Rede uitgesproken door Prof. dr. Anton Jan van Zonneveld ter gelegenheid van zijn afscheid als hoogleraarNierziekten, in het bijzonder de experimentele vasculaire geneeskunde aan de Universiteit... Show moreRede uitgesproken door Prof. dr. Anton Jan van Zonneveld ter gelegenheid van zijn afscheid als hoogleraarNierziekten, in het bijzonder de experimentele vasculaire geneeskunde aan de Universiteit Leiden op vrijdag 31 mei 2024 Show less
By the early eighteenth century Edo (present-day Tokyo) was one of the largest cities in the world. Sex and erotic allure could be found in many guises in this commercialized urban setting, both in... Show moreBy the early eighteenth century Edo (present-day Tokyo) was one of the largest cities in the world. Sex and erotic allure could be found in many guises in this commercialized urban setting, both in the city’s streets and in print. This chapter sets out to argue that sex assumed a multiplicity of meanings in this context that ranged from pleasure and procreation to potential pathology. To this purpose, it begins by tracing various discourses surrounding the three phenomena that have arguably received the most sustained attention in research to date, namely the sex trade, male same-sex desire, and the erotically explicit materials known as ‘spring pictures’ (Japanese shunga 春画/ shunpon 春本). The final sections aim to move beyond the standard narrative of the Edo period’s flourishing erotic culture by focusing on the female reproductive body, as well as medical and health discourses, thus aspiring to unsettle the paradigmatic character of this (male) pleasure-centred mode of sex and repudiate the monolithic view of early modern Japanese sexuality as unregulated. Show less
Objectives Multiple studies have proven the prognostic value of molecular classification for stage I–III endometrial cancer patients. However, studies on the relevance of molecular classification... Show moreObjectives Multiple studies have proven the prognostic value of molecular classification for stage I–III endometrial cancer patients. However, studies on the relevance of molecular classification for stage IV endometrial cancer patients are lacking. Hypothetically, poor prognostic molecular subtypes are more common in higher stages of endometrial cancer. Considering the poor prognosis of stage IV endometrial cancer patients, it is questionable whether molecular classification has additional prognostic value. Therefore, we determined which molecular subclasses are found in stage IV endometrial cancer and if there is a correlation with progression-free and overall survival.Methods A retrospective multicenter cohort study was conducted using data from five Dutch hospitals. Patients with stage IV endometrial cancer at diagnosis who were treated with primary cytoreductive surgery or cytoreductive surgery after induction chemotherapy between January 2000 and December 2018 were included. Exclusion criteria were age <18 years or recurrent disease. The molecular classification was performed centrally on all tumor samples according to the World Health Organization 2020 classification (including POLE and estrogen receptor status). The Kaplan–Meier method was used to calculate progression free and overall survival in the molecular subclasses, for the different histological subtypes and for estrogen receptor positive versus estrogen receptor negative tumors. Groups were compared using the log-rank test.Results 164 stage IV endometrial cancer patients were molecularly classified. Median age of the patients was 67 years (range 33–86). Most patients presented with a non-endometrioid histological subtype (58%). Intra-abdominal complete cytoreductive surgery was achieved in 60.4% of the patients. 101 tumors (61.6%) were classified as p53 abnormal, 35 (21.3%) as no specific molecular profile, 21 (12.8%) as mismatch repair deficient, and 6 (3%) as POLE mutated. Molecular classification had no significant impact on progression free (p=0.056) or overall survival (p=0.12) after cytoreductive surgery. Overall survival was affected by histologic subtype (p<0.0001) and estrogen receptor status (p=0.013).Conclusion The distribution of the molecular subclasses in stage IV endometrial cancer patients differed substantially from the distribution in stage I–III endometrial cancer patients, with the unfavorable subclasses being more frequently present. Although the molecular classification was not prognostic in stage IV endometrial cancer, it could guide adjuvant treatment decisions. Show less
Importance Multiple patient-reported outcome measures (PROMs) for health-related quality of life (HRQL) exist for patients with psoriasis. Evidence for the content validity and other measurement... Show moreImportance Multiple patient-reported outcome measures (PROMs) for health-related quality of life (HRQL) exist for patients with psoriasis. Evidence for the content validity and other measurement properties of these PROMs is critical to determine which HRQL PROMs could be recommended for use.Objective To systematically review the validity of HRQL-focused PROMs used in patients with psoriasis.Evidence Review Using PubMed and Embase, full-text articles published in English or Spanish on development or validation studies for psoriasis-specific, dermatology-specific, or generic HRQL PROMs were included. Development studies included original development studies, even if not studied in psoriasis patients per Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) recommendations. If a study included multiple diagnoses, more than 50% of patients had to have psoriasis or psoriasis-specific subgroup analyses available. Data extraction and analysis followed the COSMIN guidelines. Two independent reviewers extracted and analyzed the data, including PROM characteristics, quality of measurement properties (structural validity, internal consistency, cross-cultural validity, reliability, measurement error, criterion validity, construct validity, and responsiveness), and level of evidence. PROMs were classified into 3 levels of recommendations: (1) PROM recommended for use; (2) PROM requires further validation; and (3) PROM not recommended for use.Findings Overall, 97 articles were identified for extraction. This included 19 psoriasis-specific, 8 skin-specific, and 6 generic PROMs. According to COSMIN standards, most measures identified received a B recommendation for use, indicating their potential but requiring further validation. Only the Rasch reduced version of the Impact of Psoriasis Questionnaire (IPSO-11 Rasch) received an A recommendation for use given that it had sufficient content validity, structural validity, and internal consistency.Conclusions and Relevance This study identified a significant lack of information concerning the quality of HRQL measures in psoriasis. This gap in knowledge can be attributed to the fact that traditional measures were developed using validation criteria that differ from the current standards in use. Consequently, additional validation studies in accordance with contemporary standards will be useful in aiding researchers and clinicians in determining the most suitable measure for assessing HRQL in patients with psoriasis. Show less
The search for biomarkers that quantify biological aging (particularly 'omic'-based biomarkers) has intensified in recent years. Such biomarkers could predict aging-related outcomes and could serve... Show moreThe search for biomarkers that quantify biological aging (particularly 'omic'-based biomarkers) has intensified in recent years. Such biomarkers could predict aging-related outcomes and could serve as surrogate endpoints for the evaluation of interventions promoting healthy aging and longevity. However, no consensus exists on how biomarkers of aging should be validated before their translation to the clinic. Here, we review current efforts to evaluate the predictive validity of omic biomarkers of aging in population studies, discuss challenges in comparability and generalizability and provide recommendations to facilitate future validation of biomarkers of aging. Finally, we discuss how systematic validation can accelerate clinical translation of biomarkers of aging and their use in gerotherapeutic clinical trials.Robust validation of biomarkers of aging will be critical to their clinical translation; here, authors review the key challenges and propose recommendations to overcome them. Show less
This Viewpoint discusses the potential drawbacks of the use of artificial intelligence (AI) in medicine, for example, the loss of certain skills due to the reliance on AI, and how physicians should... Show moreThis Viewpoint discusses the potential drawbacks of the use of artificial intelligence (AI) in medicine, for example, the loss of certain skills due to the reliance on AI, and how physicians should consider how to take advantage of the potential benefits of AI without losing control over their profession. Show less
Rosendal, C.; Arlien-Soborg, M.C.; Nielsen, E.H.; Andersen, M.S.; Feltoft, C.L.; Kistorp, C.; ... ; J. dal 2024
Acromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an... Show moreAcromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an epidemiological perspective and describe the temporal evolution of the disease pertaining to epidemiological variables, clinical presentation and mortality. We present updated epidemiological data from the population-based Danish cohort of patients with acromegaly (AcroDEN), along with meta-analyses of existing estimates from around the world.Based on this, we conclude that the incidence, prevalence and age at acromegaly diagnosis are all steadily increasing, but with considerable variation between studies. An increased number of incidental cases may contribute to the increase in incidence and age at diagnosis, respectively. The clinical features at presentation are trending toward a milder disease phenotype at diagnosis, and advances in therapeutic options have reduced the mortality of patients with acromegaly to a level similar to that of the general population. Moreover, the underlying cause of death has shifted from cardiovascular to malignant neoplastic diseases. Show less
Stoel, B.C.; Staring, M.; Reijnierse, M.; Helm-van Mil, A.H.M. van der 2024
Artificial intelligence techniques, specifically deep learning, have already affected daily life in a wide range of areas. Likewise, initial applications have been explored in rheumatology. Deep... Show moreArtificial intelligence techniques, specifically deep learning, have already affected daily life in a wide range of areas. Likewise, initial applications have been explored in rheumatology. Deep learning might not easily surpass the accuracy of classic techniques when performing classification or regression on low-dimensional numerical data. With images as input, however, deep learning has become so successful that it has already outperformed the majority of conventional image-processing techniques developed during the past 50 years. As with any new imaging technology, rheumatologists and radiologists need to consider adapting their arsenal of diagnostic, prognostic and monitoring tools, and even their clinical role and collaborations. This adaptation requires a basic understanding of the technical background of deep learning, to efficiently utilize its benefits but also to recognize its drawbacks and pitfalls, as blindly relying on deep learning might be at odds with its capabilities. To facilitate such an understanding, it is necessary to provide an overview of deep-learning techniques for automatic image analysis in detecting, quantifying, predicting and monitoring rheumatic diseases, and of currently published deep-learning applications in radiological imaging for rheumatology, with critical assessment of possible limitations, errors and confounders, and conceivable consequences for rheumatologists and radiologists in clinical practice.Deep learning is a powerful technique with great potential for the analysis and interpretation of rheumatological images. To successfully use deep learning, rheumatologists should understand the tasks involved in image processing and the potential confounders and limitations that can affect the analysis of clinical data.The number of research studies on deep learning in rheumatological imaging has grown rapidly during the past 5 years, but they mainly consist of pilot studies that require external validation.Confounding factors and errors in deep-learning methods need to be ruled out before deep learning can be applied in clinical practice, for which the intended use should be strictly defined.Deep-learning techniques, together with mapping to explain their reasoning, will enable hypothesis-free image analysis and could identify new imaging biomarkers.Deep learning might assist rheumatologists and radiologists in interpreting rheumatological images, increasing their diagnostic, prognostic and monitoring accuracy, and decreasing workloads and costs. Show less
Schenning, L.C.M.; Ottevanger, R.; Quint, K.D.; Tas, S.W. 2024
Hiel, B. van der; Aalbersberg, E.A.; Eertwegh, A.J.M. van den; Veen, L.J.D.V. de van der; Stokkel, M.P.M.; Lopez-Yurda, M.; ... ; Haanen, J.B.A.G. 2024
Purpose: The aims of this study were to investigate whether (early) PERCIST response monitoring with F-18-FDG PET/CT is predictive for progression-free survival (PFS) in unresectable stage III or... Show morePurpose: The aims of this study were to investigate whether (early) PERCIST response monitoring with F-18-FDG PET/CT is predictive for progression-free survival (PFS) in unresectable stage III or IV melanoma patients treated with BRAF/MEK inhibitor (MEKi) and to define dissemination patterns at progression with a lesion-based evaluation in direct comparison to baseline to improve our understanding of F-18-FDG PET/CT during BRAF/MEKi.Patients and methods: This prospective multicenter single-arm study included 70 patients with unresectable stage III/IV BRAF-mutated melanoma who underwent contrast-enhanced CT and F-18-FDG PET/CT at baseline and 2 and 7 weeks during treatment with vemurafenib plus cobimetinib and at progression if possible. Tumor response assessment was done with RECIST1.1 and PERCIST. Follow-up PET/CT scans were visually compared with baseline to assess dissemination patterns.Results: Using RECIST1.1, PFS was not significantly different between the response groups (P = 0.26). At 2 weeks, PERCIST median PFS was 15.7 months for patients with complete metabolic response (CMR) versus 8.3 months for non-CMR (P = 0.035). The hazards ratio (HR) for progression/death in non-CMR versus CMR was 1.99 (95% confidence interval [CI], 1.03-3.84; P = 0.040) and 1.77 (95% CI, 0.91-3.43; P = 0.0935) when adjusting for lactate dehydrogenase (LDH). At 7 weeks, median PFS for PERCIST CMR was 16.7 months versus 8.5 months for non-CMR (P = 0.0003). The HR for progression/death in the non-CMR group was significantly increased (HR, 2.94; 95% CI, 1.60-5.40; P = 0.0005), even when adjusting for LDH (HR, 2.65; 95% CI, 1.43-4.91; P = 0.0020). At week 7, F-18-FDG PET/CT was false-positive in all 4 (6%) patients with new FDG-avid lesions but CMR of known metastases. When F-18-FDG PET/CT was performed at progressive disease, 18/22 (82%) patients had progression of known metastases with or without new F-18-FDG-avid lesions.Conclusions: This study shows that PERCIST response assessment at week 7 is predictive for PFS, regardless of LDH. At 2 weeks, patients with CMR have longer PFS than patients with non-CMR, but different PET parameters should be investigated to further evaluate the added value of early F-18-FDG PET/CT. Disease progression on PET/CT is predominated by progression of known metastases, and new F-18-FDG-avid lesions during BRAF/MEKi are not automatically a sign of recurrent disease. Show less
Background. Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited. Methods. The Amsterdam, LEiden, GROningen trial is a randomized,... Show moreBackground. Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited. Methods. The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation. The primary endpoint was kidney transplant function at 24 mo. Results. A total of 295 participants were included in the intention-to-treat analysis. Noninferiority was shown for the primary endpoint; estimated glomerular filtration rate at 24 mo was 45.3 mL/min/1.73 m(2) in the early steroid withdrawal group, 49.0 mL/ min/1.73 m2 in the standard immunosuppression group, and 44.7 mL/min/1.73 m2 in the tacrolimus minimization group. Participants in the early steroid withdrawal group were significantly more often treated for rejection (P = 0.04). However, in this group, the number of participants with diabetes mellitus during follow-up and total cholesterol at 24 mo were significantly lower. Conclusions. Tacrolimus minimization can be considered in kidney transplant recipients who do not have an increased immunological risk. Before withdrawing steroids the risk of rejection should be weighed against the potential metabolic advantages. Show less
Aims Due to its indolent clinical behaviour, the treatment paradigm of atypical cartilaginous tumours (ACTs) in the long bones is slowly shifting from intralesional resection (curettage) and local... Show moreAims Due to its indolent clinical behaviour, the treatment paradigm of atypical cartilaginous tumours (ACTs) in the long bones is slowly shifting from intralesional resection (curettage) and local adjuvants, towards active surveillance through wait-and-scan follow-up. In this retrospective cohort study performed in a tertiary referral centre, we studied the natural behaviour of ACT lesions by active surveillance with MRI. Clinical symptoms were not considered in the surveillance programme. Methods The aim of this study was to see whether active surveillance is safe regarding malignant degeneration and local progression. In total, 117 patients were evaluated with MRI assessing growth, cortical destruction, endosteal scalloping, periosteal reaction, relation to the cortex, and perilesional bone marrow oedema. Patients received up to six follow-up scans. Results At the time of the first follow-up MRI, 8% of the lesions showed growth (n = 9), 86% remained stable (101), and 6% decreased in size (n = 7). During the third follow-up, with a mean follow-up time of 60 months (SD 23), 24 patients were scanned, of whom 13% had lesions that had grown and 13% lesions that had decreased in size. After 96 months (SD 37), at the sixth follow-up MRI, 100% of the lesions remained stable. None of the lesions showed malignant progression and although some lesions grew in size (mean 1 mm (SD 0.8)), no malignant progression occurred. Conclusion We conclude that active surveillance with MRI is safe for ACTs in the long bones in the short- and mid-term follow-up. Show less
Wemelsfelder, M.L.; Weem, R.H.G. van de; Luken, J.S.; Haas, M. de; Niessen, R.W.L.M.; Schoot, C.E. van der; ... ; Janssen, M.P. 2024
Background and ObjectivesRed blood cell (RBC) transfusions pose a risk of alloantibody development in patients. For patients with increased alloimmunization risk, extended preventive matching is... Show moreBackground and ObjectivesRed blood cell (RBC) transfusions pose a risk of alloantibody development in patients. For patients with increased alloimmunization risk, extended preventive matching is advised, encompassing not only the ABO-D blood groups but also the most clinically relevant minor antigens: C, c, E, e, K, Fya, Fyb, Jka, Jkb, S and s. This study incorporates patient-specific data and the clinical consequences of mismatching into the allocation process.Materials and MethodsWe have redefined the MINimize Relative Alloimmunization Risks (MINRAR) model to include patient group preferences in selecting RBC units from a finite supply. A linear optimization approach was employed, considering both antigen immunogenicity and the clinical impact of mismatches for specific patient groups. We also explore the advantages of informing the blood bank about scheduled transfusions, allowing for a more strategic blood distribution. The model is evaluated using historical data from two Dutch hospitals, measuring shortages and minor antigen mismatches.ResultsThe updated model, emphasizing patient group-specific considerations, achieves a similar number of mismatches as the original, yet shifts mismatches among patient groups and antigens, reducing expected alloimmunization consequences. Simultaneous matching for multiple hospitals at the distribution centre level, considering scheduled demands, led to a 30% decrease in mismatches and a 92% reduction in shortages.ConclusionThe reduction of expected alloimmunization consequences by incorporating patient group preferences demonstrates our strategy's effectiveness for patient health. Substantial reductions in mismatches and shortages with multi-hospital collaboration highlights the importance of sharing information in the blood supply chain. Show less
Koning, M.A. de; Ramirez, P.A.P.; Haak, M.C.; Han, X.; Ruiterkamp-Versteeg, M.H.; Leeuw, N. de; ... ; Suerink, M. 2024
Fetal hydrops as detected by prenatal ultrasound usually carries a poor prognosis depending on the underlying aetiology. We describe the prenatal and postnatal clinical course of two unrelated... Show moreFetal hydrops as detected by prenatal ultrasound usually carries a poor prognosis depending on the underlying aetiology. We describe the prenatal and postnatal clinical course of two unrelated female probands in whom de novo heterozygous missense variants in the planar cell polarity gene CELSR1 were detected using exome sequencing. Using several in vitro assays, we show that the CELSR1 p.(Cys1318Tyr) variant disrupted the subcellular localisation, affected cell-cell junction, impaired planar cell polarity signalling and lowered proliferation rate. These observations suggest that deleterious rare CELSR1 variants could be a possible cause of fetal hydrops. Show less
Background: There is ambiguity whether frail patients with atrial fibrillation (AF) managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC).Methods... Show moreBackground: There is ambiguity whether frail patients with atrial fibrillation (AF) managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC).Methods: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older AF patients living with frailty (age >= 75 years plus a Groningen Frailty Indicator (GFI) score >= 3) were randomized to switch from INR-guided VKA treatment to a NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mLmin(-1)1.73 m(-2) or with valvular AF were excluded. Follow-up was 12 months. The cause-specific hazard ratio (HR) was calculated for occurrence of the primary outcome which was a major or clinically relevant non-major bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events.Results: Between January 2018 and June 2022, a total of 2,621 patients were screened for eligibility and 1,330 patients were randomized (mean age 83 years, median GFI 4). After randomization 6 patients in the switch to NOAC arm and 1 patient in the continue with VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to a NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The HR for our primary outcome was 1.69 (95% CI 1.23-2.32). The HR for thromboembolic events was 1.26 (95% CI 0.60 to 2.61).Conclusions: Switching INR-guided VKA treatment to a NOAC in frail older patients with AF was associated with more bleeding complications compared to continuing VKA treatment, without an associated reduction in thromboembolic complications. Show less
