Amsterdam University Medical Centers

Ultra-weak Photon Emission (UPE) is thought to represent chemiluminescence from oxidative metabolic processes. This study aimed to characterize UPE dynamics during transient ischemia and reperfusion, while systematically assessing the reproducibility of both baseline and intervention-induced UPE measurements. UPE was recorded from the hands of 30 participants across two separate sessions using a custom-built photon-counting system. Transient ischemia was induced by a two-minute upper-arm tourniquet application. The stability and reproducibility of these measurements were evaluated using Bland-Altman analysis, Pearson correlations, and within-subject Coefficient of Variation (wsCV). UPE intensity exhibited a distinct multiphasic response to blood flow restriction: A sharp decline during ischemia (reaching ∼85% of baseline) followed by stabilization during reperfusion at approximately 95% of baseline. Baseline measurements exhibited high intrasession reproducibility (r=0.97, wsCV=11.3%) but only moderate intersession reproducibility (r=0.59, wsCV=34.4%). During the intervention, reproducibility was moderate in the ischemic phase (r=0.66, wsCV=43.6%), whereas the reperfusion phase showed substantially greater variability (r=0.32, wsCV=99.9%). In contrast, normalized AUC quantification produced stronger intersession linear associations and improved reproducibility across both the baseline-ischemia (r=0.83, wsCV=28.3%) and reperfusion segments (r=0.80, wsCV=35.1%). UPE is able to capture a dynamic physiological response to blood flow restriction that follows a consistent temporal trend despite significant individual variability. This study establishes quantitative benchmarks for UPE measurement stability, positioning it for future consideration as a non-invasive tool for monitoring oxidative metabolic activity in vivo.

In patients with contact allergy to Chinese propolis, co-reactivity to the four fragrance markers present in the European baseline series ( Myroxylon pereirae resin [balsam of Peru], colophonium, fragrance mixes 1 and 2) has been well documented. The co-reactivity pattern of Brazilian propolis has not yet been sufficiently analysed. To investigate co-reactivity patterns to the fragrance markers and to the fragrances linalool hydroperoxides and limonene hydroperoxides in patients reacting to Chinese and Brazilian propolis. Retrospective analysis of patch test results in a cohort of 701 patients tested with Chinese propolis and a cohort of 2509 individuals tested with Brazilian propolis investigated in Amsterdam during 2019-2025. For Chinese propolis, we found significant associations with the four fragrance markers and limonene hydroperoxides. For Brazilian propolis, there were significant associations with all four fragrance markers and both limonene and linalool hydroperoxides. There were indications of a closer relationship between Brazilian propolis and fragrances than of Chinese propolis and fragrances, possibly resulting in many more positive patch test reactions to the Brazilian variety. Significant co-reactivity to fragrances and -marker(s) was confirmed for patients allergic to Chinese propolis and established for patients with positive patch tests to Brazilian propolis.

The objective of this study was to evaluate the Diabetes Eating Problems Survey-Revised (DEPS-R) against the Eating Disorder Diagnostic Interview (EDDI). Specific aims were to (1) assess the ability of the DEPS-R to identify Diagnostic and Statistical Manual-5 (DSM-5) eating disorders, including sensitivity and specificity of the current DEPS-R cutoff ≥20 and (2) report the correlation of each item to the presence of any eating disorder. Baseline data from 293 women (14-35 years) with type 1 diabetes (T1D) and body image concerns enrolled in a multinational randomized controlled trial were examined. Receiver operating characteristic (ROC) analysis, univariate logistic regression and two-sample t-test were performed. The ROC analysis demonstrated good accuracy of the DEPS-R with an area under the curve (AUC) of 0.82 (95% CI 0.79-0.94). The cutoff of ≥20 yielded a sensitivity of 87.5% (95% CI 83.6%-91.3%) and a specificity of 60.4% (95% CI 54.8%-66.0%). Univariate logistic regression identified 12 items as significantly correlated with the presence of any eating disorder. The highest odds ratios (OR) were observed for items 9 (OR = 3.64), 8 (OR = 2.85), 13 (OR = 2.36), 14 (OR = 2.23), 15 (OR = 1.99) and 5 (OR = 1.99). This is the first study to investigate the ability of the DEPS-R to identify DSM-5 eating disorder diagnosis established via a diagnostic interview using a ROC-analysis. DEPS-R cutoff ≥20 correctly identified most cases with eating disorders but showed moderate specificity, considered acceptable as an initial screening tool for disordered eating. In clinical care, specific DEPS-R items may be emphasized to explore the presence of disordered eating behaviours and eating disorders.

Azacitidine/venetoclax is the standard treatment for patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy. Cytochrome P450 3A4 (CYP3A4) is the major metabolizing enzyme for venetoclax, and its inhibition can boost venetoclax. In the HOVON 171 phase 2 trial, patients with AML were treated with azacitidine/venetoclax/cobicistat. This 2-stage, open-label, multicenter phase 2 trial included a crossover run-in phase followed by an ongoing extension phase. In cycle 1, patients received standard-dose azacitidine/venetoclax. In cycle 2, cobicistat was added, and venetoclax was reduced to 50 mg. The primary end point was pharmacokinetic equivalence, defined as 90% confidence interval (CI) of geometric mean ratios (GMRs) >0.8 for area under the curve over 24 hours (AUC0-24h) and maximum plasma concentration (Cmax). Polymorphisms in genes encoding for CYP enzymes were determined. In vitro assays were performed to assess cobicistat's impact on the antileukemic effect of azacitidine/venetoclax in AML cell lines. In 13 evaluable patients, cobicistat-boosted venetoclax at 50 mg achieved higher exposure than standard 400-mg dosing. GMRs were 2.0 (90% CI, 1.4-2.8) for AUC0-24h and 1.4 (90% CI, 1.0-2.0) for Cmax. In the intention-to-treat population, 65% achieved complete remission (CR) or CR with incomplete hematologic recovery. Interpatient variability in venetoclax exposure because of CYP3A4 polymorphisms was reduced by cobicistat. No unexpected toxicities were observed. In in vitro, cobicistat enhanced azacitidine/venetoclax antileukemic effects. In conclusion, cobicistat enhances and optimizes venetoclax exposure, enabling an eightfold dose reduction while maintaining efficacy. The potentiated antileukemic activity positions cobicistat as a promising complementary agent in AML therapy. This trial was registered at www.clinicaltrials.gov as NCT06014489.

Starting dialysis is challenging for both patients and their informal caregivers. Caregivers help patients adapt and adhere to treatment by providing practical and emotional support, but these responsibilities can take a considerable toll on them. Because little is known about how caregiver experiences evolve after dialysis initiation, we (1) assessed the trajectory of experiences and health-related quality of life (HRQoL) of caregivers of patients on dialysis during the first year of dialysis, (2) assessed whether differences in these trajectories exist between caregivers of home dialysis patients and those of in-center hemodialysis (ICHD) patients, and (3) explored in which domains caregivers desire support over time. Multicenter, longitudinal cohort study. 202 dyads of incident dialysis patients and their adult informal caregivers. Home dialysis and ICHD. Positive experiences, caregiver burden, depressive symptoms, and HRQoL. Descriptive analyses of desired support and linear mixed models to assess and compare trajectories. All but 2 of the caregiver outcomes deteriorated over the first year of dialysis. The change over time was significant for positive experiences (β, -1.44 [95% CI, -2.36 to -0.51]), depressive symptoms (β, 5.20 [95% CI, 3.15-7.25]), physical HRQoL (β, -5.73 [95% CI, -9.20 to -2.26]), general HRQoL (β, -0.13 [95% CI, -0.17 to -0.07]), and perceived health status (β, -9.40 [95% CI, -15.12 to -3.67]), but not for caregiver burden (β, 0.85 [95% CI, -0.02 to 1.72]) or mental HRQoL (β, -2.99, [95% CI, -6.93 to 0.94]). No differences in the trajectories were found between caregivers of patients receiving home dialysis and ICHD, but these groups did differ in desired support. Small sample size of subgroups. Informal caregivers experience significant challenges during the first year of dialysis, marked by a notable decline in positive experiences, physical and general HRQoL, and perceived health status, alongside an increase in depressive symptoms, regardless of dialysis location. These findings underscore the need for targeted support for informal caregivers in dialysis care. The initiation of maintenance dialysis treatments presents notable challenges not only to patients but also to their informal caregivers, such as spouses, other family members, or friends. However, there is limited understanding of how these caregivers are affected over time. Therefore, we studied caregivers' experiences and health-related quality of life (HRQoL) during the first year of dialysis treatments received by the individual for whom they provide care. We found that caregivers reported a decline in positive experiences, worse physical and general HRQoL, and more depressive symptoms over time, whether dialysis was implemented in the home or a dialysis center. However, the types of support needed by caregivers of home and in-center dialysis patients differed. These findings underscore the need for targeted support for informal caregivers in dialysis care.