Background: Chronic heart failure (CHF) is amajorcauseof morbidity and mortality worldwide, placing a significant burden on health care systems. The concept of telemedicine for CHF was first introduced in the late 1990s, and since 2010, studies have demonstrated its potential to improve patient outcomes and reduce health care costs. Over the following decade, technological advancements and changes in health care policy led to the development of more sophisticated telemedicine solutions for CHF, including remote patient management through invasive or noninvasive telemonitoring devices, mobile apps, and virtual consultations. Years of public funding in Germany have generated evidence that remote patient management improves outcomes for patients with CHF, such as quality of life, and reduces hospital admissions. Based on these data, the Federal Joint Committee (Gemeinsamer Bundesausschuss; G-BA) decided, independently of the current European Society of Cardiology recommendations, to incorporate telemedicine as a standard digital intervention for high-risk patients with reduced left ventricular ejection fraction in Germany in 2020. Objective: This review aims to illustratethejourney from the initial concept through pioneering studies that led to telemedicine's integration into standard care, and to share current experiences that have positioned Germany as a leader in cardiovascular telemedicine. Methods: We review and discuss existing literature and evidence on the development and implementation of telemonitoring for CHF in Germany over the past 20 years. Relevant studies, reports, and guidelines were identified through a comprehensive search of electronic databases, including PubMed, Google Scholar, and specialized journals focused on CHF telemonitoring. Results: Pioneering studies, such as the TIM-HF2 (Telemedical Interventional Management in Heart Failure II) and IN-TIME (Influence of Home Monitoring on Mortality and Morbidity in Heart Failure Patients with Impaired Left Ventricular Function) trials, demonstrated the effectiveness of remote patient management applications for patients with CHF in Germany and their applicability to current practices involving both invasive and noninvasive methods. Collaborations between researchers and technology developers overcame barriers, leading to sustainable improvements in patient care. Ongoing research on artificial intelligence applications for prioritizing and interpreting individual health data will continue to transform digital health care. Conclusions: The establishment of telemedical care for patients with HF across Europe is likely to benefit from experiences in Germany, where significant improvements have been achieved in the care of patients with HF.

Background: Dementia management presents a significant challenge for individuals affected by dementia, as well as their families, caregivers, and health care providers. Digital applications may support those living with dementia; however only a few dementia-friendly applications exist. Objective: This paper emphasizes the necessity of considering multiple perspectives to ensure the high-quality development of supportive health care applications. The findings underscore the importance of incorporating input from stakeholders and the needs of affected families into application development. Method: A qualitative approach was chosen, consisting of three interviews and an expert workshop. The interviews and the workshop were recorded and transcribed, and qualitative content analysis was carried out according to the methodology Results: During the development phases of the application, team meetings and discussions took place. We found that general practitioners and family caregivers play pivotal roles in the treatment and care of people with dementia, often expressing specific preferences and suggestions regarding supportive and assistive technologies. Moreover, the successful development of a useful tablet application requires robust scientific and multidisciplinary discussions and teamwork within the health care community. Conclusion: This paper underscores the necessity of including multiple scientific, clinical, and technical perspectives to ensure the high-quality development of supportive health care applications. Furthermore, adopting a spiral development approach inclusive of feedback loops is imperative for iterative refinement and enhancement of the application.

Mammalian cells produce and metabolize almost exclusively L-lactate, bacterial species have the capacity to produce both D-lactate and L-lactate. The aim of this study was to evaluate the intrinsic production of D- and L-lactate in the most common pathogenic microorganisms causing septic arthritis (SA) and periprosthetic joint infection (PJI) as a potential biomarker for the diagnosis of infection. Following microorganisms were grown according to ATCC culture guides and tested for production of D- and L-lactate: Staphylococcus aureus (ATCC 43300), Staphylococcus epidermidis (ATCC 35984), Enterococcus faecalis (ATCC 19433), Streptococcus pyogenes (ATCC 19615), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Cutibacterium acnes (ATCC 11827), and Candida albicans (ATCC 90028). Pathogens were inoculated in 8 ml of appropriate liquid media and incubated as planktonic or biofilm form in either aerobic, anaerobic or CO2 atmosphere up to 312 h. D- and L-lactate measurements were performed at different time points: 0, 6, 9, 12 and 24 h, then once per day for slow-growing pathogens. Samples were serially diluted and plated for colony counting. Liquid culture media without microorganisms served as a negative control. Production of D-lactate was observed in all tested microorganisms, whereas no L-lactate was detected in E. coli, P. aeruginosa, and C. albicans. Maximal concentration of D-lactate was produced by S. aureus (10.99 mmol/L), followed by E. coli (1.22 mmol/L), and S. epidermidis (0.48 mmol/L). Maximal L-lactate concentration was observed in S. pyogenes (10.12 mmol/L), followed by S. aureus (9.71 mmol/L), E. faecalis (2.64 mmol/L), and S. epidermidis (2.50 mmol/L). S. epidermidis bacterial biofilm produced significantly higher amount of D- and L-lactate compared to planktonic form (p = 0.015 and p = 0.002, respectively). Our study has demonstrated that the most common pathogenic microorganisms causing SA and PJI have the capability to generate measurable amounts of D-lactate in both planktonic and biofilm form, highlighting the practical value of this biomarker as an indicator for bacterial and fungal infections. In contrast to D-lactate, the absence of L-lactate production in certain tested bacteria, as well as in fungi, suggests that L-lactate is not eligible as a biomarker for diagnosing microbial infections.

Intrawound application of vancomycin is becoming increasingly controversial for the prevention of surgical site infection (SSI). As children undergoing spinal fusion for secondary scoliosis are at high risk for SSIs, evidence regarding the impact of intraoperative vancomycin installation on SSI rates in these patients is of utmost importance. Methodology: A single surgeon cohort of patients under 18 years of age undergoing surgery for secondary scoliosis in 2017 was analyzed with regard to the development of SSIs requiring surgical revision and adverse events. Use of vancomycin was restricted to cases with higher risk of infection. Patients undergoing distraction surgery for growing devices were excluded. Results: After exclusions, 64 patients remained (vancomycin n = 39, control n = 25). The SSI rates were 12.8% in patients receiving vancomycin (n = 5/39) and 4% in the control group (n = 1/25, p = 0.785). None of the patients suffered from adverse events. Univariable logistic regression revealed younger age (p = 0.03) and meningomyelocele as predictors for SSI (p = 0.006), while the high-risk group receiving vancomycin was not at higher odds for SSI, also after adjustment for possible confounders such as age or MMC (p = 0.031; p = 0.009). Discussion: SSI rates were comparable between groups, suggesting a normalization of SSI risk in the vancomycin-treated patients with a preoperatively increased risk of SSI. Future, larger studies in these rare diseases are needed to confirm these results.

Background Several commercially available software packages exist for the analysis of three-dimensional cine phase-contrast cardiovascular magnetic resonance (CMR) with three-directional velocity encoding (four-dimensional (4D) flow CMR). Only sparse data are available on the impact of these different software solutions on quantitative results. We compared two different commercially available and widely used software packages and their impact on the forward flow volume (FFV), peak velocity (PV), and maximum wall shear stress (WSS) per plane.Materials and methods 4D flow CMR datasets acquired by 3 Tesla magnetic resonance imaging of 10 healthy volunteers, 13 aortic stenosis patients, and 7 aortic valve replacement patients were retrospectively analyzed for FFV, PV, and WSS using two software packages in six analysis planes along the thoracic aorta. Absolute (AD) and relative differences (RD), intraclass correlation coefficients (ICC), Bland-Altman analysis, and Spearman's correlation analysis were calculated.Results For the FFV and PV in healthy volunteers, there was good to excellent agreement between both software packages [FFV: ICC = 0.93-0.97, AD: 0.1 +/- 5.4 ml (-2.3 +/- 2.4 ml), RD: -0.3 +/- 8% (-5.7 +/- 6.0%); PV: ICC = 0.81-0.99, AD: -0.02 +/- 0.02 ml (-0.1 +/- 0.1 ml), RD: -1.6 +/- 2.1% (-9.3 +/- 6.1%)]. In patients, the FFV showed good to excellent agreement [ICC: 0.75-0.91, AD: -1.8 +/- 6.5 ml (-8.3 +/- 9.9 ml), RD: -2.2 +/- 9.2% (-13.8 +/- 17.4%)]. In the ascending aorta, PV showed only poor to moderate agreement in patients (plane 2 ICC: 0.33, plane 3 ICC: 0.72), whereas the rest of the thoracic aorta revealed good to excellent agreement [ICC: 0.95-0.98, AD: -0.03 +/- 0.07 (-0.1 +/- 0.1 m/s), RD: -3.5 +/- 7.9% (-7.8 +/- 9.9%)]. WSS analysis showed no to poor agreement between both software packages. Global correlation analyses revealed good to very good correlation between FFV and PV and only poor correlation for WSS.Conclusions There was good to very good agreement for the FFV and PV except for the ascending aorta in patients when comparing PV and no agreement for WSS. Standardization is therefore necessary.

A 6-year-old female spayed Podenco-crossbreed dog was presented with an unusual type of focal impaired awareness seizures, including sensory ataxia and postictal rest. Magnetic resonance imaging examination revealed pre- and post-contrast agent T1-weighted bilateral symmetric hyperintensities in the lentiform nuclei and globus pallidus. Repeated cerebrospinal fluid sampling showed lymphocytic pleocytosis. Cerebrospinal fluid immunoglobulin G autoantibodies to myelin basic protein (MBP) were detected by immunofluorescence examination with strong binding to myelinated fiber tracts. The absence of binding to MBP-depleted mouse brains confirmed MBP as an antigenic target. Although the patient had minor seizure episodes every 2 months, and the owners avoided seizure triggers, they refused medical treatment before presenting to the veterinarian. To the best of our knowledge, this is the first description of MBP autoantibody-positive encephalitis in a dog.

During inflammation, human neutrophils engage beta 2-integrins to migrate from the blood circulation to inflammatory sites with high cytokine but low oxygen concentrations. We tested the hypothesis that the inhibition of prolyl hydroxylase domain-containing enzymes (PHDs), cytokines, and beta 2-integrins cooperates in HIF pathway activation in neutrophils. Using either the PHD inhibitor roxadustat (ROX) (pseudohypoxia) or normobaric hypoxia to stabilize HIF, we observed HIF1 alpha protein accumulation in adherent neutrophils. Several inflammatory mediators did not induce HIF1 alpha protein but provided additive or even synergistic signals (e.g., GM-CSF) under pseudohypoxic and hypoxic conditions. Importantly, and in contrast to adherent neutrophils, HIF1 alpha protein expression was not detected in strictly suspended neutrophils despite PHD enzyme inhibition and the presence of inflammatory mediators. Blocking beta 2-integrins in adherent and activating beta 2-integrins in suspension neutrophils established the indispensability of beta 2-integrins for increasing HIF1 alpha protein. Using GM-CSF as an example, increased HIF1 alpha mRNA transcription via JAK2-STAT3 was necessary but not sufficient for HIF1 alpha protein upregulation. Importantly, we found that beta 2-integrins led to HIF1 alpha mRNA translation through the phosphorylation of the essential translation initiation factors eIF4E and 4EBP1. Finally, pseudohypoxic and hypoxic conditions inducing HIF1 alpha consistently delayed apoptosis in adherent neutrophils on fibronectin under low serum concentrations. Pharmacological HIF1 alpha inhibition reversed delayed apoptosis, supporting the importance of this pathway for neutrophil survival under conditions mimicking extravascular sites. We describe a novel beta 2-integrin-controlled mechanism of HIF1 alpha stabilization in human neutrophils. Conceivably, this mechanism restricts HIF1 alpha activation in response to hypoxia and pharmacological PHD enzyme inhibitors to neutrophils migrating toward inflammatory sites.

Thyroid hormone receptor alpha (THR alpha) is a nuclear hormone receptor that binds triiodothyronine (T3) and acts as an important transcription factor in development, metabolism, and reproduction. In mammals, THR alpha has two major splicing isoforms, THR alpha 1 and THR alpha 2. The better-characterized isoform, THR alpha 1, is a transcriptional stimulator of genes involved in cell metabolism and growth. The less-well-characterized isoform, THR alpha 2, lacks the ligand-binding domain (LBD) and is thought to act as an inhibitor of THR alpha 1 activity. The ratio of THR alpha 1 to THR alpha 2 splicing isoforms is therefore critical for transcriptional regulation in different tissues and during development. However, the expression patterns of both isoforms have not been studied in healthy human tissues or in the developing brain. Given the lack of commercially available isoform-specific antibodies, we addressed this question by analyzing four bulk RNA-sequencing datasets and two scRNA-sequencing datasets to determine the RNA expression levels of human THRA1 and THRA2 transcripts in healthy adult tissues and in the developing brain. We demonstrate how 10X Chromium scRNA-seq datasets can be used to perform splicing-sensitive analyses of isoforms that differ at the 3 '-end. In all datasets, we found a strong predominance of THRA2 transcripts at all examined stages of human brain development and in the central nervous system of healthy human adults.

Animal manure is applied in agriculture to improve soil fertility and crop yield. Nonetheless, manure can also carry Escherichia coli (E. coli), including antibiotic-resistant strains. Therefore, it may pose a risk for environmental contamination. This review includes 50 studies which were identified from the search terms related to the transmission of E. coli through manure. The review outlines the potential routes of E. coli transmission from manure to soil, water and crops and which factors most critically determine persistence and contamination. The persistence of E. coli in soil is highly variable, ranging from <30 days for composted manures to more than 200 days in cooler conditions. These differences depend on the type of manure used, the environmental conditions and the treatment employed. While crops can be contaminated directly through application of manure, contaminated irrigation water may be a more important pathway. The foremost cause of surface water contamination seems to be rainfall runoff, whereas groundwater contamination is rather uncommon, mainly happening in areas with specific soil conditions. Composting and adherence to pre-harvest intervals are very effective mitigation strategies that can greatly reduce contamination risks. Overall, this review identifies research gaps on water contamination pathways and the persistence of resistant strains. Moreover, it sets up the basis for the development of robust risk assessments and evidence-informed approaches to address the contamination risks that are linked to animal manure.

Background Remote patient management may improve prognosis in heart failure. Daily review of transmitted data for early recognition of patients at risk requires substantial resources that represent a major barrier to wide implementation. An automated analysis of incoming data for detection of risk for imminent events would allow focusing on patients requiring prompt medical intervention. Methods We analysed data of the Telemedical Interventional Management in Heart Failure II (TIM-HF2) randomized trial that were collected during quarterly in-patient visits and daily transmissions from non-invasive monitoring devices. By application of machine learning, we developed and internally validated a risk score for heart failure hospitalisation within seven days following data transmission as estimate of short-term patient risk for adverse heart failure events. Score performance was assessed by the area under the receiver-operating characteristic (ROCAUC) and compared with a conventional algorithm, a heuristic rule set originally applied in the randomized trial. Results The machine learning model significantly outperformed the conventional algorithm (ROCAUC 0.855 vs. 0.727, p < 0.001). On average, the machine learning risk score increased continuously in the three weeks preceding heart failure hospitalisations, indicating potential for early detection of risk. In a simulated one-year scenario, daily review of only the one third of patients with the highest machine learning risk score would have led to detection of 95% of HF hospitalisations occurring within the following seven days. Conclusions A machine learning model allowed automated analysis of incoming remote monitoring data and reliable identification of patients at risk of heart failure hospitalisation requiring immediate medical intervention. This approach may significantly reduce the need for manual data review.

Gaussian states of bosonic quantum systems enjoy numerous technological applications and are ubiquitous in nature. Their significance lies in their simplicity, which in turn rests on the fact that they are uniquely determined by two experimentally accessible quantities, their first and second moments. But what if these moments are only known approximately, as is inevitable in any realistic experiment? What is the resulting error on the Gaussian state itself, as measured by the most operationally meaningful metric for distinguishing quantum states, namely, the trace distance? In this work, we fully resolve this question by demonstrating that if the first and second moments are known up to an error ε, the trace distance error on the state also scales as ε, and this functional dependence is optimal. To prove this, we establish tight bounds on the trace distance between two Gaussian states in terms of the norm distance of their first and second moments. As an application, we improve existing bounds on the sample complexity of tomography of Gaussian states.

Background: The use of mammalian target of rapamycin inhibitors (mTORis) in kidney transplantation increases the risk of donor-specific human leukocyte antigen (HLA) antibody formation and rejection. Here, we investigated the long-term consequences of early mTORi treatment compared to calcineurin inhibitor (CNI) treatment. Methods: In this retrospective single-center analysis, key outcome parameters were compared between patients participating in randomized controlled immunosuppression trials between 1998 and 2011, with complete follow-up until 2018. The outcomes of eligible patients on a CNI-based regimen (n = 384) were compared with those of patients randomized to a CNI-free mTORi-based regimen (n = 81) and 76 patients randomized to a combination of CNI and mTORi treatments. All data were analyzed according to the intention-to-treat (ITT) principle. Results: Deviation from randomized immunosuppression for clinical reasons occurred significantly more often and much earlier in both mTORi-containing regimens than in the CNI treatment. Overall patient survival, graft survival, and death-censored graft survival did not differ between the treatment groups. Donor-specific HLA antibody formation and BPARs were significantly more common in both mTORi regimens than in the CNI-based immunosuppression. Conclusions: The tolerability and efficacy of the mTORi treatment in kidney graft recipients are inferior to those of CNI-based immunosuppression, while the long-term patient and graft survival rates were similar.

Achiral molecules can be made temporarily chiral by excitation with electric fields, in the sense that an average over molecular orientations displays a net chiral signal [D. S. Tikhonov et al., Sci. Adv. 8, eade0311 (2022)]. Here, we go beyond the assumption of molecular orientations to remain fixed during the excitation process. Treating both rotations and vibrations quantum mechanically, we identify conditions for the creation of chiral vibrational wave packets, with net chiral signals, in ensembles of achiral molecules which are initially randomly oriented. Based on the analysis of symmetry and controllability, we derive excitation schemes for the creation of chiral wave packets using a combination of (a) microwave and IR pulses and (b) a static field and a sequence of IR pulses. These protocols leverage quantum rotational dynamics for pump-probe spectroscopy of chiral vibrational dynamics, extending the latter to regions of the electromagnetic spectrum other than the UV.

Squeezing is a nonclassical feature of quantum states that is a useful resource, for example, in quantum sensing of mechanical forces. Here, we show how to use optimal control theory to maximize squeezing in an optomechanical setup with two external drives and determine how fast the mechanical mode can be squeezed. For the autonomous drives considered here, we find the inverse cavity decay to lower-bound the protocol duration. At and above this limit, we identify a family of protocols leveraging a two-stage control strategy, where the mechanical mode is cooled before it is squeezed. Identification of the control strategy allows for two important insights: to determine the factors that limit squeezing and to simplify the time dependence of the external drives, making our protocol readily applicable in experiments.

Seit die Philosophie sich aus dem umfassenden Fundament der Metaphysik entlassen hatte, fächerte sie sich, ähnlich den Wissenschaften, in fachliche Segmente auf: Epistemologie, Ontologie, Geschichtsphilosophie, politische Philosophie, Naturphilosophie, Existenzphilosophie, praktische Philosophie, Ethik, Wissenschaftstheorie etc. Für das Wirtschaftliche im Philosophischen etablierte sich ab etwa Ende des 19. Jahrhunderts der Name ‘Wirtschaftsphilosophie’. Aus der Wirtschaftsphilosophie wurde aber bislang keine eigene philosophische Teildisziplin, vielmehr wurde sie auf unbestimmte Weise dem weiten Bereich der Praktischen Philosophie zugeschlagen. Wirtschaftsphilosophie ist aber vielmehr ein Reflexionsraum, der alle fachlich ausdifferenzierten Segmente des Philosophischen durchzieht. Das zeigt sich vor allem daran, auf welch verschiedene Art Wirtschaftsphilosophie heute betrieben wird: beispielsweise als epistemologische Befragung der vorherrschenden Semantik der Ökonomik, als Hinterfragen der Rationalitätsphilosophie der modern economics, als gabenökonomische Spurenanalyse einer Reziprozitätsphilosophie im Ökonomischen, als geschichtsphilosophische Rekonstruktion des Kapitalismus und seiner Industrialisierungswirkungen, als Rhetorik des Ökonomischen und ihrer narrativen Ausprägungen, als medienphilosophische Rekonstruktion der Finanzökonomie, als ethische Analyse von Normengeltung im Ökonomischen, als Philosophie der Dynamik der Ordnungsvorstellungen in der Geschichte, als politische Philosophie der politischen Ökonomie u.a. Es bildet sich kein Standardmodell heraus, sondern 2 ein bewegliches Feld philosophischer Reflektion des Ökonomischen, zum Teil “in rücksichtsloser Überschreitung” (Rorty) etablierter Begriffssysteme, um Neubeschreibungen und neue Interpretationen zu leisten. Die Philosophie hat immer schon das wirtschaftliche Handeln des Menschen thematisiert. Einschlägige Ansätze finden sich von Platon und Aristoteles über Thomas von Aquin, John Locke, Wolff, Rousseau, Fichte, Hegel, Marx und Nietzsche bis zu Bataille, Baudrillard, Derrida, Rawls, Sen und anderen. Diese Ansätze bildeten sich aber nicht zu einer spezifischen Wirtschaftsphilosophie aus, sondern blieben Reflexionen des Ökonomischen im Kontext der je eigenen Positionen und Ansätze. Heute zeigt sich: Die Philosophie, soweit sie das Wirtschaften reflektiert, denkt über die Wirtschaft als Sphäre nach, polyvalent, in all ihren Dimensionen, die das Effiziente weit übersteigen. Sie kann die Wirtschaft in ihrer Spannung zwischen Überfluss, Freiheit und Notwendigkeit reflektieren, ohne Dogmen, Mythen oder Ideologien aufzusitzen. Dieses intellektuelle Potenzial wird jedoch nicht genutzt, wenn man die Wirtschaftsphilosophie auf praktische Philosophie bzw. auf Wirtschaftsethik einschränkt. Angemessen wäre es heute, Wirtschaftsphilosophie als ein disziplinenübergreifendes Projekt anzusehen, innerhalb dessen die Reflexion erkenntnistheoretischer und methodologischer Aspekte und deren praktische Konsequenzen sowohl für die ökonomische Theoriebildung als auch das wirtschaftliche Handeln im Vordergrund stehen. Eine solche Ausfaltung des wirtschaftsphilosophischen Reflexionspotentials umfasst ein Spektrum von philosophischen Ansätzen über ökonomische Grundlagenfragen, Theorien und Praktiken, wodurch kein einheitliches Feld entsteht, sondern sich verschiedene Methoden, Narrationen, Systeme und Diskurse bilden. Ziel wirtschaftsphilosophischer Konsolidierung sollte es daher nicht sein, eine ähnliche fachliche Konsistenz wie die Wirtschaftswissenschaften erlangen zu wollen (ein Ideal, das derzeit auch innerhalb der Ökonomik herausgefordert wird), sondern einen Reflexionsraum zu schaffen, der die verschiedenen ökonomischen Theorien und Praktiken spiegeln kann (vor allem in Bezug auf ihre kontextuelle und kulturelle Einbettung). Vor diesem Hintergrund fasst das Positionspapier die wichtigsten Ergebnisse des Workshops zusammen, beschreibt die Potentiale und Probleme der Wirtschaftsphilosophie und macht Vorschläge für die Positionierung der Wirtschaftsphilosophie in Forschung, Lehre und Öffentlichkeit.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized systemic autoinflammatory disease caused by somatic mutations in hematopoietic progenitor cells. This case series of four patients with VEXAS syndrome and comorbid myelodysplastic syndrome (MDS) aims to describe clinical, imaging, and hematologic disease presentations as well as response to therapy. Four patients with VEXAS syndrome and MDS are described. A detailed analysis of imaging features, hemato-oncological presentation including bone marrow microscopy and clinical-rheumatological disease features and treatment outcomes is given. All patients were male; ages ranged between 64 and 81 years; all were diagnosed with MDS. CT imaging was available for three patients, all of whom exhibited pulmonary infiltrates of varying severity, resembling COVID-19 or hypersensitivity pneumonitis without traces of scarring. Bone marrow microscopy showed maturation-disordered erythropoiesis and pathognomonic vacuolation. Somatic mutation in the UBA1 codon 41 were found in all patients by next-generation sequencing. Therapy regimes included glucocorticoids, JAK1/2-inhibitors, nucleoside analogues, as well as IL-1 and IL-6 receptor antagonists. No fatalities occurred (observation period from symptom onset: 18-68 months). Given the potential underreporting of VEXAS syndrome, we highly recommend contemporary screening for UBA1 mutations in patients presenting with ambiguous signs of systemic autoinflammatory symptoms which persist over 18 months despite treatment. The emergence of cytopenia, especially macrocytic hyperchromic anemia, should prompt early testing for UBA1 mutations. Notably conspicuous, pulmonary alterations in CT imaging of patients with therapy-resistant systemic autoinflammatory symptoms should be discussed in interdisciplinary medical teams (Rheumatology, Hematology, Radiology and further specialist departments) to facilitate timely diagnosis during the clinical course of the disease.