Asymptomatic Onset of Autoimmune Hepatitis does not Mean Better Prognosis

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Inter-method reliability of brainstem volume segmentation algorithms in preschoolers with ASD

Introduction: The brainstem has a potential role in the pathophysiology of Autism Spectrum Disorders (ASD) (Roger, 2013). In particular, alterations in brainstem volume and their relationship with sensory/motor abnormalities have been suggested (Trevarthen & Delafield-Butt, 2013). However, the findings in volume alterations of subjects with ASD with respect to matched controls are controversial both in adults and children cohorts (Hardan, 2001; Piven, 1992; Kleiman, 1992). Moreover, the contribution to variability of brainstem volume measurements performed with different automated methods is still unclear. Methods: T1-weighted MRI brain scans of a cohort of 80 preschoolers (20 male controls, 20 male subjects with ASD, 20 female controls, 20 female subjects with ASD, mean age controls 49 months, std 12 months, mean age ASD 49 months, std 14) were processed with three different automated methods to measure the brainstem volume: Freesurfer 5.3 (Fischl, 2002), FSL-FIRST (Patenaude, 2011) and ANTs (Avants, 2011). Analysis of variance was then carried out taking into account gender and total brain volume in order to investigate potential brainstem volume differences between controls/ASD subjects for each method. A direct comparison of brainstem volume assessments in native space was then performed to assess inter-method reliability (correlation has been calculated by Pearson coefficient) and Dice similarity indexes were calculated to evaluate the segmentation agreement across methods. Results:The brainstem volume measurements are reported in scatter plots in Fig. 1 to show the agreement in terms of volume (in mm3) between different methods. The color represents the Dice similarity index (range 0-1 were 1 means total agreement) of the brainstem segmentations obtained by the methods under investigation. In Fig. 2 four examples of brainstem segmentations with the different methods are shown in sagittal view (brainstem segmentations are reported in red, green, blue for Freesurfer, FSL-FIRST and ANTs respectively). Pearson correlation coefficient between FSL-FIRST and Freesurfer brainstem volume assessments was 0.27 (p-value=0.02). It was 0.51 (p-value0.05).Conclusions:The inter-method reliability of automated algorithms for brainstem volume assessment is limited (the mean Dice similarity index barely reaches 0.8 in just one out of 3 comparisons). Inconsistencies across previous studies on brainstem and more in general the lack of evidence for brain biomarkers in ASD may in part be a result of this poor agreements in the extraction of structural features with different methods. Inter-method brainstem volume differences can be attributed to varying definitions of brainstem structure, the use of different templates (e.g. in our study only ANTs processed the brain scans by using an age-specific brain template) and the varying effects of imaging artifacts and acquisition settings. This study suggests that research on brain structure alterations should cross-validate findings across multiple methods before providing biological interpretations

Non—Organ-Specific Autoantibodies in Children with Chronic Hepatitis C: Clinical Significance and Impact on Interferon Treatment

We evaluated the prevalence and clinical significance of non-organ-specific autoantibodies (NOSAs) in 47 hepatitis C virus (HCV)-positive children with abnormal alanine transaminase levels and analyzed the association between NOSAs and virus level, genotype, human leukocyte antigen status, and interferon (IFN) response. Forty-two hepatitis B virus (HBV)-positive children and 25 age- and sex-matched healthy children served as control subjects. NOSAs were found in 34% of the HCV-positive children, 12% of the HBV-positive controls, and none of the healthy control subjects. Liver-kidney microsomal antibody type 1 (LKM1) was detected in 11% of the HCV-positive children but in none of the controls. The HCV load was significantly higher in NOSA-negative than in NOSA-positive children. HCV genotype distribution and human leukocyte antigen alleles were similar, irrespective of NOSA status. Long-term response to IFN therapy was achieved by 18% of the NOSA-positive and 55% of the NOSA-negative subjects. Two LKM1-positive children developed acute, self-limited hepatocellular necrosis while receiving IFN therapy. NOSAs are frequently present in children with hepatitis C, who are less likely to benefit from IFN therapy

Association of unicuspid unicommissural aortic valve and complex congenital heart disease depicted by cardiac magnetic resonance

A 12-year-old male child was referred for follow-up cardiac magnetic resonance (CMR) of complex congenital heart disease, characterized by aortic decoarctation, interventricular and interatrial septal defects (VSD and ASD) closure and bicuspid aortic valve.peer-reviewe

Mesenchymal Stem Cell Treatment Perspectives in Peripheral Nerve Regeneration: Systematic Review

Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords “nerve regeneration”, “stem cells”, “peripheral nerve injury”, “rat”, and “human” were used. Additionally, a “MeSH” research was performed in PubMed using the terms “stem cells” and “nerve regeneration”. The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported

Imbalance of Neutrophils and Lymphocyte Counts Can Be Predictive of Hepatocellular Carcinoma Occurrence in Hepatitis C-related Cirrhosis Treated With Direct-acting Antivirals

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Brainstem morphometric differences in children with autism spectrum disorder, developmental coordination disorder, and those typically developing

Background: The brainstem is a neglected topic in autism research, despite major lines of evidence indicating its active involvement in sensory, motor, affect, arousal, and social regulation (Dadalko & Travers, 2018). It is the substrate of what affective neuroscience identifies as the ‘Core Self’ (Alcaro, Carta, & Panksepp, 2017), and disruption to its growth and function appears to disturb core conscious experience in autism (Delafield-Butt & Trevarthen, 2017; Trevarthen & Delafield-Butt, 2013). Yet, although evidence indicates brainstem growth is disrupted in early childhood (Bosco et al., 2018), how these growth differences compare to closely related neurodevelopmental disorders, such a Developmental Coordination Disorder (DCD), is not yet understood. Objectives: To determine brainstem morphometric differences between children with ASD, DCD, and those typically developing (TD). Methods: Study participants were 87 youths ages 8 to 17 assigned to the ASD (n = 30, 7 female), DCD (n =24, 12 female) or TD (n = 33, 12 female) group. Exclusion criteria for all groups included IQ <80. TD were excluded if they had any neuropsychological or psychopathological disorder. DCD eligibility additionally included performance 16th percentile on the MABC-2 and no concern about an ASD diagnosis. ASD participants had a previous clinical diagnosis confirmed by ADOS-2 and ADI-R. Individuals were excluded if they had another neuropsychological disorder, except attention deficit or anxiety disorder. T1-weighted MPRAGE (1mm isotropic resolution) MRI data were acquired on a 3T MAGNETOM Prisma (Siemens). Brainstem morphology was analysed using SPHARM-MAT (http://lishenlab.com/spharm/), a 3D Fourier surface representation method¬¬¬. A typical surface was calculated for the TD group, and distances from this norm computed for each vertex. Mean distances at each vertex were computed for each group (ASD, DCD, TD) and compared, taking into account age, gender and supratentorial volume as covariates. Results: Significant brainstem morphological differences were identified between all three (TD, ASD and DCD; Figure 1). Significant differences between TD and ASD (p<0.01) were identified in a large region of the anterior-most surface, extending caudally along the right posterior surface. Differences between TD and DCD groups were similar with reduced significance (p0.01), and the pattern diverged with more inclusion of the anterior ventricular surface and less pronouncement at the right anterior border. Finally, significant differences were found between ASD and DCD groups (p<0.01), specifically at the anterior midline either side of the ventricular surface, and especially in two long anteroposterior columns on the left side adjacent and parallel to the fourth ventricle. Conclusions: Surface morphology differences indicate alterations in local nuclei and/or tract growth within the brainstem, especially approaching the anterior surface in ASD and DCD children, and differentially between them at the ventricular surface. The former may relate to specific nerve growth of the pons, and the latter to cerebellar peduncle connectivity differences, superficial nuclei growth such as the hypoglossal, intercalatus, or vagus and associated tracts, or deeper nuclei such as the inferior olivary nucleus. Brainstem structural differences likely disturbs the integrative function of the Core Self. Higher resolution 7T MRI is required to resolve the underlying differential composition

Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis

Background: Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Patients and methods: We performed a retrospective study of data (from 19 centres in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 months). Patients were categorized according to their response to SOC. Patients in group 1 (n=108) had a complete response to the SOC, but were switched to second line therapy due to side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n=93) had not responded to SOC. Results: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P=.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P=.682). Significantly more group 2 patients given tacrolimus compared to MMF had a complete response (56.5 % vs. 34%, P=.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P=.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous non-responder patients compared to MMF

ARIANNA: A research environment for neuroimaging studies in autism spectrum disorders

The complexity and heterogeneity of Autism Spectrum Disorders (ASD) require the implementation of dedicated analysis techniques to obtain the maximum from the interrelationship among many variables that describe affected individuals, spanning from clinical phenotypic characterization and genetic profile to structural and functional brain images. The ARIANNA project has developed a collaborative interdisciplinary research environment that is easily accessible to the community of researchers working on ASD (https://arianna.pi.infn.it). The main goals of the project are: to analyze neuroimaging data acquired in multiple sites with multivariate approaches based on machine learning; to detect structural and functional brain characteristics that allow the distinguishing of individuals with ASD from control subjects; to identify neuroimaging-based criteria to stratify the population with ASD to support the future development of personalized treatments. Secure data handling and storage are guaranteed within the project, as well as the access to fast grid/cloud-based computational resources. This paper outlines the web-based architecture, the computing infrastructure and the collaborative analysis workflows at the basis of the ARIANNA interdisciplinary working environment. It also demonstrates the full functionality of the research platform. The availability of this innovative working environment for analyzing clinical and neuroimaging information of individuals with ASD is expected to support researchers in disentangling complex data thus facilitating their interpretation