The performance of different classification criteria sets for spondyloarthritis in the worldwide ASAS-COMOSPA study

Background: In this study, we sought to compare the performance of spondyloarthritis (SpA) classification criteria sets in an international SpA cohort with patients included from five continents around the world. Methods: Data from the (ASAS) COMOrbidities in SPondyloArthritis (ASAS-COMOSPA) study were used. ASAS-COMOSPA is a multinational, cross-sectional study with consecutive patients diagnosed with SpA by rheumatologists worldwide. Patients were classified according to the European Spondyloarthropathy Study Group (ESSG), modified European Spondyloarthropathy Study Group (mESSG), Amor, modified Amor, Assessment of SpondyloArthritis international Society (ASAS) axial Spondyloarthritis (axSpA), ASAS peripheral spondyloarthritis (pSpA) and ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria. Overlap between the classification criteria sets was assessed for patients with and without back pain. Furthermore, patients fulfilling different arms of the ASAS axSpA criteria (imaging arm, clinical arm, both arms) were compared on the presence of SpA features. Results: A total of 3942 patients (5 continents, 26 countries) were included. The mean age was 43.6 years, 65.0% were male, 56.2% were human leucocyte antigen B27-positive and 64.4% had radiographic sacroiliitis (based on modified New York criteria). Of the patients, 85.5% were classified by the ASAS SpA criteria (87.7% ASAS axSpA, 12.3% ASAS pSpA). Fulfilment of the Amor, ESSG and CASPAR criteria was present in 83.3%, 88.4% and 21.6% of patients, respectively. Of the patients with back pain (n = 3227), most were classified by all three of Amor, ESSG and ASAS axSpA criteria (71.4%). Patients fulfilling the imaging arm and the clinical arm of the ASAS axSpA criteria had similar presentations of SpA features. In patients without back pain, overlap between classification criteria sets was seen, although to a lesser extent. Conclusions: Most patients with a clinical diagnosis of axial SpA in the worldwide ASAS-COMOSPA study fulfil several classification criteria sets, and a substantial overlap between different criteria sets is seen, which suggests a high level of credibility of the criteria. Large inter-regional differences in the fulfilment of classification criteria were not found. Patients fulfilling the clinical arm were remarkably similar to patients fulfilling the imaging arm with respect to the presence of most SpA features

Proton therapy for seminoma testis

Seminoma testis wordt gekenmerkt door een hoge ziektevrije en algehele overleving. Bij beperkt lymfogeen gemetastaseerde ziekte is para-aortale en para-iliacale radiotherapie een curatieve behandeloptie. Het belangrijkste nadeel van deze behandeling is het verhoogde risico op secundaire maligniteiten nadien. Dit lijkt voornamelijk te gelden voor tumoren van de maag, pancreas, nieren en blaas. Het risico op tumorinductie is afhankelijk van de bestralingsdosis die op het orgaan komt. Met protonentherapie is het mogelijk om de dosis op deze organen te verminderen ten opzichte van fotonentherapie. Vanaf maart 2022 wordt deze behandeling aangeboden in de drie Nederlandse protonencentra. Dit artikel beschrijft de indicaties en onderbouwing voor het gebruik van protonentherapie bij patiënten met een seminoom. Daarnaast worden enkele technische aspecten besproken.Seminoma testis patients have high cure and survival rates. Radiotherapy to the para-aortic and para-iliac lymph nodes is a curative treatment option for patients with limited lymph node metastases. The most important risk following treatment is secondary tumor induction. This seems to be the case especially for tumors of the stomach, pancreas, kidneys and urinary bladder. The risk of tumor induction depends on the radiation dose delivered to a specific organ. Proton therapy has the unique capacity to reduce dose to these organs, when compared to conventional photon therapy. Starting in March 2022, proton therapy is offered in all three proton centers in the Netherlands. This article describes indications for treatment, technical aspects and scientific grounds for the use of proton therapy in seminoma patients.</p

Proton therapy for seminoma testis

Seminoma testis wordt gekenmerkt door een hoge ziektevrije en algehele overleving. Bij beperkt lymfogeen gemetastaseerde ziekte is para-aortale en para-iliacale radiotherapie een curatieve behandeloptie. Het belangrijkste nadeel van deze behandeling is het verhoogde risico op secundaire maligniteiten nadien. Dit lijkt voornamelijk te gelden voor tumoren van de maag, pancreas, nieren en blaas. Het risico op tumorinductie is afhankelijk van de bestralingsdosis die op het orgaan komt. Met protonentherapie is het mogelijk om de dosis op deze organen te verminderen ten opzichte van fotonentherapie. Vanaf maart 2022 wordt deze behandeling aangeboden in de drie Nederlandse protonencentra. Dit artikel beschrijft de indicaties en onderbouwing voor het gebruik van protonentherapie bij patiënten met een seminoom. Daarnaast worden enkele technische aspecten besproken.Seminoma testis patients have high cure and survival rates. Radiotherapy to the para-aortic and para-iliac lymph nodes is a curative treatment option for patients with limited lymph node metastases. The most important risk following treatment is secondary tumor induction. This seems to be the case especially for tumors of the stomach, pancreas, kidneys and urinary bladder. The risk of tumor induction depends on the radiation dose delivered to a specific organ. Proton therapy has the unique capacity to reduce dose to these organs, when compared to conventional photon therapy. Starting in March 2022, proton therapy is offered in all three proton centers in the Netherlands. This article describes indications for treatment, technical aspects and scientific grounds for the use of proton therapy in seminoma patients.</p

Histological response to radiotherapy is an early event in myxoid liposarcoma

Myxoid liposarcoma; Personalized medicine; RadiotherapyLiposarcoma mixoide; Medicina personalizada; RadioterapiaLiposarcoma mixoide; Medicina personalitzada; RadioteràpiaCompared to other sarcomas, myxoid liposarcoma (MLS) is exceptionally sensitive to radiation therapy, but the underlying mechanism remains unknown. The objective was to assess the tissue-based changes in MLS during and after neoadjuvant radiotherapy in 26 patients of the DOREMY trial. Morphological assessment was performed on biopsies pre-treatment, after 8 fractions, 16 factions, and after surgical resection and included percentage of viable tumor cells, hyalinization, necrosis, and fatty maturation. Furthermore, immunohistochemistry was performed for apoptosis (cleaved caspase-3), anti-apoptosis (Bcl-2), activity of mTOR signaling (phospho-S6), hypoxia (CAIX), proliferation (Ki67), inflammation (CD45 and CD68), and microvessel density (CD34 Chalkley count). A pronounced reduction in vital tumor cells was observed early with a drop to 32.5% (median) tumor cells (IQR 10–93.8%) after 8 fractions. This decreased further to 10% (IQR 5–30%) after 16 fractions and 7.5% (IQR 5–15%) in the surgical specimen. All but one patient had an excellent response with < 50% remaining tumor cells. Inversely, treatment response was mainly observed as hyalinization and less often as fatty maturation. Additionally, a decrease of inflammatory cells was noticed especially during the first eight fractions. Microvessel density remained stable over time. Immunohistochemical markers for apoptosis, anti-apoptosis, activity of mTOR signaling, proliferation, and hypoxia did not show any marked changes within the remaining tumor cells during and after radiotherapy. As a modest dose of neoadjuvant radiotherapy induces profound tissue changes in MLS, mainly during the first 8 fractions, current findings might suggest that in a carefully selected patient population further deintensification of radiotherapy might be explored

Central Asia and the globalisation of the contemporary legal consciousness

What is the logic which governs the processes of legal globalization? How does the transnational proliferation of legal forms operate in the contemporary geo-juridical space? What are the main defining characteristics of the currently dominant mode of transnational legal consciousness and how can the concept of legal consciousness help us understand better the historical ebb and flow of the Western-led projects of good governance promotion in regions like Central Asia after the fall of the Soviet Union? Using Duncan Kennedy’s seminal essay Three Globalizations of Law and Legal Thought as its starting platform, this essay seeks to explore these and a series of other related questions, while also drawing on the work of the Greek Marxist lawyer-philosopher Nicos Poulantzas to help elucidate some latent analytical stress-points in Kennedy’s broader theoretical framework. Reacting against the neo-Orientalist tone adopted across much of the contemporary field of Central Asian studies, it develops an alternative account of the internal history of the legal-globalizational encounter between the Western-based reform entrepreneurs and the national legal-political elites in Central Asia in the post-1991 period, complementing it with a detailed description of the general institutional and discursive structures within which this encounter took place

New polymorphic DNA marker close to the fragile site FRAXA

Abstract DNA from a human-hamster hybrid cell line, 908-K1B17, containing a small terminal portion of the long arm of the human X chromosome as well as the pericentric region of 19q was used as starting material for the isolation of an X-chromosome-specific DNA segment, RN1 (DXS369), which identifies a XmnI RFLP. Linkage analysis in fragile X families resulted in a maximum lod score of 15.3 at a recombination fraction of 0.05 between RN1 and fra(X). Analysis of recombinations around the fra(X) locus assigned RN1 proximal to fra(X) and distal to DXS105. Analysis of the marker content of hybrid cell line 908K1B17 suggests the localization of RN1 between DXS98 and fra(X). Heterozygosity of DXS369 is approximately 50%, which extends the diagnostic potential of RFLP analysis in fragile X families significantly

eZinCh-2: a versatile, genetically encoded FRET sensor for cytosolic and intraorganelle Zn2+ imaging

Zn2+ plays essential and diverse roles in numerous cellular processes. To get a better understanding of intracellular Zn2+ homeostasis and the putative signaling role of Zn2+, various fluorescent sensors have been developed that allow monitoring of Zn2+ concentrations in single living cells in real time. Thus far, two families of genetically encoded FRET-based Zn2+ sensors have been most widely applied, the eCALWY sensors developed by our group and the ZapCY sensors developed by Palmer and co-workers. Both have been successfully used to measure cytosolic free Zn2+, but distinctly different concentrations have been reported when using these sensors to measure Zn2+ concentrations in the ER and mitochondria. Here, we report the development of a versatile alternative FRET sensor containing a de novo Cys2His2 binding pocket that was created on the surface of the donor and acceptor fluorescent domains. This eZinCh-2 sensor binds Zn2+ with a high affinity that is similar to that of eCALWY-4 (Kd = 1 nM at pH 7.1), while displaying a substantially larger change in emission ratio. eZinCh-2 not only provides an attractive alternative for measuring Zn2+ in the cytosol but was also successfully used for measuring Zn2+ in the ER, mitochondria, and secretory vesicles. Moreover, organelle-targeted eZinCh-2 can also be used in combination with the previously reported redCALWY sensors to allow multicolor imaging of intracellular Zn2+ simultaneously in the cytosol and the ER or mitochondria