Universitätsklinikum Carl Gustav Carus Dresden

Bispecific T‐cell engagers (BTCEs) represent a paradigm shift in the treatment of relapsed/refractory multiple myeloma (RRMM). Talquetamab, a GPRC5DxCD3 BTCE, has shown promising results in the MonumenTAL‐1 trial and was recently approved by the Food and Drug Administration and the European Medicines Agency. However, treatment under real‐world conditions may not represent patient characteristics in clinical trials with restricted enrollment criteria. We performed a retrospective real‐world analysis including 138 RRMM patients treated with talquetamab at 21 German centers. Of evaluable patients, 43% had ISS stage III, 37% had extraosseous disease, and 48% had high‐risk cytogenetics. After a median of six prior therapy lines, 58% of patients would not have been eligible for MonumenTAL‐1. With a median follow‐up of 8.2 months, we observed an overall response rate of 65% and a median progression‐free survival of 6.4 months (95% confidence interval 5.1–9.0). Prior BTCE exposure, ISS stage III, extraosseous disease, and penta‐drug refractory disease were associated with unfavorable outcomes. Grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 5.1% and 1.5% of patients, respectively. In summary, our real‐world study confirms the efficacy and safety of talquetamab, despite a high proportion of patient‐ and disease‐related risk factors. These results support its use as bridging or long‐term treatment, even in advanced stages.

IgE‐mediated allergies play a significant role in respiratory diseases. Given the similar mucosal epithelium of the upper and lower respiratory tracts and their shared (patho)physiological immune responses, the “unified airways” concept views these tracts as a single system. Recently, this model has been extended to include the middle ear, with studies confirming that the Eustachian tube and middle ear are both anatomically and functionally part of the upper airways. However, the relationship between allergies and middle ear disorders remains controversial, with conflicting findings regarding pathogenesis and treatment. The increasing prevalence of allergies highlights the importance of further research. In Germany, the current sensitization rate to aeroallergens is 33.6%, with similar trends across Europe, where rates commonly range up to 30%. This widespread increase underscores the urgent need for a deeper understanding of the correlation between allergies and middle ear disorders across diverse European populations. Ineffective pharmacotherapy or possibly harmful medication for acute and chronic OME, such as systemic steroids, is most likely used globally in an uninformed way, due to a lack of evidence on the connection between allergic inflammation and eustachian tube dysfunction. Further research is essential to clarify the mechanisms linking IgE‐mediated allergies to middle ear pathologies and to develop effective treatment strategies. Addressing these knowledge gaps is critical for improving patient outcomes and managing the rising burden of allergic diseases.

Background: Patients having emergency surgery due to ischemia caused by a popliteal artery aneurysm (PAA) have worse outcomes in all endpoints (operation time, major adverse limb events (MALE), amputation-free survival) than after elective treatment, mostly due to a limited crural vessel runoff. This study investigates the relationship between PAA diameter, volume, and luminal thrombus load in relation to the preoperative crural runoff. Patients and methods: Retrospective single-centre evaluation of surgically treated patients with PAA and semi-automated quantitative CT analysis of PAA morphologies (diameter, volume and intraluminal thrombus volume). Primary endpoints were the correlations these characteristics with the number of patent crural vessels. Results: A total of 89 PAAs (61 patients, median age 75, IQR 12; 94.4% male) were identified, of which 47.2% were symptomatic with 18 acute limb ischemia (ALI). The diameter at surgery was 33.8 ± 12.1mm and the volume 68.5 ± 13.6mm ³ . A median of two lower leg vessels were patent (elective 3 [ 1 , 2 , 3 ] vs. emergency 1 [ 1 , 2 ], p=0.1) upon preoperative CTA. 77 PAAs underwent elective surgery, five PAAs (5.6%) received endovascular treatment. The surgical complication rate was 23.6% without immediate or early occlusion. The follow-up was 42.5 [39–45] months. The overall mortality rate was 11.2% and the primary patency rate 73.9%. While the total aneurysm volume correlated well with the diameter (r=0.77, p<0.01), the intraluminal thrombus volume (ILT) showed the clearest correlation with the crural runoff (r=–0.34, p=0.01). No correlation between the diameter and crural runoff was observed (r=–0.17, p=0.1). A reduced crural run-off was significantly associated with impaired amputation-free survival (p=0.01). A subgroup analysis (n=21) with sequential CTs showed a tendency towards greater increase of thrombus volume compared to plain diameter during PAA growth. The thrombus volume index (=ILT/total PAA volume) was significantly higher in emergency patients (p=0.01), while diameters tended to be smaller (p=0.57). Conclusions: The increasing intraluminal thrombus volume correlates most distinctly with a reduced crural runoff in PAAs and should therefore be considered prognostically important, especially in the presence of an increased growth rate compared to the diameter.

Background A reduction of dose and/or acquisition duration of PET examinations is desirable in terms of radiation protection, patient comfort and throughput, but leads to decreased image quality due to poorer image statistics. Recently, different deep-learning based methods have been proposed to improve image quality of low-count PET images. For example, one such approach allows the generation of AI-enhanced PET images (AI-PET) based on ultra-low count PET/CT scans. The performance of this algorithm has so far only been clinically evaluated on patient data featuring limited scan statistics and unknown actual activity concentration. Therefore, this study investigates the performance of this deep-learning algorithm using PET measurements of a phantom resembling different lesion sizes and count statistics (from ultra-low to high) to understand the capabilities and limitations of AI-based post processing for improved image quality in ultra-low count PET imaging. Methods A previously trained pix2pixHD Generative Adversarial Network was evaluated. To this end, a NEMA PET body phantom filled with two sphere-to-background activity concentration ratios (4:1 and 10:1) and two attenuation scenarios to investigate the effects of obese patients was scanned in list mode. Images were reconstructed with 13 different acquisition durations ranging from 5 s up to 900 s. Image noise, recovery coefficients, SUV-differences, image quality measurement metrics such as the Structural Similarity Index Metric, and the contrast-to-noise-ratio were assessed. In addition, the benefits of the deep-learning network over Gaussian smoothing were investigated. Results The presented AI-algorithm is very well suitable for denoising ultra-low count PET images and for restoring structural information, but increases image noise in ultra-high count PET scans. The generated AI-PET scans strongly underestimate SUV especially in small lesions with a diameter ≤ 17 mm, while quantitative measures of large lesions ≥ 37 mm in diameter were accurately recovered. In ultra-low count or low contrast images, the AI algorithm might not be able to recognize small lesions ≤ 13 mm in diameter. In comparison to standardized image post-processing using a Gaussian filter, the deep-learning network is better suited to improve image quality, but at the same time degrades SUV accuracy to a greater extent than post-filtering and quantitative SUV accuracy varies for different lesion sizes. Conclusions Phantom-based validation of AI-based algorithms allows for a detailed assessment of the performance, limitations, and generalizability of deep-learning based algorithms for PET image enhancement. Here it was confirmed that the AI-based approach performs very well in denoising ultra-low count PET images and outperforms traditional Gaussian post-filtering. However, there are strong limitations in terms of quantitative accuracy and detectability of small lesions.

Lipoprotein apheresis (LA) is often the last option to adequately reduce lipoproteins in patients with familial hypercholesterolemia and lipoprotein (a) hyperlipidemia. Characterized by mild side effects, it is now the most effective method of preventing major cardiovascular events (CVEs). This benefit is due not only to the lowering of lipoprotein levels, but probably also to many other pleiotropic effects that have been extensively described in the literature. These include the reduction of inflammatory signaling substances, fibrinogen, plasminogen or components of the oxidative stress response. Here, we performed a proteomic analysis of 12 patients treated with therapeutic apheresis using two different pore size filters to quantify the effect on age-related plasma proteins. This study showed that important proteins such as α-2-macroglobulin, apolipoprotein C-III, complement C1s subcomponent, C4b-binding protein alpha chain, CD5 antigen-like and pregnancy zone protein, whose role in numerous aging processes has been well described, were significantly reduced by apheresis treatment. We conclude that therapeutic apheresis may be a promising approach to reduce these age-related proteins and that these treatments may become an essential part of managing cardiovascular risk in an aging population.

Glioblastoma (GBM) employs various strategies to resist therapy, resulting in poor patient survival. A key aspect of its survival mechanisms lies in metabolic regulation, maintaining rapid growth and evading cell death. Recent studies revealed the connection between therapy resistance and ferroptosis, a lipid peroxidation-dependent cell death mechanism triggered by metabolic dysfunction. Our aim was to identify novel regulators of therapy resistance in GBM cells. We conducted a comprehensive analysis combining RNA-sequencing data from a panel of human GBM cell models and TCGA GBM patient datasets. We focused on the top-12 differentially expressed gene candidates associated with poor survival in GBM patients and performed an RNA interference-mediated screen to uncover the radiochemosensitizing potential of these molecules and their impact on metabolic activity, DNA damage, autophagy, and apoptosis. We identified exostosin glycosyltransferase 2 (EXT2), an enzyme previously described in heparan sulfate biosynthesis, as the most promising candidate. EXT2 depletion elicited reduced cell viability and proliferation as well as radiochemosensitization in various GBM cell models. Mechanistically, we explored EXT2 function by conducting untargeted and targeted metabolomics and detected that EXT2-depleted GBM cells exhibit a differential abundance of metabolites belonging to S-adenosylmethionine (SAM) metabolism. Considering these metabolic changes, we determined lipid peroxidation and found that the diminished antioxidant capacity resulting from decreased levels of metabolites in the transsulfuration pathway induces ferroptosis. Moreover, modifications of specific SAM and transsulfuration metabolism associated enzymes revealed a prosurvival and ferroptosis-reducing function when EXT2 is depleted. Collectively, our results uncover a novel role of EXT2 in GBM cell survival and response to X-ray radiation, which is controlled by modulation of ferroptosis. These findings expand our understanding of how GBM cells respond to radio(chemo)therapy and may contribute to the development of new therapeutic approaches.

Patients at risk of developing chronic pain are often significantly impaired in their daily, social and work activities. An early interdisciplinary multimodal assessment (IMA) includes a systematically integrated view of medical, psychosocial and functional factors to direct patients to need-based treatment services. This multicentre, randomised, controlled trial examined the effects of an IMA on preventing chronic pain and improving care for adult patients. The intervention group (IG) received an IMA in accordance with standardised guidelines. The control group (CG) was offered a unimodal medical pain assessment (MPA). Data from the Characteristic Pain Intensity (PI) and Disability Score (DS), as primary outcomes, were collected at assessment and 3 and 6 months later together with secondary outcomes (e.g. depression, anxiety, stress, catastrophizing, health-related quality of life). A total of 620 (68.4%) valid questionnaires were available at the 6-month follow-up. The mean reduction (numerical rating scale, 0–10) in terms of improvement within both groups (IG/CG) was 1.6/1.7 points for PI and 1.9/1.8 points for DS. Most secondary outcomes improved as well. However, the differences between the two groups did not reach statistical significance, although there was a tendency for the IG to have a greater effect on some psychological outcomes. Regarding the recommended treatment approaches, the focus in the IG was more on physical activity and psychological and psychosomatic interventions, whereas in the CG there was also a preference for adjusting the medication. Both early MPA and IMA seem to have a positive effect on outcomes such as pain intensity, functional limitations and psychological factors for patients at risk of developing chronic pain. We critically reflect on the results of the primary research question by discussing the limitations in detail and conclude that further research should ensure that the control conditions reflect standard care and that the follow-up period is long enough. German Clinical Trials Register (DRKS-ID: DRKS00015443).

Introduction Ratings of treatment goals for patients with schizophrenia have been studied in both patients and physicians. However, in most studies so far, treatment goals were assessed either by psychiatrists or by patients, but not by both for an individual patient case. Therefore, our study assessed treatment goals from matched physician-patient pairs. Methods First, an expert panel created a questionnaire with treatment goals, based on a systematic literature search. These goals were rated for their relevance in the treatment of schizophrenia by 24 independent psychiatrists. In the second part of the study, questionnaires were sent to psychiatrists all over Germany. Psychiatrists were asked to rate treatment goals for up to 3 specific patients. Furthermore, these same patients were asked to rate the goals for themselves. Results In the first part of the study, the 24 psychiatrists agreed that 30 out of 31 treatment goals chosen by the expert panel were relevant. In the second part, effectiveness and quality of life were more often seen as the most important treatment goal categories than tolerability by both patients and physicians in matched pairs of 80 patients and 28 physicians. There was a substantial agreement between physicians and patients. However, patients expressed apprehension about possible side effects of the medication, a concern not recognized in its extent by physicians. Patients also prioritized treatment goals related to tasks of daily life and coping with illness, whereas physicians put greater emphasis on preventing relapses and re-hospitalizations. Conclusion We found that experts agree upon the importance of 30 treatment goals from three categories. Physicians and patients largely align on treatment goals. More emphasis may be placed on clarifying potential medication side effects. Physicians should be aware that patients’ priorities could be more focused on improving quality of life and gaining autonomy rather than symptom management.

As part of the COGNITION diagnostic registry program, residual tumor material after neoadjuvant therapy (NAT) of patients with early breast cancer (eBC), who are still at high-risk for relapse after NAT, is analyzed by next generation sequencing to identify biomarkers and actionable alterations. This strategy aims to stratify patients for subsequent genomics-guided therapies to reduce the significant risk of metastatic dissemination and hence to improve disease-free survival. COGNITION-GUIDE is a multicenter umbrella phase-II-trial to translate molecular biomarker profiles generated in the COGNITION platform into six molecular-guided post-neoadjuvant therapeutic options in addition to standard-of-care treatment. Patients can be allocated to The primary endpoint is invasive disease-free survival (IDFS) four years after surgery. Secondary endpoints include IDFS in each study arm separately, distant disease-free survival, overall survival and safety. 240 patients will be enrolled within four years. The COGNITION-GUIDE trial, which was activated in June 2023 and will recruit in different centers in Germany, empowers a risk-adapted, biomarker-guided therapy escalation algorithm in eBC patients who are still at high risk of metastasis.

In contrast to chimeric antigen receptor T cells, T cell receptor (TCR)-engineered T cells can target intracellular tumor-associated antigens crucial for treating solid tumors. However, most trials published so far show limited clinical activity. Here we report interim data from a first-in-human, multicenter, open-label, 3 + 3 dose-escalation/de-escalation phase 1 trial studying IMA203, an autologous preferentially expressed antigen in melanoma (PRAME)-directed TCR T cell therapy in HLA-A*02⁺ patients with PRAME⁺ recurrent and/or refractory solid tumors, including melanoma and sarcoma. Primary objectives include the evaluation of safety and tolerability and the determination of the maximum tolerated dose (MTD) and/or recommended dose for extension. Secondary objectives include the evaluation of IMA203 TCR-engineered T cell persistence in peripheral blood, tumor response as well as duration of response. A total of 27 patients were enrolled in the phase 1a dose escalation and 13 patients in the phase 1b dose extension. IMA203 T cells were safe, and the MTD was not reached. Of the 41 patients receiving treatment (that is, who started lymphodepletion), severe cytokine release syndrome was observed in 4.9% (2/41), and severe neurotoxicity did not occur. In the 40 patients treated with IMA203, an overall response rate consisting of patients with unconfirmed or confirmed response (u/cORR) of 52.5% (21/40) and a cORR of 28.9% (11/38) was observed with a median duration of response of 4.4 months (range, 2.4–23.0, 95% confidence interval: 2.6–not reached) across multiple indications. Rapid T cell engraftment and long-term persistence of IMA203 T cells were observed. IMA203 T cells trafficked to all organs, and confirmed responses were more frequent in patients with higher dose. T cell exhaustion was not observed in the periphery; deep responses were enriched at higher PRAME expression; and higher T cell infiltration resulted in longer progression-free survival. Overall, IMA203 showed promising anti-tumor activity in multiple solid tumors, including refractory melanoma. ClinicalTrials.gov identifier: NCT03686124.

Background Over the last century infectious diseases have been kept under control in industrialized countries thanks to advances in hygiene, prevention and antimicrobial treatments. However, the emergence of HIV, the COVID-19 pandemic, and the rise of resistant bacteria exemplify that infectious diseases continue to pose a global threat. A comprehensive understanding of the caseload, spectrum of infectious diseases and the economic impact they pose is required to develop strategies for managing infectious diseases in a resilient healthcare system. Objectives (i) to determine the proportion of adult patients discharged from German hospitals with primary diagnoses classified as an infectious disease, (ii) to describe the clinical spectrum of these diagnoses, case characteristics, and hospital settings, and (iii) to estimate the total economic burden that these cases contribute to the in-patient sector of the healthcare system. Methods A retrospective case-control study was performed using publicly available data on ICD10 codes assigned as primary diagnoses, case characteristics, treatment settings, and cost weights from all patients discharged from German hospitals in 2022. Results 1,728,824 adult patients (12% of all adult patients) were discharged with a primary diagnosis classified as an infectious disease. They were assigned 912 individual ICD10 codes. The 15 and 79 most frequently used codes comprised 40% (top 40% ID population) and 80% (top 80% ID population) of all infectious disease cases, respectively. In the top 80% ID population, patients were older, were more likely to be male, and had higher complexity and comorbidity levels than the reference population, which consisted of all adult patients minus the patients in the top 80% ID population. The mean length of stay of patients forming the top 80% ID population was 8.0 days vs. 6.1 days in the reference population. The median (IQR) cost weight was 0.663 (0.544–1.030) translating into €2,541 per case. Conclusions In Germany, patients with infectious diseases constitute a significant proportion of all inpatients, with a broad spectrum of conditions. These patients are generally older, more severely ill, and require longer hospital stays than those without a primary infectious disease diagnosis, contributing substantially to the overall economic burden on the healthcare system.

Objective: To describe an innovative anticoagulation strategy in a 20-year-old woman with innate jejunal atresia and ultrashort bowel syndrome who was dependent on long-term parenteral nutrition and suffered from multiple venous thrombotic events and bleeding complications since infancy. Design: Single-patient case report. Setting: Dresden University Hospital, Dresden, Germany. Patient: Being fully CVC-dependent since birth, our patient repeatedly developed catheter-related thrombosis (CRT) since infancy and was treated with daily low-molecular-weight heparin injections for more than 15 years. Despite this, clotting, severe gastrointestinal bleeding and osteoporosis remained a persistent problem, causing numerous hospitalizations over the years, significant developmental delays, and a decline of the patient’s body mass index (BMI). A short period of rivaroxaban treatment had to be stopped owing to acute gastrointestinal bleeding. After failure of all approved anticoagulant concepts, compassionate use access was granted to the investigational drug osocimab, a human monoclonal antibody inhibitor of factor XIa. Hereditary FXI deficiency as well as FXI inhibition in animal models have been shown to reduce arterial and venous thrombosis without increasing bleeding. Consistent with this, short-term osocimab treatment has shown clinical efficacy in preventing postoperative venous thromboembolism after knee replacement surgery and in reducing dialysis conduit clotting compared with placebo in patients undergoing hemodialysis, without increasing the rate of clinically relevant bleeding versus comparators. After initiating osocimab, the patient experienced no further clotting complications and bleeding decreased in frequency and severity. The patient’s BMI decline immediately stopped; her weight increased by over 10% in the subsequent 20 months, and menstruation started 3 months later without signs of menorrhagia. Now, with 2.5 years of uninterrupted exposure outside of a clinical trial, this patient has experienced the longest duration of factor XIa inhibition to date. She continues to receive osocimab under the compassionate use program and maintains a positive change in well-being and quality of life.

Zusammenfassung Hintergrund Die Diagnostik vor ohrchirurgischen Eingriffen ist wichtiger Bestandteil der ohrenärztlichen Tätigkeit in Kliniken. Bislang existiert national und international noch kein Diagnostikstandard. Vielmehr sind die genutzten Testbatterien abhängig von klinikeigenen Lehrmeinungen. Fragestellung Ziel der Arbeit war es, durch eine Umfrage im deutschsprachigen Raum die Routinediagnostikmethoden vor verschiedenen ohrchirurgischen Eingriffen zu erfassen. Methoden Es wurde ein Online-Fragebogen mit 18 allgemeinen Fragen zur Ausstattung der Klinik und Verfügbarkeit von Tests sowie je sechs Fragen zu spezifischen Ohroperationen an die Klinikleiter/-innen versendet. Ergebnisse Von 180 angeschriebenen Kliniken nahmen 56 Kliniken (31 %) an der Umfrage teil. Für acht spezifische Operationen (sanierende Ohr-Operation mit und ohne Cholesteatom, hörverbessernde Operation, Stapesplastik, Gehörgangsstenosen-Operation, Gehörgangsatresie-Operation, Implantation von aktiven Mittelohrimplantaten und Cochleaimplantat-Operationen) konnten die im deutschsprachigen Raum mehrheitlich genutzten Testbatterien bestimmt werden. Es zeigte sich, dass bei klar definierten Diagnostikbatterien diese mehrheitlich in den klinikeigenen Diagnostikschritten implementiert werden. Eine apparative neurootologische Diagnostik erfolgt im deutschsprachigen Raum vorzugsweise vor einer Hörimplantatversorgung, hat jedoch bei mittelohrchirurgischen Eingriffen in den deutschsprachigen Kliniken nur einen geringen Stellenwert. Schlussfolgerung Im deutschsprachigen Raum zeigt sich eine Inhomogenität der Diagnostikpfade vor ohrchirurgischen Eingriffen. Die Ergebnisse dieser Umfrage liefern eine weitere Diskussionsgrundlage zur Erarbeitung eines Diagnostikstandards, welcher in entsprechenden Leitlinien und Konsensuspapieren zu erarbeiten ist.

Purpose 203/212Pb is a promising theranostic isotope pair for targeted alpha therapy (TAT) of neuroendocrine tumors (NET). VMT-α-NET is a novel SSTR2 targeting peptide that can be labeled with both isotopes. The aim of this work was to perform first clinical investigations of [203/212Pb]Pb-VMT-α-NET regarding imaging, biokinetics, tolerability and response. Methods 12 patients (9 m/3 w; mean age 71, range 60–84) with progressive metastatic GEP-NET grade 1–3 received diagnostic imaging with [²⁰³Pb]Pb-VMT-α-NET (4.9 MBq/kg bw) up to 24 h p.i. (whole body & SPECT/CT) and, if eligible, a single dose of [²¹²Pb]Pb-VMT-α-NET therapy (1.2 MBq/kg bw) after exhaustion of all current therapies (including [¹⁷⁷Lu]Lu- & [²²⁵Ac]Ac-DOTATATE), and post-treatment imaging with [²¹²Pb]Pb-VMT-α-NET up to 24 h p.i. (whole body & SPECT/CT). Clinical and laboratory parameters were monitored. A visual and quantitative comparison was made with [⁶⁸ Ga]Ga-DOTATATE PET scans before and 3 months after therapy. Results No high-grade adverse effects were observed in all patients evaluated with [²⁰³Pb]Pb-VMT-α-NET. All patients showed an initial high, but lesion-dependent heterogeneous intratumoral accumulation, comparable to [⁶⁸ Ga]Ga-DOTATATE PET. Treatment with [²¹²Pb]Pb-VMT-α-NET was also well tolerated by all patients without high-grade or serious adverse side effects. Post-therapeutic PET scans and tumor marker controls showed stable findings in all patients up to 3 months after treatment. Conclusion Imaging with [²⁰³Pb]Pb-VMT-α-NET followed by a single dose of [²¹²Pb]Pb-VMT-α-NET appears to be well tolerated with promising efficacy, even in a heterogenous and heavily pretreated patient population. Further studies are warranted to examine tolerability and efficacy over multiple treatment cycles in larger patient populations.

Background Distal pancreatectomy (DP) can worsen pancreatic endocrine function. Effects on glucose metabolism and underlying mechanisms after DP remains a topic of significant interest and not yet fully understood. This study aimed to examine the impact of DP on blood glucose homeostasis with a particular focus on metabolic outcomes and development of postoperative diabetes. Methods Considered were all patients who underwent DP between 01/2010 and 09/2021 and participated simultaneously in extended blood glucose monitoring with a 12 months follow-up. Blood samples were analyzed for markers of pancreatic endocrine function both fasting and after an oral glucose tolerance test preoperatively and 3 and 12 months after DP. Results Included patients (n = 69) were preoperatively categorized into three groups according to American Diabetes Association (ADA) criteria: 17 patients (24.6%) were normoglycemic (NG), 22 (31.9%) had prediabetes (impaired fasting glucose / impaired glucose tolerance – IFG/IGT) and 30 (43.5%) had diabetes mellitus (DM). In the NG subgroup, beta-cell function (HOMA2%B - updated homeostasis model assessment) significantly decreased from 117.4% (101.1–135%) to 66.9% (49.7–102.1%) at 12 months postoperatively (p < 0.05). Insulin sensitivity (HOMA2%S) significantly increased from 48.2% (33.4–66.9%) to 63.5% (49.8–86%) at 12 months postoperatively (p < 0.05). In the IFG/IGT subgroup, there was a non-significant trend of decreased HOMA2%B and increased HOMA2%S postoperatively. Postoperatively, 11.8% of NG patients and 60% of prediabetic patients developed DM. Conclusion DP already leads to significant changes in glucose metabolism within a 12 month follow-up period. Patients with preoperative prediabetes are particularly at high risk of developing postoperative DM. Therefore, the indication for DP should be critically evaluated, especially in cases with a relative indication for surgery. If possible parenchymal sparing surgical options should be contemplated. Trial registration Not applicable.

Enhancing the secondary use of data from routine care through external data enrichment methods can significantly boost its quality. This paper demonstrates a process-driven prototyping approach that separates sensitive and non-sensitive data, empowering medical experts to map medical concepts in free text to standardized terminology codes, all while granting data protection and information security. This approach is based on a prototype-oriented framework developed through discussions in a focus group. It consists of four integral components: (A) Clinical Data Repository, (B) Transition Database, (C) Mapping Tools and (D) Validation Tools. Data flows between the components contain medical concepts in free text and structured lists of suggested or validated standard codes. They are operated with the help of extract, transform and load processes as well as workflow management tools. By utilizing the components along the process, quality-assured medical concepts and their mapping can be provided for the secondary use of routine patient data for research.

Heterogeneous data formats complicate unified analysis in multisite clinical studies. Standardizing data in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) requires Extract-Transform-Load (ETL) processes, which are complex and time-consuming to develop, especially with different source data specifications. The aim of our work is to develop a generalized, metadata-driven ETL process to transform Fast Healthcare Interoperability Resources (FHIR) into OMOP CDM. In this paper, we present first results of the developed metadata-driven ETL process on the example of two different Patient FHIR specifications.