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Changes in Chronic Graft-versus-Host Disease Treatment Over Time: A 15-Years Survey Within Allogeneic Hematopoietic Stem Cell Transplant Centers in Germany, Austria, and Switzerland
No full textBackground
Chronic graft-versus-host disease (cGVHD) represents a major complication after allogeneic stem cell transplantation (alloHSCT). In 2009 and 2018 a survey among German, Austrian, and Swiss transplant centers showed a homogeneous 1st-line treatment practice, while 2nd-line treatment as well as management of progressive onset type and bronchiolitis obliterans syndrome (BOS) displayed significant heterogeneity. Since the last survey, ruxolitinib (rux) has been approved and other new agents are explored in treatment of cGVHD.
Objective
We conducted a follow-up survey in 2024 to document the impact of recent approvals and new agents on treatment pattern focusing on management of 2nd-line treatment, progressive onset type, BOS, and sclerotic manifestations.
Study design
A paper-and-pencil-based questionnaire was sent electronically to 60 German speaking centers performing alloHSCT. 20 centers responded, representing 45% of the patients receiving an alloHSCT in 2023 in Germany, Austria, and Switzerland.
Results
In 1st-line treatment of classic standard risk cGVHD, single agent prednisone represents standard of care (14/20 centers) which may be combined with calcineurin inhibitor (CNI) (4/20), while rux is used in selected cases only. In 2nd-line treatment rux is now used by the majority of centers (19/20). In the presence of cytopenia, rux remains the preferred agent (12/20) while use of extracorporeal photopheresis (ECP) is considered by 8 of 20 centers. In case of active infections, ECP is preferred by 15 of 20 centers and both agents are regarded as steroid-sparing agents in 2nd-line treatment of steroid-dependent cGVHD. Rux would be applied in the presence of active infections by 5/20 centers only. Moreover, rux (15/20) and ECP (6/20) are also preferred treatment modalities in treatment of progressive onset cGVHD. For BOS, systemic and inhalative corticosteroids, montelukast and azithromycin (FAM, 13/20), rux (15/20), ECP (17/20) and CNI (10/20) are frequently applied agents, while abatacept (8/20), belumosudil (7/20), imatinib (5/20), mycophenolate mofetil (MMF) (5/20), everolimus (4/20) and ibrutinib (3/20) are used as salvage options in selected patients only. In case of new sclerotic manifestations after failure of 2nd-line treatment including steroids, CNI and rux, most centers would use ECP (14/20), whereas subsequent or alternative salvage treatment of sclerotic manifestations remains heterogenous comprising belumosudil (13/20), ibrutinib (5/20), imatinib (5/20), rituximab (4/20), cyclosporine (3/20), tacrolimus (3/20), everolimus (3/20), sirolimus (3/20), methotrexate (3/20) and MMF (3/20). The preferred taper sequence of immunosuppressive agents in case of response applied in 12/20 centers is initial taper of steroids, followed by taper of CNI and final termination of rux.
Conclusion
The survey documents the effect of evidence and approval on clinical care with single agent prednisone representing the standard of care in 1st-line treatment while rux combined with steroids defines the new standard for 2nd-line treatment of cGVHD. ECP is used in case of contraindication for rux and both agents are also used in progressive onset cGVHD. In contrast, treatment of BOS and sclerotic cGVHD beyond 2nd-line treatment remains heterogeneous with new agents being integrated in the treatment landscape
Screening for Borna disease virus 1 (BoDV-1) in Austria: Absence of human cases in a retrospective case-finding study
No full textBackground:
Borna disease virus 1 (BoDV-1) is a zoonotic virus with a recently confirmed potential to cause rare but severe cases of encephalitis in humans. While the bicolored white-toothed shrew (Crocidura leucodon), which represents the reservoir, is widely distributed over eastern, central, and southern Europe as well as south-west Asia, human infections have so far only been reported from Germany. As infections in sentinels such as horses indicate the endemic circulation of the virus also in circumscribed regions of neighboring countries (Austria, Liechtenstein, Switzerland), we initiated a retrospective case-finding study to investigate whether there were so far undetected human infections in Austria.
Methods:
For this purpose, biobank samples from the Center for Virology in Vienna were selected based on available clinical characteristics consistent with possible neurological symptoms of human BoDV-1 infections to be screened for BoDV-1 RNA (859 cerebrospinal fluid samples) and anti-BoDV-1 IgG antibodies (366 corresponding serum samples).
Results:
BoDV-1 RNA or confirmed anti-BoDV-1 IgG antibodies were not detected in any of the cerebrospinal fluid or serum samples, respectively.
Conclusion:
Our result demonstrates that if human BoDV-1 infections occur in Austria, they must be very rare even in patients with neurological symptoms. Further research using samples with a more distinct geographical link to the circumscribed endemic rural region in Upper Austria, however, will be necessary to complement the preliminary finding of this study
A fluorescent MTP‐based Detection Platform for Hydrogen Peroxide, Glucose, and Lactate
Full text linkHydrogen peroxide (H2O2) is an important small metabolite often quantified with commercially available multistep fluorescence-based assays. A new microtiter plate (MTP)-based platform that allows a rapid, one-step assay with a ratiometric readout function is developed. Specifically, 10-Acetyl-3,7-dihydroxyphenoxazine (ADHP) in a polyurethane-based hydrogel sensor membrane is embedded. For a ratiometric set-up, the membranes are loaded with polystyrene nanoparticles containing a Cy5-based reference which allowed for the compensation for variations in membrane thickness. These knife-coated µm-thin films are mounted onto bottomless MTPs with double-sided adhesive tape. Optimized membranes provide measurement times of 3 min upon sample addition and a limit of detection (LOD) in phosphate-buffered saline that is 10x lower than that of the ADHP-using Amplex Red commercial kit of 100 nmol L−1 H2O2. These ADHP hydrogels can be stored at room temperature for at least 22 months. Horseradish peroxidase (HRP) is nanospotted alone or together with either lactate oxidase or glucose oxidase for the detection of H2O2, lactate, and glucose, respectively. With 50 v% glycerol as cryoprotectant in the spotting solution, the HRP ADHP platform is stable for at least 13 weeks at –20 °C. Enhanced simplicity and comparable performance to multistep assays suggest that the platform can simplify MTP-based assays in the future
Elektronenspinresonanz an einzelnen Molekülen
Full text linkElektronenspinresonanz (ESR) ist eine weit verbreitete spektroskopische Methode zur Untersuchung von Systemen mit ungepaarten Elektronenspins, wie beispielsweise molekularen Radikalen. In der Regel sind viele Milliarden Spins erforderlich, um ein ESR-Signal zu erhalten, das dadurch einer starken Ensemblemittelung unterliegt. Das Herunterskalieren der ESR auf einzelne Moleküle ermöglicht es, die Signaturen der Moleküle einzeln zu messen – etwa bei Biomolekülen in ihrer natürlichen Umgebung. Die Einzelmolekül-ESR eröffnet mehrere neue Forschungsrichtungen, unter anderem im Bereich der Quantendetektion mit einem einzelnen Molekül. In den letzten Jahrzehnten wurden vier verschiedene Ansätze der Einzelmolekül-ESR entwickelt, die entweder auf optisch detektierter Magnetresonanz oder auf Rastersondenmikroskopie beruhen. Hier wird ein Überblick über diese vier Ansätze sowie deren Verwendung in wegweisenden Arbeiten vermittelt
Datenbanksysteme für Business, Technologie und Web (BTW 2025), 21. Fachtagung des GI-Fachbereichs ,,Datenbanken und Informationssysteme" (DBIS), 03.-07, März 2025, Bamberg, Germany, Proceedings
No full textNear-Infrared Spectroscopy Patterns as Indicator of Perioperative Stroke in Acute Type A Aortic Dissection
No full textNeurologic complications remain a major cause of morbidity in patients undergoing surgical repair of acute type A aortic dissection (ATAAD). Near-infrared spectroscopy (NIRS) is used for continuous, noninvasive monitoring of cerebral oxygenation during cardiopulmonary bypass; however, its utility in predicting perioperative stroke remains inadequately defined. A retrospective cohort study was conducted in 175 patients who underwent ATAAD repair between 2015 and 2023. Patients were stratified by the occurrence of perioperative stroke (n = 47, 26.9%). Intraoperative NIRS data, including cerebral regional oxygen saturation (crSO2) values at key procedural timepoints and signal variability with band power and crest factor, were analyzed in conjunction with demographic, anatomic, and postoperative variables. Patients with stroke exhibited significantly lower minimum NIRS values during deep hypothermic circulatory arrest (DHCA) (left: 46.7 (15.7–69.4) vs. 52.2 (22.0–81.6); right: 47.0 (23.3–78.5) vs. 56.3 (20.2–85.0); p = 0.03 and p < 0.01). Within the stroke group, NIRS signal variability was significantly greater (crest factor and standard deviation; p < 0.05) and showed blunted recovery post-DHCA. crSO2 values below 50% were more frequent in the stroke group (p = 0.04). Right common carotid artery dissection was more prevalent in the stroke group (40% vs. 23%, p = 0.04). ICU length of stay was significantly increased in patients with stroke. Cerebral desaturation and NIRS signal instability during DHCA are significantly associated with perioperative stroke in ATAAD repair. These findings support the prognostic value of intraoperative cerebral oximetry in detecting critical ischemic thresholds and identifying at-risk perfusion patterns
Retrospektive Evaluation der verschiedenen radiologisch-interventionellen Behandlungsoptionen der akuten Pfortaderthrombose
No full textDie akute PVT ist eine seltene Gefäßerkrankung. Die Datenlage zur optimalen Behandlungsstrategie ist spärlich und ein Vergleich mit der Literatur ist aufgrund der geringen Patientenzahlen nur mit Vorbehalt möglich.
In der Zusammenschau aller Ergebnisse lässt sich feststellen, dass momentan noch kein einheitliches Protokoll für die Therapie der akuten PVT verfasst wurde. Die Literatur ist geteilter Meinung: Einige Studien empfehlen eine TIPSS-Anlage mit mechanischer Thrombektomie oder direkter Thrombolyse, denn diese führen schnell zu sichtbaren Erfolgen und lindern sofort die Symptome; andere Studien warnen jedoch vor den Blutungskomplikationen und entscheiden sich lieber für die bewährte gefahrlosere konservative Antikoagulationstherapie (Wang et al., 2010; Chawla et al., 2009). Außerdem deuten andere Ergebnisse darauf hin, dass eine kombinierte Behandlung die besten Erfolge liefert (Hollingshead et al., 2005; Zhang et al., 2021). Weitere Autoren vertreten die Meinung, dass eine interventionelle thrombolytische Therapie aufgrund des erhöhten Blutungsrisikos ausschließlich bei multimorbiden Patienten durchgeführt werden sollte (Chawla et al., 2009; Manzano-Robleda et al., 2015; Kumar et al., 2015).
In unserer Studie wurden die unterschiedlichen radiologisch-interventionellen Behandlungsoptionen eingehender beleuchtet. Eine komplette Rekanalisation durch den TIPSS oder die Lysebehandlung erfolgte bei 18,2% der Erkrankten. Überdies machte die Offenheitsrate des TIPSS 66,7% aus. Peri- und postinterventionelle Komplikationen kamen bei 36,4% der Patienten vor. Außerdem lag die 1-Jahres-Überlebensrate bei 86,4%, die 5-Jahres-Überlebensrate bei 77,3% und es verstarb nur ein Patient infolge der Intervention.
Zusammenfassend stellen die verschiedenen endovaskulären Verfahren zur Behandlung der akuten PVT eine vielversprechende Alternative zur Antikoagulation dar, wobei die erhöhte Erfolgsquote mit einem höheren periinterventionellen Komplikationsrisiko einhergeht
Multiplexed immune profiling and 3D co-culture assays to assess the individual checkpoint therapy response in head and neck squamous cell carcinoma
No full textBackground: Immune checkpoint inhibitors (ICIs) have become an integral part of cancer therapy, but only a minority of patients experience durable responsiveness. Response rates vary greatly and are often unpredictable, highlighting the urgent need for predictive biomarkers to guide treatment decisions.
Methods: We investigated immune- and tumor-specific expression and secretion profiles in peripheral blood and tumor samples derived from patients with head and neck squamous cell carcinoma (HNSCC). We combined flow cytometry, LEGENDplex™ immune profiling, and preoperative/postoperative serum cytokine analyses to determine checkpoint molecules (e.g., PD-1, TIM-3, LAG-3), immune cell profiles, as well as key markers on tumor cells (CD44, PD-L1, MHC class I/II). In addition, a 3D co-culture model using tumor slices and autologous mononuclear cells from selected HNSCC patients were analyzed upon atezolizumab and pembrolizumab treatment.
Results: Co-expression of PD-1 and TIM-3 on a subset of CD8+ tumor-infiltrating T cells was frequently observed, alongside a pronounced infiltration of myeloid cells in the tumor microenvironment. In the peripheral blood, we detected elevated levels of soluble CD27 in patients compared to controls and distinct preoperative cytokine profiles (e.g., reduced IFN-γ, CCL3, CCL20; elevated IL-15/IL-16). Postoperatively, most cytokines showed lower levels compared to healthy controls but significantly higher CCL2 levels. Furthermore, tumor–immune co-cultures from selected patients showed a stronger apoptotic response and phenotypic differences (e.g., increased PD-1 and CD137 expression) upon atezolizumab treatment. Individual changes in soluble factor release (e.g., Gal-9, sPD-L1, sCD25, and sTIM-3) was noticeable upon co-culture under immune checkpoint therapy.
Conclusions: This study provides proof-of-principle data suggesting that a combined multiplexed marker profiling and a functional 3D co-culture assay may help to explore predictive ICI response for HNSCC patients in the future. However, extensive studies with larger cohorts are warranted to validate and refine this approach
The Religion-Based Reconciliation. How the Clergy Uses Religion for Peacebuilding. A Case Study of Ex-Yugoslav Conflicts, 1991-2018
No full textNumerous interreligious dialogue and peace organisations promote the role of religion and clerics in peacebuilding and post-conflict reconciliation. Historically, there has been scepticism toward religious peacebuilding, since religious institutions and figures have sometimes contributed negatively through hate speech, warmongering, or political instrumentalisation. Yet this does not mean that religious actors, institutions, rituals, and values cannot be mobilised for peace. Religion has functioned both as divider and connector in the peacebuilding processes of ex-Yugoslav countries. Theological language, however, rarely resonates with local communities, which means peacebuilding relies more on clerics’ personal commitment to a peace narrative. Absolutist statements or ambiguity can hinder dialogue, even though clergy typically condemn violence despite “just war” precedents in their traditions.
Case studies from Bosnia and Herzegovina, Kosovo, and Macedonia show dynamic grassroots initiatives, often described as the Dialogue of Life. These activities foster connectedness in divided societies. Such efforts seek to position religion as a discourse that raises crucial questions and provides community bridges. Their success depends largely on whether religious institutions can sustain authority and legitimacy in the future. Yet religious communities remain tied to ethnic territories and political parties, often reflecting nationalist rhetoric and historical divisions. Peacebuilding efforts are frequently confined to enclaves, separated from broader political and social movements. Clerics sometimes collaborate with political parties to strengthen partisanship, while those engaging with NGOs or pursuing independent initiatives risk marginalisation or punishment from their authorities.
Among interreligious initiatives, only the Interreligious Council of Bosnia and Herzegovina has developed a substantial organisational structure with local branches. While similar councils exist in Kosovo and Macedonia, they have been less effective. In all three contexts, high-level clerics publicly affirm peacebuilding, though their statements often remain general and shaped by political conditions. Local-level engagement varies: some boards run numerous projects, others struggle. This raises the question of whether these structures truly advance reconciliation. Dialogue is often treated as the mere exchange of positions rather than a process of mutual learning. When consensus is absent, dialogue breaks down, reflecting persistent distrust. Training in dialogue skills remains a pressing need. A further obstacle is “religious-centric” defensiveness, in which participants speak primarily from the perspective of protecting their own tradition. This creates barriers for others and undermines deeper trust.
Clerics in the case studies tend to remain in the “harmony” stage of dialogue, avoiding difficult or contentious issues. Yet post-conflict societies entrenched in negative peace cannot remain indefinitely in a harmony model. To move toward reconciliation, they must adopt approaches closer to conflict or liberation models, engaging political action and critical confrontation of differences. Otherwise, spoilers may dismiss interreligious dialogue as ineffective, claiming that it merely reduces tension without generating tangible change. Dialogue can then become an excuse to avoid further engagement, especially when slow progress benefits the status quo. While religious peacebuilding has reduced animosity and built some connections, it has yet to fulfil its potential in the post-Yugoslav context.
Historically, there has been scepticism toward religious peacebuilding, since religious institutions and figures have sometimes contributed negatively through hate speech, warmongering, or political instrumentalisation. Yet this does not mean that religious actors, institutions, rituals, and values cannot be mobilised for peace. Religion has functioned both as divider and connector in the peacebuilding processes of ex-Yugoslav countries. While institutions often reinforce ethnoreligious identities, peacebuilding activities may transform these identities, emphasising coexistence. Theological language, however, rarely resonates with local communities, which means peacebuilding relies more on clerics’ personal commitment to a peace narrative. Absolutist statements or ambiguity can hinder dialogue, even though clergy typically condemn violence despite “just war” precedents in their traditions