Landeskrankenhaus Feldkirch

Abstract Introduction Remnant cholesterol (RC) represents the cholesterol content of ApoB48- and ApoB100-containing atherogenic triglyceride-rich lipoproteins, such as chylomicrons, very-low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL) and is calculated as total cholesterol minus low-density lipoprotein cholesterol (LDL-C) minus high-density lipoprotein cholesterol (HDL-C). RC has gained attention as a marker for cardiovascular event risk and mortality. Purpose The purpose of the study was to investigate whether RC predicts all-cause mortality in patients with established coronary artery disease, independent of the total ApoB particle count. Methods We included 1,481 patients with angiographically confirmed coronary artery disease. The mean age was 65.1 ± 10.4 years, 415 (28%) of the patients were female. The mean follow-up period was 11.3 ± 5.1 years. Results During follow-up, 52.2% (n=773) of our patients died. At baseline, the mean RC level was 23 ± 23 mg/dL, and the mean ApoB level was 96 ± 29 mg/dL. A Cox regression model demonstrated that RC was a significant predictor of all-cause mortality after adjustment for age, smoking, LDL-C, HDL-C, hypertension, type 2 diabetes, BMI, and also ApoB, with a hazard ratio (HR) for all-cause mortality of 1.14 (95% CI: 1.01–1.27, p=0.028). In contrast, ApoB was not associated with all-cause mortality after adjustment for RC (HR 0.998, 95% CI: 0.793–1.13, p=0.524). Conclusion We conclude that RC is an independent predictor of all-cause mortality, irrespective of the ApoB particle count. This finding underscores the atherogenic significance of the cholesterol content, rather than the ApoB particle count, of triglyceride-rich lipoproteins.

Abstract Smoking is one of the single most important preventable risk factors for cancer and other adverse health outcomes 1,2 . Smoking cessation represents a key public health intervention with the potential to reduce its negative health outcomes 2–4 . While epidemiological, cross-sectional, and individual longitudinal ‘omic’ or biomarker studies have evaluated the impact of smoking cessation, no study to date has systematically profiled molecular and clinical changes in several organ systems or tissues longitudinally over the course of smoking cessation that could allow for more detailed assessment of response biomarkers and the identification of interindividual differences in the recovery of physiological functions. Here, we report the first human longitudinal multi-omic study of smoking cessation, evaluating 2,501 unique single or composite features from 1,094 longitudinal samples. Our comprehensive analysis, leveraging over half a million longitudinal data points, revealed a profound effect of smoking cessation on epigenetic biomarkers and microbiome features across multiple organ systems within 6 months of smoking cessation, alongside shifts in the immune and blood oxygenation system. Moreover, our multi-omic analysis provided unprecedented granularity that allows for identification of new cross-ome associations for mechanistic discovery. We anticipate that data and an interactive app from the Tyrol Lifestyle Atlas ( eutops.github.io/lifestyle-atlas ), comprising the current study and a parallel study arm evaluating the impact of diet on biomarkers of health and disease, will provide the basis for future discovery, biomarker benchmarking in their responsiveness to health-promoting interventions, and study of individualised response group, representing a major advance for personalised health monitoring using biomarkers.

Summary Extending human healthspan requires understanding how lifestyle interventions impact molecular systems across tissues and time. Here, we present the TirolGESUND Lifestyle Atlas (ClinicalTrials.gov: NCT05678426 ), a longitudinal, multi-modal resource profiling 156 healthy women (aged 30-60 years) undergoing 6-month intermittent fasting (n=114) or smoking cessation (n=42) interventions. Participants were sampled up to four times across seven tissues and fluids, generating >3,450 biospecimens with harmonised DNA methylation, metabolomics, microbiome, and immune profiling, alongside skin histology, barrier measurements, and rich clinical metadata. We demonstrate the utility of this dataset through: (i) multi-omics-wide association studies linking traits to molecular features; (ii) integrative factor modelling revealing coordinated cross-tissue signatures; (iii) epigenetic-biomarker cross-omic associations, and (iv) CpG-level variance decomposition mapping stable, individual-specific, tissue-restricted, and intervention-responsive methylation patterns. We further show that ageing-linked features are selectively malleable: highly compliant intermittent fasting participants exhibited attenuated or even age-opposing molecular trajectories within six months. The atlas enables unprecedented within-cohort comparisons across omic layers and tissues, supporting discovery of context-dependent biomarkers, cross-system coordination, and intervention responsiveness. Data are available via an interactive portal, with sensitive data under controlled access ( https://eutops.github.io/lifestyle-atlas/ ). This resource provides a foundation for exploring biomarker association and multi-tissue epigenetics, enabling hypothesis generation and benchmarking for systems biology and human healthspan research. Graphical abstract Highlights Multi-tissue multi-modal profiling of two clinically-relevant lifestyle interventions in 156 women aged 30-60 Intermittent fasting modifies ageing-linked molecular features in an age-opposing direction Cross-tissue epigenetic biomarker mapping links immunity, metabolism, and microbiome Tissue-specific epigenetic plasticity maps reveal candidate meQTLs, Data sharing and interactive portal enable broad reuse for hypothesis generation and exploration

ObjectiveChronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease with no validated criteria for assessing disease activity (DA), inactive disease, or remission. To date, DA assessment has relied on subjective judgments from patients, rheumatologists, and/or radiologists. Evaluations based on composite DA measures are emerging. The Pediatric CNO (PedCNO) response score documents relative DA changes during follow‐up in analogy to the Pediatric American College of Rheumatology score for juvenile idiopathic arthritis. The international Childhood Arthritis and Rheumatology Research Alliance (CARRA) CNO initiative proposed a numeric composite DA score (CDAS) on the basis of the patient global assessment of DA (PAG), patient assessment of pain (PAP), and clinically active CNO lesions. We aim to propose different composite scores for assessment of DA, including physician assessment of DA and magnetic resonance imaging (MRI) findings; to evaluate the previously published CNO CDAS and the PedCNO response score using established registry data; and to suggest a PedCNO 90% improvement (PedCNO90) category.MethodsNewly diagnosed patients with CNO were enrolled between 2015 and 2020 and analyzed for clinical course and DA measures (physician global assessment of DA [PGDA]/PAG and pain scores) for up to 4 years of follow‐up (YFU) in the National Pediatric Rheumatologic Database.ResultsA total of 400 patients were enrolled. In single numeric scores only, clinical and MRI lesion scores reached significant changes (from baseline to 3 YFU: P = 0.003/P = 0.004). Composite scores, which include MRI DA scores consisting of one clinical patient‐based assessment parameter (PAG/PAP of DA), the PGDA and MRI lesion count are less dependent on subjective measures and demonstrate more pronounced changes over time of supposed CNO DA compared with the CNO CDAS. A PedCNO90 response score gradually increased during follow‐up, ultimately reaching a PedCNO90 in half of the remaining patients after 4 years.ConclusionComposite scores, including MRI lesions and PGDA, seem to be promising tools for describing the activity of CNO and are proposed. The composition of DA scores seems essential for future studies.

ZusammenfassungWundinfektionen sind weiterhin eine interdisziplinäre und interprofessionelle Herausforderung, da sie insbesondere bei Menschen mit chronischen Wunden zahlreiche Komplikationen verursachen können. In diesem Themengebiet gibt es aktuell viele unterschiedliche Begrifflichkeiten und Vorgehensweisen. Daher wollte WundDACH als Dachorganisation der deutschsprachigen Wundheilungsgesellschaften zu dieser wichtigen Thematik ein Positionspapier erstellen. Durch eine interdisziplinäre und interprofessionelle Expertengruppe aus den verschiedenen deutschsprachigen Ländern wurden in einem modifizierten Delphi‐Verfahren Definitionen und Vorgehensweisen für Nomenklatur, Diagnostik sowie Therapie von Wundinfektionen bei Menschen mit chronischen Wunden entwickelt.In dieser Übersicht wird herausgestellt, wie essenziell die korrekte Diagnose von Wundinfektionen ist, um eine frühzeitige und spezifische Behandlung zu ermöglichen. Für die differenzierte Beurteilung wurde eine vereinfachte Darstellung des Kontinuums der Wundinfektion mit den Stadien Kontamination, Kolonisation, lokale und systemische Infektion und den entsprechenden therapeutischen Konsequenzen beschrieben. Viele Bakterien in Wunden können bereits durch wiederholte Wundspülung und Débridement entfernt werden. Lokale Wundinfektionen können mittels klinischer Infektionszeichen sowie unterstützend mit dem TILI‐Score diagnostiziert werden. Die Behandlung erfolgt dann ausschließlich lokal, beispielsweise mit modernen Antiseptika wie Polihexanid. Erst bei Auftreten von Zeichen einer systemischen Infektion sollte zusätzlich die systemische Gabe von Antibiotika erwogen werden. Die Indikation einer antimikrobiellen Wundtherapie sollte spätestens nach 10–14 Tagen kritisch überprüft werden.

PurposeTo provide recommendations for the treatment of patients with first‐time patellar dislocation (FTPD). Part 2 focused on nonoperative treatment, bracing, rehabilitation, indications for surgery and surgical strategies.MethodsThe consensus was performed according to the European Society for Sports Traumatology, Knee Surgery and Arthroscopy consensus methodology.ResultsThe consensus comprised 32 questions and statements, 19 of which will be presented in this part. Eight statements achieved strong agreement (median 9; range 7–9), and 11 statements achieved relative agreement (median 9; range 5–9). None were Grade A, 2 were Grade B, 11 were Grade C and 5 were Grade D. In summary, treatment decisions for FTPD should prioritize individualized care, balancing patient‐specific risks and demands. Surgical options are increasingly considered for skeletally immature patients and those with increased recurrence risk. Medial patellofemoral ligament (MPFL) reconstruction is the preferred surgical technique for addressing medial soft tissue stabilizers, offering better outcomes than repair methods. Combining MPFL reconstruction with corrections of relevant bony risk factors might further reduce the risk of recurrence and revision surgery, although specific thresholds for intervention remain debated. Physical therapy is recommended as an essential complement to both operative and nonoperative treatments, but bracing offers no clear long‐term benefit. Chondral or osteochondral lesions should be repaired when the defect is at least 1 cm² in the patellofemoral joint contact area. Fragment refixation or other cartilage restoration techniques are preferred, and delayed repair is favoured over fragment removal when immediate surgery is not needed.ConclusionThe consensus consists of recommendations for evaluation and treatment strategies for managing FTPD. High levels of agreement were reached by experts throughout Europe. In areas without clear scientific evidence, this consensus aimed at providing recommendations and guidance on the basis of expert opinion and pointed out areas where further studies are necessary.Level of EvidenceLevel I, consensus.