehr in 6,6% (11 von 167 Patienten). Die Anzahl der Initialtumoren zeigt einen signifikanten Einfluss auf die Rezidivrate bei Nachresektion: Pa­tienten mit multifokalen Tumoren hatte ein Rezidivrate von 69%, im Gegensatz zu 46,3% bei solitaren Tumoren. Ebenso zeigte sich ein tendenzieller Einfluss fur die Tumorgrose und fur das Vorhandensein von Detrusor im Praparat. T1 high grade-Blasentumoren zeigten eine relevante Rate von Rezidivtumoren in der Nachresektion, was nach unseren Ergebnissen die leitliniengerechte obligate Nachresektion rechtfertigt. Einen signifikanten Einfluss zugunsten einer tumorfreien Nachresektion zeigt sich in unseren Daten fur solitare Tumoren. Ein tendenzieller Einfluss konnte fur Detrusor im Praparat gezeigt werden. Es scheint somit die Tiefe der Initialresektion von Bedeutung zu sein. Fur das optimale Zeitintervall zur Nachresektion gibt es derzeit noch keine Daten.

Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics., This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative, the Red Temática de Investigación Cooperativa en Cáncer (RTICC); grant SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain and; grant DTS15/00119 from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain.

The gluon momentum density xg ( x , Q 2 ) of the proton was extracted at Q 2 = 20 GeV 2 for small values of x between 4 × 10 −4 and 10 −2 from the scaling violations of the proton structure function F 2 measured recently by ZEUS in deep inelastic neutral current ep scattering at HERA. The extraction was performed in two ways. Firstly, using a global NLO fit to the ZEUS data on F 2 at low x constrained by measurementsfrom NMC at larger x ; and secondly using published approximate methods for the solution of the GLAP QCD evolution equations. Consistent results are obtained. A substantial increase of the gluon density is found at small x in comparison with the NMC result obtained at larger values of x .

Ursache fur eine Galleabflussstorung nach kephaler Pankreatoduodenektomie konnen Strikturen der im Rahmen der Operation angelegten Hepaticojejunostomie, Passagestorungen im Bereich der anastomosierten Jejunalschlinge, Konkremente oder sehr selten ingestierte Fremdkorper im Ductus hepaticus sein. Die aufgehobene Funktion des Sphincter Oddi nach Anlage einer Hepaticojejunostomie kann – ebenso wie nach endoskopischer Papillotomie oder der fruher haufig praktizierten Anlage einer Seit-zu-Seit-Choledochoduodenostomie – zum Auftreten eines enterobiliaren Refluxes fuhren, was die Migration oral aufgenommener Fremdkorper oder faseriger Nahrungsbestandteile in den Gallengang begunstigt. Ausgehend von der Schilderung eines derartigen Falles wird eine Ubersicht der verfugbaren Literatur uber das seltene Phanomen des fremdkorperinduzierten mechanischen Ikterus gegeben.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivative Works 3.0 Unported License.-- EuroFlow Consortium (EU-FP6, LSHB-CT-2006-018708): et al., The EU-supported EuroFlow Consortium aimed at innovation and standardization of immunophenotyping for diagnosis and classification of hematological malignancies by introducing 8-color flow cytometry with fully standardized laboratory procedures and antibody panels in order to achieve maximally comparable results among different laboratories. This required the selection of optimal combinations of compatible fluorochromes and the design and evaluation of adequate standard operating procedures (SOPs) for instrument setup, fluorescence compensation and sample preparation. Additionally, we developed software tools for the evaluation of individual antibody reagents and antibody panels. Each section describes what has been evaluated experimentally versus adopted based on existing data and experience. Multicentric evaluation demonstrated high levels of reproducibility based on strict implementation of the EuroFlow SOPs and antibody panels. Overall, the 6 years of extensive collaborative experiments and the analysis of hundreds of cell samples of patients and healthy controls in the EuroFlow centers have provided for the first time laboratory protocols and software tools for fully standardized 8-color flow cytometric immunophenotyping of normal and malignant leukocytes in bone marrow and blood; this has yielded highly comparable data sets, which can be integrated in a single database., The research activities of the EuroFlow Consortium were supported by the European Commission (grant STREP EU-FP6, LSHB-CT-2006-018708, entitled ‘Flow cytometry for fast and sensitive diagnosis and follow-up of hematological malignancies’) and the following national grants: Spanish Network of Cancer Research Centers (ISCIII RTICC-RD06/0020/0035-FEDER), FIS 08/90881 from the ‘Fondo de Investigación Sanitaria’, Ministerio de Ciencia e Innovación (Madrid, Spain), SA016-A-09 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain, and PIB2010BZ-00565 from the Dirección General de Cooperación Internacional y Relaciones Institucionales, Secretaría de Estado de Investigación, Ministerio de Ciencia e Innovación (Madrid, Spain). T Kalina, E Mejstrikova and O Hrusak were supported by the Czech Ministry of Education Grant No. MSM0021620813, Czech Ministry of Health grant NT/12425-4 and TK is supported as an ISAC Scholar by The International Society for Advancement of Cytometry.

Fludarabine and cyclophosphamide in combination with alemtuzumab in patients with primary high-risk, relapsed or refractory chronic lymphocytic leukemia

Nowadays, the presence of specific genetic aberrations is progressively used for classification and treatment stratification, because acute leukemias with the same oncogenetic aberration generally form a clinically and diagnostically homogenous disease entity with comparable prognosis. Many oncogenetic aberrations in acute leukemias result in a fusion gene, which is transcribed into fusion transcripts and translated into fusion proteins, which are assumed to play a critical role in the oncogenetic process. Fusion gene aberrations are detected by karyotyping, FISH, or RT-PCR analysis. However, these molecular genetic techniques are laborious and time consuming, which is in contrast to flow cytometric techniques. Therefore we developed a flow cytometric immunobead assay for detection of fusion proteins in lysates of leukemia cell samples by use of a bead-bound catching antibody against one side of the fusion protein and fluorochrome-conjugated detection antibody. So far, we have been able to design such fusion protein immunobead assays for BCR-ABL, PML-RARA, TEL-AML1, E2A-PBX1, MLL-AF4, AML1-ETO and CBFB-MYH11. The immunobead assay for detection of fusion proteins can be performed within 3 to 4 hours in a routine diagnostic setting, without the need of special equipment other than a flow cytometer. The novel immunobead assay will enable fast and easy classification of acute leukemia patients that express fusion proteins. Such patients can be included at an early stage in the right treatment protocols, much faster than by use of current molecular techniques. The immunobead assay can be run in parallel to routine immunophenotyping and is particularly attractive for clinical settings without direct access to molecular diagnostics. © 2010 Elsevier Ltd. All rights reserved., The research and development of the flow cytometric immunobead assay and the EuroFlow Consortium were supported by the European Commission (grant STREP EU-FP6, LSHB-CT-2006- 018708).

The purpose of this study was to prospectively analyze minimal residual disease(MRD) kinetics after reduced-intensity allogeneic stem cell transplantation (allo-SCT) in high-risk chronic lymphocytic leukemia (CLL). Subjects were the first 30 consecutive patients from a prospective clinical trial, and seven pilot patients treated identically. Using real-time quantitative-PCR (RQ-PCR) and/or flow-based MRD monitoring (sensitivity >or=10(-4)), five distinct patterns of MRD kinetics could be identified: patients who promptly achieved durable MRD negativity without direct evidence of graft-versus-leukemia (GVL) effects (Group 1) (n=4; no clinical relapse); patients with complete and sustained MRD response after GVL induced by immunosuppression tapering (Group 2) or donor lymphocyte infusions (Group 3) (n=18; one relapse); patients without MRD response due to lack of GVL (Group 4) (n=2; two relapses); patients with incomplete and transient MRD response to GVL (Group 5) (n=4; three relapses). In summary, this study provides a comprehensive map of possible MRD courses and their prognostic implications after T-replete allo-SCT in high-risk CLL, indicating that effective GVL activity is induced virtually in all patients who develop chronic GVHD. However, in a significant proportion of cases, this does not translate into sustained disease control due to development of secondary GVL resistance.

Role of CD20 expression and other pre-treatment risk factors in the development of infusion-related reactions in patients with CLL treated with obinutuzumab

The risk of endobronchial intubation during laparoscopy because of displacement of the tip of the tracheal tube is a well known problem in adults. Laparoscopy in children is increasingly performed, but there are no data available regarding the above problem. We prospectively studied 46 children aged 2 months to 15.7 years (median 4.2 years) undergoing laparoscopy. After tracheal intubation with the Microcuff Pediatric Endotracheal Tube, with the 'intubation depth marking' of the tube at the vocal cords, the distance from the tracheal tube tip to the carina was endoscopically measured with the patient in the neutral position and with 20 degrees head-down tilt, both with and without capnoperitoneum. Maximal displacement of the tip of the tracheal tube tip in cm was 0.5+(0.05xage (years)) for 20 degrees head-down tilt, 0.6+(0.09xage (years)) for capnoperitoneum alone, and 1.2+(0.11xage (years)) for 20 degrees head-down tilt with capnoperitoneum. In no patients did endobronchial intubation occur with the tracheal tube placed according to the intubation depth marking.

Background To assess the adequacy of the position of the tracheal tube cuff and tracheal tube tip in the recently introduced preformed oral Microcuff paediatric endotracheal tube (PET) using the manufacturers recommendations for Microcuff tracheal tube size selection. Methods With Hospital Ethics Committee approval and informed parental consent, the tracheas of children from birth to adolescence were orally intubated with the preformed oral Microcuff PET. First, the position of the tracheal tube's intubation depth mark in relation to the vocal cords was assessed. Second, the distance ‘tracheal tube tip-to-carina’ was endoscopically measured with the patient supine and the head in a neutral position and the tube placed with the centre mark at the lower incisors or alveolar ridge. Results A total of 166 children aged from 0.1 to 16.4 yr (median 5.9 yr) were studied. In five patients the intubation depth mark was above (5 mm each), in 22 patients at the level of and in the remaining 139 patients below the vocal cords. No endobronchial intubation occurred. In four patients the distance ‘tracheal tube tip-to-carina’ was smaller than the safety margin to prevent endobronchial intubation during head-neck flexion. Conclusion The new oral preformed cuffed tracheal tubes allow safe placement in almost all patients when inserted according to the tube bend. The critically low tube tip and the high cuff positions in a few tubes when placed according to the tube bend requires clinical alertness.

Two groups of tinnitus patients (n=93) were recruited, one of which was treated with standard infusion therapy and further acute medical intervention, while the other obtained an additional psychotherapeutic intervention. Questionnaires and interviews were taken at beginning of-the treatment, and 9 days and 3 years after treatment. The accompanying psychotherapeutic intervention consisted primarily of client-centered counseling, guided relaxational techniques from clinical hypnosis, and some standard and tinnitus-related methods for a better coping with stress. After 9 days, both treatment groups showed significant improvement in several psychological characteristics. However, there was no evidence for the superiority of the combined treatment with psychological intervention. Psychotherapeutic treatment accompanying the acute medical treatment probably shows better effectiveness in an ambulant setting with both patients and medical healthcare professionals rating it as 'very helpful'. This pilot study has contributed initial results for the integrated treatment of the acute tinnitus and has helped in the development of further therapeutic strategies as well as an evidence based concept for further evaluation. This study received one of the two scientific first prizes of the "German Tinnitus League".

Zusammenfassung: Verschluckte, im Ösophagus stecken gebliebene, Knopfbatterien müssen notfallmäßig entfernt werden, da sie trotz rascher Entfernung in kürzester Zeit durch verschiedene Mechanismen zu tiefen Verletzungen der Mukosa führen können. Dies wird anhand eines Fallbeispiels eines 2-jährigen Mädchens demonstriert, das nach rascher, unproblematischer endoskopischer Entfernung einer Knopfbatterie aus dem Ösophagus und einem zunächst guten Verlauf eine ösophagotracheale Fistel entwickelte

The prognostic impact of minimal residual disease assessment after stem cell transplantation for chronic lymphocytic leukemia: is achievement of molecular remission worthwhile?

Feeding by larvae of the crown fly, Botanophila spinosa, was found to directly reduce the growth of Onopordum acanthium rosettes during spring and to indirectly reduce the subsequent growth of flowering stems and seed production. The impact of feeding damage by larvae was greatest when plants were attacked in early spring and declined to be non-significant for plants attacked later in April and May. No pattern in attack levels was observed between patches. Within patches, there was a trend for increased attack on larger, more apparent rosettes and the distribution of attack per plant was aggregated due to variability in the egg-laying behaviour of B. spinosa, resulting in more concentrated attack on some individual plants than expected if attack were random. B. spinosa was considered capable of complementing the already released crown weevil, Trichosirocalus briesei, to extend the period of attack by biological control agents on Onopordum rosettes in Australia, particularly in the case of O. acanthium. Following host-specificity testing, it was released in 1999, though establishment has not yet been confirmed.

A single-agent dose escalating phase I and pharmacokinetic study with Cilengitide, an inhibitor of the integrins alphavbeta3 and alphavbeta5, was performed to determine its safety and toxicity. Cilengitide was administered as a one-hour infusion twice weekly without interruption to patients with histologically- or cytologically-confirmed metastatic solid tumours. Plasma pharmacokinetics were determined at days 1 and 15. 37 patients were enrolled into the study. Dose levels studied were 30, 60, 120, 180, 240, 400, 600, 850, 1200, and 1600 mg/m(2)/infusion. There was no dose-limiting toxicity (DLT). Pharmacokinetics were dose-independent and time-invariant. Apparent terminal half-life ranged from 3 to 5 h. At 120 mg/m(2)/infusion, peak plasma concentrations were attained that optimally inhibited tumour growth in preclinical models. Cilengitide can be safely administered using a continuous twice-weekly infusion regimen. As DLT was not reached, future trials should explore Cilengitide at different doses.

Listeria (L.) monocytogenes causes orally acquired infections and is of major importance in ruminants. Little is known about L. monocytogenes transmission between farm environment and ruminants. In order to determine potential sources of infection, we investigated the distribution of L. monocytogenes genetic subtypes in a sheep farm during a listeriosis outbreak by applying four subtyping methods (MALDI-TOF-MS, MLST, MLVA and PFGE). L. monocytogenes was isolated from a lamb with septicemia and from the brainstem of three sheep with encephalitis. Samples from the farm environment were screened for the presence of L. monocytogenes during the listeriosis outbreak, four weeks and eight months after. L. monocytogenes was found only in soil and water tank swabs during the outbreak. Four weeks later, following thorough cleaning of the barn, as well as eight months later, L. monocytogenes was absent in environmental samples. All environmental and clinical L. monocytogenes isolates were found to be the same strain. Our results show that the outbreak involving two different clinical syndromes was caused by a single L. monocytogenes strain and that soil and water tanks were potential infection sources during this outbreak. However, silage cannot be completely ruled out as the bales fed prior to the outbreak were not available for analysis. Faeces samples were negative, suggesting that sheep did not act as amplification hosts contributing to environmental contamination. In conclusion, farm management appears to be a crucial factor for the limitation of a listeriosis outbreak.

The aim of this study was to assess methods used to access target groups in prevention projects funded within the prevention research framework by the German Federal Ministry of Education and Research. A survey with prevention projects was conducted. Access strategies, communication channels, incentives, programme reach, and successful practical recruitment strategies were explored. 38 out of 60 projects took part in the survey. Most projects accessed their target group within structured settings (e. g., child day-care centers, schools, workplaces). Multiple communication channels and incentives were used, with written information and monetary incentives being used most frequently. Only few projects were able to report their programme reach adequately; programme reach was highest for programmes accessing the target groups in structured settings. The respondents viewed active recruitment via personal communication with the target group and key persons in the settings as the most successful strategy. The paper provides an overview on recruitment strategies used in current preven-tion projects. More systematic research on programme reach is necessary.

The level of levofloxacin was determined in serum, bone and several tissues after a single dose of 500 mg i.v. Twenty-one patients (mean age: 56.8 years) undergoing bone surgery (nine patients) or surgical debridement of a decubitus ulcer (12 patients) who received levofloxacin as perioperative prophylaxis were included in the study. During surgery, blood and tissue samples were obtained approximately 1.5 h (range 40-210 min) postdosing. Levofloxacin concentrations in 87 specimens including 21 serum samples were determined using high-performance liquid chromatography (HPLC). The mean serum concentration at 1.5 h was 8.6+/-2.3 microg/ml. Concentrations above the MIC of common pathogens were reached in all tissues during the collection period with a maximum in skin samples (19.9+/-9.9 microg/g) followed by wound tissue and granulation tissue with 17.3+/-6.5 and 13.7+/-6.4 microg/g respectively. In muscle and fatty tissue mean levofloxacin concentrations of 8.0+/-0.9 and 4.0+/-2.2 microg/g were attained. Mean levels in cancellous bone were 6.6+/-3.6 microg/g, lowest levels were measured in cortical bone (2.8+/-1.1 microg/g). Twenty-two different pathogens were cultivated from the lesions of 11 of 12 patients with pressure ulcers. MIC values for levofloxacin were determined and compared with the corresponding tissue concentrations. Levofloxacin may be useful for perioperative prophylaxis and treatment in orthopaedic patients due to its good tissue penetration.

The study describes genetic characterization of poliovirus (PV) strains isolated from sewage samples in Poland. The analyses were performed for the detection of any putative polio revertants and recombinants in three genomic regions by sequencing analysis. Thirty-six strains were analyzed. The analyzed strains were identified by neutralization assay as 7 strains of serotype P1, 10 strains of serotype P2, and 19 strains of serotype P3. Sewage isolates were sequenced in 5'UTR, VP1, and 3D genomic regions. All detected PVs were classified as vaccine strains on the basis of VP1 sequence. Mutational differences in the VP1 sequences of isolated viruses ranged from 0.0% to 0.4%, indicating a limited replication period. The genetic analysis of the 3D region showed that some strains have recombinant genomes. Nine strains were found as dipartite recombinants (seven strains--S3/S2, one strain--S2/S1, one strain--S3/S1), while one strain was found as tripartite recombinant (S3/S2/S1). No recombinants with non-PV enteroviruses were identified. None of wild-type PVs or vaccine-derived polioviruses (VDPVs) were detected. This study showed the absence of wild or VDPV circulation in the country and demonstrated the usefulness of environmental surveillance in addition to acute flaccid paralysis (AFP) surveillance in support of polio eradication initiatives.

This outcome evaluation study has investigated different diet concepts in day-care centres and their effects on health-related dietary behaviour of children and their families. No advantage of a certain approach to manage food and diet-related activities in day-care centres could be shown.

For control resection of T1 bladder tumors an exact relocalization of the previously infiltrating tumor spread can be complicated by postreactive alterations, multiple scar tissue or change of surgeons. In this study the results of control transurethral resection of the bladder (TURB) after T1 high grade bladder tumors with the focus on localization and importance of standardized exact documentation were analyzed.From July to February 2012 a control resection was performed in 167 patients due to a T1 high grade bladder cancer. The rates of residual tumor tissue and localization were investigated with standardized tumor documentation.Out of 167 patients with T1 bladder cancer who underwent a control resection tumor tissue was found in 58.1 % (97 out of 167) and in 85.6 % (83 out of 97) the primary site was affected (41.2 % only at primary site and 44.3 % additionally at other locations). In 11 patients (11.3 %) residual tumor tissue at the initial site was only detected histologically.Our results indicate that T1 high grade bladder cancers show a relevant rate of residual tumor tissue at control resection which confirms the clinical guidelines of the European Association of Urology (EAU) on mandatory resection. In most cases the primary tumor site is affected. The standardized bladder tumor documetation allows well-directed control resection also in patients with multiple scars and post-TUR alterations, even when performed by a different surgeon.

In departments with urological training of residents, part of the TURB procedures are performed as "teaching surgery". Does resection quality and early recurrence depend on the operator's experience?From July 2007 to February 2012 254 second resections (TURB) after Ta high-grade and T1 high-grade bladder tumours were performed at our institution. The surgeons were stratified into "junior residents" (first and second year of training), "experienced residents" (3rd-5th year of training), board certified urologists, consultants and chief surgeons. We analysed the risk of recurrence at second resection and characteristics of the initial TURB.87 patients presented with a Ta high-grade tumour (34.3%) and 167 had a T1 high-grade lesion (67.7%). Most TURBs were performed by "experienced residents" (3rd-5th year) and the chief of department. The recurrence rate at second resection was 52.4%. A significant association with the recurrence rate was shown for the number of initial tumours, size and T-stage. No association was found for the training level of the surgeon. Additionally, there was no different detrusor rate for the surgeons, as a parameter for a correct, muscle-deep TURB. A bias that surgeons in training had more favourable tumours (solitary, less than 3 cm) could be excluded.In our data detrusor rate and recurrence risk at second resection are independent of the surgeon's experience. The results of "teaching-TURBs" are not inferior compared to TURBs performed by board certified urologists or consultants under the conditions of undisturbed communication and personal supervision.

We have evaluated the results of second transurethral resections of the bladder (TURB) after T1 high-grade bladder cancer over a 4.5-year period.From July 2007 to February 2012, 2172 TURB procedures were performed at our institution, of which 1130 were initial resections owing to primary tumour or relapse. Of these, 258 revealed T1 high-grade bladder cancer, and here we investigated tumour characteristics of the initial TURB and results of the second resection.The incidence of T1 high-grade tumours was 22.8% (N=258). Of 167 patients who underwent a second resection, tumour was found in 58.1% (97 of 167). Tumours were mostly multifocal (61.9%) and smaller than 3 cm (69.1%). Histology of the second resection revealed Ta low-grade in 8.4%, Ta high-grade in 16.2%, T1 high-grade in 19.8% and an upstaging to T2 and more in 6.6%. A significant association with the recurrence rate was found for the number of tumours at initial TURB: patients with multiple tumours at initial TURB had a recurrence rate of 69.0% compared with only 46.3% of patients with solitary tumour. For tumour-size and detrusor muscle in specimen a non-significant association was shown.T1 high-grade bladder cancers show a relevant rate of tumour at second TURB which confirms the clinical guidelines of the EAU. A significant association for a tumour-free second TURB in our data was shown for solitary tumours. A non-significant association was shown for tumour-size and when detrusor muscle was present in the specimen. Currently there is no data to determine the best time interval before second resection.