University Medical Center Groningen

To investigate how task delegation for perioperative anticoagulation management is reported in protocols and daily practice, and how this translates to additional information in work-as-imagined and work-as-done using FRAM to identify improvement possibilities. Existing FRAM visualisations of perioperative anticoagulant management in a Dutch academic hospital were extended to include task delegation in protocols using document analysis and in daily practice using a focus group of eight healthcare professionals, analysed using content analysis. Distinguishing between formal responsibility and task execution revealed additional functions and roles in both work-as-done and work-as-imagined, resulting in more discrepancies between work-as-done and work-as-imagined. Professionals experienced responsibility for delegated tasks, even without formal accountability, and needed to feel qualified and capable as well as complete clear information to accept these tasks. Including task delegation in FRAM models improves the understanding of healthcare processes, communication about distribution of responsibilities and thereby development of more effective improvement strategies.

The mean overall satisfaction score from parents was 7.5 out of 10 (with 1 being the lowest and 10 the highest possible score). DiscussionWhile overall satisfaction was high, experiences varied, and less than half of parents achieved their goal at the end of the treatment.Some parents primarily sought guidance rather than complete dryness.A lack of dialogue about goals or treatment options may leave needs (like guidance) unmet and lead to unnecessary care (e.g.treatment for total dryness). ConclusionParents' experiences overall are positive, but can vary widely, affected by their goals and expectations.These findings highlight the importance of discussing expectations to improve outcomes and reduce healthcare use.

Fc receptor-like (FCRL) proteins constitute a receptor family that displays overlapping yet distinct features compared to classical Fc receptors. In a healthy immune system, FCRL proteins play a role in promoting and regulating the immune response through their immunoreceptor tyrosine-based motifs. FCRL proteins are expressed mainly by B cells, suggesting a primary role in B-cell responses. For several autoimmune diseases, studies have shown that particularly FCRL4, which binds to dimeric IgA, and FCRL5, which binds to IgG, may have a role in disease pathology and prognosis. These proteins and their transcripts are often enriched in blood and/or affected tissue of patients with a systemic or organ-specific autoimmune disease like rheumatoid arthritis, Sjögren's disease, systemic lupus erythematous, Graves' disease or myasthenia gravis. The expression of FCRL4 and FCRL5 appears to be disease- and context-specific, and influenced by the tissue microenvironment. Yet, the functions of FCRL proteins are still incompletely understood, and more mechanistic studies are necessary to unravel the contribution of FCRL4 and FCRL5 to pathogenic B-cell responses occurring in autoimmune diseases.

Aiming for personalization of elective clinical target volumes (CTV), we are reporting on regional lymphatic spread patterns in laryngeal squamous cell carcinoma (SCC), considering not only subsite, T-stage, and lateralization of the primary tumor, but also involvement of adjacent lymph node levels (LNLs). LNL involvement in 1005 patients with laryngeal SCC treated at University Hospital Zurich between 2013 and 2021 and UMCG Groningen between 2006 and 2023 was analyzed. LNL involvement was assessed based on imaging and, if available, pathology. Patterns of LNL involvement can be visualized on https://lyprox.org/. For T2-glottic tumors (N=193), involvement was <4% in all LNLs, supporting the hypothesis that ENI could potentially be omitted. In T3/T4-glottic patients without ipsilateral LNL II involvement (N=198), involvement of LNLs III and IV was 5% and 1%, suggesting that ENI of LNL IV could be omitted in cN0 patients. For T3/T4-glottic tumors (N=239) almost no contralateral involvement was observed for lateralized tumors (N=37), suggesting contralateral treatment could potentially be omitted or limited to LNL II in patients with clinically negative contralateral neck. For supraglottic SCC without midline extension of the primary tumor (N=75), contralateral LNL involvement was below 3%. In patients with midline extension but without contralateral LNL II involvement (N=193), involvement of downstream levels was rare (LNL III 5%, LNL IV 3%). We provided detailed information about lymphatic spread patterns of laryngeal SCC, depending on subsite, T-stage, lateralization, and upstream involvement. Subgroups of patients can be identified in whom the elective CTV or surgical approach may be reduced compared to current guidelines.

Medication reconciliation (MR) in the emergency department (ED) is essential to ensure medication safety, especially for patients admitted to the hospital. However, performing MR for all ED patients, including those discharged, can be inefficient. To optimize prioritization, an artificial intelligence (AI)-powered hospital admission prediction dashboard was introduced. The primary aim of this study was to evaluate the effect of an artificial intelligence (AI) powered hospital admission prediction dashboard on the proportion of patients admitted to the hospital with an MR performed in the ED. The secondary aim was to assess its effect on the proportion of patients discharged from the ED with an MR. This retrospective before-after study was conducted at Hospital Group Twente and included ED visits between March 15 and December 31 in both 2023 and 2024. In the pre-intervention period, MR was strived for any patient, including patients discharged directly from the ED (i.e. potentially unnecessary MR as the risk for errors is low) and for admitted patients (i.e. correct MR). In 2024, the post-intervention period, a set of Extreme Gradient Boosting (XGBoost) models was trained on historical data (2015-2022) and integrated into a real-time dashboard to prioritize patients with the highest admission probability to perform MR. Primary outcome was the proportion of patients with correct MR. Secondary outcome was the proportion of patients with a potentially unnecessary MR. Chi-square test was used to compare proportions before and after implementation of the dashboard. The study included 25,505 ED visits. Pre-intervention 12,743 ED visits were included with 5,252 MRs performed. Post-intervention 12,762 ED visits were included with 4,882 MRs. After implementing the dashboard, the proportion of patients with correct MR increased from 86.4 to 89.0% (p = 0.0002), and the proportion of patients with potentially unnecessary MR decreased from 17.9 to 12.6% (p < 0.0001). The AI-powered hospital admission prediction dashboard improved the prioritization of MR in the ED. The proportion of patients with potentially unnecessary MR remains substantial and requires further improvement.

Natural hydrogels (e.g., collagen hydrogels) show good potential in understanding cell-matrix interaction and find application in tissue engineering. However, it remains challenging to bioprint cell-laden natural hydrogels with good printability, shape retention and stability. In this study, non-water-soluble short collagen type I microfibers (COL-I μFiber) were blended with water-soluble methacrylated collagen peptide (COPMA) and xanthan gum (XG), forming an interpenetrated network, and bioprinted into stable natural-derived COPMA-μFiber-XG constructs, followed by in situ stem cell proliferation and differentiation. First, to enhance the printability and the mechanical properties of COPMA, a COPMA-μFiber-XG bioink was developed, featuring rapid UV-curing and self-healing properties. The encapsulated human mesenchymal stem cells (hMSCs) spread along the COL-I μFibers in the bioprinted constructs, with increased metabolic activity and production of extracellular matrix and bioactive proteins (COL-I and scleraxis) in 28 days. The internal biophysical and biochemical signals provided by COL-I μFibers and the fibrous COPMA matrix synergistically interacted with exogenous biochemical signals (e.g., transforming growth factor-beta 3) to further promote stem cell differentiation. Overall, bioprinted fibrous COPMA-μFiber-XG constructs are biocompatible and bioactive matrices to support hMSCs proliferation and differentiation.

RET fusions appear in 1%-2% of non-small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET-altered NSCLC and RET fusion-positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion-positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion-positive NSCLCs, confirming previous findings with longer follow-up.

Follow-up of radiologically suspicious lung nodules from screening programs remains complex and unstandardized. This study analyses distribution and characteristics of solid and part-solid non-calcified nodules ≥100mm3 and non-solid nodules ≥8mm detected at baseline in the UK Lung cancer Screening (UKLS) trial, with insights into their relationship to screen-detected lung cancers. UKLS participants with baseline indeterminate and positive lung nodules were included. Nodule location was categorized by lobe and by attachment: intraparenchymal, juxta pleural or pleural-based. Solid and part-solid were classified based on semi-automated volume: 100-300mm3 and ≥300mm3, and non-solid nodules based on diameter ≥8mm. This measurement approach aligns with UKLS protocol and the British Thoracic Society (BTS) guideline. Their relationship to screen-detected lung cancer was based on histological outcomes after a 2-year follow-up period. 279 UKLS participants with 373 solid or part-solid lung nodules ≥100mm3 and 57 participants with 62 nonsolid nodules ≥8mm were included. Among solid and part-solid nodules, 233 were 100-300mm3, with 39.5% in upper lobes and 72.5% intraparenchymal; 140 nodules were ≥300mm3, with 51.4% in upper lobes and 53.6% intraparenchymal. Nodules ≥300mm3 group were more likely to be in the upper lobes (OR 1.97 [95% CI 1.12-3.48]). Within 2years, 34 solid or part-solid nodules were diagnosed as lung cancer, yielding a 2-year cancer probability of 9.1% (95% CI 6.6-12.5). The 2-year lung cancer probability was higher in nodules ≥300mm3 (RR 18.1, 95% CI 5.6-58.4; p<0.001) and in upper lobe nodules (RR 2.7, 95% CI 1.3-5.5; p=0.009). Solid and part-solid nodules with volume ≥300mm3 were more often found in the upper lobes and were associated with a higher probability of lung cancer within a two-year follow-up period.