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Purpose The optimal dose intensity for conditioning prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) for chronic lymphocytic leukemia (CLL) is unknown. Methods We retrospectively compared outcomes of patients who received a first alloHCST after non-myeloablative (NMA) and reduced intensity conditioning (RIC). Data of 432 patients with a median age of 55 years were included, of which 86 patients underwent NMA and 346 RIC. Results The median follow-up after alloHSCT was 4.3 years. Compared to the RIC group, more NMA patients had purine-analog-sensitive disease, were in complete remission and received matched related donor transplantation. After RIC, the probabilities for 5-year OS, EFS, CIR, and NRM were 46%, 38%, 28%, and 35% and after NMA the respective probabilities were 52%, 43%, 25%, and 32%. In multivariate analysis, remission status prior to conditioning but not RIC versus NMA conditioning had a significant impact on CIR, EFS, and OS. Conclusion Presumed higher anti-leukemic activity of RIC versus NMA conditioning did not translate into better outcomes after alloHSCT, but better remission status prior to conditioning did. Effective pathway inhibitor-based salvage therapies combined with NMA conditioning might thus represent the most attractive contemporary approach for alloHSCT for patients with CLL.

Rationale: Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) analysis of covalent 5‐lipoxygenase inhibitors is challenging due to unknown amino acid specificity and low posttranslational modification (PTM)‐identification rates. The analysis of the amino‐acid specificity and of the characteristic fragmentation of chemically modified peptides is considered to improve knowledge for the analysis of chemically modified peptides and proteins by MALDI‐MS. Methods: Various compounds were used to investigate the modification of synthetic peptides carrying reactive amino acid residues. Mass spectra were recorded using a MALDI‐LTQ Orbitrap XL for high‐resolution mass spectrometry and ion trap MALDI‐MS2. UV-Vis‐based reduction and radical scavenging analysis was conducted. The on‐plate digestion method described by Rühl et al was utilized for modification‐site analysis at 5‐lipoxygenase. Results: The analysis of amino‐acid‐specific reactivity revealed the reactivity of quinones towards cysteine residues and the potential occurrence of a subsequent oxidative process was observed by an UV-Vis‐based reduction assay. MALDI collision‐induced dissociation tandem mass spectrometry (CID‐MS2) indicated a prominent fragmentation mechanism of modified cysteine and histidine residues. Fragmentation included highly abundant neutral‐loss signals which could be used to identify new modifications induced by chemical modifiers at the cysteine‐159 residue of 5‐lipoxygenase. Conclusions: Specificity and fragmentation analysis provides crucial information for the analysis of chemically modified cysteines and histidines by MALDI‐MS. Elucidation of binding sites by MALDI‐MS has been significantly improved using an easy‐to‐run peptide assay and gives background information for the analysis in the case of chemically modified 5‐lipoxygenase.

For young patients with high-risk CLL, BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. Patients with a low risk of non-relapse mortality (NRM) but a high risk of failure of targeted therapy may benefit most from alloHCT. We performed Cox regression analyses to identify risk factors for 2-year NRM and 5-year event-free survival (using EFS as a surrogate for long-term disease control) in a large, updated EBMT registry cohort (n = 694). For the whole cohort, 2-year NRM was 28% and 5-year EFS 37%. Higher age, lower performance status, unrelated donor type and unfavorable sex-mismatch had a significant adverse impact on 2-year NRM. Two-year NRM was calculated for good-and poor-risk reference patients. Predicted 2-year-NRM was 11 and 12% for male and female good-risk patients compared with 42 and 33% for male and female poor-risk patients. For 5-year EFS, age, performance status, prior autologous HCT, remission status and sex-mismatch had a significant impact, whereas del(17p) did not. The model-based prediction of 5-year EFS was 55% and 64%, respectively, for male and female good-risk patients. Good-risk transplant candidates with high-risk CLL and limited prognosis either on or after failure of targeted therapy should still be considered for alloHCT.

Zielsetzung: Stürze haben eine hohe individuelle und gesellschaftliche Bedeutung. Während im Akut-Krankenhaus von einer mittleren Sturzrate von 7% [ref:1] ausgegangen wird, ermittelten Sherrington et al. [ref:2] für die Rehabilitation rund 15% Sturzrate der[zum vollständigen Text gelangen Sie über die oben angegebene URL], Alterstraumatologie Kongress 2016

Fragestellung: Stürze haben eine hohe individuelle und gesellschaftliche Bedeutung. Im Akut-Krankenhaus wird von 1,3 bis 8,9 Stürzen pro Belegungstag ausgegangen. Heinze berichtete über 3,5% Stürze bei 3012 Krankenhauspatienten, wobei nur 67% keine Sturzfolgen aufwiesen.[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2015)

Objectives: “Fungal InfectioN Database” (FIND) represents international database of invasive fungal infections in Czech and Slovak hematooncological departments. FIND - aspergillus covers all case of invasive aspergillosis (IA) in participating centers since 2001. Methods: The goal of our retrospective analysis was to evaluate incidence, early diagnostic procedures and effect of antifungal therapy in proven and probable IA that occurred in 16 institutions participating in FIND database between 2001–2011. Till 2009 we followed EORTC/MSG 2002 and from 2010 EORTC/MSG 2008 criteria in evaluation of IA diagnosis and therapy response. Results: 256 probable and 58 proven IA (91% isolated pulmonary IA, IPA) have been documented. Prolonged and profound neutropenia (61%) and long-term use of corticosteroids (28%) were identified as the major risk factors of IA. 68% pts. had consecutive positivity of serum-galactomannan (S-GM) (OD index >0.5). 83% pts. with IPA and bronchoalveolar lavage (BAL) had positive GM in BAL fluid (OD index >0.5). In pts. with IPA only 7.6% BAL fluids and 8.4% sputum samples had positive microscopic result for filamentous fungi and 2.2% BAL fluids and 1.8% sputum samples had positive culture for Aspergillus spp. The primary antifungal therapy of IA was used in 89% pts. - 41% voriconazole (VORI), 7% echinocandins (ECHINO), 23% VORI+ECHINO, 7% amphotericine B deoxycholate (C-AMB) and 9% lipid- based AMB (LBA). Overall RR to primary therapy of IA was 46% - VORI 55%, VORI+ECHINO 54%, C-AMB 35%, LBA 39%, ECHINO 25%. There was a statistically significant difference in overall RR to targeted therapy in pts. with neutrophil count 1.0x10e9/L at the end of therapy (21% vs. 71%). The overall mortality rate was 61%, with 39% attributable to IA. Conclusion: On the basis of our analysis we confirm typical risk factors for IA and critical role of S-GM and CT for early diagnosis and prompt start of antifungal therapy of IA. A reasonable treatment response was achieved using VORI, VORI+ECHINO or LBA in primary therapy of IA. We have confirmed neutropenia at the end of antifungal therapy as the major predictive factor for therapeutic response. On behalf of CELL - The Czech leukemia study group for life.

Recently, we published that nitro-fatty acids (NFA) are potent electrophilic molecules which inhibit 5-lipoxygenase (5-LO) by interacting with catalytically cysteine residues next to a substrate entry channel. The electrophilicity is derived from an intramolecular Michael acceptor moiety consisting of an electron-withdrawing group in close proximity to a double bond. The potential of the Michael acceptor moiety to interact with functionally relevant cysteines of proteins potentially renders them effective and sustained enzyme activity modulators. We screened a large library of naturally derived and synthetic electrophilic compounds to investigate whether other types of Michael acceptor containing drugs suppress 5-LO enzyme activity. The activity was measured by assessing the effect on the 5-LO product formation of intact human polymorphonuclear leukocytes. We demonstrated that a number of structurally different compounds were suppressive in the activity assays and showed that Michael acceptors of the quinone and nitro-alkene group produced the strongest inhibition of 5-LO product formation. Reactivity with the catalytically relevant cysteines 416 and 418 was confirmed using mutated recombinant 5-LO and mass spectrometric analysis (MALDI-MS). In the present study, we show for the first time that a number of well-recognized naturally occurring or synthetic anti-inflammatory compounds carrying a Michael acceptor, such as thymoquinone (TQ), the paracetamol metabolite NAPQI, the 5-LO inhibitor AA-861, and bardoxolone methyl (also known as "RTA 402", "CDDO-methyl ester") are direct covalent 5-LO enzyme inhibitors that target the catalytically relevant cysteines 416 and 418.