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Objective: To report outcomes from routine clinical practice of liver transplantation (LT) following normothermic liver machine perfusion (NLMP) and compare to LT after static cold storage (SCS)., Background: NLMP is emerging as a clinical routine in LT as has recently received renewed attention, however outcomes outside of clinical trials are lacking., Methods: All adult LT between February 2018 and January 2023 were included. Comprehensive viability assessment was applied during NLMP. Outcomes were compared between NLMP and SCS recipients, as well as benchmark and non-benchmark cases., Results: Of the 332 LT included, 174 underwent NLMP and 158 were transplanted following SCS. Sixty-seven organs were accepted and transplanted only under the premise of NLMP. One-year graft survival for SCS and NLMP recipients was 83.8% vs. 81.3% and 93.4% for benchmark cases in the overall cohort. Total preservation time had no influence on graft survival in the NLMP group but was associated with inferior 1-year graft survival in the SCS group. NLMP usage increased significantly over the duration of the study period, as did the median total preservation time. With increasing NLMP use and longer preservation times, nighttime surgery decreased significantly from 41.9% to 4.2%., Conclusions: Prolonged preservation times ease logistics and enable daytime surgery. The possibility of NLMP offers to expand liver transplantation without negatively affecting outcomes., Competing Interests: Conflicts of interest: Not directly related to the manuscript., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

External quality assessment (EQA) enhances patient safety through the evaluation of the quality of laboratory-based and point of care testing. Regulatory agencies and accreditation organizations utilize the results and the laboratory's response to them as part of assessing the laboratory's fitness to practice. In addition, where EQA samples are commutable and the assigned value has been determined using reference measurement procedures (RMPs), EQA data contributes to the verification of metrological traceability of assays as part of the post-market surveillance of in vitro diagnostic (IVD) medical devices (IVD-MDs). More broadly, the scientific and medical communities use EQA data to demonstrate that medical laboratory examination procedures are fit for clinical purposes, to evaluate common reference intervals, and inclusion of data in clinical databases. Scientific groups, the IVD industry, reference laboratories and National Metrology Institutes can work with EQA providers to identify measurands, which should urgently be supported by the development of reference materials or methods. The ability of health systems to respond effectively to fast-evolving medical challenges, such as the Coronavirus Disease-19 (COVID-19) pandemic, is reliant on EQA to demonstrate confidence in the performance of new laboratory methods and testing services. EQA providers are uniquely positioned to assess the performance of IVD-MDs in addition to individual laboratories and testing sites. Although the primary focus of EQA providers remains the improvement of the performance of individual laboratories, there are many stakeholders who benefit from EQA performance data., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Reported tick-borne-encephalitis (TBE) cases have been increasing in Western Austria, but no data are available on vaccination- and infection-specific seroprevalence. This study aimed to estimate current TBEV-seroprevalence in the region and inform prevention programs by comparing anti-NS1-based-incidence rates with reported case numbers and vaccination coverage. Between December 2023 and February 2024, serum samples from 4619 blood donors in Western Austria were collected and analyzed using TBEV- and WNV-IgG-ELISA assays. Seropositive samples were tested with a TBEV-anti-NS1-IgG-ELISA to distinguish infections from vaccinations. Borderline samples were retested with serum neutralization and triple-NS1-assays. The overall anti-TBEV-IgG-seroprevalence was 80.1% (95%CI 78.9-81.3); 2.7% (95%CI 2.3-3.2) of donors tested positive for anti-TBEV-NS1 IgG antibodies, indicating previous infection. The notified incidence rate in Western Austria was 2.7/100 000/year, compared to 136.2/100 000/year based on anti-TBEV-NS1-seropositive donors, denoting a substantial number of unreported cases (mean manifestation index 1.9%). The number of donors with TBEV-infections varied considerably by district, highlighting potential hotspots for TBEV-infections. The high anti-NS1-based, estimated annual TBE incidence rates show significant differences between districts, highlighting the need for targeted prevention programs. The high rate of undiagnosed TBE cases further suggests that estimated anti-NS1-based incidence rates should be considered when defining high-risk areas., (© 2024 Wiley Periodicals LLC.)

Background/Objectives: Antibodies against the hepatitis B surface antigen (anti-HBs) are a marker of immunity against hepatitis B virus (HBV) infections. There is uncertainty about the anti-HBs seroprevalence in the general population of Austria. Methods : We conducted a cross-sectional analysis in blood donors from the Federal State of Tyrol in Austria (August-September 2023) to estimate anti-HBs seroprevalence and median antibody levels. Results : We enrolled 3935 blood donors (median age 47.6 years [25th-75th percentile: 33.3-56.6]; 40.7% female), who were hepatitis B surface antigen negative and had no detectable HBV-DNA. Overall seroprevalence was 51.4% (95% CI: 49.8-52.9%). Anti-HBs seropositivity decreased with higher age ( p < 0.001), with 70.3% (66.1-74.3%) being seropositive among participants < 25 years of age and 30.2% (24.2-36.9%) in those aged ≥ 65 years. More females than males were seropositive (54.3% [51.8-56.7%] vs. 49.4% [47.4-51.4%]; p = 0.003). Seroprevalence was significantly higher in urban than in rural areas in participants aged 40 to <55 ( p = 0.045) and ≥55 years ( p = 0.001). Among 2022 seropositive participants, the overall median anti-HBs antibody level was 539.3 IU/L (25th-75th percentile: 116.3-5417.0). Furthermore, 5% of the participants had an anti-HBs antibody level between 10 and <20 IU/L, 18% between 20 and <100 IU/L, and 77% ≥100 IU/L. Conclusions : Anti-HBs seroprevalence in blood donors from Tyrol, Austria, was 51.4% between August and September 2023 and differed across age, sex, and residence area. Catch-up vaccination programs, especially targeting the elderly living in rural areas, are needed to close HBV immunity gaps.

Background: We aimed to evaluate the effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations in previously SARS-CoV-2-infected adults in the general population of Austria during the Delta wave and with extended follow-up., Methods: In a nationwide retrospective cohort study, we calculated age-, sex-, and nursing home residency-adjusted Cox proportional hazard ratios (HRs) of coronavirus disease 2019 (COVID-19) deaths, SARS-CoV-2 infections, and non-COVID-19 deaths from 1 October to 31 December 2021, and secondarily with extended follow-up to 30 June 2022. Relative vaccine effectiveness (rVE) is rVE = (1 - HR) × 100., Results: Among 494 646 previously infected adults, 169 543 had received 2 vaccine doses, 133 567 had received 1 dose, and 190 275 were unvaccinated at baseline. We recorded 17 COVID-19 deaths (6 vaccinated, 11 unvaccinated) and 8209 SARS-CoV-2 infections. Absolute risk of COVID-19 deaths was 0.003%. rVE estimates for COVID-19 deaths and reinfections exceeded 75% until the end of 2021 but decreased substantially with extended follow-up. The risk of non-COVID-19 death was lower in those vaccinated versus unvaccinated., Conclusions: First and second SARS-CoV-2 vaccine doses appear effective in the short-term, but with diminishing effectiveness over time. The extremely low COVID-19 mortality, regardless of vaccination, indicates strong protection of previous infection against COVID-19 death. Lower non-COVID-19 mortality in the vaccinated population might suggest a healthy vaccinee bias., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Anti-Spike IgG antibodies against SARS-CoV-2, which are elicited by vaccination and infection, are correlates of protection against infection with pre-Omicron variants. Whether this association can be generalized to infections with Omicron variants is unclear. We conducted a retrospective cohort study with 8457 blood donors in Tyrol, Austria, analyzing 15,340 anti-Spike IgG antibody measurements from March 2021 to December 2022 assessed by Abbott SARS-CoV-2 IgG II chemiluminescent microparticle immunoassay. Using a Bayesian joint model, we estimated antibody trajectories and adjusted hazard ratios for incident SARS-CoV-2 infection ascertained by self-report or seroconversion of anti-Nucleocapsid antibodies. At the time of their earliest available anti-Spike IgG antibody measurement (median November 23, 2021), participants had a median age of 46.0 years (IQR 32.8-55.2), with 45.3% being female, 41.3% having a prior SARS-CoV-2 infection, and 75.5% having received at least one dose of a COVID-19 vaccine. Among 6159 participants with endpoint data, 3700 incident SARS-CoV-2 infections with predominantly Omicron sublineages were recorded over a median of 8.8 months (IQR 5.7-12.4). The age- and sex-adjusted hazard ratio for SARS-CoV-2 associated with having twice the anti-Spike IgG antibody titer was 0.875 (95% credible interval 0.868-0.881) overall, 0.842 (0.827-0.856) during 2021, and 0.884 (0.877-0.891) during 2022 (all p < 0.001). The associations were similar in females and males (P interaction  = 0.673) and across age (P interaction  = 0.590). Higher anti-Spike IgG antibody titers were associated with reduced risk of incident SARS-CoV-2 infection across the entire observation period. While the magnitude of association was slightly weakened in the Omicron era, anti-Spike IgG antibody continues to be a suitable correlate of protection against newer SARS-CoV-2 variants., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Hemoglobin levels are commonly assessed to prevent causing or worsening of anemia in prospective blood donors. We compared head-to-head the accuracy of different technologies for measuring hemoglobin suitable for use in mobile donation units. We included 144 persons donating platelets at the Central Institute for Blood Transfusion and Immunology in Innsbruck, Austria. Hemoglobin levels were measured in venous blood using the portable hemoglobinometer HemoCue Hb-801 and noninvasively using OrSense NBM-200, and compared to values obtained with the Sysmex XN-430, an automated hematology analyzer employing the sodium lauryl sulphate method, which is broadly used as reference method in everyday clinical practice. Mean age of participants was 34.2 years (SD 13.0); 34.0% were female. Hemoglobin values measured with HemoCue were more strongly correlated with the Sysmex XN-430 (r = 0.90 [95% CI: 0.87-0.93]) than measured with OrSense (r = 0.49 [0.35-0.60]). On average, HemoCue overestimated hemoglobin by 0.40 g/dL (0.31-0.48) and OrSense by 0.75 g/dL (95% CI: 0.54-0.96). When using OrSense, we found evidence for higher overestimation at higher hemoglobin levels (proportional bias) specifically in females but not in males (P difference = .003). Sensitivity and specificity for classifying donors according to the hemoglobin donation thresholds were 99.2% (95% CI: 95.3%-100.0%) and 43.8% (23.1%-66.8%) for HemoCue vs 95.3% (89.9%-98.0%) and 12.5% (2.2%-37.3%) for OrSense. Areas under the receiver operating characteristic curves were higher using HemoCue vs OrSense both in females (0.933 vs 0.547; P = .044) and males (0.948 vs 0.628; P < .001). HemoCue Hb-801 measures hemoglobin more accurately than OrSense NBM-200 in the setting of mobile blood donation units. Our findings are particularly relevant for females, having in mind that anemia is more prevalent in females than in males., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: P.W. reports consultancy fees from Novartis Pharmaceuticals unrelated to this manuscript. The authors have no other conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: To provide updated estimates on SARS-CoV-2 antibody seroprevalence and average antibody titres for Central Europe., Methods: In repeat cross-sectional investigations (1 May 2022 to 9 March 2023) involving 28,768 blood donors in the Federal State of Tyrol, Austria (participation rate: 87.0%), we measured Spike receptor-binding domain (RBD) and Nucleocapsid IgG antibodies (37,065 and 12,645 samples), and estimated monthly seroprevalences and geometric mean titres., Results: Median age of participants was 45.4 years (range 18-70); 43.2% were female. Spike RBD IgG antibody seroprevalence was 96.3% (95% CI: 95.6-96.9%) in May 2022, 97.4% (96.7-98.0%) in December 2022, and 97.9% (96.4-98.8%) in March 2023. Among seropositive participants, geometric mean titres increased from 1400 BAU/mL (95% CI: 1333-1471) in May 2022 to 1821 BAU/mL (1717-1932) in December 2022, and dropped to 1559 BAU/mL (1405-1729) by March 2023. Furthermore, titres differed markedly by vaccination status and history of infection, with being the highest in participants with booster vaccination and prior infection. In autumn 2022, Nucleocapsid IgG antibody seroprevalence ranged from 36.5% (35.0-38.1) in September to 39.2% (37.2-41.2) in December 2022., Conclusion: Seroprevalence of SARS-CoV-2 antibodies in blood donors from Tyrol, Austria, was remarkably stable from May 2022 to March 2023. In contrast, average Spike RBD IgG antibody titres peaked in December 2022.

The rare, but emerging mold Aspergillus terreus is an important pathogen in some geographical areas, like Tyrol (Austria) and Houston (Texas). The reason for this high prevalence is unknown. The present serosurveillance study aimed to evaluate the trends in levels of A. terreus -specific IgG antibodies in various regions of Tyrol and to compare the results to the environmental spread of A. terreus in Tyrol. Therefore, 1058 serum samples from healthy blood donors were evaluated. Data revealed a significant difference between the Tyrolean Upland and Lowland. Moreover, female participants had higher A. terreus IgG antibody levels than male participants. The differences found in our study are consistent with the distributional differences in environmental and clinical samples described in previous studies, supporting that A. terreus IgG antibody levels reflect the environmental epidemiology of A. terreus in Tyrol.

Inflammatory responses are orchestrated by a plethora of lipid mediators, and perturbations of their biosynthesis or degradation hinder resolution and lead to uncontrolled inflammation, which contributes to diverse pathologies. Small molecules that induce a switch from pro-inflammatory to anti-inflammatory lipid mediators are considered valuable for the treatment of chronic inflammatory diseases. Commonly used non-steroidal anti-inflammatory drugs (NSAIDs) are afflicted with side effects caused by the inhibition of beneficial prostanoid formation and redirection of arachidonic acid (AA) into alternative pathways. Multi-target inhibitors like diflapolin, the first dual inhibitor of soluble epoxide hydrolase (sEH) and 5-lipoxygenase-activating protein (FLAP), promise improved efficacy and safety but are confronted by poor solubility and bioavailability. Four series of derivatives bearing isomeric thiazolopyridines as bioisosteric replacement of the benzothiazole core and two series additionally containing mono- or diaza-isosteres of the phenylene spacer were designed and synthesized to improve solubility. The combination of thiazolo[5,4-b]pyridine, a pyridinylen spacer and a 3,5-Cl 2 -substituted terminal phenyl ring (46a) enhances solubility and FLAP antagonism, while preserving sEH inhibition. Moreover, the thiazolo[4,5-c]pyridine derivative 41b, although being a less potent sEH/FLAP inhibitor, additionally decreases thromboxane production in activated human peripheral blood mononuclear cells. We conclude that the introduction of nitrogen, depending on the position, not only enhances solubility and FLAP antagonism (46a), but also represents a valid strategy to expand the scope of application towards inhibition of thromboxane biosynthesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Extracorporeal photopheresis (ECP) treatment, mostly based on apheresis technology, is used for immunomodulation in various diseases such as cutaneous T-cell lymphoma, graft versus host disease and other (auto)immune disorders. The aim of this study was to collect high cell counts and purity in shorter procedure times using an ECP off-line system with an increased collection flow rate of 2 mL/min to a target volume of 200 mL buffy coat., Study Design and Methods: In this prospective study, data of routinely performed off-line photopheresis treatments were collected and analyzed at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken, to assess absolute cell counts and procedure times and to calculate collection efficiencies (CE2)., Results: A total of 22 patients participated in this study. The processed blood volume was 4312 mL, the collection time 120 min, overall procedure time 157 min and the absolute cell counts of treated white blood cells (WBC) and mononuclear cells (MNC) were 5.0 and 4.3 × 10 9 respectively (median values). The calculated CE2 for WBC and MNC was 21.1% and 58.5%, the proportion of treated MNCs of the total number of MNCs present was 55.0%., Conclusion: The data presented in this study show high therapeutically effective cell counts collected with a high MNC purity within a shorter overall collection/procedure time due to an increased collection flow rate., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Objective: To reevaluate the frequency of perioperative blood transfusion, transfusion triggers, and survival impact in patients with incident, surgically treated head and neck cancer (HNC) in restrictive transfusion regimens., Methods: Retrospective analysis of surgically treated patients with incident HNC with and without perioperative blood transfusion between 2008 and 2019 at the Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, according to the department's clinical Head and Neck Tumor Registry., Results: Of the 590 patients included, perioperative transfusions were administered in 6.3% (n = 37, transfusion group). Following multivariable logistic regression, likelihood of blood transfusions was increased in patients with poorer general health conditions (ASA score III/IV; OR 3.7; 95% CI 1.9-8.6; p = 0.002), hemoglobin <12.5 g/dL (OR 2.7; 95% CI 1.1-6.4; p = 0.03), longer duration of surgery (OR 1.006 per minute of surgery time; 95% CI 1.003-1.008; p < 0.001), and negative p16 status (OR 5.3; 95% CI = 1.1-25; p = 0.03). Based on 14 matching variables related to survival and perioperative blood transfusion, a control group of 37 matching patients without perioperative transfusion was identified. Using univariate analysis, overall survival in transfusion and control groups did not differ significantly (p = 0.25). After adjusting for four parameters with limited matching accuracy (Chi square p < 0.2) in Cox regression analysis, a transfusion related hazard ratio close to 1 (HR 0.92; 95% CI 0.34-2.51; p = 0.87) was observed., Conclusion: Considering current restrictive transfusion regimens and general transfusion risks, the administration of blood products in HNC patients during the perioperative period is not associated with additional oncologic hazard., Level of Evidence: 3 Laryngoscope, 133:1638-1644, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

After COVID-19, patients have reported various complaints such as fatigue, neurological symptoms, and insomnia. Immune-mediated changes in amino acid metabolism might contribute to the development of these symptoms. Patients who had had acute, PCR-confirmed COVID-19 infection about 60 days earlier were recruited within the scope of the prospective CovILD study. We determined the inflammatory parameters and alterations in tryptophan and phenylalanine metabolism in 142 patients cross-sectionally. Symptom persistence (pain, gastrointestinal symptoms, anosmia, sleep disturbance, and neurological symptoms) and patients' physical levels of functioning were recorded. Symptoms improved in many patients after acute COVID-19 ( n = 73, 51.4%). Still, a high percentage of patients had complaints, and women were affected more often. In many patients, ongoing immune activation (as indicated by high neopterin and CRP concentrations) and enhanced tryptophan catabolism were found. A higher phenylalanine to tyrosine ratio (Phe/Tyr) was found in women with a lower level of functioning. Patients who reported improvements in pain had lower Phe/Tyr ratios, while patients with improved gastrointestinal symptoms presented with higher tryptophan and kynurenine values. Our results suggest that women have persistent symptoms after COVID-19 more often than men. In addition, the physical level of functioning and the improvements in certain symptoms appear to be associated with immune-mediated changes in amino acid metabolism.

Post-infectious fatigue is a common complication that can lead to decreased physical efficiency, depression, and impaired quality of life. Dysbiosis of the gut microbiota has been proposed as a contributing factor, as the gut-brain axis plays an important role in regulating physical and mental health. This pilot study aimed to investigate the severity of fatigue and depression, as well as the quality of life of 70 patients with post-infectious fatigue who received a multi-strain probiotic preparation or placebo in a double-blind, placebo-controlled trial. Patients completed questionnaires to assess their fatigue (fatigue severity scale (FSS)), mood (Beck Depression Inventory II (BDI-II)), and quality of life (short form-36 (SF-36)) at baseline and after 3 and 6 months of treatment. Routine laboratory parameters were also assessed, including immune-mediated changes in tryptophan and phenylalanine metabolism. The intervention was effective in improving fatigue, mood, and quality of life in both the probiotic and placebo groups, with greater improvements seen in the probiotic group. FSS and BDI-II scores declined significantly under treatment with both probiotics and placebo, but patients who received probiotics had significantly lower FSS ( p < 0.001) and BDI-II ( p < 0.001) scores after 6 months. Quality of life scores improved significantly in patients who received probiotics ( p < 0.001), while patients taking a placebo only saw improvements in the "Physical limitation" and "Energy/Fatigue" subcategories. After 6 months neopterin was higher in patients receiving placebo, while no longitudinal changes in interferon-gamma mediated biochemical pathways were observed. These findings suggest that probiotics may be a promising intervention for improving the health of patients with post-infectious fatigue, potentially through modulating the gut-brain axis.

Introduction: Babesia is a tick-borne intraerythrocytic parasite that is globally ubiquitous, yet understudied. Several species of Babesia have been shown to be transfusion-transmissible. Babesia has been reported in blood donors, animals, and ticks in the Tyrol (Western Austria), and regional cases of human babesiosis have been described. We sought to characterize the risk of Babesia to the local blood supply., Methods: Prospective molecular testing was performed on blood donors who presented to regional, mobile blood collection drives in the Tyrol, Austria (27 May to October 4, 2021). Testing was conducted using the cobas ® Babesia assay (Roche Molecular Systems, Inc.), a commercial PCR assay approved for blood donor screening that is capable of detecting the 4 primary species causing human babesiosis (i.e., B. microti , B. divergens , B. duncani , and B. venatorum ). A confirmatory algorithm to manage initial PCR-reactive samples was developed, as were procedures for donor and product management., Results: A total of 7,972 donors were enrolled and screened; 4,311 (54.1%) were male, with a median age of 47 years (IQR = 34-55). No positive cases of Babesia were detected, corresponding with an overall prevalence of 0.00% (95% CI: 0.00%, 0.05%)., Discussion: The findings suggest that the prevalence of Babesia is low in Austrian blood donors residing in the Tyrol, even during months of peak tick exposure. Although one cannot conclude the absence of Babesia in this population given the limited sample size, the findings suggest that the regional risk of transfusion-transmitted babesiosis is low., Competing Interests: Evan M. Bloch reports personal fees and non-financial support from Terumo BCT, Abbott Laboratories, Tegus, and UpToDate, outside of the submitted work. Steven J. Drews is a paid consultant to Roche and has received research support from Abbott, outside of the submitted work. Harald Schennach reports personal fees from Cerus Corp outside of the submitted work. Anita Siller, Laura Tonnetti, Bryan Spencer, Doris Hedges, Tessa Mergenthal, Marijke Weber-Schehl, Manfred Astl, Eshan Patel, and Manfred Gaber have no conflict of interest to declare. Evan M. Bloch is a member of the US Food and Drug Administration (FDA) Blood Products Advisory Committee. Any views or opinions that are expressed in this manuscript are those of the author's, based on his own scientific expertise and professional judgment; they do not necessarily represent the views of either the Blood Products Advisory Committee or the formal position of FDA, and do not bind or otherwise obligate or commit either Advisory Committee or the Agency to the views expressed., (Copyright © 2023 by The Author(s). Published by S. Karger AG, Basel.)

Phyllobilins are natural products derived from the degradation of chlorophyll, which proceeds via a common and strictly controlled pathway in higher plants. The resulting tetrapyrrolic catabolites-the phyllobilins-are ubiquitous in nature; despite their high abundance, there is still a lack of knowledge about their physiological properties. Phyllobilins are part of human nutrition and were shown to be potent antioxidants accounting with interesting physiological properties. Three different naturally occurring types of phyllobilins-a phylloleucobilin, a dioxobilin-type phylloleucobilin and a phylloxanthobilin (PxB)-were compared regarding potential antioxidative properties in a cell-free and in a cell-based antioxidant activity test system, demonstrating the strongest effect for the PxB. Moreover, the PxB was investigated for its capacity to interfere with immunoregulatory metabolic pathways of tryptophan breakdown in human blood peripheral mononuclear cells. A dose-dependent inhibition of tryptophan catabolism to kynurenine was observed, suggesting a suppressive effect on pathways of cellular immune activation. Although the exact mechanisms of immunomodulatory effects are yet unknown, these prominent bioactivities point towards health-relevant effects, which warrant further mechanistic investigations and the assessment of the in vivo extrapolatability of results. Thus, phyllobilins are a still surprisingly unexplored family of natural products that merit further investigation.

Because a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies. We quantified anti-Spike IgG antibody levels in 22,607 individuals that donated blood between October 2021 and April 2022 across Tyrol, Austria (participation rate: 96.0%). Median age of participants was 45.3 years (IQR: 30.9−55.1); 41.9% were female. From October 2021 to April 2022, seropositivity increased from 84.9% (95% CI: 83.8−86.0%) to 95.8% (94.9−96.4%), and the geometric mean anti-Spike IgG levels among seropositive participants increased from 283 (95% CI: 271−296) to 1437 (1360−1518) BAU/mL. The percentages of participants in categories with undetectable levels and detectable levels at <500, 500−<1000, 1000−<2000, 2000−<3000, and ≥3000 BAU/mL were 15%, 54%, 15%, 10%, 3%, and 3% in October 2021 vs. 4%, 18%, 17%, 18%, 11%, and 32% in April 2022. Of 2711 participants that had repeat measurements taken a median 4.2 months apart, 61.8% moved to a higher, 13.9% to a lower, and 24.4% remained in the same category. Among seropositive participants, antibody levels were 16.8-fold in vaccinated individuals compared to unvaccinated individuals (95% CI: 14.2−19.9; p-value < 0.001). In conclusion, anti-SARS-CoV-2 seroprevalence in terms of seropositivity and average antibody levels has increased markedly during the winter 2021/2022 SARS-CoV-2 waves in Tyrol, Austria.

Background: Extracorporeal photopheresis (ECP) is a blood-based therapeutic procedure increasingly used for modulation of immune dysregulation in various underlying disease settings. The aim of this study was to compare the procedure times and blood collection efficiencies between the two approaches currently utilized in European centers: the integrated versus the multistep nonintegrated procedures., Methods: A retrospective data analysis was conducted, comparing treatment data from patients who received ECP therapy at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken GmbH, where the integrated and multistep nonintegrated procedures are routinely used in an approximated setup., Results: During the observation period, a total of 15 patients who were treated with alternating systems on 2 consecutive days were identified. This allowed treatment pair comparisons with minimal interpatient variabilities, similar to a cross-over design even though analyzed retrospectively. Total average procedure times with the integrated system were 99.3 vs 122.0 minutes with the multistep nonintegrated procedures, respectively. Significant differences were observed for all steps of the ECP procedure: (a) time for buffy coat collection, 66.5 vs 74.7; (b) handling/transfer, 2.8 vs 18.7; (c) irradiation, 20.3 vs 11.7; and (d) reinfusion/handling time, 9.6 vs 16.3 minutes. The calculated collection throughput was 7.79 mL/min for the integrated and 7.84 mL/min for the multistep nonintegrated procedures, and with a white blood cell (WBC) collection efficiency of 34.2% and 21.0%, respectively., Conclusion: The data presented in this study show a significant shorter overall procedure time and higher WBC collection efficiency for the integrated ECP system., (© 2022 Therakos UK Ltd. Journal of Clinical Apheresis published by Wiley Periodicals LLC.)

There is uncertainty about the seroprevalence of anti-SARS-CoV-2 antibodies in the general population of Austria and about the waning of antibodies over time. We conducted a seroepidemiological study between June 2020 and September 2021, enrolling blood donors aged 18-70 years across Tyrol, Austria (participation rate: 84.0%). We analyzed serum samples for antibodies against the spike or the nucleocapsid proteins of SARS-CoV-2. We performed a total of 47,363 samples taken from 35,193 individuals (median age, 43.1 years (IQR: 29.3-53.7); 45.3% women; 10.0% with prior SARS-CoV-2 infection). Seroprevalence increased from 3.4% (95% CI: 2.8-4.2%) in June 2020 to 82.7% (95% CI: 81.4-83.8%) in September 2021, largely due to vaccination. Anti-spike IgG seroprevalence was 99.6% (95% CI: 99.4-99.7%) among fully vaccinated individuals, 90.4% (95% CI: 88.8-91.7%) among unvaccinated individuals with prior infection and 11.5% (95% CI: 10.8-12.3%) among unvaccinated individuals without known prior infection. Anti-spike IgG levels were reduced by 44.0% (95% CI: 34.9-51.7%) at 5-6 months compared with 0-3 months after infection. In fully vaccinated individuals, they decreased by 31.7% (95% CI: 29.4-33.9%) per month. In conclusion, seroprevalence in Tyrol increased to 82.7% in September 2021, with the bulk of seropositivity stemming from vaccination. Antibody levels substantially and gradually declined after vaccination or infection.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hemolytic disease driven by impaired complement regulation. Mutations in genes encoding the enzymes that build the GPI anchors are causative, with somatic mutations in the PIG-A gene occurring most frequently. As a result, the important membrane-bound complement regulators CD55 and CD59 are missing on the affected hematopoietic stem cells and their progeny, rendering those cells vulnerable to complement attack. Immune escape mechanisms sparing affected PNH stem cells from removal are suspected in the PNH pathogenesis, but molecular mechanisms have not been elucidated. We hypothesized that exuberant complement activity in PNH results in enhanced immune checkpoint interactions, providing a molecular basis for the potential immune escape in PNH. In a series of PNH patients, we found increased expression levels of the checkpoint ligand programmed death-ligand 1 (PD-L1) on granulocytes and monocytes, as well as in the plasma of PNH patients. Mechanistically, we demonstrate that complement activation leading to the decoration of particles/cells with C3- and/or C4-opsonins increased PD-L1 expression on neutrophils and monocytes as shown for different in vitro models of classical or alternative pathway activation. We further establish in vitro that complement inhibition at the level of C3, but not C5, inhibits the alternative pathway-mediated upregulation of PD-L1 and show by means of soluble PD-L1 that this observation translates into the clinical situation when PNH patients are treated with either C3 or C5 inhibitors. Together, the presented data show that the checkpoint ligand PD-L1 is increased in PNH patients, which correlates with proximal complement activation., (Copyright © 2022 by The American Association of Immunologists, Inc.)