Sylvia Mink

Private University in the Principality of Liechtenstein

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Peter Fraunberger

Private University in the Principality of Liechtenstein

Patrick Reimann

Private University in the Principality of Liechtenstein

Christoph H. Saely

Vorarlberg Institute for Vascular Investigation and Treatment

Heinz Drexel

Vorarlberg Institute for Vascular Investigation and Treatment

Andreas Leiherer

Vorarlberg Institute for Vascular Investigation and Treatment

Matthias Frick

Landeskrankenhaus Feldkirch

Janne Cadamuro

Paracelsus Medical University

Magdalena Benda

Private University in the Principality of Liechtenstein

Wolfgang Hitzl

Paracelsus Medical University

Thomas Winder

Landeskrankenhaus Feldkirch

Cooperative Institutions

Landeskrankenhaus Feldkirch

Private University in the Principality of Liechtenstein

Vorarlberg Institute for Vascular Investigation and Treatment

Innsbruck Medical University

Universität Innsbruck

Medical University of Vienna

University Hospital Innsbruck

AGO Austria

Ordensklinikum Linz Barmherzige Schwestern

Medical University of Graz

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Tick‐Borne Encephalitis Virus Surveillance—Vaccination‐ and Infection‐Induced Seroprevalences in Western Austria 2024

Journal of Medical Virology (2024)

Anita Siller Lidia Chitimia‐Dobler Wolfgang Hitzl Manfred Astl Harald Schennach

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.

Seroprevalence

Tick-borne encephalitis

Tick-borne encephalitis virus

10.1002/jmv.70109

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Efficacy and safety of heterologous booster vaccination with Ad26.COV2.S after BNT162b2 mRNA COVID‐19 vaccine in haemato‐oncological patients with no antibody response

British Journal of Haematology (2021)

Patrick Reimann Hanno Ulmer Beatrix Mutschlechner Magdalena Benda Luciano Severgnini

Patients with haemato-oncological malignancies are one of the high-risk groups for a severe course in case of COVID-19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato-oncological patients without antibody response after double-dose BNT162b2 messenger (m-)RNA COVID-19 vaccine. A total of 32 haemato-oncological non-responders to double-dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double-dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato-oncological patients.

Booster dose

Booster (rocketry)

10.1111/bjh.17982

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Exploring the impact of Durvalumab on biliary tract cancer- insights from real world clinical data

Research Square (Research Square) (2024)

Bernhard Doleschal Ilektra-Antonia Mavroeidi Patrick Reimann Gerald W. Prager Georg Schreil

Abstract Introduction This study assesses the effectiveness of durvalumab with platinum and gemcitabine for biliary tract cancers (BTC). It aims to confirm the Topaz-1 trial results in a real-world context and explore the link between BTC molecular profiles and patient outcomes. Methods A retrospective analysis was conducted on 102 BTC patients treated with durvalumab, platinum, and gemcitabine at five cancer centers in Austria and one in Germany from 2022 to 2024. Molecular profiling used targeted DNA and RNA assays. Clinical endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed using log-rank tests and Cox regression, with correlations to second-line molecular-targeted therapies. Results Among 102 patients, 60.8% had intrahepatic cholangiocarcinoma. The treatment achieved a disease control rate of 71.57% and an overall response rate of 35.11%. Median PFS was 6.51 months, and OS was 13.61 months. Patients under 65 had significantly better OS. Alterations in Chromatin Remodeling or Homologous Recombination Repair genes were not predictive of survival benefit (HR 0.45; p=0.851 and HR 1.63; p=0.26, respectively). Patients with molecular-informed second-line therapy showed a trend towards survival benefit (HR 0.23, p=0.052). Conclusion This study confirms the phase 3 trial results of durvalumab with platinum and gemcitabine, providing a substantial real-world dataset with detailed molecular characterization. No specific patient subgroup showed a markedly better response to durvalumab based on conventional NGS panels. Further research is needed to explore the link between immunotherapy responses and molecular subgroups

Durvalumab

Biliary Tract Cancer

10.21203/rs.3.rs-4840712/v1

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Authors reply: Evaluation of SARS‐CoV‐2 antibody levels on hospital admission as a correlate of protection against mortality

Journal of Internal Medicine (2023)

Sylvia Mink Christoph H. Saely Heinz Drexel Peter Fraunberger

The authors declare that they have no conflict of interests.

2019-20 coronavirus outbreak

Betacoronavirus

10.1111/joim.13631

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Evaluation of SARS‐CoV‐2 antibody levels on hospital admission as a correlate of protection against mortality

Journal of Internal Medicine (2023)

Sylvia Mink Wolfgang List Guenter Hoefle Matthias Frick Alois Suessenbacher

Millions of people have now been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is still unclear which antibody levels provide protection against mortality. It is further unknown whether measuring antibody concentrations on hospital admission allows for identifying patients with a high risk of mortality.To evaluate whether anti-SARS-CoV2-spike antibodies on hospital admission predict in-hospital mortality in patients with coronavirus disease 2019.We conducted a prospective, multicentre cohort study on 1152 hospitalized patients who tested positive for SARS-CoV-2 with a polymerase chain reaction-based assay. Patients were classified by vaccination status. Anti-SARS-CoV-2 spike antibodies were determined on hospital admission. The investigated end point was in-hospital mortality for any cause.Spike antibodies on hospital admission were significantly lower in non-survivors in both non-vaccinated (73 U/ml, 95%CI 0-164 vs. 175 U/ml, 95%CI 124-235, p = 0.002) and vaccinated patients (1056 U/ml, 95%CI 701-1411 vs. 1668 U/ml, 95%CI 1580-1757, p < 0.001). Further, spike antibodies were significantly lower in fully vaccinated and boostered patients who died compared to those who survived (mean 883 U/ml, 95%CI 406-1359 vs. 1292 U/ml, 95%CI 1152-1431, p = 0.017 and 1485 U/ml, 95%CI 836-2133 vs. 2050 U/ml, 95%CI 1952-2149, p = 0.036). Patients infected with the currently prevailing Omicron variant were three times more likely to die if spike antibodies were <1200 U/ml (OR 3.458, 95%CI 1.562-7.656, p = 0.001). After adjusting for potential confounders, this value increased to an aOR of 4.079 (95%CI 1.809-9.198, p < 0.001).Anti-SARS-CoV2 spike-antibody levels on hospital admission are inversely associated with in-hospital mortality. Hospitalized patients with lower antibody levels have a higher risk of mortality.

Hospital admission

10.1111/joim.13606

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Prognostic value of anti-SARS-CoV-2 antibodies: a systematic review

Clinical Chemistry and Laboratory Medicine (CCLM) (2024)

Sylvia Mink Patrick Reimann Peter Fraunberger

Abstract Objectives Globally, over 772 million cases of COVID-19 have been reported. New variants of interest with corresponding spikes in case numbers continue to be identified. Vulnerable patients, including older adults or patients with severe comorbidities, continue to be at risk. A large body of evidence has been accumulated regarding anti-SARS-CoV-2-antibodies and COVID-19 but the usefulness of antibody measurements remains unclear. This systematic review aims to assess the prognostic value of anti-SARS-CoV-2-antibodies and their usefulness for guiding booster vaccinations. Methods Studies in English and published between January 2020 and October 2023 were included. Studies that relied on multiparameter-models or comprised fewer than 100 participants were excluded. PubMed and via the WHO COVID-19 research database, Embase and Medline databases were searched. Study selection and quality assessment was conducted independently by two researchers. Results After screening 1,160 studies, 33 studies comprising >30 million individuals were included. Anti-SARS-CoV-2-antibodies were strongly associated with reduced risk of SARS-CoV-2-infection and better outcomes, including mortality. Risk of infection and COVID-19 severity decreased with increasing antibody levels. Conclusions Anti-SARS-CoV-2-antibodies are useful for early identification of high-risk patients and timely adjustment of therapy. Protective thresholds may be applied to advise booster vaccinations but verification in separate cohorts is required.

10.1515/cclm-2023-1487

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CSF-interleukin 6 for early diagnosis of ventriculitis in a broad intensive care setting

Clinical Chemistry and Laboratory Medicine (CCLM) (2022)

Sylvia Mink Wolfgang List Patrick Reimann Peter Fraunberger

Article CSF-interleukin 6 for early diagnosis of ventriculitis in a broad intensive care setting was published on May 1, 2022 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 60, issue 6).

Ventriculitis

10.1515/cclm-2021-1233

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Antibody levels versus vaccination status in the outcome of older adults with COVID-19

JCI Insight (2024)

Sylvia Mink Christoph H. Saely Andreas Leiherer Patrick Reimann Matthias Frick

BACKGROUNDDespite the currently prevailing, milder Omicron variant of COVID-19, older adults remain at elevated risk of hospital admission, critical illness, and death. Loss of efficacy of the immune system, including reduced strength, quality, and durability of antibody responses, may render generalized recommendations on booster vaccinations inadequate. There is a lack of data on the efficacy of antibody levels in older adults and on the utility of vaccination status versus antibody levels as a correlate of protection. It is further unclear whether antibody levels may be used to guide the timing of booster vaccinations in older adults.METHODSWe conducted a prospective multicenter cohort study comprising hospitalized patients with COVID-19. Anti-SARS-CoV-2 spike antibodies were measured on hospital admission. The primary endpoint was in-hospital mortality. Patients were stratified by age, antibody levels, and vaccination status. Multiple logistic regression and Cox regression analyses were conducted.RESULTSIn total, 785 older patients (≥60 years of age [a]) and 367 controls (<60a) were included. After adjusting for confounders, risk of mortality, ICU admission, endotracheal intubation, and oxygen administration was 4.9, 2.6, 6.5, and 2.3 times higher, respectively, if antibody levels were < 1,200 BAU/mL (aOR, 4.92 [95%CI, 2.59-9.34], P < 0.0001; aOR, 2.64 [95%CI, 1.52-4.62], P = 0.0006; aOR, 6.50 [95%CI, 1.48-28.47], P = 0.013; aOR, 2.34 [95%CI, 1.60-3.343], P < 0.0001). Older adults infected with the Omicron variant were approximately 6 times more likely to die if antibody levels were < 1,200 BAU/mL (aOR, 6.3 [95% CI, 2.43-16.40], P = 0.0002).CONCLUSIONAntibody levels were a stronger predictor of in-hospital mortality than vaccination status. Monitoring antibody levels may constitute a better and more direct approach for safeguarding older adults from adverse COVID-19 outcomes.

Clinical endpoint

10.1172/jci.insight.183913

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Coronary Event Risk Test (CERT) as a Risk Predictor for the 10-Year Clinical Outcome of Patients with Peripheral Artery Disease

Journal of Clinical Medicine (2023)

Andreas Leiherer Axel Muendlein Christoph H. Saely Kathrin Geiger Eva‐Maria Brandtner

(1) Background: Ceramides are a new kind of lipid biomarker and have already been demonstrated to be valuable risk predictors in coronary patients. Patients with peripheral artery disease (PAD) are a population with a worse prognosis and higher mortality risk compared to coronary artery disease (CAD) patients. However, the value of ceramides for risk prediction in PAD patients is still vague, as addressed in the present study. (2)Methods: This observational study included 379 PAD patients. The primary endpoint was all-cause mortality at 10 years of follow-up. A set of ceramides was measured by LC-MS/MS and combined according to the Coronary Event Risk Test (CERT) score, which categorizes patients into one of four risk groups (low risk, moderate risk, high risk, very high risk). (3) Results: Kaplan-Meier survival curves revealed that the overall survival of patients decreased with the increasing risk predicted by the four CERT categories, advancing from low risk to very high risk. Cox regression analysis demonstrated that each one-category increase resulted in a 35% rise in overall mortality risk (HR = 1.35 [1.16-1.58]). Multivariable adjustment, including, among others, age, LDL-cholesterol, type 2 diabetes, and statin treatment before the baseline, did not abrogate this significant association (HR = 1.22 [1.04-1.43]). Moreover, we found that the beneficial effect of statin treatment is significantly stronger in patients with a higher risk, according to CERT. (4) Conclusions: We conclude that the ceramide-based risk score CERT is a strong predictor of the 10-year mortality risk in patients with PAD.

Clinical endpoint

10.3390/jcm12196151

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Enhanced recovery and reduced conversion rates in robotic rectal cancer surgery: a single-center retrospective cohort study

Langenbeck s Archives of Surgery (2024)

Markus P. Weigl Christian Attenberger Benedikt Feurstein Tarkan Jäger Klaus Emmanuel

Cardiothoracic surgery

Single Center

Vascular surgery

10.1007/s00423-024-03453-2

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