Tumour necrosis factor alpha blockade in treatment resistant pigmented villonodular synovitis

BACKGROUND: Pigmented villonodular synovitis (PVNS) is considered to be a neoplastic-like disorder of the synovium histologically characterised by villonodular hyperplasia, resulting in dense fibrosis and haemosiderin deposition. The pathogenesis of the disease is still unknown. CASE REPORT: A patient presented with severe treatment resistant PVNS of the right knee joint. Several conventional treatment regimens, including open surgical synovectomy and intra-articular injections of yttrium-90 ((90)Y) failed to control the disease. After finding marked tumour necrosis factor alpha (TNF alpha) expression in arthroscopic synovial tissue samples, treatment with an anti-TNF alpha monoclonal antibody (infliximab) at a dose of 5 mg/kg was started. Additional courses with the same dose given 2, 6, 14, and 20 weeks later, and bimonthly thereafter up to 54 weeks, controlled the signs and symptoms. Immunohistological analysis at follow up identified a marked reduction in macrophage numbers and TNF alpha expression in the synovium. DISCUSSION: This is probably the first case which describes treatment with TNF alpha blockade of PVNS in a patient who is refractory to conventional treatment. It provides the rationale for larger controlled studies to elucidate further the efficacy of TNFalpha blockade treatment in refractory PVNS

Investigating the Radiobiological Response to Peptide Receptor Radionuclide Therapy Using Patient-Derived Meningioma Spheroids

Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA-TATE has recently been evaluated for the treatment of meningioma patients. However, current knowledge of the underlying radiation biology is limited, in part due to the lack of appropriate in vitro models. Here, we demonstrate proof-of-concept of a meningioma patient-derived 3D culture model to assess the short-term response to radiation therapies such as PRRT and external beam radiotherapy (EBRT). We established short-term cultures (1 week) for 16 meningiomas with high efficiency and yield. In general, meningioma spheroids retained characteristics of the parental tumor during the initial days of culturing. For a subset of tumors, clear changes towards a more aggressive phenotype were visible over time, indicating that the culture method induced dedifferentiation of meningioma cells. To assess PRRT efficacy, we demonstrated specific uptake of 177Lu-DOTA-TATE via somatostatin receptor subtype 2 (SSTR2), which was highly overexpressed in the majority of tumor samples. PRRT induced DNA damage which was detectable for an extended timeframe as compared to EBRT. Interestingly, levels of DNA damage in spheroids after PRRT correlated with SSTR2-expression levels of parental tumors. Our patient-derived meningioma culture model can be used to assess the short-term response to PRRT and EBRT in radiobiological studies. Further improvement of this model should pave the way towards the development of a relevant culture model for assessment of the long-term response to radiation and, potentially, individual patient responses to PRRT and EBRT.</p

Genetic polymorphism of miR-196a-2 is associated with bone mineral density (BMD)

MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate the translation of messenger RNAs. Given the crucial role of miRNAs in gene expression, genetic variants within miRNA-related sequences may affect miRNA function and contribute to disease risk. Osteoporosis is characterized by reduced bone mass, and bone mineral density (BMD) is a major diagnostic proxy to assess osteoporosis risk. Here, we aimed to identify miRNAs that are involved in BMD using data from recent genome-wide association studies (GWAS) on femoral neck, lumbar spine and forearm BMD. Of 242 miRNA-variants available in the GWAS data, we found rs11614913:C > T in the precursor miR-196a-2 to be significantly associated with femoral neck-BMD (p-value = 9.9 × 10-7, β = −0.038) and lumbar spine-BMD (p-value = 3.2 × 10-11, β = −0.061). Furthermore, our sensitivity analyses using the Rotterdam study data showed a sex-specific association of rs11614913 with BMD only in women. Subsequently, we highlighted a number of miR-196a-2 target genes, expressed in bone and associated with BMD, that may mediate the miRNA function in BMD. Collectively, our results suggest that miR-196a-2 may contribute to variations in BMD level. Further biological investigations will give more insights into the mechanisms by which miR-196a-2 control expression of BMD-related genes

Post-Traumatic Stress Disorder after Civilian Traumatic Brain Injury: A Systematic Review and Meta-Analysis of Prevalence Rates

Post-traumatic stress disorder (PTSD) is a commonly diagnosed psychiatric disorder following traumatic brain injury (TBI). Much research on PTSD and TBI has focused on military conflict settings. Less is known about PTSD in civilian TBI. We conducted a systematic review and meta-analysis on the prevalence of PTSD after mild and moderate/severe TBI in civilian populations. We further aimed to explore the influence of methodological quality and assessment methods. A systematic literature search was performed on studies reporting on PTSD in civilian TBI, excluding studies on military populations. The risk of bias was assessed using the MORE (Methodological evaluation of Observational REsearch) checklist. Meta-analysis was conducted for overall prevalence rates for PTSD with sensitivity analyses for the severity of TBI. Fifty-two studies were included, of which 31 were graded as low risk of bias. Prevalence rates of PTSD in low risk of bias studies varied widely (2.6–36%) with a pooled prevalence rate of 15.6%. Pooled prevalence rates of PTSD for mild TBI (13.5%, 95% confidence interval [CI]: 11.7–15.3; I2 = 2%) did not differ from moderate/severe TBI (11.8, 95% CI: 7.5–16.1; I2 = 63%). Similar rates were reported in studies using different approaches and times of assessment. Although most studies that compared participants with TBI with trauma patients and healthy controls found no difference in prevalence rates of PTSD, a meta-analysis across studies revealed a higher prevalence of PTSD in patients with TBI (odds ratio [OR]: 1.73, 95% CI: 1.21–2.47). This review highlights variability between studies and emphasizes the need for higher-quality studies. Further research is warranted to determine risk factors for the development of PTSD after TBI

New early Eocene tapiromorph perissodactyls from the Ghazij Formation of Pakistan, with implications for mammalian biochronology in Asia

Early Eocene mammals from Indo-Pakistan have only recently come under study. Here we describe the first tapiromorph perissodactyls from the subcontinent. Gandheralophus minor n. gen. and n. sp. and G. robustus n. sp. are two species of Isectolophidae differing in size and in reduction of the anterior dentition. Gandheralophus is probably derived from a primitive isectolophid such as Orientolophus hengdongensis from the earliest Eocene of China, and may be part of a South Asian lineage that also contains Karagalax from the middle Eocene of Pakistan. Two specimens are referred to a new, unnamed species of Lophialetidae. Finally, a highly diagnostic M3 and a molar fragment are described as the new eomoropid chalicothere Litolophus ghazijensis sp. nov. The perissodactyls described here, in contrast to most other mammalian groups published from the early Eocene of Indo-Pakistan, are most closely related to forms known from East and Central Asia. Tapiromorpha are diverse and biochronologically important in the Eocene there and our results allow the first biochronological correlation between early Eocene mammal faunas in Indo-Pakistan and the rest of Asia. We suggest that the upper Ghazij Formation of Pakistan is best correlated with the middle or late part of the Bumbanian Asian Land-Mammal Age, while the Kuldana and Subathu Formations of Pakistan and India are best correlated with the Arshantan Asian Land-Mammal Age

Systematic assessment of the growth plates of the wrist in young gymnasts: Development and validation of the Amsterdam MRI assessment of the Physis (AMPHYS) protocol

Objectives To develop and validate a protocol for MRI assessment of the distal radial and ulnar periphyseal area in gymnasts and non-gymnasts. Methods Twenty-four gymnasts with wrist pain, 18 asymptomatic gymnasts and 24 non-gymnastic controls (33 girls) underwent MRI of the wrist on a 3T scanner. Sequences included coronal proton density-weighted images with and without fat saturation, and three-dimensional water-selective cartilage scan and T2 Dixon series. Skeletal age was determined using hand radiographs. Three experienced musculoskeletal radiologists established a checklist of possible (peri)physeal abnormalities based on literature an

The Muonium Atom as a Probe of Physics beyond the Standard Model

The observed interactions between particles are not fully explained in the successful theoretical description of the standard model to date. Due to the close confinement of the bound state muonium ($M = \mu^+ e^-$) can be used as an ideal probe of quantum electrodynamics and weak interaction and also for a search for additional interactions between leptons. Of special interest is the lepton number violating process of sponteanous conversion of muonium to antimuonium.Comment: 15 pages,6 figure

Prehospital Trauma Care among 68 European Neurotrauma Centers: Results of the CENTER-TBI Provider Profiling Questionnaires

The first hour following traumatic brain injury (TBI) is considered crucial to prevent death and disability. It is, however, not established yet how the prehospital care should be organized to optimize recovery during the first hour. The objective of the current study was to examine variation in prehospital trauma care across Europe aiming to inform comparative effectiveness analyses on care for neurotrauma patients. A survey on prehospital trauma care was sent to 68 neurotrauma centers from 20 European countries participating in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. The survey was developed using literature review and expert opinion and was pilot tested in 16 centers. All participants completed the questionnaire. Advanced life support was used in half of the centers (n = 35; 52%), whereas the other centers used mainly basic life support (n = 26; 38%). A mobile medical team (MMT) could be dispatched 24/7 in most centers (n = 66; 97%). Helicopters were used in approximately half of the centers to transport the MMT to the scene (n = 39; 57%) and the patient to the hospital (n = 31, 46%). Half of the centers used a stay-and-play approach at the scene (n = 37; 55%), while the others used a scoop-and-run approach or another policy. We found wide variation in prehospital trauma care across Europe. This may reflect differences in socio-economic situations, geographic differences, and a general lack of strong evidence for some aspects of prehospital care. The current variation provides the opportunity to study the effectiveness of prehospital interventions and systems of care in comparative effectiveness research