CO2-Emissionen im Personenverkehr: Einfluss von Soziodemographie, Wohnort und Einkommen

Für verschiedene Bevölkerungsgruppen wurde untersucht, welchen Einfluss Soziodemografie, Wohnort und Einkommen auf die durchschnittlichen jährlichen CO2-Emissionen haben. Die Analysen zeigen, dass die durchschnittlichen CO2-Emissionen von Stadt- und Landbevölkerung nahezu identisch sind, jedoch mit dem Haushaltseinkommen ansteigen. Datengrundlage der detaillierten Analysen zu den CO2-Emissionen im Personenverkehr ist ein Datensatz, der die Gesamtmobilität der in Deutschland lebenden Bevölkerung umfasst, d. h. alle Verkehrsmodi sowie Wege und Fahrten im In- und Ausland

Pharmacogenetic analysis of liver toxicity after busulfan/cyclophosphamide-based allogeneic hematopoietic stem cell transplantation

Unlabelled: THE AIM of this study was to evaluate the impact of genomic polymorphisms of methylene-tetrahydrofolate-reductase (MTHFR-C677T, MTHFR-A1298C) and various glutathione S-transferases (GSTP1-Ilel05Val, GSTA1*a/b, GSTM1, GSTT1) on the occurrence of liver toxicity in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Patients and methods: Eighty-four adult patients were enrolled in this retrospective study. All patients were treated with busulfan/cyclophosphamide as a conditioning regimen and received cyclosporine and short-course MTX for GvHD prophylaxis. Genotyping was performed using PCR based restriction-fragment-length-polymorphism (RFLP) techniques. Results: Multivariate analysis identified the MTHFR-A1298C polymorphism as an independent predictor for maximum levels of bilirubin (p=0.0025) and duration of hyperbilirubinaemia (p=0.013). Furthermore, there was an association between this polymorphism and the occurrence of the sinusoidal obstruction syndrome (SOS) (p=0.048). No significant associations between the MTHFR-C677T or the various GST polymorphisms and liver toxicity were observed. Conclusion: The MTHFR-A1298C polymorphism might be associated with liver toxicity in patients receiving allogeneic HSCT

EXACT: a collaboration toolset for algorithm-aided annotation of images with annotation version control

In many research areas, scientific progress is accelerated by multidisciplinary access to image data and their interdisciplinary annotation. However, keeping track of these annotations to ensure a high-quality multi-purpose data set is a challenging and labour intensive task. We developed the open-source online platform EXACT (EXpert Algorithm Collaboration Tool) that enables the collaborative interdisciplinary analysis of images from different domains online and offline. EXACT supports multi-gigapixel medical whole slide images as well as image series with thousands of images. The software utilises a flexible plugin system that can be adapted to diverse applications such as counting mitotic figures with a screening mode, finding false annotations on a novel validation view, or using the latest deep learning image analysis technologies. This is combined with a version control system which makes it possible to keep track of changes in the data sets and, for example, to link the results of deep learning experiments to specific data set versions. EXACT is freely available and has already been successfully applied to a broad range of annotation tasks, including highly diverse applications like deep learning supported cytology scoring, interdisciplinary multi-centre whole slide image tumour annotation, and highly specialised whale sound spectroscopy clustering

Improving tuberculosis surveillance by detecting international transmission using publicly available whole genome sequencing data

Improving the surveillance of tuberculosis (TB) is one of the eight core activities identified by the World Health Organization (WHO) and the European Respiratory Society to achieve TB elimination, defined as less than one incident case per million [1]. Monitoring transmission is especially important for multidrug-resistant (MDR) Mycobacterium tuberculosis isolates – defined as being resistant to rifampicin and isoniazid – and for extensively drug-resistant (XDR) M. tuberculosis isolates – defined as MDR isolates with additional resistance to at least one of the fluoroquinolones and at least one of the second-line injectable drugs. In 2017, the WHO estimated that worldwide more than 450,000 people fell ill with MDR-TB and among these, more than 38,000 fell ill with XDR-TB [2]. The rapid advance in molecular typing technology – especially the availability of whole genome sequencing (WGS) to identify and characterise pathogens – gives us the chance to integrate this information into disease surveillance. For TB surveillance, it is possible to combine the results of molecular typing of isolates from the M. tuberculosis complex with traditional epidemiological information to infer or to exclude TB transmission [3,4]. This is of particular relevance if transmission occurs among multiple countries, where epidemiological data such as social contacts are more difficult to get and where data exchange is more difficult to organise. The European Centre for Disease Prevention and Control (ECDC) reported 44 events of international transmission (international clusters) of MDR-TB in different European countries between 2012 and 2015 [5]. In that report, the authors inferred TB transmission using the mycobacterial interspersed repetitive units variable number of tandem repeats (MIRU-VNTR) typing method. However, this method has limitations such as low correlation with epidemiological information in outbreak settings and low discriminatory power [3,6]. In comparison, WGS analysis offers a much higher discriminatory power and allows inferring (or excluding) TB transmission at a higher resolution [4]. In a recent systematic review, van der Werf et al. identified three studies that used WGS to investigate the international transmission of TB [7]. In recent years, the amount of available WGS data is increasing, especially because sequencing has become cheaper [8]. In addition, more and more authors deposit the raw data of their projects in open access public repositories such as the Sequence Read Archive (SRA) of the National Center for Biotechnology Information (NCBI) [9]. These publicly available raw WGS data for thousands of isolates enable the re-use and the additional analyses at a large and global scale [10]. For example, it is possible to compare genomic data among different studies or countries since the data are available in a single place. Moreover, new software tools can be tested using the same raw WGS data [11]. However, standards in bioinformatics analysis and interpretation of these WGS data for surveillance purposes are not yet fully established [12]. We aimed to assess the usefulness of raw WGS data of global MDR/XDR M. tuberculosis isolates available in public repositories to improve TB surveillance. Specifically, we wanted to identify potential international events of TB transmission and to compare the international isolates with a collection of M. tuberculosis isolates collected in Germany in 2012 and 2013.Peer Reviewe

Major central nervous system complications after allogeneic stem cell transplantation: A large retrospective study on 888 consecutive adult patients.

AbstractObjectivesMajor complications affecting the central nervous system (CNS) present a challenge after allogeneic stem cell transplantation (allo‐SCT).MethodsIncidence, risk factors, and outcome were retrospectively analyzed in 888 patients in a monocentric study.ResultsCumulative incidence (CI) of major CNS complications at 1 year was 14.8% (95%CI 12.3%‐17.2%). Median follow‐up is 11 months. CNS complications were documented in 132 patients: in 36 cases, classified metabolic; 26, drug‐related neurotoxicity (14 attributed to cyclosporine A, 4 to antilymphocyte globulin); 11, cerebrovascular (ischemic n = 8, bleeding n = 3); 9, infections; 9, psychiatric; and 9, malignant. The cause of CNS symptoms remained unclear for 37 patients (28%). Multivariate analysis demonstrated an association of CNS complication with patient age (P < .001). The estimated OS of patients with any CNS complication was significantly lower than in patients without neurological complications (P < .001), and the CI of non‐relapse mortality (NRM) was higher for patients with CNS complication (P < .001). A significant negative impact on survival can only be demonstrated for metabolic CNS complications and CNS infections (NRM, P < .0001 and P = .0003, respectively), and relapse (P < .0001).ConclusionCNS complications after allo‐SCT are frequent events with a major contribution to morbidity and mortality. In particular, the situations of unclear neurological complications need to be clarified by intensive research

Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis

Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against coronavirus disease 2019 (COVID-19), especially in fragile patients. We aimed to systematically analyze the outcomes of patients with hematological malignancies who received vaccination and to identify specific groups with differences in outcomes. The primary end point was antibody response after full vaccination (2 doses of mRNA or one dose of vectorbased vaccines). We identified 49 studies comprising 11,086 individuals. Overall risk of bias was low. The pooled response for hematological malignancies was 64% (95% confidence interval [CI]: 59-69; I²=93%) versus 96% (95% CI: 92-97; I²=44%) for solid cancer and 98% (95% CI: 96-99; I²=55%) for healthy controls (P<0.001). Outcome was different across hematological malignancies (P<0.001). The pooled response was 50% (95% CI: 43-57; I²=84%) for chronic lymphocytic leukemia, 76% (95% CI: 67-83; I²=92%) for multiple myeloma, 83% (95% CI: 69-91; I²=85%) for myeloproliferative neoplasms, 91% (95% CI: 82-96; I²=12%) for Hodgkin lymphoma, and 58% (95% CI: 44-70; I²=84%) for aggressive and 61% (95% CI: 48-72; I²=85%) for indolent non-Hodgkin lymphoma. The pooled response for allogeneic and autologous hematopoietic cell transplantation was 82% and 83%, respectively. Being in remission and prior COVID-19 showed significantly higher responses. Low pooled response was identified for active treatment (35%), anti-CD20 therapy ≤1 year (15%), Bruton kinase inhibition (23%), venetoclax (26%), ruxolitinib (42%), and chimeric antigen receptor T-cell therapy (42%). Studies on timing, value of boosters, and long-term efficacy are needed. This study is registered with PROSPERO (clinicaltrials gov. Identifier: CRD42021279051)

Comparison of immune reconstitution between anti-T-lymphocyte globulin and posttransplant cyclophosphamide as acute graft-versus-host disease prophylaxis in allogeneic myeloablative peripheral blood stem cell transplantation

Anti-T-cell lymphocyte globulin (ATLG) and posttransplant cyclophosphamide (PTCy) are now widely used strategies to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Data comparing immune reconstitution (IR) between ATLG and PTCy is scarce. This retrospective study conducted at the University Medical Center Hamburg-Eppendorf (UKE) compares PTCy (n=123) and ATLG (n=476) after myeloablative allogeneic peripheral blood stem cell transplant. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100 and 180 posttransplant. Incidence of infections, viral reactivations, GVHD and relapse were collected. Neutrophil engraftment was significantly delayed in the PTCy group (median day 12 vs. day 10, P<0.001) with a high incidence of infection before day+100 in the PTCy arm but a higher Epstein-Barr virus reactivation in the ATLG arm and comparable cytomegalovirus reactivation. Overall incidence of acute GVHD was similar but moderate/severe chronic GVHD was seen more often after PTCy (44% vs. 38%, P=0.005). ATLG resulted in a faster reconstitution of CD8+ T, NK, NKT and gdT cells while CD4 T cells and B cells reconstituted faster after PTCy. Similar reconstitution was observed for T-regulatory cells and B cells. Non-relapse mortality relapse incidence, disease-free survival, and overall survival did not differ significantly between both arms. Even though differences in IR were related to a decreased incidence of infection and moderate/severe cGVHD in the ATLG group they had no impact on any of the other long-term outcomes. However, it remains undetermined which regimen is better as GVHD prophylaxis

Impact of the NK Cell Receptor LIR-1 (ILT-2/CD85j/LILRB1) on Cytotoxicity against Multiple Myeloma

The role of different receptors in natural-killer- (NK-) cell-mediated cytotoxicity against multiple myeloma (MM) cells is unknown. We investigated if an enhancement of NK-cell-mediated cytotoxicity against MM could be reached by blocking of the inhibitory leukocyte immunoglobulin-like receptor 1 (LIR-1). Our investigations revealed high levels of LIR-1 expression not only on the NK cell line NK-92, but also on myeloma cells (MOLP-8, RPMI8226) as well as on a lymphoblastoid cell line (LBCL; IM-9). Subsequent cytotoxicity assays were designed to show the isolated effects of LIR-1 blocking on either the effector or the tumor side to rule out receptor-receptor interactions. Although NK-92 was shown to be capable of myeloma cell lysis, inhibition of LIR-1 on NK-92 did not enhance cytotoxicity. Targeting the receptor on MM and LBCL did not also alter NK-92-mediated lysis. We come to the conclusion that LIR-1 alone does not directly influence NK-cell-mediated cytotoxicity against myeloma. To our knowledge, this work provides the first investigation of the inhibitory capability of LIR-1 in NK-92-mediated cytotoxicity against MM and the first functional evaluation of LIR-1 on MM and LBCL

HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation

The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large cohort of German patients and their donors for HLA-DRB3/4/5 compatibility and to correlate the HLA-DRB3/4/5 matching status with the outcome of unrelated hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their respective donors were HLA-DRB3/4/5 and HLA-DPB1 typed by amplicon-based nextgeneration sequencing (NGS). All patients included received their first allogeneic transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in the antigen recognition domain (ARD) of HLA-DRB3/4/5 genes were correlated with clinical outcome. HLA-DRB3/4/5 incompatibility was seen in 12.5% (n = 296) and 17.8% (n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively. HLA-DRB3/4/5 mismatches in the ARD associated with a worse overall survival (OS), as shown in univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses [hazard ratio (HR) 1.25, 95% CI 1.02–1.54, p = 0.034] in the otherwise 10/10 HLAmatched subgroup. The worse outcome was mainly driven by a significantly higher nonrelapse mortality (HR 1.35, 95% CI 1.05–1.73, p = 0.017). In the 9/10 HLA-matched cases, the effect was not statistically significant. Our study results suggest that mismatches within the ARD of HLA-DRB3/4/5 genes significantly impact the outcome of otherwise fully matched uHSCT and support their consideration upon donor selection in the future