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Objectives ChatGPT, a tool based on natural language processing (NLP), is on everyone’s mind, and several potential applications in healthcare have been already proposed. However, since the ability of this tool to interpret laboratory test results has not yet been tested, the EFLM Working group on Artificial Intelligence (WG-AI) has set itself the task of closing this gap with a systematic approach. Methods WG-AI members generated 10 simulated laboratory reports of common parameters, which were then passed to ChatGPT for interpretation, according to reference intervals (RI) and units, using an optimized prompt. The results were subsequently evaluated independently by all WG-AI members with respect to relevance, correctness, helpfulness and safety. Results ChatGPT recognized all laboratory tests, it could detect if they deviated from the RI and gave a test-by-test as well as an overall interpretation. The interpretations were rather superficial, not always correct, and, only in some cases, judged coherently. The magnitude of the deviation from the RI seldom plays a role in the interpretation of laboratory tests, and artificial intelligence (AI) did not make any meaningful suggestion regarding follow-up diagnostics or further procedures in general. Conclusions ChatGPT in its current form, being not specifically trained on medical data or laboratory data in particular, may only be considered a tool capable of interpreting a laboratory report on a test-by-test basis at best, but not on the interpretation of an overall diagnostic picture. Future generations of similar AIs with medical ground truth training data might surely revolutionize current processes in healthcare, despite this implementation is not ready yet.

Potential users of Safe and Sustainable by Design (SSbD) approaches, in particular small and medium sized enterprises, struggle to find their way in the sheer amount of existing knowledge, testing methods and tools. To better guide them in making decisions throughout their entire design process of advanced nanomaterials, a user-friendly online intelligent SSbD Decision Support System (DSS) is developed within the HARMLESS project. Previous experience and stakeholder analysis is used to integrate existing as well as numerous newly generated NAM-based data & models and integrated approaches to testing and assessment (IATAs) into a unified HARMLESS SSbD framework. We propose a modular approach in which all data, knowledge and models are captured in stand-alone, interconnected FAIR components. HARMLESS will A) use eNanoMapper as a database to store experimental data, B) launch a new FAIR Data Point to capture all knowledge and decision rules, C) launch a novel Model FAIRpoint with runnable algorithms and D) launch a new Decision Support System interface. The DSS interface connects to the HARMLESS FAIR components, but can also connect to external components (e.g. NanoCommons Data Warehouse, Jaqpot, NanoInformaTIX). The decision support process is based on a well-established concept of Risk Informed Decision Making adopted by NASA and US NRC, based on the fusion of deterministic and probabilistic risk assessment. To this end, Bayesian network modelling is used to integrate existing and new knowledge, data and models into an integrative reasoning model that captures uncertainty. This information is presented in an interactive visualization presenting an overview of all important decision criteria augmented with SSbD advice allowing the user to interactively work with the tool to improve their design. Oral presentation, by Wouter Fransmann (TNO), at the nanoSAFE 2023 Conference (5-9.06.2023, Grenoble, France) on 6th June 2023-Session:Methods, Tools, & Technologies for SSbD Purposes

Objectives Even though most physicians and professionals in laboratory medicine have received basic training in statistics, experience shows that a general understanding of data analysis is not yet available on a broad scale. Therefore, data literacy, data-driven decision making, and computational thinking should be implemented in future educational training. To evaluate the state of digital competence among young scientists (YS) in laboratory medicine, we launched a worldwide online survey. Methods A global online survey was conducted from 25/05/2022 to 26/06/2022 and was disseminated to YS who are listed in three large networks: YS of the DGKL, the EFLM Task Group-YS, and IFCC Task Force-YS and its corresponding members, covering a base of 53 countries. Results 119 young scientists from 40 countries participated in this survey. 80 % did not learn digital skills in their academic education but 96 % felt they needed to. Digital literacy was associated with terms such as programming, artificial intelligence and machine learning, statistics, communication, Big Data and data analytics. Conclusions The results of our survey show that more knowledge and training in the area of digital skills is not just necessary, but also wanted by young scientists. A varied learning environment consisting of tutorial articles, videos, exercises, technical articles, collection of helpful links, online meetings and in person bootcamps is crucial to meet the challenges of an international project with different languages, health systems and time zones.

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. There are few targeted therapies for these patients, leading to an unmet need for new biomarkers. The present study aimed to investigate the expression of PD-L1, CTLA-4, GLU, and VIM in CTCs of TNBC patients. Ninety-five patients were enrolled in this study: sixty-four TNBC and thirty-one luminal. Of these patients, 60 were in the early stage, while 35 had metastatic disease. Protein expression was identified by immunofluorescence staining experiments and VyCAP analysis. All the examined proteins were upregulated in TNBC patients. The expression of the GLU+VIM+CK+ phenotype was higher (50%) in metastatic TNBC compared to early TNBC patients (17%) (p = 0.005). Among all the BC patients, a significant correlation was found between PD-L1+CD45−CK+ and CTLA-4+CD45−CK+ phenotypes (Spearman test, p = 0.024), implying an important role of dual inhibition in BC. Finally, the phenotypes GLU+VIM+CK+ and PD-L1+CD45−CK+ were associated with shorter OS in TNBC patients (OS: log-rank p = 0.048, HR = 2.9, OS: log-rank p < 0.001, HR = 8.7, respectively). Thus, PD-L1, CTLA-4, GLU, and VIM constitute significant biomarkers in TNBC associated with patients’ outcome, providing new therapeutic targets for this difficult breast cancer subtype.

Pathogen inactivation techniques for blood products have been implemented to optimize clinically safe blood components supply. The INTERCEPT system uses amotosalen together with ultraviolet light wavelength A (UVA) irradiation. Irradiation-induced inactivation of nucleic acids may actually be accompanied by modifications of chemically reactive polyunsaturated fatty acids known to be important mediators of platelet functions. Thus, here, we investigated eicosanoids and the related fatty acids released upon treatment and during storage of platelet concentrates for 7 days, complemented by the analysis of functional and metabolic consequences of these treatments. Metabolic and functional issues like glucose consumption, lactate formation, platelet aggregation, and clot firmness hardly differed between the two treatment groups. In contrast to gamma irradiation, here, we demonstrated that INTERCEPT treatment immediately caused new formation of

Objectives Legal regulations and guidelines such as the Guidelines of the German Medical Association for the Quality Assurance of Laboratory Medical Examinations (Rili-BAEK) and ISO 15189 apply to electronic laboratory reports. However, many laboratories struggle with practical implementation of these regulations and guidelines. Methods Laboratory and legal experts analyse the relevant guidelines and provide checklists and practical recommendations for implementation. Results Laboratories have less control over the display of electronic laboratory reports than over paper documents. However, an electronic report alone is legally sufficient and need not be accompanied by a paper copy. Rili-BAEK and ISO 15189 stipulate a set of minimum information in every report. The laboratory must verify that reports are transmitted and displayed correctly. To help laboratories do so, agreements between laboratories and the report recipients can clarify responsibilities. Conclusions Electronic laboratory reports can improve patient care, but laboratories need to verify their quality. Towards this end, Rili-BAEK and ISO 15189 set out helpful provisions.

Potential users of Safe and Sustainable by Design (SSbD) approaches, in particular small and medium sized enterprises, suffer from the sheer vastness and variety of existing knowledge, testing methods and tools. To better guide them in making decisions throughout their entire design process on safety and sustainability of advanced nanomaterials and HARNs, the HARMLESS project is developing a user-friendly intelligent SSbD Decision Support System (DSS) as an online IT tool.

High levels of tissue factor pathway inhibitor (TFPI), caused by a longer TFPIα half-life after binding to a factor V splice variant and variants in the F5 gene, were recently identified in 2 families with an as-yet-unexplained bleeding tendency. This study aimed to investigate free TFPIα in a well-characterized cohort of 620 patients with mild to moderate bleeding tendencies and its association to genetic alterations in the F5 gene. TFPIα levels were higher in patients with bleeding compared with healthy controls (median [interquartile range], 8.2 [5.5-11.7] vs 7.8 [4.3-11.1]; P = .026). A higher proportion of patients had free TFPIα levels more than or equal to the 95th percentile compared with healthy controls (odds ratio [OR] [95% confidence interval (CI)], 2.82 [0.98-8.13]). This was pronounced in the subgroup of patients in whom no bleeding disorder could be identified (bleeding of unknown cause [BUC; n = 420]; OR [95% CI], 3.03 [1.02-8.98]) and in platelet function defects (PFDs) (n = 121; OR [95% CI], 3.47 [1.09-11.08]). An increase in free TFPIα was associated with a mild delay in thrombin generation (prolonged lag time and time to peak), but not with alterations in routinely used global clotting tests. We could neither identify new or known genetic variations in the F5 gene that are associated with free TFPIα levels, nor an influence of the single-nucleotide variant rs10800453 on free TFPIα levels in our patient cohort. An imbalance of natural coagulation inhibitors such as TFPIα could be an underlying cause or contributor for unexplained bleeding, which is most probably multifactorial in a majority of patients.

Introduction Transvenous lead extraction (TLE) is critical in the long-term management of patients with cardiac implanted electronic devices (CIEDs). The aim of the study is to evaluate the outcomes of TLE and to investigate the impact of infection. Methods and results Data of patients undergoing extraction of permanent pacemaker and defibrillator leads during October 2014-September 2019 were prospectively analyzed. Overall, 242 consecutive patients (aged 71.0 ± 14.0 years, 31.4% female), underwent an equal number of TLE operations for the removal of 516 leads. Infection was the commonest indication (n = 201, 83.1%). Mean implant-to-extraction duration was 7.6 ± 5.4 years. Complete procedural success was recorded in 96.1%, and clinical procedural success was achieved in 97.1% of attempted lead extractions. Major complications occurred in two (0.8%) and minor complications in seven (2.9%) patients. Leads were removed exclusively by using locking stylets in 65.7% of the cases. In the subgroup of noninfective patients, advanced extraction tools were more frequently required compared to patients with CIED infections, to extract leads (success only with locking stylet: 55.8% vs. 67.8%, p = .032). In addition, patients without infection demonstrated lower complete procedural success rates (90.7% vs. 97.2%, p = .004), higher major complication rates (2.4% vs. 0.5%, p = .31) and longer procedural times (136 ± 13 vs. 111 ± 15 min, p = .001). Conclusions Our data demonstrate high procedural efficacy and safety and indicate that in patients with noninfective indications, the procedure is more demanding, thus supporting the hypothesis that leads infection dissolves and/or prohibits the formation of fibrotic adherences.

Gamma-irradiation of blood products is mandatory to avoid graft versus host disease in patients with immunosuppressed clinical conditions. Pathogen inactivation techniques were implemented to optimize safe blood component supply. The INTERCEPT treatment uses amotosalen together with UVA irradiation. The functional and molecular implications of these essential treatments have not yet been systematically assessed. The irradiation-induced inactivation of nucleic acids may actually be accompanied with modifications of chemically reactive polyunsaturated fatty acids, known to be important mediators of platelet functions. Thus, here we investigated eicosanoids and related fatty acids released upon treatment and during platelet storage for 7 days, complemented by the analysis of functional and metabolic consequences of these treatments. In contrast to gamma-irradiation, here we demonstrate that UVA treatment attenuated the formation of ALOX12-products such as 12-HETE and 12-HEPE but induced the formation of trans-arachidonic acids in addition to 11-HETE and HpODEs. Metabolic and functional issues like glucose consumption, lactate formation, platelet aggregation and clot firmness hardly differed between the two treatment groups. In vitro synthesis of trans-arachidonic acids (trans-AA) out of arachidonic acid in the presence of β-mercaptoethanol suggested that thiol radicals formed by UVA treatment are responsible for the INTERCEPT-specific effects observed in platelet concentrates. It is plausible to assume that trans-AA and other UVA-induced molecules may have specific biological effects on the recipients, which need to be addressed in future studies.Key pointsA previously unrecognized radical mechanisms for the generation of trans-fatty acids by UVA was identifiedIrradiation with UVA was found to immediately affect the generation of polyunsaturated fatty acid oxidation products

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) was considered a promising treatment for patients with peritoneal metastasis from colorectal cancer. However, the recently published randomized controlled PRODIGE 7 trial failed to demonstrate survival benefits through the addition of short-term oxaliplatin-based HIPEC. Constituting a complex multifactorial treatment, we investigated HIPEC in a preclinical model concerning the elimination of minimal tumor residues, thereby aiming to better understand the size of effects and respective clinical trial results. Patient samples of peritoneal perfusates obtained during HIPEC treatments and oxaliplatin-containing solutions at clinically relevant dosages, conforming with established HIPEC protocols, were assessed regarding their ability to eliminate modelled ~100 µm thickness cancer cell layers. Impedance-based real-time cell analysis and classical end-point assays were used. Flow cytometry was employed to determine the effect of different HIPEC drug solvents on tumor cell properties. Effectiveness of peritoneal perfusate patient samples and defined oxaliplatin-containing solutions proved limited but reproducible. HIPEC simulations for 30 min reduced the normalized cell index below 50% with peritoneal perfusates from merely 3 out of 9 patients within 72 h, indicating full-thickness cytotoxic effects. Instead, prolonging HIPEC to 1 h enhanced these effects and comprised 7 patients’ samples, while continuous drug exposure invariably resulted in complete cell death. Further, frequently used drug diluents caused approximately 25% cell size reduction within 30 min. Prolonging oxaliplatin exposure improved effectiveness of HIPEC to eliminate micrometastases in our preclinical model. Accordingly, insufficient penetration depth, short exposure time, and the physicochemical impact of drug solvents may constitute critical factors.