Search Results (52)

Background: Large language models (LLMs) such as ChatGPT, Google Gemini, and Microsoft Copilot are increasingly used by patients seeking medical information online. While these tools provide accessible and conversational explanations, their accuracy and safety in emotionally sensitive scenarios—such as an incidental cancer diagnosis—remain uncertain. Objective: To evaluate the quality, completeness, readability, and safety of responses generated by three state-of-the-art LLMs to common patient questions following the incidental discovery of a kidney tumor. Methods: A standardized use-case scenario was developed: a patient learns of a suspicious renal mass following a computed tomography (CT) scan for back pain. Ten plain-language prompts reflecting typical patient concerns were submitted to ChatGPT-4o, Microsoft Copilot, and Google Gemini 2.5 Pro without additional context. Responses were independently assessed by five board-certified urologists using a validated six-domain rubric (accuracy, completeness, clarity, currency, risk of harm, hallucinations), scored on a 1–5 Likert scale. Two statistical approaches were applied to calculate descriptive scores and inter-rater reliability (Fleiss’ Kappa). Readability was analyzed using the Flesch Reading Ease (FRE) and Flesch–Kincaid Grade Level (FKGL) metrics. Results: Google Gemini 2.5 Pro achieved the highest mean ratings across most domains, notably in accuracy (4.3), completeness (4.3), and low hallucination rate (4.6). Microsoft Copilot was noted for empathetic language and consistent disclaimers but showed slightly lower clarity and currency scores. ChatGPT-4o demonstrated strengths in conversational flow but displayed more variability in clinical precision. Overall, 14% of responses were flagged as potentially misleading or incomplete. Inter-rater agreement was substantial across all domains (κ = 0.68). Readability varied between models: ChatGPT responses were easiest to understand (FRE = 48.5; FKGL = 11.94), while Gemini’s were the most complex (FRE = 29.9; FKGL = 13.3). Conclusions: LLMs show promise in patient-facing communication but currently fall short of providing consistently accurate, complete, and guideline-conform information in high-stakes contexts such as incidental cancer diagnoses. While their tone and structure may support patient engagement, they should not be used autonomously for counseling. Further fine-tuning, clinical validation, and supervision are essential for safe integration into patient care. Full article

Background/Objectives: Kidney transplantation is associated with an increased risk of renal cell carcinoma (RCC). This study aimed to evaluate the outcomes of de novo RCC in kidney transplant recipients (KTRs). Methods: We retrospectively identified 50 de novo RCC cases among 4012 KTRs transplanted from 2005 to 2024. Data on patient characteristics and outcomes were collected. Propensity score matching (PSM) compared 34 localized RCC cases in KTRs with 34 non-transplant RCC cases. The statistical analyses used Kaplan–Meier estimates, the log-rank test, and the Cox regression. Results: The RCC incidence was 0.64 per 1000 person-years, with a standardized incidence ratio of 4.40 (95% CI: 3.33–5.80). In the KTR cohort, clear cell RCC was present in 42%, and papillary RCC was present in 42%. RCC developed predominantly in native kidneys (92%). UICC stage I was present in 74%. The treatment for the non-metastatic RCC was nephrectomy in the majority of cases (91%). For the metastatic RCC, 71% received a tyrosine kinase inhibitor (TKI). In the KTR cohort, the 3- and 5-year overall survival (OS) rates were 85% and 72%, respectively, with a median OS of 199 months; the synchronous metastasized (M1) patients had a median OS of 14 months. Rejection, age, advanced UICC stage, higher pT stage, clinical positive lymph nodes, M1, and higher grade were significantly associated with poor OS. The 5-year OS (96% vs. 84%, p = 0.72) and MFS (92% vs. 93%, p = 0.61) were comparable in the PSM cohort between the KTRs and the non-KTRs in the localized RCC. Conclusions: KTRs have a higher risk of RCC and present at a localized stage with comparable OS rates to non-transplant RCC patients. Adverse tumor characteristics, including synchronous metastases, significantly affect the prognosis, highlighting the need for surveillance and individualized treatment, particularly for metastatic RCC. Full article

Background/Objectives: The aim of this study was to investigate the prognostic value of established response assessment tools for hepatocellular carcinoma (HCC) treated with high-dose-rate interstitial brachytherapy (iBT) alone or with transarterial chemoembolization (cTACE). Methods: (Non-)responders were categorized using size-based RECIST 1.1 and WHO criteria, enhancement-based mRECIST and EASL criteria, and the LI-RADS Treatment Response Algorithm (LR-TRA). The outcomes were the overall survival (OS), progression-free survival (PFS), and time to progression (TTP). The statistics used included Fisher’s exact test, a t-test, the Mann–Whitney-U test, and a Kaplan–Meier analysis. The median OS, PFS, and TTP were higher in patients following iBT (26.3, 9.1, and 13.0 months) than following cTACE/iBT (23.3, 7.6, and 9.2 months). Results: The enhancement-based criteria identified more responders and predicted PFS and TTP better compared to the size-based criteria. At two months, the cTACE/iBT responders showed improved PFS (mRECIST and EASL: 11.3 vs. 2.3 and 11.0 vs. 2.3, p < 0.01) and TTP (mRECIST and EASL: 11.9 vs. 2.4 months, p < 0.01) by the enhancement-based criteria. An EASL assessment at five months predicted improved survival following both cTACE/iBT (PFS: 11.9 vs. 5.1 months, p = 0.03; TTP: 12.4 vs. 5.0, p < 0.01) and iBT (11.1 vs. 5.1 months, p = 0.04; 13.0 vs. 5.3, p < 0.01). The LR-TRA showed OS benefits at five months for cTACE/iBT responders. Size-based criteria were not prognostic. Conclusions: Extending follow-up post-iBT or post-iBT/cTACE may improve responder stratification and prognostication. Full article

Background: Treatment of multiple myeloma has advanced tremendously with the approval of anti-CD38 antibodies. Their efficacy is impressive but still controversial in the 1q amplification subgroup (amp1q). This retrospective study aims to provide real-world data. Methods: This trial is analyzing 74 patients with relapsed/refractory multiple myeloma treated with CD38Abs at the Medical University of Innsbruck (2016–2023). High-risk (HR) cytogenetics according to R-ISS (t(4;14), t(14;16), t(14;20), del(17p)), the presence of amp(1q21), the frequency of two HR markers (double hit), and the high-risk criteria agreed at IMS 2024 (HR-IMS24) were considered. Results: The median age of the 74 patients (62.1% male) was 62 years, with a median follow-up of six years. Most patients received third-line therapy (37.8%). R-ISS HR was documented in 39.2% of patients, double hit in 13.5% of patients, and HR-IMS24 in 32.4% of patients, while amp1q was detected in 35.1% of patients. The median OS was 66 months (35–89), and the median PFS was 17 months (6.5–26.9). While neither R-ISS HR nor isolated amp1q had an impact on progression-free survival (e.g., amp1q 7.03: 1.95–22.44; p = 0.347), the occurrence of a double-hit pattern significantly impaired PFS and OS (6.2: 1.4–16.4 months; p = 0.044; OS, 42.8: 25.9–74.6 months; p = 0.035). Patients fulfilling the HR-IMS24 criteria (32.4%, 24 patients) also exhibited an impaired PFS and OS (7: 2.7–18.1 months, p = 0.023; 40.12: 21.1–74.5 months, p = 0.01). Conclusions: This retrospective study highlights the durable effect of daratumumab on cytogenetic abnormalities, particularly amp1q. However, patients who meet the criteria for double-hit myeloma or the high-risk IMS2024 criteria remain a difficult-to-treat patient population who require early access to new treatment approaches. Full article

Background/Objectives: Adult-onset Still’s disease (AOSD) is an autoinflammatory disorder that can be challenging to diagnose and manage. The aim of this study was to analyze retrospective data to provide insights into the clinical presentation, disease activity, and treatment patterns and outcomes of AOSD during routine clinical care prior to the release of new AOSD guidelines. Methods: This retrospective database analysis evaluated adult patients (≥18 years) with a diagnosis of AOSD who engaged in a clinical visit between 1 January 2010 and 31 December 2020. The evaluated outcomes included demographic characteristics, symptoms, disease activity, and treatment. Results: Our study included 120 patients (67 [55.8%] of whom were female) diagnosed with AOSD according to the Yamaguchi criteria at ten German rheumatology centers. The median (quartile [Q] 1, Q3) age was 51 (36, 62) years, and the median (Q1, Q3) time from diagnosis was 9 (4, 11) years. Approximately half (66 [55.0%]) had a polycyclic disease course. The most frequent symptoms at initial diagnosis were arthralgia (105 [87.5%]) and fever (86 [71.7%]), and these symptoms continued for a substantial proportion of patients at the current visit (35 [29.2%] and 22 [18.3%], respectively). High neutrophil and ferritin levels were also common. The mean Still Activity Score, a measure of disease activity, improved from 4.66 at initial diagnosis to 1.97 at the most recent visit. The treatments most frequently used at some point in the disease course were glucocorticoids (118 [98.3%]), interleukin (IL)-1 inhibitors (89 [74.2%]), and methotrexate (85 [70.8%]). The most common current treatments were IL-1 inhibitors (55 [45.8%]), followed by methotrexate (29 [24.2%}) and glucocorticoids (28 [23.3%]). Conclusions: Our cohort of patients with AOSD seen at German rheumatology clinics showed strong improvements in symptoms and disease activity from initial diagnosis, but a high symptom burden remained for some patients. Future studies may be able to build on our data to document the impact of new guidelines on treatment patterns. Full article

Eribulin is a preferred treatment for patients with advanced breast cancer (BC) following anthracyclines and taxanes. The final analysis of the IRENE study assessed the incidence and resolution of eribulin-induced peripheral neuropathy (EIPN), along with safety and quality of life (QoL), in patients with advanced/metastatic BC. IRENE was an observational, single-arm, prospective, multicenter cohort study. Patients aged ≥18 years with locally advanced/metastatic BC that progressed after 1–3 prior chemotherapeutic regimens received eribulin and were monitored for new-onset or worsening EIPN. Secondary endpoints included time to disease progression, safety, and health-related QoL. In total, 108 (32.2%) out of 335 patients experienced EIPN; 18 (5.4%) experienced grade ≥3 EIPN. Median time to EIPN resolution (EIPN ended or returned to baseline) was 78.7 weeks (95% CI 77.1—not estimable). Median time to disease progression was 4.5 months (95% CI 3.9–5.5). Treatment-emergent adverse events (TEAEs) occurred in 322 (96.1%) patients; serious TEAEs occurred in 185 (55.2%) patients. Incidence and resolution rates of EIPN were comparable with existing evidence from previous trials. TEAEs were consistent with the established eribulin safety profile, with no new safety signals. Eribulin treatment did not appear to affect QoL, as measured by EQ-5D-3L and EQ-VAS, or patient-reported neuropathy symptoms, as measured by the PNQ. Full article

Background/Objectives: Artificial intelligence (AI), particularly natural language processing (NLP) models such as ChatGPT, presents novel opportunities for patient education and informed consent. This study evaluated ChatGPT’s use as a support tool for informed consent before penile prosthesis implantation (PPI) in patients with erectile dysfunction (ED) following radical prostatectomy. Methods: ChatGPT-4 answered 20 frequently asked questions across four categories: ED and treatment, PPI surgery, complications, and postoperative care. Three senior urologists independently rated information quality using the DISCERN instrument on a Likert scale ranging from 1 (poor quality) to 5 (good quality). Readability was assessed using the Flesch Reading Ease (FRE) and Flesch–Kincaid Grade Level (FKGL) formulas, and inter-rater reliability was measured using intraclass correlation coefficients. Results: The inter-rater reliability coefficient was 0.76 (95% CI 0.71–0.80). Mean DISCERN scores indicated moderate quality: 2.79 ± 0.92 for ED and treatment, 2.57 ± 0.98 for surgery, 2.65 ± 0.86 for complications, and 2.74 ± 0.90 for postoperative care. High scores (>4) were achieved for clarity and relevance, while complex issues, such as risks and alternative treatments, scored the lowest (<2). The FRE scores ranged from 9.8 to 28.39, and FKGL scores ranged from 14.04 to 17.41, indicating complex readability suitable for college-level comprehension. Conclusions: ChatGPT currently provides variable and often inadequate quality information without sufficient comprehensibility for informed patient decisions, indicating the need for further improvements in quality and readability. Full article

Background: Despite being the most commonly performed valvular intervention, risk prediction for aortic valve replacement in patients with severe aortic stenosis by currently used risk scores remains challenging. The study aim was to develop a biomarker-based risk score by means of a neuronal network. Methods: In this multicenter study, 3595 patients were divided into test and validation cohorts (70% to 30%) by random allocation. Input variables to develop the ABC-AS score were age, the cardiac biomarker high-sensitivity troponin T, and a patient history of cardiac decompensation. The validation cohort was used to verify the scores’ value and for comparison with the Society of Thoracic Surgery Predictive Risk of Operative Mortality score. Results: Receiver operating curves demonstrated an improvement in prediction by using the ABC-AS score compared to the Society of Thoracic Surgery Predictive Risk of Operative Mortality (STS prom) score. Although the difference in predicting cardiovascular mortality was most notable at 30-day follow-up (area under the curve of 0.922 versus 0.678), ABC-AS also performed better in overall follow-up (0.839 versus 0.699). Furthermore, univariate analysis of ABC-AS tertiles yielded highly significant differences for all-cause (p < 0.0001) and cardiovascular mortality (p < 0.0001). Head-to-head comparison between both risk scores in a multivariable cox regression model underlined the potential of the ABC-AS score (HR per z-unit 2.633 (95% CI 2.156–3.216), p < 0.0001), while the STS prom score failed to reach statistical significance (p = 0.226). Conclusions: The newly developed ABC-AS score is an improved risk stratification tool to predict cardiovascular outcomes for patients undergoing aortic valve intervention. Full article

Photon-counting CT systems generally allow for acquiring multiple spectral datasets and thus for decomposing CT images into multiple materials. We introduce a prior knowledge-free deterministic material decomposition approach for quantifying three material concentrations on a commercial photon-counting CT system based on a single CT scan. We acquired two phantom measurement series: one to calibrate and one to test the algorithm. For evaluation, we used an anthropomorphic abdominal phantom with inserts of either aqueous iodine solution, aqueous tungsten solution, or water. Material CT numbers were predicted based on a polynomial in the following parameters: Water-equivalent object diameter, object center-to-isocenter distance, voxel-to-isocenter distance, voxel-to-object center distance, and X-ray tube current. The material decomposition was performed as a generalized least-squares estimation. The algorithm provided material maps of iodine, tungsten, and water with average estimation errors of 4% in the contrast agent maps and 1% in the water map with respect to the material concentrations in the inserts. The contrast-to-noise ratio in the iodine and tungsten map was 36% and 16% compared to the noise-minimal threshold image. We were able to decompose four spectral images into iodine, tungsten, and water. Full article

Memristors, since their inception, have demonstrated remarkable characteristics, notably the exceptional reconfigurability of their memory. This study delves into electroforming-free ${\mathrm{YMnO}}_3$ (YMO)-based resistive switches, emphasizing the reconfigurable memory effect in multiferroic YMO thin films with metallically conducting electrodes and their pivotal role in achieving adaptable frequency responses in impedance circuits consisting of reconfigurable YMO-based resistive switches and no reconfigurable passive elements, e.g., inductors and capacitors. The multiferroic YMO possesses a network of charged domain walls which can be reconfigured by a time-dependent voltage applied between the metallically conducting electrodes. Through experimental demonstrations, this study scrutinizes the impedance response not only for individual switch devices but also for impedance circuitry based on YMO resistive switches in both low- and high-resistance states, interfacing with capacitors and inductors in parallel and series configurations. Scrutinized Nyquist plots visually capture the intricate dynamics of impedance circuitry, revealing the potential of electroforming-free YMO resistive switches in finely tuning frequency responses within impedance circuits. This adaptability, rooted in the unique properties of YMO, signifies a paradigm shift heralding the advent of advanced and flexible electronic technologies. Full article

So far, the cellular origin of glioblastoma (GBM) needs to be determined, with prevalent theories suggesting emergence from transformed endogenous stem cells. Adult neurogenesis primarily occurs in two brain regions: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Whether the proximity of GBM to these neurogenic niches affects patient outcome remains uncertain. Previous studies often rely on subjective assessments, limiting the reliability of those results. In this study, we assessed the impact of GBM’s relationship with the cortex, SVZ and SGZ on clinical variables using fully automated segmentation methods. In 177 glioblastoma patients, we calculated optimal cutpoints of minimal distances to the SVZ and SGZ to distinguish poor from favorable survival. The impact of tumor contact with neurogenic zones on clinical parameters, such as overall survival, multifocality, MGMT promotor methylation, Ki-67 and KPS score was also examined by multivariable regression analysis, chi-square test and Mann–Whitney-U. The analysis confirmed shorter survival in tumors contacting the SVZ with an optimal cutpoint of 14 mm distance to the SVZ, separating poor from more favorable survival. In contrast, tumor contact with the SGZ did not negatively affect survival. We did not find significant correlations with multifocality or MGMT promotor methylation in tumors contacting the SVZ, as previous studies discussed. These findings suggest that the spatial relationship between GBM and neurogenic niches needs to be assessed differently. Objective measurements disprove prior assumptions, warranting further research on this topic. Full article

Overall survival (OS) of patients with metastatic breast cancer (MBC) has improved within controlled clinical trials. Whether these advances translate into improved OS in routine care is controversial. We therefore analyzed retrospectively unselected female patients from five oncology group practices and one university outpatient clinic, whose initial diagnosis of MBC was between 1995 and 2022. A total of 1610 patients with a median age of 63 years (23–100) were evaluated. In all, 82.9% had hormone-receptor-positive disease, and 23.8% were HER2-positive. Evaluation in time cohorts by initial MBC diagnosis date showed a continuous prolongation of median OS from 31.6 months (0.5–237.3+) (1995–2000) to 48.4 months (0.4–61.1+) (2018–2022) (p = 0.003). Univariable analyses showed a significant dependence on the time cohort of diagnosis, metastatic status at initial diagnosis, age at metastasis, hormone and HER2 status, general condition, metastasis localization, and the number of affected organs. A multivariable analysis revealed a significant dependence of survival probability on receptor status, general condition, and number of metastatic sites, as well as the time between initial breast cancer diagnosis and the diagnosis date of MBC in months. In sum, OS of patients with MBC has improved continuously and significantly in routine care over the last 27 years. Full article

The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia. Full article

σ₁ receptors play a crucial role in various neurological and neurodegenerative diseases including pain, psychosis, Alzheimer’s disease, and depression. Spirocyclic piperidines represent a promising class of potent σ₁ receptor ligands. The relationship between structural modifications and σ₁ receptor affinity and selectivity over σ₂ receptors led to the 2-fluoroethyl derivative fluspidine (2, K_i = 0.59 nM). Enantiomerically pure (S)-configured fluspidine ((S)-2) was prepared by the enantioselective reduction of the α,β-unsaturated ester 23 with NaBH₄ and the enantiomerically pure co-catalyst (S,S)-24. The pharmacokinetic properties of both fluspidine enantiomers (R)-2 and (S)-2 were analyzed in vitro. Molecular dynamics simulations revealed very similar interactions of both fluspidine enantiomers with the σ₁ receptor protein, with a strong ionic interaction between the protonated amino moiety of the piperidine ring and the COO^- moiety of glutamate 172. The ¹⁸F-labeled radiotracers (S)-[¹⁸F]2 and (R)-[¹⁸F]2 were synthesized in automated syntheses using a TRACERlab FX FN synthesis module. High radiochemical yields and radiochemical purity were achieved. Radiometabolites were not found in the brains of mice, piglets, and rhesus monkeys. While both enantiomers revealed similar initial brain uptake, the slow washout of (R)-[¹⁸F]2 indicated a kind of irreversible binding. In the first clinical trial, (S)-[¹⁸F]2 was used to visualize σ₁ receptors in the brains of patients with major depressive disorder (MDD). This study revealed an increased density of σ₁ receptors in cortico-striato-(para)limbic brain regions of MDD patients. The increased density of σ₁ receptors correlated with the severity of the depressive symptoms. In an occupancy study with the PET tracer (S)-[¹⁸F]2, the selective binding of pridopidine at σ₁ receptors in the brain of healthy volunteers and HD patients was shown. Full article

This paper describes a new underwater pumped storage hydropower concept (U.PSH) that can store electric energy by using the high water pressure on the seabed or in deep lakes to accomplish the energy transition from fossil to renewable sources. Conventional PSH basically consists of two storage reservoirs (upper and lower lake) at different topographical heights. It needs special topographic conditions, which are only limitedly available in mountain regions. Furthermore, due to the lack of acceptance and the environmental impact, new conventional PSH projects are very unlikely to be built in larger numbers in Europe in the near future. The presented solution solves these issues by placing the storage system on the seabed, thus having other geographical requirements. It operates as follows: in contrast to well-known conventional PSH plants, which use two separated water reservoirs of different heights, the U.PSH concept uses the static pressure of the water column in deep waters by installing a hollow concrete sphere in deep water. Storage of electricity is achieved by using a reversible pump in the hollow sphere. Upon opening a valve, water flows into the sphere, driving a turbine/generator, thereby discharging the storage device. In order to re-charge, the water is pumped out of the sphere against the pressure of the surrounding water. The power and energy, respectively, are proportional to the surrounding water pressure at the seabed. The amount of energy stored depends on the water depth and the volume of the spheres. The spheres need a cable connection to the shore or to a close-by floating transformer station (e.g., an offshore wind plant). No other connections such as pipes are needed. The functional principle of this energy storage technology, its state of the art, its storage capacity and the shape and size of the required spheres are discussed in this paper. Full article