Metastatic skull tumors: MRI features and a new conventional classification

Skull metastases are malignant bone tumors which are increasing in incidence. The objectives of this study were to characterize the MR imaging features, locations, and extent of metastatic skull tumors to determine the frequency of the symptomatic disease, and to assess patient outcomes. Between September 2002 and March 2008, 175 patients undergoing routine head MR imaging were found to have metastatic skull tumors. Contrast-enhanced study with fat suppression was used in some cases when required. Classification of metastases was simplified to three yes/no questions: first, with regard to location (either in the calvarium or in the cranial base); second, with regard to distribution within the plane of the cranial bone (either “circumscribed” meaning clearly demarcated and confined to one bone, or “diffuse” and likely to spread across a suture to another bone); and third, with regard to invasion (“intraosseous” in cranial bones only, or “invasive” spreading from the skull, either out into the scalp or inward to the dura and perhaps further in). Primary sites were breast cancer (55%), lung cancer (14%), prostate cancer (6%), malignant lymphoma (5%), and others (20%). The mean time from primary diagnosis to skull metastasis diagnosis was 71 months for cases of breast cancer, 26 months for prostate cancer, 9 months for lung cancer, and 4 months for malignant lymphoma. Calvarial circumscribed intraosseous metastases were found most frequently (27%). The patients were mainly asymptomatic. However, some patients suffered from local pain or cranial nerve palsies that harmed their quality of life. Treatment, mainly for symptomatic cases, was by local or whole-skull irradiation. Metastatic skull tumors are not rare, and most are calvarial circumscribed intraosseous tumors. MR images contribute to understanding their type, location, and multiplicity, and their relationship to the brain, cranial nerves, and dural sinuses. Radiation therapy improved the QOL of patients with neurological symptoms

Spontaneous dural tear leading to intracranial hypotension and tonsillar herniation in Marfan syndrome: a case report

<p>Abstract</p> <p>Background</p> <p>We describe the case of a 38 year old male with Marfan syndrome who presented with orthostatic headaches and seizures.</p> <p>Case Presentation</p> <p>The patient was diagnosed with Spontaneous Intracranial Hypotension secondary to CSF leaks, objectively demonstrated by MR Myelogram with intrathecal contrast. Epidural autologus blood patch was administered at the leakage site leading to significant improvement.</p> <p>Conclusion</p> <p>Our literature search shows that this is the second reported case of a Marfan patient presenting with symptomatic spontaneous CSF leaks along with tonsillar herniation.</p

A threshold level of NFATc1 activity facilitates thymocyte differentiation and opposes notch-driven leukaemia development.

International audienceNFATc1 plays a critical role in double-negative thymocyte survival and differentiation. However, the signals that regulate Nfatc1 expression are incompletely characterized. Here we show a developmental stage-specific differential expression pattern of Nfatc1 driven by the distal (P1) or proximal (P2) promoters in thymocytes. Whereas, preTCR-negative thymocytes exhibit only P2 promoter-derived Nfatc1beta expression, preTCR-positive thymocytes express both Nfatc1beta and P1 promoter-derived Nfatc1alpha transcripts. Inducing NFATc1alpha activity from P1 promoter in preTCR-negative thymocytes, in addition to the NFATc1beta from P2 promoter impairs thymocyte development resulting in severe T-cell lymphopenia. In addition, we show that NFATc1 activity suppresses the B-lineage potential of immature thymocytes, and consolidates their differentiation to T cells. Further, in the pTCR-positive DN3 cells, a threshold level of NFATc1 activity is vital in facilitating T-cell differentiation and to prevent Notch3-induced T-acute lymphoblastic leukaemia. Altogether, our results show NFATc1 activity is crucial in determining the T-cell fate of thymocytes

Euclid preparation: V. Predicted yield of redshift 7<z<9 quasars from the wide survey

We provide predictions of the yield of 7 < z < 9 quasars from the Euclid wide survey, updating the calculation presented in the Euclid Red Book in several ways. We account for revisions to the Euclid near-infrared filter wavelengths; we adopt steeper rates of decline of the quasar luminosity function (QLF; Φ) with redshift, Φ ∝ 10k(z−6) , k = −0.72, and a further steeper rate of decline, k = −0.92; we use better models of the contaminating populations (MLT dwarfs and compact early-type galaxies); and we make use of an improved Bayesian selection method, compared to the colour cuts used for the Red Book calculation, allowing the identification of fainter quasars, down to JAB ∼ 23. Quasars at z > 8 may be selected from Euclid OY JH photometry alone, but selection over the redshift interval 7 < z < 8 is greatly improved by the addition of z-band data from, e.g., Pan-STARRS and LSST. We calculate predicted quasar yields for the assumed values of the rate of decline of the QLF beyond z = 6. If the decline of the QLF accelerates beyond z = 6, with k = −0.92, Euclid should nevertheless find over 100 quasars with 7.0 < z < 7.5, and ∼ 25 quasars beyond the current record of z = 7.5, including ∼ 8 beyond z = 8.0. The first Euclid quasars at z > 7.5 should be found in the DR1 data release, expected in 2024. It will be possible to determine the bright-end slope of the QLF, 7 < z < 8, M1450 < −25, using 8 m class telescopes to confirm candidates, but follow-up with JWST or E-ELT will be required to measure the faint-end slope. Contamination of the candidate lists is predicted to be modest even at JAB ∼ 23. The precision with which k can be determined over 7 < z < 8 depends on the value of k, but assuming k = −0.72 it can be measured to a 1σ uncertainty of 0.07

Euclid preparation: V. Predicted yield of redshift 7 < z < 9 quasars from the wide survey

We provide predictions of the yield of 7 8 may be selected from Euclid OY JH photometry alone, but selection over the redshift interval 7 7.5 should be found in the DR1 data release, expected in 2024. It will be possible to determine the bright-end slope of the QLF, 7 < z < 8, M1450 < −25, using 8 m class telescopes to confirm candidates, but follow-up with JWST or E-ELT will be required to measure the faint-end slope. Contamination of the candidate lists is predicted to be modest even at JAB ∼ 23. The precision with which k can be determined over 7 < z < 8 depends on the value of k, but assuming k = −0.72 it can be measured to a 1σ uncertainty of 0.07

NOTCH1 mediates a switch between two distinct secretomes during senescence

Senescence, a persistent form of cell-cycle arrest, is often associated with a diverse secretome, which provides complex functionality for senescent cells within the tissue microenvironment. We show that oncogene-induced senescence is accompanied by a dynamic fluctuation of NOTCH1 activity, which drives a TGF-β-rich secretome, while suppressing the senescence-associated pro-inflammatory secretome through inhibition of C/EBPβ. NOTCH1 and NOTCH1-driven TGF-β contribute to 'lateral induction of senescence' through a juxtacrine NOTCH-JAG1 pathway. In addition, NOTCH1 inhibition during senescence facilitates upregulation of pro-inflammatory cytokines, promoting lymphocyte recruitment and senescence surveillance in vivo. As enforced activation of NOTCH1 signalling confers a near mutually exclusive secretory profile compared with typical senescence, our data collectively indicate that the dynamic alteration of NOTCH1 activity during senescence dictates a functional balance between these two distinct secretomes: one representing TGF-β and the other pro-inflammatory cytokines, highlighting that NOTCH1 is a temporospatial controller of secretome composition.This work was supported by the University of Cambridge, Cancer Research UK and Hutchison Whampoa. The M.N. laboratory is supported by Cancer Research UK Cambridge Institute Core Grant (C14303/A17197). M.H. was supported by CRUK Translational Medicine Research Fellowship and CRUK Clinician Scientist Fellowship (C52489/A19924). This work was also supported by a Wellcome Trust PRF (WT101835) to P.J.L., a Wellcome Trust Senior Fellowship to M.P.W. (108070/Z/15/Z), a Wellcome Trust Training Fellowship to N.J.M. (093964/Z/10/Z), and a Wellcome Trust Intermediate Fellowship (097162/Z/11/Z) to S.S. L.Z. was funded by the German Research Foundation (DFG; grants FOR2314 and SFB685), the Gottfried Wilhelm Leibniz Program, the European Research Council (projects ‘CholangioConcept’), the German Ministry for Education and Research (BMBF) (eMed-Multiscale HCC), the German Universities Excellence Initiative (third funding line: ‘future concept’), the German Center for Translational Cancer Research (DKTK) and the German–Israeli Cooperation in Cancer Research (DKFZ–MOST).This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/ncb3397

Implant survivorship analysis after minimally invasive sacroiliac joint fusion using the iFuse Implant System&reg;

Daniel J Cher,1 W Carlton Reckling,2 Robyn A Capobianco1 1Department of Clinical Affairs, SI-BONE, Inc., 2Department of Medical Affairs, SI-BONE, Inc., San Jose, CA, USA Introduction: Surgical revision rate is a key outcome with all permanent implants. The iFuse Implant System&reg; is a permanent implant used to perform minimally invasive sacroiliac joint fusion. The purpose of this study is to determine the surgical revision rate after sacroiliac joint fusion surgery with this system. Methods: Using two internal sources of information, revision surgeries were identified and linked to index surgeries. The likelihood of revision surgery was calculated using the Kaplan&ndash;Meier life table approach. Predictors of revision were explored. Results: Four-year survivorship free from implant revision was 96.46%. Revision rate did not differ by sex and was lower for age &gt;65. In all, 24% of revisions occurred within the first 30 days after surgery; 63.5% occurred within year 1. Implant survivorship has improved annually since the device was introduced in 2009. Conclusion: The survivorship rate with this implant is high and improving; the rate is somewhat higher than total hip replacement but lower than that of lumbar spine procedures. Keywords: safety, sacroiliac joint fusion, iFuse Implant System, revisio