Klinikum Hanau

A virtual endoscopy simulator with a 3D-printed endoscope handle ("Endonix®") that can be used without dedicated equipment ("plug and play") to train endoscope handling has yet not been tested. We prospectively evaluated the simulator's validity, feasibility, and usability in novices, beginners, and experienced endoscopists. Delegates at two congresses (DGVS and ENDOCLUBNORD, both 2024 in Germany) were invited. 310 complete datasets (146 DGVS, 164 ENDOCLUBNORD) were analyzed. Each participant performed two different simulation modules and completed a survey comprising questions on endoscopy experience, simulator evaluation, as well as the System Usability Scale (SUS) and the National Aeronautics and Space Administration Task Load Index (NASA-TLX). The simulator demonstrated good face validity, but only merely sufficient content validity as 67.8% of all participants favored its implementation into endoscopy training. Construct validity was also favorable as experienced endoscopists completed both modules faster than novices or beginners (P < 0.001). In line, criterion validity was given as performance correlated with self-assessed experience. The SUS yielded 75 out of 100 points (corresponding to good usability) with no discernible difference between novices, beginners, and experienced endoscopists. The NASA-TLX, ranging from 0 to 600 points, reflecting level of exhaustion, exhibited a higher score in novices and beginners than experienced endoscopists (285 vs. 210 vs. 225 points, respectively, P < 0.001). Only 16.1% of participants had access to a simulator at their respective institutions, while 79.4% wished for the incorporation of simulators into endoscopy training. The first validation of a novel virtual simulator demonstrated its feasibility and usability, with mostly sufficient validity. Many participants favored its implementation in endoscopy training, particularly for novice and beginner endoscopists, who were identified as the most suitable target learners.

Background/Objectives: The aim of this study was to determine whether incomplete follow-up and competing event risks may be associated with the clinical course after treatment and with known risk factors, such as chronic limb-threatening ischemia (CLTI), in peripheral artery disease (PAD) patients. Methods: Patients hospitalized with PAD who were treated by endovascular or open-surgical means and followed up were included in this retrospective observational study. The primary outcome was reintervention-free survival (RFS); the secondary outcomes and competing events were major amputation and death. The follow-up index (FUI), defined as the ratio between the real and the maximal follow-up interval, was determined for each patient. Results: The FUI depended significantly on the disease stage of CLTI (estimate: -0.16; p: 0.003), endovascular (0.17; p: 0.007) or open-surgical intervention (0.21; p: 0.007) and intra-hospital re-operation (-0.29; p: 0.002) and tended to decrease with age (-0.004; p: 0.09). Independent of disease stage, patients with claudication or CLTI with an FUI < 0.5 had shorter RFS than patients with a FUI ≥ 0.5 (Cox regression, p: 0.07; log-rank test, p: 0.03). When both the FUI and competing risks were considered using Fine-Gray regression analysis, CLTI was associated with RFS (p: 0.016), while FUI (p: 0.004), CLTI (p < 0.001), and the involvement of common femoral (p < 0.001) and posterior tibial arteries (p < 0.001) were associated with major amputation-free survival. Conclusions: Incomplete follow-up is associated with advanced PAD and may itself mask a worse outcome, such as reintervention, restenosis, major amputation, or death. Competing events should also be considered potential sources of bias. Therefore, the FUI and competing events should be reported, and conclusions should be drawn cautiously in both observational and randomized prospective clinical studies.

In asymptomatic Seropositive/ACPA positive Rheumatoid Arthritis (RA) patients, we used a novel screening protocol for early subclinical detection of interstitial lung disease (ILD) based on lung function testing (PFT) and lung ultrasound (LUS). (Reichenberger et al BMJ Respir Med 2024). In a subset of patients, thoracic CT scan (TCT) has been performed in addition. We investigated 202 patients (76% female, mean age 60 +/- 12 years, 43% active or previous smokers) without symptoms of pulmonary disease. By means of LUS we found ILD suspicious changes in 56 patients (28%). A reduced DLCOc-SB</=80% were detected in 95 patients (47%), and a FVC </= 80% predicted were present in 30 patients (15%). In 31 patients (15%) early ILD was suspected based on reduced DLCOc-SB </=80% pred and noticeable changes in LUS. Patients with suspected ILD changes were significantly older, were more often active or ex smokers, had a significantly lower FVC and diffusion capacity, a lower VO2 at peak exercise and AT, a higher EQCO2 slope but no difference in disease duration of RA, disease activity of RA (DAS28-CRP Score), CCP titer, and biometric parameters. A TCT was performed in 42 patients, among them 14 with early signs of ILD. <table-wrap><object-id>erj;66/suppl_69/OA6453/TB1</object-id><object-id>T1</object-id><object-id>TB1</object-id><table><colgroup><col></col><col></col><col></col><col></col><col></col><col></col></colgroup><tbody><tr><td>Suspected ILD by Means of</td><td>ILD on TCT (n=14)</td><td>no ILD on TCT (n=28)</td><td>sens</td><td>spez</td><td>npv</td></tr><tr><td>DLCOc<80%</td><td>10</td><td>25</td><td>0,71</td><td>0,11</td><td>0,11</td></tr><tr><td>LUS positive</td><td>13</td><td>11</td><td>0,93</td><td>0,61</td><td>0,98</td></tr><tr><td>combination DLCO and LUS</td><td>12</td><td>17</td><td>0,86</td><td>0,61</td><td>0,96</td></tr></tbody></table></table-wrap> <bold>Conclusion:</bold> In asymptomatic RA-patients, signs of ILD based on PFT and LUS were consistently found in 15 % of patients. In a subset of 42 Patients who underwent TCT, LUS/PFT criteria has a NPV of 96% to exclude subclinical ILD

Wilson disease, a well-established genetic disorder characterized by impaired copper excretion and toxic copper accumulation in the liver, has clear clinical presentations and diagnostic criteria. However, the metabolic and molecular pathways leading to liver injury - a critical hallmark of the disease - remain largely cryptic and require new analytical approaches to elucidate underlying mechanisms. In Wilson disease, supraphysiological and toxic amounts of hepatic copper arise due to genetically reduced biliary excretion. Interestingly, hepatic iron accumulation of unknown etiology is also observed. Both metals contribute to the production of reactive oxygen species (ROS), including singlet oxygen, superoxide anions, and highly disruptive hydroxyl radicals generated via the Haber-Weiss and Fenton reactions. Historically, liver injury has been attributed to copper-induced toxicity (cuproptosis) without sufficient consideration of ROS involvement, neglecting the significant ROS burden in hepatic tissue. A revised concept of cuproptosis incorporates ROS, particularly hydroxyl radicals, which convert copper ions into reactive intermediates such as copper peroxyl, copper hydroperoxyl, and copper superoxyl species. These intermediates induce mitochondrial oxidative stress by covalently binding to mitochondrial constituents including lipoylated dihydrolipoamide S-acetyltransferase (DLAT), leading to its aggregation and triggering regulated cell death via cuproptosis. Thus, copper ions must first be converted into reactive intermediates to initiate cuproptosis effectively. Furthermore, singlet oxygen and superoxide anion hydroxyl radicals generated by hepatic iron ions may promote regulated cell death via ferroptosis. This process involves the accumulation of lipid peroxides derived from polyunsaturated fatty acids in mitochondrial membranes, with malondialdehyde (MDA) serving as a diagnostic marker. Consequences include enhanced mitochondrial membrane rigidity, disruption of plasma membrane integrity, and ultimately cell death. This mechanistic pathway requires the activity of iron-dependent enzymes such as lipoxygenases, ferroptosis suppressor protein 1, glutathione peroxidase 4, dihydroorotate dehydrogenase, and lysosomal iron release from ferritin stores. To sum up, the definition of cuproptosis requires refinement to incorporate its mechanistic dependence on ROS, and its quantitative contribution to liver injury should be reassessed alongside hepatic iron and ferroptosis.