Ziekenhuis Amstelland

Malignant and non-malignant cells within the tumor microenvironment (TME) actively secrete extracellular vesicles (EVs) that may mediate intercellular communication or enter the blood stream. Circulating EVs in Diffuse Large B-Cell Lymphoma (DLBCL) patients are a promising source of liquid biopsy biomarkers; however, whether different cellular components of the TME preferentially secrete small (S-) and/or large (L-) EVs is still unknown. With an established density-gradient separation protocol and tunable resistive pulse sensing analysis, we demonstrate that DLBCL cells in culture produce 100-1000-fold higher numbers of S-EVs (50-200nm) compared with L-EVs (200-1000nm) and very large EVs (>1000nm). In contrast, the plasma from DLBCL patients contains comparable concentrations of S- and L-EVs, consistent with various cellular origins. Small RNA sequencing showed minor differences in miRNA content between plasma S- and L-EVs; however, messenger RNA sequencing revealed stark differences in cargo between EV-size subtypes and between healthy donors and patients. Deconvolution analysis with single-cell sequencing data from 17 DLBCL tumor tissues as reference using the Statescope algorithm indicated that circulating S-EVs from malignant cells outnumber the L-EVs. In contrast, TME macrophage-, T cell-, and natural killer-derived L-EVs outnumber S-EVs. Together, these findings suggest that circulating S- and L-EVs can originate from distinct cellular compartments within the DLBCL TME, representing complementary biological information. These observations have important implications for the development of EV-based liquid biopsy strategies.

BackgroundDementia risk reduction through lifestyle modification has much potential but is not widely implemented in routine care. Patients referred to memory clinics are at high risk for dementia and tend to have worse health and lifestyle profiles. There is currently no service available to help these persons make lifestyle changes. We aim to improve lifestyle profiles through implementing a personalized and multidomain lifestyle intervention in the memory clinic. Here, we describe the design of our study assessing the effectiveness of this intervention.MethodLifestyle Intervention in the memory clinics of General and academic Hospitals Trial (LIGHT) is a 12‐month multicentre randomized controlled trial investigating the effects of an innovative lifestyle intervention. Starting early 2025, the trial aims to include 300 older adults (≥ 50 years) with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) who have ≥2 modifiable dementia risk factors (to ensure room for improvement) primarily from the memory clinics of Maastricht UMC+ and Amsterdam UMC. Participants are randomized 1:1 to the intervention or usual care with general health advice. The intervention comprises three components: 1) Three individual sessions with a certified lifestyle coach to work on personal goals, 2) Vouchers for access to brain‐healthy activities from local providers, and 3) Online access to a recently developed risk self‐management platform (www.breinzorg.nl). Primary outcome is the 12‐month change in participants dementia risk profiles as measured by the LIfestyle for BRAin Health (LIBRA) index. Secondary outcomes include cognitive functioning, health‐related quality of life, activities of daily living, psychological measures, as well as individual lifestyle components.ResultLIGHT provides insight into the implementability and (cost‐) effectiveness of a lifestyle intervention in a memory clinic setting. Recruitment has started early 2025 and will continue until 2027.ConclusionLIGHT may provide evidence for a personalized multidomain lifestyle intervention for preventing dementia. The results would support implementing personalized lifestyle coaching in the regular service offered by Dutch memory clinics.

<p>This Supplementary Issue of the <em data-start="877" data-end="937">Journal of Natural Built Social Environment Health (NBSEH)</em> hosts the <em data-start="948" data-end="967">Book of Abstracts</em> of the 25th International Congress on Industry, Environment, and Health (CIIES25), held in Casablanca, Morocco, 15–17 May 2025. All abstracts were reviewed and approved by the scientific committee of the congress. They are published under a single DOI as part of NBSEH’s mission to ensure scientific dissemination, archiving, and long-term accessibility.</p>

CDK4/6 inhibitors (CDK4/6i) improve outcome in patients with advanced estrogen receptor-positive, HER2- breast cancer. The phase 3 SONIA trial compared the addition of CDK4/6i to first- versus second-line endocrine therapy for time to disease progression after second-line treatment (progression-free survival after two lines of treatment (PFS2)), as well as for secondary outcomes overall survival, PFS after one line of treatment (PFS1), health-related quality of life (HRQOL), toxicity and cost-effectiveness. No significant difference in PFS2 was observed; however, on an individual patient level this may be different. Using prespecified circulating tumor DNA analyses, we performed an exploratory study to evaluate whether pretreatment circulating tumor DNA (ctDNA) levels in plasma can identify patients that benefit from CDK4/6i during their first-line treatment. Cell free DNA before start of first-line treatment from 409 female patients participating in SONIA was analyzed with the modified fast aneuploidy screening test-sequencing system. This assay yields a genome-wide aneuploidy score, indicative of ctDNA levels. Cox proportional hazard analyses for PFS1 and PFS2 were performed separately for the ctDNA high group (aneuploidy score ≥ 5) and the ctDNA low group (aneuploidy score < 5). In total, 141 of the 409 included patients had a high genome-wide aneuploidy score at baseline. PFS2 in the first- compared to the second-line CDK4/6i strategy showed hazard ratios of 0.58 (95% confidence interval 0.38-0.88) and 1.36 (95% confidence interval 0.95-1.96) in the high and low aneuploidy group, respectively. A significant interaction was demonstrated between treatment strategy and aneuploidy score for PFS2 (P = 0.004). In conclusion, this study demonstrated that pretreatment ctDNA levels can be used to identify patients that benefit from first-line CDK4/6i treatment. ClinicalTrials.gov registration: NCT03425838 .

To enhance social interaction of residents living with dementia and their (in)formal carers in nursing homes, we examined the effects of a digital, person-centred, Photo-Activity (PA) versus a conversation activity (control). An explorative randomized controlled trial was conducted in 81 resident-informal carer (IC) dyads and 51 formal carers (FC) with three measurements (pre/post-test, 2-week follow-up). Intervention effects were tested using Mann–Whitney U’s, and ANCOVA’s with pre-test scores as covariates. Interaction effects were examined between dementia severity (DS; less/more) and condition (PA/control). A post-test effect was observed in social interaction (INTERACT-subscale: Mood [p = 0.037, ηp2 = 0.07]), with PA residents showing better mood than controls. Residents with less DS showed more positive effects of PA than residents with more DS (interaction effects: INTERACT-subscales Mood [p = 0.017, ηp2 = 0.092], Stimulation Level [p = 0.011, ηp2 = 0.106], and Need for Prompting [p = 0.013, ηp2 = 0.099]). Higher QUALIDEM Positive Affect scores were observed in the PA group, post-test (p = 0.025, ηp2 = 0.082), and follow-up (p = 0.042, d = 0.39). PA FC showed less empathy (IRI; p = 0.006, ηp2 = 0.185;) than controls, but reported getting to know the residents better (p = 0.035, r = 0.299). PA improved mood and positive affect of residents with dementia and led to FC knowing the residents better. Less empathy was observed in FC providing PA, requiring further investigation.

Abstract Objectives The impact of preoperative glycometabolic profile of diabetic patients on the risk of penile prosthesis (PP) infection remains uncertain. Current data are conflicting but the studies to date have been limited by retrospective design and by including heterogenous cohorts of patients (both diabetic and non-diabetic). Hence, the available evidence on the impact of diabetes mellitus (DM) and glycemic control on infection rate after PP implantation was systematically reviewed. Methods A comprehensive Medline, Embase, and Cochrane search was performed including the keywords penile prosthesis and diabetes mellitus. English-language articles between January 1st, 1969, up to May 31st, 2024 were included. Primary outcome was the PP infection rate in patients with DM. Secondary endpoints included the contribution of glycometabolic control on PP infection rate. Random-effect model was uniformly applied. Robust meta-analytical techniques were employed to control for heterogeneity and undetected bias including sensitivity analyses and regression linear adjusted models where appropriate. The protocol of this study (CRD42024557982) was published on PROSPERO. Results Out of 182 retrieved articles, 9 were included in the study (3 prospective and 6 retrospective) accounting for 5493 subjects with a mean age of 59.7 years, and a mean follow-up of 29.4 months. Overall, a PP infection rate of up to 7% was observed. The PP infection rate increased according to baseline HbA1c levels and was confirmed in multivariate analysis adjusting for age and trial duration (B = 7.8 ± 0.2%; p &amp;lt; 0.0001). PP infection rate was almost 3-times higher when trials with a mean HbA1c greater than 8% were compared to the rest of the sample (9.1 (7.5;11.0) vs. 3.8(3.2;13.5)%; Q = 43.18; p &amp;lt; 0.0001). Conclusions The present study suggests a significantly increased risk of PP infection for patients with DM and pre-operative HbA1c greater than 8%. A multidisciplinary approach to optimise preoperative glycometabolic control in patients with DM may be the key element for successful PP implant outcomes. However, better quality studies are needed to better guide clinical practice and preoperative optimisation. Conflicts of Interest nil.

The purpose of this study was to investigate the effect of coronectomy on postoperative quality of life in older adults. Coronectomy is an alternative to complete surgical removal of a mandibular third molar that lies close to the inferior alveolar nerve. This prospective study included patients >60 years old who had an indication for coronectomy of a mandibular third molar. Patients were asked to complete the Dutch version of the Oral Health Impact Profile-14 (OHIP-14) daily during the first postoperative week. Postoperative pain, swelling, limited mouth opening, chewing ability and infection were also recorded. Furthermore, the effect of the impaction pattern, state of eruption, presence of preoperative pathology, patient health status according to the American Society of Anaesthesiologists score, gender, smoking on the postoperative OHIP-14 and pain scores were investigated. Thirty patients (16 males, 14 females) with a mean age of 71.2 (SD 8.3, range 60-91) years were included in the study. OHIP-14 and pain scores were highest on the first postoperative day and gradually declined during the first postoperative week. Patients who underwent coronectomy of a fully impacted mandibular third molar had significantly higher OHIP-14 scores on the first postoperative day than those who underwent coronectomy on a (partially) erupted mandibular third molar. We did not observe any postoperative complications up to 1 year after the surgery. Mandibular third molar coronectomy seems to present a valid treatment option in older adults.

BackgroundFrailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent. MethodsThe HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID). Results137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients. ConclusionHRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.