Diagnostic value of bright spotty lesions on MRI after a first episode of acute myelopathy

Background and purposeTo determine the diagnostic value of bright spotty lesions (BSLs) for aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD^AQP4+), the predictive value of axial-BSLs for AQP4-IgG seropositivity, and the radio-clinical differences in NMOSD^AQP4+ patients with and without axial-BSLs.Materials and methodsRetrospective study that included patients aged ≥ 16 years, with a first acute spinal cord syndrome between 2005 and 2018 and abnormal spinal cord MRI with axial and sagittal T2 sequences. Patients with MRI findings consistent with compressive myelopathy were excluded. All spinal cord MRI were retrospectively evaluated for the presence of BSLs by 2 radiologists blinded to the diagnosis of acute myelopathy.ResultsA total of 82 patients were included; 15 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients (NMOSD^AQP4+), and 67 other patients, considered as the other causes of myelopathy (OM) group. The specificity of axial-BSLs for NMOSD^AQP4+ patients was 94.0% (95% CI [85.6 to 97.7]). The sensitivity was 40.0% (95% CI [19.8 to 64.3]). In the multivariable analysis, the only MRI characteristic associated with AQP4-IgG positivity was the presence of axial-BSLs (OR: 9.2, 95% CI [1.2 to 72.9]; P = 0.022). In NMOSD^AQP4+ patients, the median of cord expansion ratio was higher with axial-BSL (1.2, IQR [1.1–1.3]) than without axial-BSL (1.1, IQR [1.0–1.2]; P = 0.046).ConclusionAfter a first acute spinal cord syndrome, the presence of axial-BSLs on spinal cord MRI seems very specific for NMOSD^AQP4+ and seems to be a predictor radiological marker of AQP4-IgG positivity.     

Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site

Background Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs.Methods Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [{"type":"clinical-trial","attrs":{"text":"NCT02428842","term_id":"NCT02428842"}}NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed.Results Episomal HPV was much less frequent in CC as compared to anal carcinoma (p < 0.0001). We identified >300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011).Conclusions This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability.Subject terms: Oncology, Molecular medicine, Biomarkers, Molecular biology     

Author’s reply to letter at the editor: primary hyperparathyroid surgery under local anaesthesia: benefits of hypnosis

European Archives of Oto-Rhino-Laryngology - The hypnosis gives more comfort to the patient and can be used in patients at risk of a general anaesthesia.     

Long-term outcomes in temporal lobe epilepsy with glutamate decarboxylase antibodies

Journal of Neurology - To assess the long-term outcomes of patients with temporal lobe epilepsy and CSF anti-glutamate decarboxylase antibodies (GAD65-Abs). We retrospectively analyzed the clinical...     

Signaling pathways involved in the T‐cell‐mediated immunity against Epstein‐Barr virus: Lessons from genetic diseases

Primary immunodeficiencies (PIDs) provide researchers with unique models to understand in vivo immune responses in general and immunity to infections in particular. In humans, impaired immune control of Epstein‐Barr virus (EBV) infection is associated with the occurrence of several different immunopathologic conditions; these include non‐malignant and malignant B‐cell lymphoproliferative disorders, hemophagocytic lymphohistiocytosis (HLH), a severe inflammatory condition, and a chronic acute EBV infection of T cells. Studies of PIDs associated with a predisposition to develop severe, chronic EBV infections have led to the identification of key components of immunity to EBV – notably the central role of T‐cell expansion and its regulation in the pathophysiology of EBV‐associated diseases. On one hand, the defective expansion of EBV‐specific CD8 T cells results from mutations in genes involved in T‐cell activation (such as RASGRP1, MAGT1, and ITK), DNA metabolism (CTPS1) or co‐stimulatory pathways (CD70, CD27, and TNFSFR9 (also known as CD137/4‐1BB)) leads to impaired elimination of proliferating EBV‐infected B cells and the occurrence of lymphoma. On the other hand, protracted T‐cell expansion and activation after the defective killing of EBV‐infected B cells is caused by genetic defects in the components of the lytic granule exocytosis pathway or in the small adapter protein SH2D1A (also known as SAP), a key activator of T‐ and NK cell‐cytotoxicity. In this setting, the persistence of EBV‐infected cells results in HLH, a condition characterized by unleashed T‐cell and macrophage activation. Moreover, genetic defects causing selective vulnerability to EBV infection have highlighted the role of co‐receptor molecules (CD27, CD137, and SLAM‐R) selectively involved in immune responses against infected B cells via specific T‐B cell interactions.     

The grades that clinical teachers give students modifies the grades they receive

Prior studies have shown a correlation between the grades students receive and how they rate their teacher in the classroom. In this study, the authors probe this association on clinical rotations and explore potential mechanisms. All In-Training Evaluation Reports (ITERs) for students on mandatory clerkship rotations from April 1, 2013 to January 31, 2015 were matched with the corresponding student’s rating of their teacher (SRT). The date and time that ITERs and SRTs were submitted was used to divide SRTs into those submitted before versus after the corresponding ITER was submitted. Multilevel, mixed effects linear regression was used to examine the association between SRT, ITER rating, and whether the ITER was submitted before or after SRT. Of 2373 paired evaluations, 1098 (46.3%) SRT were submitted before the teacher had submitted the ITER. There was a significant interaction between explanatory variables: when ITER ratings had not yet been submitted, the regression coefficient for this association was 0.25 (95% confidence interval [0.17, 0.33], p < 0.001), whereas the regression coefficient was significantly higher when ITER ratings were submitted prior to SRT (0.40 [0.31, 0.49], p < 0.001). Finding an association between SRT and ITER when students do not know their ITER ratings suggests that SRTs can capture attributes of effective teaching, but the effect modification when students have access to their ITER rating supports grade satisfaction bias. Further studies are needed to explain the mechanism of grade satisfaction and to identify other biases that may impact the validity of SRT.