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Risk factors associated with complications of palliative drainage of ascites with tunneled peritoneal catheters
Full text linkBackground: Medically intractable ascites causes substantial distress in patients with palliative disease. Tunneled peritoneal catheters have been established as a feasible treatment option allowing patient-controlled paracentesis in a homecare setting. However, while a range of complications is associated with these drainages, risk factors for complications have not been identified so far. Objectives: To explore potential risk factors associated with complications of tunneled peritoneal catheters. Design: Retrospective observational cohort study. Methods: Single-center cohort comprising 49 patients with palliative disease receiving 57 tunneled peritoneal catheters at a tertiary care hospital. Results: Catheter placement was successful in all patients and associated with low numbers of severe complications. Our data suggest a higher risk for severe late complications in patients with benign disease, with drainage replacement, and when performed by less experienced physicians. Conclusion: Tunneled peritoneal catheters are an effective and safe option to treat symptomatic ascites in patients with end-stage palliative disease. The indication should be carefully considered in patients with benign disease and after removal or dislocation of a previous catheter
Harnessing naturally occurring mutations for T-cell therapy: a potential new avenue to enhance treatment efficacy
Full text linkKS is supported by grants from the German Federal Ministry of Education and Research (BMBF, project-IDs 01KI2013 and 031L0290B), the Else Kröner-Fresenius-Stiftung (project-ID 2020_EKEA.127), the German Research Foundation (DFG) through the research training group RTG 2504 (project-ID 401821119), the Interdisciplinary Center for Clinical Research of the University Hospital of Erlangen (project-ID A98) and the European Union (Yellow4FLAVI consortium, project-ID 101137459). JR is supported by grants from the German Research Foundation (DFG) (project-ID 210592381 – SFB 1054, project-ID 395357507 – SFB 1371, project-ID 369799452 – TRR 237, project-ID 452881907 – TRR 338, project-ID 435874434 – RTG 2668, RU 695/12-1), The Leukemia & Lymphoma Society, and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 834154).JR is supported by grants from the German Research Foundation (DFG) (project-ID 210592381 – SFB 1054, project-ID 395357507 – SFB 1371, project-ID 369799452 – TRR 237, project-ID 452881907 – TRR 338, project-ID 435874434 – RTG 2668, RU 695/12-1), The Leukemia & Lymphoma Society, and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 834154)
Profiling with trust: system monitoring from trusted execution environments
Full text linkLarge-scale attacks on IoT and edge computing devices pose a significant threat. As a prominent example, Mirai is an IoT botnet with 600,000 infected devices around the globe, capable of conducting effective and targeted DDoS attacks on (critical) infrastructure. Driven by the substantial impacts of attacks, manufacturers and system integrators propose Trusted Execution Environments (TEEs) that have gained significant importance recently. TEEs offer an execution environment to run small portions of code isolated from the rest of the system, even if the operating system is compromised. In this publication, we examine TEEs in the context of system monitoring and introduce the Trusted Monitor (TM), a novel anomaly detection system that runs within a TEE. The TM continuously profiles the system using hardware performance counters and utilizes an application-specific machine-learning model for anomaly detection. In our evaluation, we demonstrate that the TM accurately classifies 86% of 183 tested workloads, with an overhead of less than 2%. Notably, we show that a real-world kernel-level rootkit has observable effects on performance counters, allowing the TM to detect it. Major parts of the TM are implemented in the Rust programming language, eliminating common security-critical programming errors.Open Access funding enabled and organized by Projekt DEAL.Bundesministerium für Bildung und Forschunghttp://dx.doi.org/10.13039/501100002347Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659Ruhr-Universität Bochum (1007
Association of interictal epileptiform discharges and serum concentration of levetiracetam and lamotrigine
Full text linkBackground Interictal epileptiform discharges (IEDs) are an electrographic biomarker of epilepsy. Despite their crucial role in diagnosing epilepsy, heterogeneous findings exist on the mechanisms underlying their occurrence and the effects of anti-seizure medications (ASMs) on IEDs. Methods We conducted a study to investigate the association between IED frequency and the serum concentration of two commonly used ASMs, levetiracetam (LEV) and lamotrigine (LTG). We included 56 patients undergoing a continuous video EEG monitoring in our center with tapering of ASM. IED frequency was analyzed using automated and semiautomated methods and serum samples were collected sequentially throughout the stay. Results The cohort consisted of 41 patients (23 female, 18 male), between 19 and 64 years (mean 37.42 years), most of which were diagnosed with focal epilepsy (93%). IED frequency increased after ASM reduction revealing a negative correlation similarly with LEV and LTG serum concentrations ( p = 0.0057 and p = 0.0426, respectively). Discussion Notably, we observed a significant increase in IED frequency following dose reduction or discontinuation of both medications. This effect was reversed after ASM were re-dosed. This may indicate the suppressive properties of LEV and LTG against epileptic seizures. Furthermore, our study highlights the importance of ASM discontinuation, which may be required for capturing IEDs during diagnostic continuous EEG monitoring, and not be fully explained by circadian or ultradian rhythms alone. Conclusion Our findings contribute to the understanding of ASM effects on IED frequency dynamics and suggest seizure suppressive properties of LEV and LTG
Census-based estimates of Mediterranean Oligocene–Miocene reef carbonate production
Full text linkCensus-based approaches to reefal carbonate budgets are increasingly being used to project the near-future fate of tropical coral reefs. Some of the census parameters are difficult to achieve in fossil reef systems, which may be the reason why no census-based estimates of fossil reef carbonate production have been published until now. Here, we apply a census-based estimate of gross carbonate production in two reef systems from southeastern Italy to (1) test if reasonable estimates are possible and (2) assess the variability of carbonate production rates over time and reef environment. We confirm that estimates of late Oligocene and late Miocene reef gross carbonate production are within the range of modern coral reefs with the late Oligocene reef front showing the greatest carbonate production (6.1 ± 1.3 kg CaCO3 m−2 year−1) and the late Miocene reef front exhibiting the lowest production (1.7 ± 0.5 kg CaCO3 m−2 year−1). The decline of reef carbonate production from the Oligocene to the Miocene is accompanied by a decline of reef builder biodiversity but driven by the lower coral cover and coral growth rates in the Miocene. The decline of reefal carbonate production may be related to late Cenozoic cooling.Open Access funding enabled and organized by Projekt DEAL.Open Access funding enabled and organized by Projekt DEAL.Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659EUFriedrich-Alexander-Universität Erlangen-Nürnberg (1041
Comparison of the transcriptome, lipidome, and c-di-GMP production between BCGΔBCG1419c and BCG, with Mincle- and Myd88-dependent induction of proinflammatory cytokines in murine macrophages
Full text linkWe have previously reported the transcriptomic and lipidomic profile of the first-generation, hygromycin-resistant (Hyg R ) version of the BCGΔBCG1419c vaccine candidate, under biofilm conditions. We recently constructed and characterized the efficacy, safety, whole genome sequence, and proteomic profile of a second-generation version of BCGΔBCG1419c, a strain lacking the BCG1419c gene and devoid of antibiotic markers. Here, we compared the antibiotic-less BCGΔBCG1419c with BCG. We assessed their colonial and ultrastructural morphology, biofilm, c-di-GMP production in vitro, as well as their transcriptomic and lipidomic profiles, including their capacity to activate macrophages via Mincle and Myd88. Our results show that BCGΔBCG1419c colonial and ultrastructural morphology, c-di-GMP, and biofilm production differed from parental BCG, whereas we found no significant changes in its lipidomic profile either in biofilm or planktonic growth conditions. Transcriptomic profiling suggests changes in BCGΔBCG1419c cell wall and showed reduced transcription of some members of the DosR, MtrA, and ArgR regulons. Finally, induction of TNF-α, IL-6 or G-CSF by bone-marrow derived macrophages infected with either BCGΔBCG1419c or BCG required Mincle and Myd88. Our results confirm that some differences already found to occur in Hyg R BCGΔBCG1419c compared with BCG are maintained in the antibiotic-less version of this vaccine candidate except changes in production of PDIM. Comparison with previous characterizations conducted by OMICs show that some differences observed in BCGΔBCG1419c compared with BCG are maintained whereas others are dependent on the growth condition employed to culture them.BAYLA
A retrospective, multicentric, nationwide analysis of the impact of splenectomy on survival of pancreatic cancer patients
Full text linkObjective Splenectomy is regularly performed in total and distal pancreatectomy due to technical reasons, lymph node dissection and radicality of the operation. However, the spleen serves as an important organ for competent immune function, and its removal is associated with an increased incidence of cancer and a worse outcome in some cancer entities (Haematologica 99:392–398, 2014 ; Dis Colon Rectum 51:213–217, 2008 ; Dis Esophagus 21:334–339, 2008 ). The impact of splenectomy in pancreatic cancer is not fully resolved (J Am Coll Surg 188:516–521, 1999 ; J Surg Oncol 119:784–793, 2019 ). Methods We therefore compared the outcome of 193 pancreatic cancer patients who underwent total or distal pancreatectomy with (Sp) or without splenectomy (NoSp) between 2015 and 2021 using the StuDoQ|Pancreas registry of the German Society for General and Visceral Surgery. In addition, we integrated our data into the existing literature in a meta-analysis of studies on splenectomy in pancreatic cancer patients. Results There was no difference between the Sp and NoSp groups regarding histopathological parameters, number of examined or affected lymph nodes, residual tumor status, or postoperative morbidity and mortality. We observed a significantly prolonged survival in pancreatic cancer patients who underwent total pancreatectomy, when a spleen-preserving operation was performed (median survival: 9.6 vs. 17.3 months, p = 0.03). In this group, splenectomy was identified as an independent risk factor for shorter overall survival [HR (95%CI): 2.38 (1.03 – 6.8)]. In a meta-analysis of the existing literature in combination with our data, we confirmed splenectomy as a risk factor for a shorter overall survival in pancreatic cancer patients undergoing total pancreatectomy, distal pancreatectomy, or pancreatic head resection [HR (95%CI): 1.53 (1.11 – 1.95)]. Conclusion Here, we report on a strong correlations between removal of the spleen and the survival of pancreatic cancer patients undergoing total pancreatectomy. This should encourage pancreatic surgeons to critically assess the role of splenectomy in total pancreatectomy and give rise to further investigations.Open Access funding enabled and organized by Projekt DEAL.Technische Universität München (1025
Metabolic rewiring controlled by HIF-1α tunes IgA-producing B-cell differentiation and intestinal inflammation
Full text linkGerminal centers where B cells undergo clonal expansion and antibody affinity maturation are hypoxic microenvironments. However, the function of hypoxia-inducible factor (HIF)-1α in immunoglobulin production remains incompletely characterized. Here, we demonstrated that B cells lacking HIF-1α exhibited significantly lower glycolytic metabolism and impaired IgA production. Loss of HIF-1α in B cells affects IgA-producing B-cell differentiation and exacerbates dextran sodium sulfate (DSS)-induced colitis. Conversely, promoting HIF-1α stabilization via a PHD inhibitor roxadustat enhances IgA class switching and alleviates intestinal inflammation. Mechanistically, HIF-1α facilitates IgA class switching through acetyl-coenzyme A (acetyl-CoA) accumulation, which is essential for histone H3K27 acetylation at the Sα region. Consequently, supplementation with acetyl-CoA improved defective IgA production in Hif1a -deficient B cells and limited experimental colitis. Collectively, these findings highlight the critical importance of HIF-1α in IgA class switching and the potential for targeting the HIF-1α-dependent metabolic‒epigenetic axis to treat inflammatory bowel diseases and other inflammatory disorders
Investigation of iron oxide nanoparticle formation in a spray-flame synthesis process using laser-induced incandescence
Full text linkIn this work, iron-oxide nanoparticle formation in the spray-flame synthesis (SFS) process of the standardized SpraySyn 2.0 burner was investigated in situ using laser-induced incandescence (LII). For the evaluation of these measurements, prior LII-experiments within iron-oxide aerosols (Fe3O4 and α-Fe2O3) with known primary particle size distribution and morphological properties were performed to determine the thermal accommodation coefficient (TAC) α, which led to approx. α = 0.08. The applicability of the TAC results within the flame was validated using spectrally and temporally resolved measurements in the flame at 65 mm HAB employing a spectrograph. Data for a bimodal particle size distribution, obtained from Transmission Electron Microscopy (TEM), were used in the LII-evaluation. The validated TAC was then used to evaluate the primary particle size evolution from in situ Time-Resolved (TiRe) LII-measurements using PMTs along the centre axis of the burner, ranging from 10 mm to 50 mm HAB. These measurements reveal a relatively constant effective particle diameter along HAB with dp,eff ≈ 300 nm. To further investigate particle formation in SFS, 2-dimensional time-resolved LII-measurements in the SFS flame were performed, showing a clear particle formation region up to approx. 30 mm HAB, from where on a constant particle mass is observed.Open Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
Plastics in the environment in the context of UV radiation, climate change and the Montreal Protocol: UNEP Environmental Effects Assessment Panel, Update 2023
Full text linkThis Assessment Update by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) considers the interactive effects of solar UV radiation, global warming, and other weathering factors on plastics. The Assessment illustrates the significance of solar UV radiation in decreasing the durability of plastic materials, degradation of plastic debris, formation of micro- and nanoplastic particles and accompanying leaching of potential toxic compounds. Micro- and nanoplastics have been found in all ecosystems, the atmosphere, and in humans. While the potential biological risks are not yet well-established, the widespread and increasing occurrence of plastic pollution is reason for continuing research and monitoring. Plastic debris persists after its intended life in soils, water bodies and the atmosphere as well as in living organisms. To counteract accumulation of plastics in the environment, the lifetime of novel plastics or plastic alternatives should better match the functional life of products, with eventual breakdown releasing harmless substances to the environment.Open Access funding enabled and organized by CAUL and its Member InstitutionsMurdoch Universit