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Drug-resistant Gram-negative and Gram-positive bacteria are now increasingly identified as a cause of infections in immunocompromised hosts. Bacteria identified include the multidrug-resistant (MDR) and even pandrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, as well as carbapenem-resistant Enterobacteriaceae spp. The threat from MDR pathogens has been well-documented in the past decade with warnings about the consequences of inappropriate use of antimicrobial drugs. Resistant bacteria can substantially complicate the treatment of infections in critically ill patients and can have a substantial effect on mortality. Inappropriate antimicrobial treatment can affect morbidity, mortality, and overall health-care costs. Evidence-based data for prevention and control of MDR pathogen infections in haematology are scarce. Although not yet established a bundle of infection control and prevention measures with an anti-infective stewardship programme is an important strategy in infection control, diagnosis, and antibiotic selection with optimum regimens to ensure a successful outcome for patients.

Natural killer (NK) cells are innate lymphocytes that lack antigen-specific rearranged receptors, a hallmark of adaptive lymphocytes. In some people infected with human cytomegalovirus (HCMV), an NK cell subset expressing the activating receptor NKG2C undergoes clonal-like expansion that partially resembles anti-viral adaptive responses. However, the viral ligand that drives the activation and differentiation of adaptive NKG2C + NK cells has remained unclear. Here we found that adaptive NKG2C + NK cells differentially recognized distinct HCMV strains encoding variable UL40 peptides that, in combination with pro-inflammatory signals, controlled the population expansion and differentiation of adaptive NKG2C + NK cells. Thus, we propose that polymorphic HCMV peptides contribute to shaping of the heterogeneity of adaptive NKG2C + NK cell populations among HCMV-seropositive people. NK cells constrain infection by cytomegalovirus. Romagnani and colleagues show that human NKG2C + NK cells recognize distinct HCMV UL40 viral peptides, which can vary among viral isolates. NKG2C + NK cells thereby demonstrate adaptive-like recognition that can discriminate between closely related viral strains.

Background Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited. Methods We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD ( n  = 2567), 9/10 ( n  = 723), or 8/10 ( n  = 108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results HLA matching had no impact on engraftment ( p  = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II–IV acute graft-versus-host disease (GVHD) ( p  = 0.0002), similar rates of chronic GVHD ( p  = 0.138) but increased incidence of its extensive form ( p  = 0.047). Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS) ( p  = 0.005) and overall survivals (OS) (56.7, 46.1, and 50.2 %, respectively, p  = 0.005), while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p  = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p  = 0.0001), and OS (HR 1.27, p  = 0.0001). There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD. Conclusions Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other alternative donor transplant strategies.

Background Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated. Methods We analyzed 1554 adults with AML transplanted from MSD ( n  = 961) or UD ( n  = 593, HLA-matched 10/10, n  = 481; 9/10, n  = 112). Compared to MSD, UD recipients were older (49 vs 52 years, p  = 0.001), transplanted more recently (2009 vs 2006, p  = 0.001), and with a longer interval to transplant (10 vs 9 months, p  = 0.001). Conditioning regimen was more frequently myeloablative for patients transplanted with a MSD (61 vs 46 %, p  = 0.001). Median follow-up was 28 (range 3–157) months. Results Cumulative incidence (CI) of neutrophil engraftment ( p  = 0.07), grades II–IV acute GVHD ( p  = 0.11), chronic GVHD ( p  = 0.9), and non-relapse mortality (NRM, p  = 0.24) was not different according to the type of donor. At 2 years, CI of relapse (relapse incidence (RI)) was 57 vs 49 % ( p  = 0.001). Leukemia-free survival (LFS) at 2 years was 21 vs 26 % ( p  = 0.001), and overall survival (OS) was 26 vs 33 % ( p  = 0.004) for MSD vs UD, respectively. Chronic GVHD as time-dependent variable was associated with lower RI (HR 0.78, p  = 0.05), higher NRM (HR 1.71, p  = 0.001), and higher OS (HR 0.69, p  = 0.001). According to HLA match, RI was 57 vs 50 vs 45 %, ( p  = 0.001) NRM was 23 vs 23 vs 29 % ( p  = 0.26), and LFS at 2 years was 21 vs 27 vs 25 % ( p  = 0.003) for MSD, 10/10, and 9/10 UD, respectively. In multivariate analysis adjusted for differences between the two groups, UD was associated with lower RI (HR 0.76, p  = 0.001) and higher LFS (HR 0.83, p  = 0.001) compared to MSD. Interval between diagnosis and transplant was the other factor associated with better outcomes (RI (HR 0.62, p  < 0.001) and LFS (HR 0.67, p  < 0.001)). Conclusions Transplantation using UD was associated with better LFS and lower RI compared to MSD for high-risk patients with AML transplanted in first relapse.

Advances across the chemical and biological (life) sciences are increasingly enabled by ideas and tools from sectors outside these disciplines, with information and communication technologies playing a key role across 21 century scientific development. In the face of rapid technological change, the Organisation for the Prohibition of Chemical Weapons (OPCW), the implementing body of the Chemical Weapons Convention (“the Convention”), seeks technological opportunities to strengthen capabilities in the field of chemical disarmament. The OPCW Scientific Advisory Board (SAB) in its review of developments in science and technology examined the potential uses of emerging technologies for the implementation of the Convention at a workshop entitled “Innovative Technologies for Chemical Security”, held from 3 to 5 July 2017, in Rio de Janeiro, Brazil. The event, organized in cooperation with the International Union of Pure and Applied Chemistry (IUPAC), the National Academies of Science, Engineering and Medicine of the United States of America, the Brazilian Academy of Sciences, and the Brazilian Chemical Society, was attended by 45 scientists and engineers from 22 countries. Their insights into the use of innovative technological tools and how they might benefit chemical disarmament and non-proliferation informed the SAB’s report on developments in science and technology for the Fourth Review Conference of the Convention (to be held in November 2018), and are described herein, as are recommendations that the SAB submitted to the OPCW Director-General and the States Parties of the Convention. It is concluded that technologies exist or are under development that could be used for investigations, contingency, assistance and protection, reducing risks to inspectors, and enhancing sampling and analysis.

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials.

To evaluate the efficacy of reduced intensity conditioning (RIC) prior to allogeneic stem cell transplantation (alloSCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1), we retrospectively analyzed the outcome of 93 consecutive patients transplanted at our institution either following RIC ( n  = 37) or standard myeloablative conditioning (MAC) ( n  = 56) between 1999 and 2007. Projected overall survival (OS) or disease-free survival (DFS) for all patients at 1, 2, and 5 years was 78 or 70%, 65 or 57%, and 61 or 53% in the RIC group versus 73 or 70%, 68 or 62%, and 56 or 54% in the standard MAC group. In the subgroup of patients with an intermediate-risk karyotype projected OS at 1, 2, and 5 years was 86, 68, and 68% following RIC ( n  = 21) or 75, 69, and 66% following standard MAC ( n  = 36). Relapse or treatment-related mortality (TRM) was 15 or 17% (RIC group) and 26 or 14% (standard MAC group). Taken together, these data suggest that RIC-alloSCT may induce stable remissions in patients with AML transplanted in CR1. In particular, patients with an intermediate-risk karyotype ineligible to transplantation following standard MAC may benefit from RIC-alloSCT in CR1 at a low TRM.

The management of patients with chronic myeloid leukemia (CML) in advanced phases is challenging and requires the consideration of different treatment approaches, including targeted therapy with tyrosine kinase inhibitors, cytotoxic chemotherapy, and allogeneic stem cell transplantation. Here, we present the case of a patient with CML in mixed phenotype blast phase illustrating the integration of these strategies and demonstrating the need for close monitoring of treatment response in order to individually adjust treatment regimens.

Objectives Recent data debate the suitability of Helios, an Ikaros family member, as a marker for thymic-derived regulatory T cells (Treg). Nevertheless, Foxp3+ Helios+ Treg may be of particular relevance in mediating immune tolerance in chronic autoimmunity, such as systemic lupus erythematosus (SLE), as they possess enhanced suppressive function, compared to Foxp3+ Helios− Treg. Methods Multicolour flow cytometry was performed to analyse Foxp3 and Helios expression in peripheral blood CD4 T cells from SLE patients, compared to healthy controls (HC) and systemic sclerosis (SSc) and rheumatoid arthritis (RA) patients. Cytokine production, chemokine receptor expression for CXCR3 and CCR4, basal signal transducer and activator of transcription 5 (STAT5)a phosphorylation levels and T-cell receptor (TCR) Vβ repertoire were analysed by flow cytometry, and the methylation status of the Foxp3 locus (Treg-specific demethylated region, TSDR) by real-time PCR. Results Frequencies of Foxp3+ Helios+ Treg, unlike Foxp3+ Helios− T cells, were significantly increased in SLE patients and positively correlated with disease activity, whereas they were unaltered in SSc and RA patients. Compared to HC, Foxp3+ Helios+ Treg in SLE predominantly displayed a CD45RA−/CD31−/FoxP3low memory phenotype with increased Ki-67 expression, enhanced basal pSTAT5a levels and a restricted TCR repertoire. Nonetheless, similar to HC, Foxp3+ Helios+ Treg in SLE lacked effector cytokine production, possessed a highly demethylated TSDR and expressed comparable levels of CXCR3 and CCR4. Conclusions Our data suggest that Helios-expressing Foxp3+ Treg with functional suppressive capacity and migratory potential into inflamed tissues are expanded in active SLE, presumably through γ-chain signalling cytokines and TCR stimulation, to compensate for autoreactive effector responses.

To determine the usefulness of high-resolution three-dimensional (3D) gadolinium-enhanced magnetic resonance venography (MRV) in the evaluation of central venous thrombo-occlusive disease of the chest. Prospective study. University hospital. Sixteen consecutive patients with clinically suspected thrombosis of the superior vena cava, subclavian, brachiocephalic/innominate, internal jugular, or axillary veins. Thirteen patients had a neoplasm, two patients had a connective tissue disease, and one patient had a history of strenuous exercise. Twelve of 16 patients had prior central venous catheter placement. MRI was correlated with color-coded duplex sonography (CCDS) in 7 of 16 patients, digital subtraction angiography (DSA) in 3 of 16 patients, and CT in 2 of 16 patients. Contrast-enhanced MRV was performed in a total of 20 examinations. A 3D data set (gradient echo; time to repeat, 4.6 ms; time to echo, 1.8 ms; flip angle, 30°; time of acquisition, 23 s; 512 matrix/64 partitions; slice thickness, 1.5 mm) was acquired in the arterial and venous phase. Overall image quality was assessed on a 5-point scale. The presence, site, and extent of thrombus, as well as presence of an intravascular device, were determined. Overall image quality was rated very good (1 point) in 7 of 16 cases (44%) and good (2 points) in 9 of 16 cases (56%). Thrombus was detected in 16 of 16 patients, and complete extent of disease could be determined in 15 of 16 patients (94%). MRV did not miss any finding obtained by CCDS, DSA, or CT, and provided additional information in 6 of 16 examinations (38%). Contrast-enhanced MRV is a fast and reliable noninvasive procedure with excellent results regarding detection and determination of the extent of thrombo-occlusive disease of the chest veins.