Helios Hospital Berlin-Buch

Understanding the causes of the exceptional rate of evolution of the mammalian placenta is likely to aid the understanding of placental development and the etiology of the human-specific pregnancy disorder pre-eclampsia (PE). As retroelements are often lineage-specific and known to be co-opted for placental function, here we consider the binding of the transcription factors GATA3 and DLX5 to retroelements. These factors are dysregulated in pre-eclampsia, as are their downstream consequences. We identify retrovirus-derived LTR8B as a placentally-relevant cis-regulatory element (CRE), not least within the PSG array, a primate-specific genomic region that exhibits high intraspecies variability. LTR8B at PSG9 is particularly influential affecting other PSG family members. Moreover, unique among PSGs, PSG9 produces both secreted and membrane-anchored isoforms. The retroelement MER65-int provides alternative polyA signals that enable the evolution of secreted PSG variants by truncating the ancestral CEACAM protein's transmembrane domain. Functional characterization finds that LTR8B/PSG9 regulates the differentiation of multinucleated trophoblasts (syncytialization) and, like chorionic gonadotropin and syncytin1, determines the identity of syncytiotrophoblasts. Notably, PSG9 is the most upregulated PSG in PE, with levels correlated with GATA3 and DLX5 levels. Retroelements contribute to the structural and expression evolution of PSG genes, facilitating lineage-specific placental evolution. The LTR8B/PSG9 regulatory network plays a central role in syncytiotrophoblast differentiation. Given the association between DLX5/GATA3 dysregulation and elevated PSG9 levels, along with PSG9's expression in the first trimester, PSG9 shows potential as a predictive biomarker for preeclampsia.

596 Background: Testicular cancer is rare. Many cases presented to the German online second-opinion platform (eKonsil) involve non- or minimally metastatic stages. Expert reviews aim to optimize care quality. Large language models (LLMs) such as ChatGPT version 5 may support this process if their recommendations are shown to be non-inferior to expert consensus. Methods: Eleven eKonsil cases with primary non- or minimally metastatic disease were evaluated. Consensus treatment recommendations were generated by three testicular cancer experts (AH, JH, HS) based on the EAU guidelines. The same cases were entered into GPT5 with reference to the EAU guidelines on different days, in different countries, and by different individuals in September 2025. Recommendations by GPT5 and expert consensus were assessed independently by three urologists using a four-point Likert scale based on 21 validated evaluation criteria. Results: We obtained 99 evaluations of adherence to expert opinion. Expert recommendations for direct treatment were available for 81 evaluations. Primary therapy suggested by GPT5 was acceptable (no or insignificant deviations from experts) in 70% (57/81). GPT5’s adherence to expert opinion was similar for localized and metastasized cases (3.14 vs. 3.38; p Wilcoxon = 0.38). Adherence differed significantly depending on suggested therapeutic alternatives (p Chi2 < .01) with chemotherapeutic compounds being suggested correctly in 85% (74/87), radiation in 78% (47/60), active surveillance in 76% (50/66) and surgery in 59% (30/51). GPT5 acceptably identified missing information ahead of therapeutic suggestions in 82% (22/27) of relevant cases. In case of deficits, an acceptable path of diagnostics was suggested in 74% (20/27). Performance in identifying informational deficits did not vary by metastatic status (p Chi2 = 0.19) and performance in suggesting diagnostics was no better than in suggesting primary therapy (3.30 vs. 3.14; p Wilcoxon = 0.48). With GPT5 failing to reach clinically acceptable ratings in over 95% for any metric, it did not meet criteria of non-inferiority to experts. Conclusions: GPT5-generated second-opinion recommendations for patients with non- or minimally metastatic testicular cancer cannot be assumed to be non-inferior to expert consensus. Caution is needed when using GPT5 as an assistant to screen cases for missing information or to generate therapeutical suggestions, particularly with surgical paths being involved. This study shows that LLMs, even when provided with guidelines, require more training and expert validation currently remains essential.

Cardiovascular disease (CVD) is the leading cause of death among women worldwide. Pregnancy serves as a natural cardiovascular stress test and universal clinical encounter, yet few approaches leverage its insights to inform long-term cardiovascular risk. To determine whether clinical measures and biomarkers obtained during pregnancy may identify women at risk of long-term CVD. This was a registry-linked, population-based cohort study of all pregnancies reaching at least 22 weeks between June 2010 and October 2013 in Southern Denmark. Primary analyses were performed in a nested prospective subcohort of Odense Child Cohort participants with available pregnancy biomarker data. Women with preexisting CVD were excluded (n = 114). Follow-up was done through December 31, 2023. Among 38 455 eligible women, 2056 had biomarker data at week 12 or week 29. Analytic subsets with complete data were used for prognostic modeling at week 12 (n = 1379) and week 29 (n = 1389). Clinical characteristics, obstetric outcomes, and pregnancy biomarkers including soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor, high-sensitivity cardiac troponin I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide. Incident maternal CVD, evaluated using Cox proportional hazards models. In the biomarker cohort (median [IQR] age, 30.4 [27.4-33.8] years), 28 women (1.4%) developed CVD during a median (IQR) follow-up of 11.9 (11.2-12.5) years. Maternal age, hypertensive disorders of pregnancy (HDPs), and third-trimester concentrations of hs-cTnI and sFlt-1 were each independently associated with higher long-term CVD risk. A combined model including age and sFlt-1 measured at week 29 improved discrimination for CVD compared with a base model of age alone (ΔAUC, 0.16; 95% CI, 0.02-0.30), whereas a clinical model consisting of age, systolic blood pressure, and non-high-density lipoprotein cholesterol did not. Results were consistent in women without prior hypertension or HDPs and in nulliparous women. CVD incidence and the predictive value of the base model were comparable between the biomarker and the contemporaneous background cohorts (n = 36 274). These findings support pregnancy as an opportunistic window for sex-specific cardiovascular risk assessment and prevention throughout a woman's life course. Further studies are warranted to validate these findings.

Abstract Background: In the KEYNOTE-522 study (NCT03036488), neoadjuvant pembrolizumab (pembro) plus chemotherapy (chemo) followed by adjuvant pembro plus chemo significantly improved pathological complete response (pCR), event-free survival, and OS compared with placebo (pbo) plus chemo in participants (pts) with early-stage TNBC. Following neoadjuvant therapy, the estimated treatment difference in pCR for pembro plus chemo vs pbo plus chemo was 13.6% (95% CI, 5.4%‒21.8%; P < 0.001) at the first interim analysis (N=602). Although pCR provides a definitive indicator of neoadjuvant treatment success, other measures, such as RECIST v1.1 and functional tumor volume (FTV), may offer an earlier signal of therapeutic activity. This prespecified exploratory analysis evaluated associations of pCR with ORR at different time points per MRI by RECIST v1.1 and FTV by blinded independent central review. Methods: Pts with previously untreated TNBC (stage T1c N1-N2 or T2-T4 N0-N2) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or pbo, each with 4 cycles of paclitaxel plus carboplatin (treatment 1) then with 4 cycles of doxorubicin or epirubicin plus cyclophosphamide (treatment 2). After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence/unacceptable toxicity. Breast MRI was performed for consenting pts at screening and after neoadjuvant treatments 1 and 2. Responders were defined as pts who achieved CR or PR per RECIST v1.1 by blinded independent central radiology review. The subgroup analyses population included the randomized pts who signed MRI consent and had baseline values by central radiology review. Results: At data cutoff (March 23, 2021), MRI subgroup analyses included 162 pts (pembro plus chemo, n = 97; pbo plus chemo, n = 65). After treatment 1, ORR per RECIST v1.1 was 91.8% for pembro plus chemo vs 84.6% for pbo plus chemo, while ORR per MRI FTV was 96.9% vs 93.8%. After treatment 2, ORR per RECIST v1.1 was 82.5% vs 90.8%, and ORR per MRI FTV was 84.5% vs 92.3% for pembro plus chemo and pbo plus chemo, respectively. In the post hoc exploratory analyses for pCR in the MRI subgroup, pCR rate (ypT0/Tis ypN0; 95% CI) was 62.9% (52.5%-72.5%) with pembro plus chemo vs 52.3% (39.5%-64.9%) with pbo plus chemo. Odds ratios (OR) for achieving pCR among pts with ORR per RECIST v1.1 or FTV across all patients (pembro plus chemo and pbo plus chemo combined) are shown in the Table. Conclusions: Across all pts (ie, for pembro plus chemo and pbo plus chemo combined), the odds of achieving pCR were higher among pts who had an objective response per either RECIST v1.1 or FTV. Citation Format: J. Cortés, R. Dent, H. McArthur, L. Pusztai, S. Kümmel, C. Denkert, J. O’Shaughnessy, P. A. Fasching, M. Untch, R. Tarnawaski, M. Mouret-Reynier, S. M. Stemmer, T. Foukakis, J. Boileau, C. Chung, M. Fernandez, J. A. Mejia, F. Beca, S. Hou, P. Schmid. Phase 3 study of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab for early-stage TNBC: KEYNOTE-522 magnetic resonance imaging (MRI) subgroup analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-24.

Periprosthetic joint infection (PJI) is one of the most severe complications in hip arthroplasty, and treatment of PJI is associated with high re-infection rates and significant loss of quality of life for patients, as well as socio-economic impact to health systems. Antimicrobial coating of implants with silver is a promising option to improve the outcome of PJI. However, there is no data from randomized control trials on silver-coated versus standard non-silver-coated implants in patients with PJI. Therefore, the aim of the current study is to assess clinical outcome for the use of silver-coated hip implants (further referred to as IP-coated) versus non-IP-coated implants in patients requiring surgical revision for hip PJI. This is a multicenter confirmatory interventional randomized controlled superiority single-blinded study with two stages: pilot stage (part A) and pivotal stage (part B). Patients indicated for unilateral cementless acetabular and hip stem revision due to chronic periprosthetic infection planned for single-stage or two-stage surgical procedures are included. Patients will randomly be assigned either to the IP-coated or the non-IP-coated implant group. The primary outcome parameter is infection-free survival within 12months after hip PJI. The underlying hypothesis is that the IP coating significantly reduces the risk of periprosthetic reinfection compared to the non-IP-coated implants. Secondary outcome parameters include data on the safety and performance of the prostheses through a 2-year clinical follow-up, including patient-related outcome parameters, such as Harris Hip Score, EQ-5D, radiographical assessment, and blood silver concentrations. An adaptive study design is planned with the inclusion of 268 subjects according to initial sample size calculations. Upon follow-up of 134 patients for 12months or inclusion of 90% of the study patients, preliminary study results will be used to re-estimate the sample size, which may be extended up to 400 subjects. The current study aims to fill the evidence gap for the idea of IP-coated implants to reduce re-infection rates in the treatment of hip PJI. To the authors' best knowledge, this is the first randomized controlled superiority trial evaluating the outcome of a silver-coated versus a non-silver-coated prosthesis for the treatment of hip PJI. The adaptive study design allows an adjustment of the initial sample size to reduce the risk of an underpowered superiority. ClinicalTrials.gov NCT06737809(date of publication 17.12.2024).

Reliable and reproducible sonographic measurements are essential for accurate liver assessment, both in daily clinical practice and in research. Reference values enable clinicians to differentiate between physiological and pathological findings and thus support diagnostic accuracy, follow-up, and therapeutic decision-making. This comprehensive review synthesizes current evidence on normal liver size as assessed by ultrasound, with a particular focus on measurement techniques, standard values, anatomical variants, and the clinical contexts in which these parameters are relevant. Special attention is given to the influence of patient-related factors such as body constitution, sex, age, and ethnicity. The role of right, left, and caudate lobe measurements is discussed in detail, outlining their relevance in conditions such as hepatomegaly, vascular disorders, or post-resection follow-up. Limitations of currently available data are acknowledged, especially regarding interobserver variability and lack of global uniformity. Future priorities include the establishment of consensus-based international reference standards and the integration of emerging technologies, such as artificial intelligence and advanced image analysis tools, to enhance reproducibility, reduce variability, and improve clinical utility. Ultimately, standardized liver measurements should form an integral part of multiparametric ultrasound examinations to optimize patient care.

To introduce an artificial intelligence-based cardiovascular magnetic resonance segmentation algorithm (Nick) for automated quantification of function and parametric mapping across cardiac phenotypes reflecting clinical routine. Nick was compared to manual gold standard (GS) segmentations in 359 multi-centre cases at 1.5T and 3T, consisting of 104 healthy individuals and 255 diseased patients with various cardiac phenotypes. Left and right ventricular (LV, RV) volumes and LV mass (LVM) were derived from short-axis segmentations. For parametric mapping, the LV myocardium was segmented to quantify T1 and T2 relaxation times. Statistical analysis comprised mean differences, correlation coefficients (R²), Bland-Altman analysis, tolerance range assessments, and paired boxplots. The number of slices and contours requiring manual correction was estimated based on slice-level differences. Nick demonstrated high agreement with the GS for LV and RV volume estimations (R²≥0.93) and LVM quantification (R²=0.86). For the ejection fractions, correlations were slightly lower (R²=0.85/0.72 for LV/RV) with small mean differences (+ 1.14%/-2.48% for LV/RV). T1 and T2 mapping values showed excellent agreement with manual reference values (R²≥0.92) and minimal biases (-1.64/0.14 ms for T1/T2). Nick underestimated LV volumes at end-diastole (-4.48ml) and end-systole (-3.28ml) as well as the RV end-diastolic volume (-5.14ml) and stroke volume (-6.75ml). Nonetheless, tolerance testing for mean deviations revealed clinically acceptable biases for all comparisons, and less than two slices per case required correction on average. Comparison to expert segmentations revealed robust performance of Nick in routine clinical cases with variable pathology, supporting its future integration into clinical workflows.

Children and adolescents with juvenile idiopathic arthritis (JIA) are at increased risk for long-term physical and psychosocial complications, making physical activity (PA) and sedentary behaviour (SB) key modifiable lifestyle factors. Although increasingly acknowledged as relevant, data on the daily distribution of these behaviours in JIA remain scarce. This study aimed to (1) describe the time-use composition of SB and PA intensities in young people with JIA, (2) identify correlates of greater relative time spent in SB, and (3) compare movement behaviour patterns to matched population controls using a compositional data analysis (CoDA) approach. Patients aged 10–20 years with JIA and individually matched population controls wore hip-worn accelerometers (ActiGraph wGT3X-BT) for eight consecutive days. Movement behaviours were categorized into SB, light-intensity PA, and moderate-to-vigorous PA (MVPA) using validated, age-specific cut-points. CoDA with log-ratio transformations was used to model associations and compare groups. Diifferences in movement composition were assessed using adjusted multivariate analysis of variance (MANOVA). Data from 126 matched pairs (mean age: 15.0 ± 2.1 years; 67% female) were analysed. Patients spent, on average, 86% of waking time in SB, 8% in light-intensity PA, and 6% in MVPA. Overall, 76% did not meet the WHO recommendation of an average of ≥ 60 min of MVPA per day. Among those who did, 87% still spent ≥ 75% of their wear time sedentary. A greater proportion of SB relative to PA was associated with female gender (B = 0.13; p = 0.042), higher age (B = 0.06; p < 0.001), and higher BMI (B = 0.01; p = 0.049). Compared to controls, patients spent more time in SB, less in light-intensity PA, and slightly more in vigorous PA (all p < 0.001). Group differences remained significant after adjustment and were consistent across weekdays and weekends. Young people with well-controlled JIA show a distinctly unbalanced movement behaviour composition compared to controls, marked by a predominance of sedentary behaviour—even among those meeting PA guidelines. This highlights the limitations of threshold-based definitions and underscores the importance of assessing full daily movement patterns. Promoting light-intensity PA may offer a feasible strategy to reduce sedentary time, particularly in girls, older adolescents, and individuals with higher BMI. The study was registered in the German Clinical Trials Register (DRKS00022258).