The development of brain metastases in patients with different therapeutic strategies for metastatic renal cell cancer

A diagnosis of brain metastasis (BM) significantly affects quality of life in patients with metastatic renal cell cancer (mRCC). Although systemic treatments have shown efficacy in mRCC, active surveillance (AS) is still commonly used in clinical practice. In this single-center cohort study, we assessed the impact of different initial treatment strategies for metastatic RCC (mRCC) on the development of BM. All consecutive patients diagnosed with mRCC between 2011 and 2022 were included at the Erasmus MC Cancer Institute, the Netherlands, and a subgroup of patients with BM was selected. In total, 381 patients with mRCC (ECM, BM, or both) were identified. Forty-six patients had BM of whom 39 had metachronous BM (diagnosed ≥1 month after ECM). Twenty-five (64.1%) of these 39 patients with metachronous BM had received prior systemic treatment for ECM and 14 (35.9%) patients were treatment naive at BM diagnosis. The median BM-free survival since ECM diagnosis was significantly longer (p =.02) in previously treated patients (29.0 [IQR 12.6–57.0] months) compared to treatment naive patients (6.8 [IQR 1.0–7.0] months). In conclusion, patients with mRCC who received systemic treatment for ECM prior to BM diagnosis had a longer BM-free survival as compared to treatment naïve patients. These results emphasize the need for careful evaluation of treatment strategies, and especially AS, for patients with mRCC.</p

Afstudeerwerk

Voorwoord bij een nieuwe rubriek met afstudeerwerk Het Bulletin KNOB biedt een podium aan zowel ervaren onderzoekers als aanstormend talent. Met een zekere regelmaat publiceren afgestudeerden een artikel op basis van hun masterscriptie of ander onderzoek dat zij aan de universiteit deden. Maar dit is slechts een topje van de ijsberg. Er is immers veel meer werk van studenten dat de aandacht van de lezer verdient. Daarom starten wij in het Bulletin KNOB een rubriek met afstudeerwerk. Eens in de twee jaar vragen wij een aantal pas afgestudeerden van wie de masterthesis of eindopdracht goed is beoordeeld hiervan een synthese te maken. Voor de eerste aflevering van deze rubriek zijn dat degenen die meedongen naar de KNOB Stimuleringsprijs 2021. Het resultaat vindt u in dit nummer: zeventien bijdragen over uiteenlopende onderwerpen, van Cubex-keuken tot herbestemming van industrieel erfgoed en van klimaatverbetering in steden tot Antwerpse zeemanshuizen. De auteurs zijn alumni van universitaire opleidingen op het gebied van architectuur- en stadsgeschiedenis, erfgoed en (landschaps)architectuur in Nederland en België. Met deze rubriek laten wij onze lezers kennisnemen van door studenten verricht onderzoek en bieden wij beginnende onderzoekers en ontwerpers een gelegenheid hun werk in het Bulletin KNOB te presenteren. Onze dank gaat daarbij uit naar collega Jeroen Goudeau, die ons het idee voor een rubriek met afstudeerwerk aan de hand deed. Wij wensen u veel leesplezier en inspiratie toe. De redactieVoorwoord bij een nieuwe rubriek met afstudeerwerk Het Bulletin KNOB biedt een podium aan zowel ervaren onderzoekers als aanstormend talent. Met een zekere regelmaat publiceren afgestudeerden een artikel op basis van hun masterscriptie of ander onderzoek dat zij aan de universiteit deden. Maar dit is slechts een topje van de ijsberg. Er is immers veel meer werk van studenten dat de aandacht van de lezer verdient. Daarom starten wij in het Bulletin KNOB een rubriek met afstudeerwerk. Eens in de twee jaar vragen wij een aantal pas afgestudeerden van wie de masterthesis of eindopdracht goed is beoordeeld hiervan een synthese te maken. Voor de eerste aflevering van deze rubriek zijn dat degenen die meedongen naar de KNOB Stimuleringsprijs 2021. Het resultaat vindt u in dit nummer: zeventien bijdragen over uiteenlopende onderwerpen, van Cubex-keuken tot herbestemming van industrieel erfgoed en van klimaatverbetering in steden tot Antwerpse zeemanshuizen. De auteurs zijn alumni van universitaire opleidingen op het gebied van architectuur- en stadsgeschiedenis, erfgoed en (landschaps)architectuur in Nederland en België. Met deze rubriek laten wij onze lezers kennisnemen van door studenten verricht onderzoek en bieden wij beginnende onderzoekers en ontwerpers een gelegenheid hun werk in het Bulletin KNOB te presenteren. Onze dank gaat daarbij uit naar collega Jeroen Goudeau, die ons het idee voor een rubriek met afstudeerwerk aan de hand deed. Wij wensen u veel leesplezier en inspiratie toe. De redacti

Gaudium: 'De draad weer oppakken'

Gaudium is a textile production firm, situated in the industrial urban fabric of Winterswijk, using a building ensemble which is owned by the municipality. Since Gaudium’s foundation it worked together with Kvadrat, which holds today the top position in Europe’s textiles market. The long-standing partnership between the Danish company and Gaudium is growing closer. Kvadrat announced that its stake in the company will increase from 10% to 87%. However, the current state of the building complexes of Gaudium cannot answer this need of Kvadrat. This has to do with on one hand sustainability, Kvadrat strives for ‘green’ solutions in terms of energy use and also comfort in their working environments. However, there is no such thing as a thermal mass or renewable energy within the current state of Gaudium’s building ensemble. Besides, for a long period there was a lot of uncertainty about the future use of this building complex. Consequently, no structural investments were taken for the management and maintenance of the ensemble. In short, there might be a major chance that the Danish textile company decides to continue with Gaudium elsewhere because of the current state of its building complex. Consequently, Winterswijk could lose a part of its identity. The craft of weaving played a role since the initiation of the settlement. Thus the aim of this design project is to stimulate all of the interested parties to start conversations about this matter before it's too late. To structure this project, the following research question is formed: ‘How can Gaudium enhance a future perspective within the current building ensemble and its setting?’KaDer GelderlandKaDEr research projectArchitecture, Urbanism and Building Sciences | Heritage & Architectur

Impact of Novel Treatments in Patients with Melanoma Brain Metastasis: Real-World Data

Background: Melanoma brain metastasis (MBM) is associated with poor outcome, but targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) have revolutionized treatment over the past decade. We assessed the impact of these treatments in a real-world setting. Methods: A single-center cohort study was performed at a large, tertiary referral center for melanoma (Erasmus MC, Rotterdam, the Netherlands). Overall survival (OS) was assessed before and after 2015, after which TTs and ICIs were increasingly prescribed. Results: There were 430 patients with MBM included; 152 pre-2015 and 278 post-2015. Median OS improved from 4.4 to 6.9 months (HR 0.67, p < 0.001) after 2015. TTs and ICIs prior to MBM diagnosis were associated with poorer median OS as compared to no prior systemic treatment (TTs: 2.0 vs. 10.9 and ICIs: 4.2 vs. 7.9 months, p < 0.001). ICIs directly after MBM diagnosis were associated with improved median OS as compared to no direct ICIs (21.5 vs. 4.2 months, p < 0.001). Stereotactic radiotherapy (SRT; HR 0.49, p = 0.013) and ICIs (HR 0.32, p < 0.001) were independently associated with improved OS. Conclusion: After 2015, OS significantly improved for patients with MBM, especially with SRT and ICIs. Demonstrating a large survival benefit, ICIs should be considered first after MBM diagnosis, if clinically feasible

Hereditary Vascular Retinopathy, Cerebroretinal Vasculopathy, and Hereditary Endotheliopathy with Retinopathy, Nephropathy, and Stroke Map to a Single Locus on Chromosome 3p21.1-p21.3

We performed a genomewide search for linkage in an extended Dutch family with hereditary vascular retinopathy associated with migraine and Raynaud phenomenon. Patients with vascular retinopathy are characterized by microangiopathy of the retina, accompanied by microaneurysms and telangiectatic capillaries. The genome search, using a high throughput capillary sequencer, revealed significant evidence of linkage to chromosome 3p21.1-p21.3 (maximum pairwise LOD score 5.25, with D3S1578). Testing of two additional families that had a similar phenotype, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke, revealed linkage to the same chromosomal region (combined maximum LOD score 6.30, with D3S1588). Haplotype analysis of all three families defined a 3-cM candidate region between D3S1578 and D3S3564. Our study shows that three autosomal dominant vasculopathy syndromes with prominent cerebroretinal manifestations map to the same 3-cM interval on 3p21, suggesting a common locus

The value of nonoperative versus operative treatment of frail institutionalized elderly patients with a proximal femoral fracture in the shade of life (FRAIL-HIP); protocol for a multicenter observational cohort study

Background: Proximal femoral fractures are strongly associated with morbidity and mortality in elderly patients. Mortality is highest among frail institutionalized elderly with both physical and cognitive comorbidities who consequently have a limited life expectancy. Evidence based guidelines on whether or not to operate on these patients in the case of a proximal femoral fracture are lacking. Practice variation occurs, and it remains unknown if nonoperative treatment would result in at least the same quality of life as operative treatment. This study aims to determine the effect of nonoperative management versus operative management of proximal femoral fractures in a selected group of frail institutionalized elderly on the quality of life, level of pain, rate of complications, time to death, satisfaction of the patient (or proxy) and the caregiver with the management strategy, and health care consumption. Methods: This is a multicenter, observational cohort study. Frail institutionalized elderly (70 years or older with a body mass index < 18.5, a Functional Ambulation Category of 2 or lower pre-trauma, or an American Society of Anesthesiologists score of 4 or 5), who sustained a proximal femoral fracture are eligible to participate. Patients with a pathological or periprosthetic fractures and known metastatic oncological disease will be excluded. Treatment decision will be reached following a structured shared decision process. The primary outcome is quality of life (Euro-QoL; EQ-5D-5 L). Secondary outcome measures are quality of life measured with the QUALIDEM, pain level (PACSLAC), pain medication use, treatment satisfaction of patient (or proxy) and caregivers, quality of dying (QODD), time to death, and direct medical costs. A cost-utility and cost-effectiveness analysis will be done, using the EQ-5D utility score and QUALIDEM score, respectively. Non-inferiority of nonoperative treatment is assumed with a limit of 0.15 on the EQ-5D score. Data will be acquired at 7, 14, and 30 days and at 3 and 6 months after trauma. Discussion: The results of this study will provide insight into the true value of nonoperative treatment of proximal femoral fractures in frail elderly with a limited life expectancy. The results may be used for updating (inter)national treatment guidelines. Trial registration: The study is registered at the Netherlands Trial Register (NTR7245; date 10-06-2018)