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Vriens, D.; Koster, E.J. de; Geus-Oei, L.F. de; Oyen, W.J.G.; EfFECTS trial consortium 2024

Preoperative stratification of cytologically indeterminate thyroid nodules by [18F]FDG-PET: can Orpheus bring back Eurydice?

Article / Letter to editor

open access

Roozen, G.V.T.; Prins, M.L.M.; Prins, C.; Janse, J.J.; Gruyter, H.L.M.D.; Pothast, C.R.; ... ; Roukens, A.H.E. 2024

Intradermal delivery of the third dose of the mRNA-1273 SARS-CoV-2 vaccine: safety and immunogenicity of a fractional booster dose

Article / Letter to editor

open access

Objectives: The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. Methods: COVID-19... Show moreObjectives: The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. Methods: COVID-19 naive adults aged 18e30 years were recruited from a previous study on primary vaccination regimens that compared 20 mg ID vaccinations with 100 mg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 mg) or the standard-of-care intramuscular (IM) booster dose (50 mg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18e40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. Results: In January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150e11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003e6322) BAU/mL; 6629 (4913e8946) BAU/mL; and 5264 (4032e6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. Discussion: Intradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness. Show less

Balsby, I.M.; Nielsen, S.M.; Christensen, R.; Henriksen, M.; Dahl, L.U.M.; Berg, J.I.; ... ; Dossing, A. 2024

Comparative effectiveness of different placebos and comparator groups for hand osteoarthritis exploring the impact of contextual factors: a systematic review and meta-analysis of randomised trials

Article / Letter to editor

open access

Objective: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. Methods: We systematically... Show moreObjective: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. Methods: We systematically searched PubMed, EMBASE and CENTRAL from inception to December 26, 2021. We included randomised controlled trials of people with hand osteoarthritis with a placebo or an untreated control group. We assessed the Risk of Bias with Cochrane Risk-of-Bias tool version 2. Each comparator was contrasted with a null-arm, imputed as having a zero change from baseline with the same standard deviation as the comparator. We combined the standardised mean differences with a random effects meta-analysis. The contextual factors’ effect was explored in meta-regression and stratified models with pain as the dependent variable. Results: 84 trials (7262 participants) were eligible for quantitative synthesis, of which 76 (6462 participants) were eligible for the stratified analyses. Placebos were superior to their matched null-arms in relieving pain with an effect size of −0.51 (95% confidence interval −0.61 to −0.42), while untreated control groups were not. When analysing all comparators, blinded trial designs and low risk of bias were associated with higher pain relief compared to an open-label trial design and some concern or high risk of bias. Conclusion: The placebo response on pain for people with hand osteoarthritis was increased by appropriate blinding and a lower risk of bias assessment. Placebos were superior to a null-arm, while untreated control groups were not. Results emphasise the importance of using appropriate comparators in clinical trials. PROSPERO registration ID: CRD42022298984 Show less

Stoelinga, A.E.C.; Biewenga, M.; Drenth, J.P.H.; Verhelst, X.; Meer, A.J.P. van der; Boer, Y.S. de; ... ; Dutch Autoimmune Hepatitis Study 2024

Diagnostic criteria and long-term outcomes in AIH-PBC variant syndrome under combination therapy

Article / Letter to editor

open access

Background & Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA).... Show moreBackground & Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Show less

Sievers, Eva; Spierenburg, M.J.; Jhagroe, S.S.; Oudenhoven, A.P. E van 2024

Place-based knowledge transfer in a local-to-global and knowledge-to-action context: key steps and facilitative factors

Article / Letter to editor

open access

Rapid global change threatens to outstrip global efforts to establish sustainable stewardship of social-ecological systems (SES). Place-based research can enhance effectiveness of global... Show moreRapid global change threatens to outstrip global efforts to establish sustainable stewardship of social-ecological systems (SES). Place-based research can enhance effectiveness of global sustainability policies and actions by providing contextualized knowledge underpinning bottom-up solutions. However, the use and transfer of place-based knowledge remains a major challenge. In this study, we analyze place-based knowledge transfer in a local-to-global and knowledge-to-action context. We aim to provide insights on when, how, and why place-based research can inform decision-making at the global scale, and lead to action towards more sustainable and just futures. Our iterative and exploratory methodology involved alternating rounds of literature reviews and interviews with interdisciplinary researchers. We identify four key steps (place-based knowledge production, knowledge synthesis, knowledge use at the global scale, and knowledge revision and lessons learned) and five facilitative factors (bridging organizations, knowledge brokers, boundary organizations, institutionalized knowledge governance and polycentric governance systems), which provide a comprehensive understanding of place-based knowledge transfer. Our conceptual framework provides suggestions on how to set up place-based knowledge transfer to be more effective, complete, and inclusive. Furthermore, our study discusses two major structural challenges that currently inhibit place-based knowledge transfer, and shows ways forward for science and policy to overcome these. We argue that place-based knowledge transfer can be an effective means to undo dominant power relations and the epistemic status quo, and enable a shift from short-termism in science and policy towards more long-term SES goals. Therefore, it is seminal to open up the predominant value system to more diverse knowledge systems, signifying a shift away from global decision-making that is guided by neoliberal capitalist principles and over-emphasizes short-term and individual gains. Finally, it is crucial to prioritize learning over knowing to exploit the long-term value of place-based knowledge transfer. Show less

Meyer, V.H. 2024

Grave matters: ambiguity, modernism, and the quest for moderate Islam in Indonesia

Article / Letter to editor

metadata only

Schoissengeier, V.; Maqboul, L.; Weber, D.; Grune, T.; Bürkle, A.; Moreno-Villaneuva, M.; ... ; Wagner, K.H. 2024

Association between bilirubin and biomarkers of metabolic health and oxidative stress in the MARK-AGE cohort

Article / Letter to editor

open access

Dekkers, N.; Dang, H.; Graaf, M. de; Nobbenhuis, K.; Verhoeven, D.A.; Kraan, J. van der; ... ; Boonstra, J.J. 2024

T1 colorectal cancer patients' perspective on information provision and therapeutic decision-making after local resection

Article / Letter to editor

open access

Background: Decision‐making after local resection of T1 colorectal cancer (T1CRC) isoften complex and calls for optimal information provision as well as active patientinvolvement.Objective: The aim... Show moreBackground: Decision‐making after local resection of T1 colorectal cancer (T1CRC) isoften complex and calls for optimal information provision as well as active patientinvolvement.Objective: The aim was to evaluate the perceptions of patients with T1CRC oninformation provision and therapeutic decision‐making.Methods: This multicenter cross‐sectional study included patients who underwentendoscopic or local surgical resection as initial treatment. Information provision wasassessed using the EORTC QLQ‐INFO25 questionnaire. In patients with high‐riskT1CRC, we evaluated decisional involvement and satisfaction regarding thechoice as to whether to undergo additional treatment after local resection, and thelevel of decisional conflict using the Decisional Conflict Scale.Results: Ninety‐eight patients with T1CRC were included (72% response rate; 79/98 endoscopic and 19/98 local surgical resection; 45/98 high‐risk T1CRC). Mediantime since local resection was 28 months (IQR 18); none had developed recurrence.Unmet information needs were reported by 29 patients (30%; 18 low‐risk, 11 high‐risk), mostly on post‐treatment related topics (follow‐up visits, recovery time,recurrence prevention). After local resection, 24 of the 45 high‐risk patients (53%)underwent additional treatment, while others were subjected to surveillance.Higher‐educated patients were more often actively involved in decision‐making(93% vs. 43%, p = 0.002) and more frequently underwent additional treatment(79% vs. 40%, p = 0.02). Decisional conflict (p = 0.19) and satisfaction (p = 0.78)were comparable between higher‐ and lower‐educated high‐risk patients. Show less

Kamdem, S.; Ojongnkpot, C.; Pinxteren, L.M.C. van 2024

Decolonizing Cameroon’s language policies: a critical assessment

Article / Letter to editor

open access

Due to its colonial history and prevalent multilingualism, Cameroon is a country where language policies have profoundly impacted socioeconomic and political life. Cameroon has 273 local languages... Show moreDue to its colonial history and prevalent multilingualism, Cameroon is a country where language policies have profoundly impacted socioeconomic and political life. Cameroon has 273 local languages and two official languages, English and French. The two official languages have been a crystallization point for discontent and civil unrest, leading to secessionist sentiments and violence. In this paper, we assess Cameroon’s language policies, firstly by providing a brief historical and legal overview based in the literature. We then present a new decolonial analytical framework, building on but extending existing theoretical frameworks. Our new analysis shows that a transition to using indigenous languages in formal education and other domains is not necessary at present. However, we argue that such a transition will become unavoidable in future. We show that it will be practically possible to use a limited number of indigenous languages as mediums of instruction, building on existing bilingualisms in the country. We believe these languages should be chosen using rational criteria and we introduce an approximate assessment of which languages are easy to learn and teach, and for speakers of which other languages. The transition we foresee requires planning and preparation. A different approach to Cameroon’s languages may help in building national unity and healing national wounds in the areas of sociolinguistic power-sharing and interregional cohabitation. We expect that our approach also holds benefits for other African countries. Show less

Andreeva, V.D.; Regeni, I.; Yang, T.; Elmanova, A.; Presselt, M.; Dietzek-Ivansic, B.; Bonnet, S.A. 2024

Red-to-blue triplet: triplet annihilation upconversion for calcium sensing

Article / Letter to editor

open access

Triplet-triplet annihilation upconversion is a bimolecular process converting low-energy photons into high-energy photons. Here, we report a calcium-sensing system working via triplet-triplet... Show moreTriplet-triplet annihilation upconversion is a bimolecular process converting low-energy photons into high-energy photons. Here, we report a calcium-sensing system working via triplet-triplet annihilation (TTA) upconverted emission. The probe itself was obtained by covalent conjugation of a blue emitter, perylene, with a calcium-chelating moiety, and it was sensitized by the red-light-absorbing photosensitizer palladium(II) tetraphenyltetrabenzoporphyrin (PdTPTBP). Sensing was selective for Ca2+ and occurred in the micromolar domain. In deoxygenated conditions, the TTA upconverted luminescence gradually appeared upon adding an increasing concentration of calcium ions, to reach a maximum upconversion quantum yield of 0.0020. Show less

Marciello, M.; Cusati, V.; Nicolosi, F.; Saavedra-Rubio, K.; Pierrat, E.; Thonemann, N.; Laurent, A. 2024

Evaluating the economic landscape of hybrid-electric regional aircraft: a cost analysis across three time horizons

Article / Letter to editor

under embargo until 2025-01-16

This article presents the results of a prospective cost analysis of future regional aviation solutions, specifically focusing on hybrid-electric regional aircraft for 50 passengers. The study spans three time horizons (short term, medium term, long term) and employs a validated workflow to estimate costs for various solutions, including conventional, hybrid-electric, and hydrogen-based architectures. A specialized cost model is introduced to assess the electric components of the powertrain, emphasizing maintenance expenses and energy costs. Despite the environmental promise of hybrid and electric solutions, the results reveal significantly higher direct operating costs (up to 69.8%) compared to conventional options. The study highlights the importance of targeted policies to incentivize sustainable alternatives, suggesting potential solutions such as discouraging kerosene-based aircraft and promoting sustainable aviation fuel. These insights provide valuable guidance for industry stakeholders navigating the path toward a more sustainable and economically viable aviation future.

Show less

Groen, R.A.; Barbero, F.L.; Fischer, S.E.; Dijkman, P.R.M. van; Bax, J.J.; Tushuizen, M.E.; ... ; Graaf, M.A. de 2024

Coronary artery calcium assessment on non-gated chest CT to optimize pre-operative cardiac screening in liver transplantation

Article / Letter to editor

open access

BackgroundGuidelines recommend standard pre-operative cardiac screening in all liver transplantation (LT) recipients, despite the relatively low prevalence of obstructive coronary artery disease.... Show moreBackgroundGuidelines recommend standard pre-operative cardiac screening in all liver transplantation (LT) recipients, despite the relatively low prevalence of obstructive coronary artery disease. Most LT recipients often have non-gated computed tomography (CT) performed of the chest and abdomen. This study evaluated the ability of coronary artery calcification (CAC) assessment on consecutively available scans, to identify a selection of low-risk patients, in whom further cardiac imaging can be safely withheld.MethodsLT recipients with prior non-gated CT chest-abdomen were included. CAC was visually scored on a semi-quantitative ordinal scale. Stress myocardial perfusion, coronary CT angiography (CCTA) and invasive coronary angiography (ICA) were used as golden standard. The sensitivity and specificity of CAC to exclude and predict obstructive CAD were assessed. In addition, peri- and postoperative mortality and cardiac events were analyzed.Results149 LT recipients (ranged 31–71 years) were included. In 75% of patients, no CAC and mild CAC could rule out obstructive CAD on CCTA and ICA with 100% certainty. The threshold of mild CAC had a sensitivity of 100% for both CCTA and ICA and a specificity of 91% and 68%, respectively. None of the patients with no or mild calcifications experienced peri- and post-operative cardiac events or died of cardiac causes.ConclusionVisual evaluation of CAC on prior non-gated CT can accurately and safely exclude obstructive CAD in LT recipients. Incorporation of these already available data can optimize cardiac screening, by safely withholding or correctly allocating dedicated cardiac imaging in LT recipients. Thereby, reducing patients' test burden and save health care expenses. Show less

Barz, M.; Parak, W.J.; Zentel, R. 2024

Concepts and approaches to reduce or avoid protein corona formation on nanoparticles: challenges and opportunities

Article / Letter to editor

open access

Spencer, H.; Parianen Lesemann, F.H.; Buisman, R.S.M.; Kraaijenvanger, E.J.; Branje, S.; Boks, M.P.M.; Bos, P.A. 2024

Facing infant cuteness: how nurturing care motivation and oxytocin system gene methylation are associated with responses to baby schema features

Article / Letter to editor

open access

Baby schema features are a specific set of physical features-including chubby cheeks, large, low-set eyes, and a large, round head-that have evolutionary adaptive value in their ability to trigger... Show moreBaby schema features are a specific set of physical features-including chubby cheeks, large, low-set eyes, and a large, round head-that have evolutionary adaptive value in their ability to trigger nurturant care. In this study among nulliparous women (N = 81; M age = 23.60, SD = 0.44), we examined how sensitivity to these baby schema features differs based on individual variations in nurturant care motivation and oxytocin system gene methylation. We integrated subjective ratings with measures of facial expressions and electroencephalography (EEG) in response to infant faces that were manipulated to contain more or less pronounced baby schema features. Linear mixed effects analyses demonstrated that infants with more pronounced baby schema features were rated as cuter and participants indicated greater motivation to take care of them. Furthermore, infants with more pronounced baby schema features elicited stronger smiling responses and enhanced P2 and LPP amplitudes compared to infants with less pronounced baby schema features. Importantly, individual differences significantly predicted baby schema effects. Specifically, women with low OXTR methylation and high nurturance motivation showed enhanced differentiation in automatic neurophysiological responses to infants with high and low levels of baby schema features. These findings highlight the importance of considering individual differences in continued research to further understand the complexities of sensitivity to child cues, including facial features, which will improve our understanding of the intricate neurobiological system that forms the basis of caregiving behavior. Show less

Bogaerts, J.M.K.; Gussekloo, J.; Jong-Schmit, B.E.M. de; Cessie, S. le; Mooijaart, S.P.; Mast, R.C. van der; ... ; Poortvliet, R.K.E. 2024

Effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life in nursing home residents with dementia (DANTON) a multicentre, open-label, blinded-outcome, randomised controlled trial

Article / Letter to editor

open access

BackgroundBased on observational studies and randomised controlled trials (RCTs), the benefit–harm balance of antihypertensive treatment in older adults with dementia is unclear.ObjectiveTo assess... Show moreBackgroundBased on observational studies and randomised controlled trials (RCTs), the benefit–harm balance of antihypertensive treatment in older adults with dementia is unclear.ObjectiveTo assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia.DesignOpen-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365.SubjectsDutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160 mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4 months (planned sample size n = 492).MeasurementsCo-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks.ResultsFrom 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6–89.5] years; 79.5% female; median SBP 134 [IQR 123–146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI –2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference − 2.5 [95% CI –6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98–2.79]). All 32-week outcomes favoured usual care.ConclusionHalfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit–harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia. Show less

Myagmardorj, R.; Fortuni, F.; Galloo, X.; Nabeta, T.; Meucci, M.C.; Butcher S.C.; ... ; Ajmone Marsan, N. 2024

Changes in global longitudinal strain after TAVI: additional prognostic value over cardiac damage in patients with severe aortic stenosis

Article / Letter to editor

open access

Background: Previous studies demonstrated the prognostic value of baseline cardiac damage staging as well as left ventricular global longitudinal strain (LVGLS) in patients undergoing transcatheter... Show moreBackground: Previous studies demonstrated the prognostic value of baseline cardiac damage staging as well as left ventricular global longitudinal strain (LVGLS) in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of the present study was to evaluate the changes in cardiac damage stage and LVGLS after TAVI and to investigate their prognostic values when integrated into the follow-up assessment. Methods: Patients with severe aortic stenosis undergoing TAVI were hierarchically classified into cardiac damage stages based on echocardiographic criteria before TAVI and at a 6-month follow-up. At the same time, LVGLS was measured. The staging system included stage 0 = no signs of cardiac damage; stage 1 = LV damage; stage 2 = mitral or left atrial damage; stage 3 = pulmonary vasculature or tricuspid damage; and stage 4 = right ventricular damage. The primary endpoint was all-cause mortality. Results: A total of 620 patients were included. At follow-up, LVGLS significantly improved, and the improvement was similar among each baseline cardiac damage stage. Follow-up LVGLS values were divided into quintiles, and each quintile was integrated into the cardiac damage staging, leading to a reclassification of 308 (50%) patients. At the time of a median follow-up at 48 (IQR 31–71) months starting from the 6-month follow-up after TAVI, 262 (38%) patients had died. A multivariable Cox regression model showed that LVGLS-integrated cardiac damage staging at follow-up had an incremental prognostic value over the baseline assessment (HR per 1-stage increase 1.384; 95% CI 1.152–1.663; p < 0.001). Conclusions: The integration of LVGLS with conventional echocardiographic parameters of cardiac damage at a 6-month follow-up after TAVI can improve patient risk-stratification. Show less

Holstein, Y. van; Mooijaart, S.P.; Oevelen, M. van; Deudekom, F.J. van; Vojinovic, D.; Bizzarri, D.; ... ; Trompet, S. 2024

The performance of metabolomics-based prediction scores for mortality in older patients with solid tumors

Article / Letter to editor

open access

Prognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality ... Show morePrognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality (MetaboHealth) and biological age (MetaboAge). This study aims to investigate the association of MetaboHealth and MetaboAge with 1-year mortality in older patients with solid tumors, and to study their predictive value for mortality in addition to established clinical predictors. This prospective cohort study included patients aged ≥ 70 years with a solid malignant tumor, who underwent blood sampling and a geriatric assessment before treatment initiation. The outcome was all-cause 1-year mortality. Of the 192 patients, the median age was 77 years. With each SD increase of MetaboHealth, patients had a 2.32 times increased risk of mortality (HR 2.32, 95% CI 1.59–3.39). With each year increase in MetaboAge, there was a 4% increased risk of mortality (HR 1.04, 1.01–1.07). MetaboHealth and MetaboAge showed an AUC of 0.66 (0.56–0.75) and 0.60 (0.51–0.68) for mortality prediction accuracy, respectively. The AUC of a predictive model containing age, primary tumor site, distant metastasis, comorbidity, and malnutrition was 0.76 (0.68–0.83). Addition of MetaboHealth increased AUC to 0.80 (0.74–0.87) (p = 0.09) and AUC did not change with MetaboAge (0.76 (0.69–0.83) (p = 0.89)). Higher MetaboHealth and MetaboAge scores were associated with 1-year mortality. The addition of MetaboHealth to established clinical predictors only marginally improved mortality prediction in this cohort with various types of tumors. MetaboHealth may potentially improve identification of older patients vulnerable for adverse events, but numbers were too small for definitive conclusions. The TENT study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22–10-2019. Show less

Heutz, J.W.; Looijen, A.E.M.; Kuijpers, J.H.S.A.M.; Schreurs, M.W.J.; Helm-van Mil, A.H.M. van der; Jong, P.H.P. de 2024

The prognostic value of IgA anti-citrullinated protein antibodies and rheumatoid factor in an early arthritis population with a treat-to-target approach

Article / Letter to editor

open access

The mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody (ACPA) and IgM rheumatoid... Show moreThe mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody (ACPA) and IgM rheumatoid factor (RF) for modern treatment outcomes remains unknown. We aimed to investigate the prognostic value of IgA-ACPA and IgA-RF for treatment outcomes in an early arthritis population. IgA-ACPA/RF isotypes were measured in baseline sera from 480 inflammatory arthritis (IA) patients, who were included in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH). The tREACH trial was a multicentre, stratified, single-blinded trial with a treat-to-target approach. The prognostic value of IgA-ACPA/RF was determined by evaluating differences in (1) quick-attained (< 6 months after diagnosis) and persistent remission rates, (2) DMARD-free remission and (3) biological use between IA patients with and without IgA-ACPA/RF over 3 years of follow-up. IgA-ACPA was present in 23% of patients and overlapped with IgG-ACPA positivity in 94%. Similarly, IgA-RF overlapped with IgM-RF in 90% of patients. IgA-ACPA positivity was associated with lower DFR rates and more biological use, but this effect was largely mediated by the presence of IgG-ACPA, since this effect disappeared after stratification for IgG-ACPA (HR 0.6, 95%CI 0.2-1.6 for DFR). No differences were observed in ‘quick-attained and persistent remission’ rates and for IgA-RF. Their seems to be no additional value of IgA-ACPA and IgA-RF for modern, long-term clinical outcomes. The effects of IgA-ACPA seen in our study are largely mediated by the presence of IgG-ACPA. Based on these results, there is no rationale for measuring these isotypes in daily practice. Show less

Fiala , J.; Roach, T.; Holzinger, A.; Husiev, Y.; Delueg, L.; Hammerle, F.; ... ; Siewert, B. 2024

The light-activated effect of natural anthraquinone parietin against candida auris and other fungal priority pathogens

Article / Letter to editor

open access

Antimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the Candida species, including the emerging pathogen C. auris. Using a modified... Show moreAntimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the Candida species, including the emerging pathogen C. auris. Using a modified EUCAST protocol, the light-enhanced antifungal activity of the natural compound parietin was explored. The photoactivity was evaluated against three separate strains of five yeasts, and its molecular mode of action was analysed via several techniques, i.e., cellular uptake, reactive electrophilic species (RES), and singlet oxygen yield. Under experimental conditions (λ = 428 nm, H = 30 J/cm2, PI = 30 min), microbial growth was inhibited by more than 90% at parietin concentrations as low as c = 0.156 mg/L (0.55 µM) for C. tropicalis and Cryptococcus neoformans, c = 0.313 mg/L (1.10 µM) for C. auris, c = 0.625 mg/L (2.20 µM) for C. glabrata, and c = 1.250 mg/L (4.40 µM) for C. albicans. Mode-of-action analysis demonstrated fungicidal activity. Parietin targets the cell membrane and induces cell death via ROS-mediated lipid peroxidation after light irradiation. In summary, parietin exhibits light-enhanced fungicidal activity against all Candida species tested (including C. auris) and Cryptococcus neoformans, covering three of the four critical threats on the WHO's most recent fungal priority list. Show less

Volinsky-Fremond, S.; Horeweg, N.; Andani, S.; Wolf, J.B.; Lafarge, M.W.; Kroon, C.D. de; ... ; Bosse, T. 2024

Author correction: prediction of recurrence risk in endometrial cancer with multimodal deep learning

Article / Letter to editor

open access

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