Antinuclear antibodies in COVID 19

We appreciated very much the interesting study by Chang et al. on the presence of antinuclear antibodies (ANAs) in patients with moderate/critical coronavirus disease 2019 (COVID 19). Both we and Chang and collaborators described the presence and significance of ANAs in patients with COVID‐19. The two experiences can be compared because Chang et al. studied a number of cases only slightly larger than us. In our opinion, the most important finding is represented by the presence of the nucleolar ANA reactivity, which, in the study by Chang et al., as in ours, is the most frequently detected among the different ANA patterns. In this regard, it is worth mentioning that the nucleolar ANA pattern is one of the several ANA pattern detectable by Indirect immunofluorescence, together with other patterns, such as speckled, homogenous, multiple nuclear dots, and rim like membranous; this pattern can be the serological marker of systemic sclerosis and its antigenic target is the topoisomerase I protein (or scl70). Interestingly, it is of major relevance to note that among the clinical manifestations of systemic sclerosis, it includes pulmonary involvement in the form of a restrictive syndrome secondary to interstitial pneumopathy resembling COVID‐19 interstitial pneumonia

Decompensated cirrhosis as presentation of LKM1/LC1 positive type 2 autoimmune hepatitis in adulthood. A rare clinical entity of difficult management

Background: Autoimmune hepatitis (AIH) is a chronic and aggressive liver disease that rapidly evolves into cirrhosis and end-stage liver disease if not timely diagnosed and treated with immunosuppressive therapy. AIH is classified into type 1 and type 2 according to the autoantibody pattern, with smooth muscle antibodies and/or antinuclear antibodies as serological markers of AIH-1, while antiliver cytosol antibody type 1 and/or antiliver/kidney microsomal antibody type 1 characterize type 2 AIH, which mainly affects children, including infants, and adolescents. Case Summary: We describe a case of type 2 AIH, clinically onset in a 34-year-old woman with decompensated cirrhosis. Only a thorough analysis of the autoantibody profile allowed for a diagnosis of an AIH-2 evolved into cirrhosis. The patient received a moderate corticosteroid therapy without achieving optimal disease control. We discuss the controversial decision of whether or not to treat the patient with immunosuppressive therapy, which should be balanced with the potential risk of infectious and other complications. A review of the literature on the management of patients with autoimmune cirrhosis is also presented. Conclusions: AIH-2 can be clinically onset in adult patients with cirrhosis and its complications, without being preceded by major clinical signs. Due to the difficult management of cirrhosis with immunosuppressive treatments, a patient-tailored strategy with a case-by-case approach is needed to prevent major complications such as infections, potentially precluding liver transplantation the only curative therapy

Smoking as a risk factor for autoimmune liver disease: what we can learn from primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterised by circulating anti-mitochondrial antibodies (AMA) as well as disease specific anti-nuclear antibodies (ANA), cholestatic liver biochemistry, and characteristic histology. The disease primarily affects middle-aged females, and its incidence is apparently increasing worldwide. Epidemiological studies have indicated several risk factors for the development of PBC, with family history of PBC, recurrent urinary tract infection, and smoking being the most widely cited. Smoking has been implicated as a risk factor in several autoimmune diseases, including the liver, by complex mechanisms involving the endocrine and immunological systems to name a few. Studies of smoking in liver disease have also shown that smoking may progress the disease towards fibrosis and subsequent cirrhosis. This review will examine the literature surrounding smoking as a risk factor for PBC, as well as a potential factor in the progression of fibrosis in PBC patients

Sympathetic arousal in children with oppositional defiant disorder and its relation to emotional dysregulation

Background: Emotional dysregulation (ED) is a trans-nosographical condition characterized by mood instability, severe irritability, aggression, temper outburst, and hyper-arousal. Pathophysiology of emotional dysregulation and its potential biomarkers are an emerging field of interest. A Child Behaviour Checklist (CBCL) profile, defined as Dysregulation Profile (DP), has been correlated to ED in youth. We examined the association between the CBCL-DP and indices of sympathetic arousal in children with Oppositional Defiant Disorder (ODD) and healthy controls. Method: The current study sought to compare the arousal level measured via electrodermal activity in response to emotional stimuli in three non-overlapping groups of children: (1) ODD+CBCL-DP (n = 28), (2) ODD without CBCL-DP (n = 35), and (3) typically developing controls (n = 25). Results: Analyses revealed a distinct electrodermal activity profile in the three groups. Specifically, children with ODD+CBCL-DP presented higher levels of sympathetic arousal for anger and sadness stimuli compared to the other two groups. Limitations: The relatively small sample and the lack of assessing causality limit the generalizability of this study which results need to be replicated in larger, different samples. Conclusion: The CBCL-DP was associated to higher levels of arousal for negative emotions, consistently with previous reports in individuals with depression and anxiety. Further work may identify potential longitudinal relationships between this profile and clinical outcomes

Paraneoplastic Anti-Tif1-gamma Autoantibody-positive Dermatomyositis as Clinical Presentation of Hepatocellular Carcinoma Recurrence

Hepatocellular carcinoma (HCC) is rarely associated with autoimmune paraneoplastic syndromes. We report a case of anti-transcriptional intermediary factor-1 gamma (TIF1-??)-positive dermatomyositis (DM) as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue, myalgia, and typical skin rash. His medical history was notable for hepatitis C-related cir-rhosis, successful treatment with direct-acting antiviral agents, and previously efficacious treatment of HCC. Labo-ratory testing showed significant rhabdomyolysis with anti-TIF1-?? antibodies at high titer, and DM was diagnosed. After a careful diagnostic workup, HCC recurrence was diagnosed. After first-line corticosteroid treatment, azathioprine and in-travenous immunoglobulin treatments were administered; unfortunately, he mounted only partial response. Owing to the compromised performance status, no HCC treatment was feasible, and, according to international guidelines, he received only best supportive care. Here, we discuss the diagnostic, prognostic, and pathogenic roles of anti-TIF1-?? antibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients. Consider-ing the TIF1 gene family???s established role in oncogenesis, we also review the role of TIF1-?? as a tumor-related neo-antigen, leading to the development of clinically overt anti-TIF1-?? antibodies-positive DM

Evaluation of altered functional connections in male children with autism spectrum disorders on multiple-site data optimized with machine learning

No univocal and reliable brain-based biomarkers have been detected to date in Autism Spectrum Disorders (ASD). Neuroimaging studies have consistently revealed alterations in brain structure and function of individuals with ASD; however, it remains difficult to ascertain the extent and localization of affected brain networks. In this context, the application of Machine Learning (ML) classification methods to neuroimaging data has the potential to contribute to a better distinction between subjects with ASD and typical development controls (TD). This study is focused on the analysis of resting-state fMRI data of individuals with ASD and matched TD, available within the ABIDE collection. To reduce the multiple sources of heterogeneity that impact on understanding the neural underpinnings of autistic condition, we selected a subgroup of 190 subjects (102 with ASD and 88 TD) according to the following criteria: male children (age range: 6.5–13 years); rs-fMRI data acquired with open eyes; data from the University sites that provided the largest number of scans (KKI, NYU, UCLA, UM). Connectivity values were evaluated as the linear correlation between pairs of time series of brain areas; then, a Linear kernel Support Vector Machine (L-SVM) classification, with an inter-site cross-validation scheme, was carried out. A permutation test was conducted to identify over-connectivity and under-connectivity alterations in the ASD group. The mean L-SVM classification performance, in terms of the area under the ROC curve (AUC), was 0.75 ± 0.05. The highest performance was obtained using data from KKI, NYU and UCLA sites in training and data from UM as testing set (AUC = 0.83). Specifically, stronger functional connectivity (FC) in ASD with respect to TD involve (p < 0.001) the angular gyrus with the precuneus in the right (R) hemisphere, and the R frontal operculum cortex with the pars opercularis of the left (L) inferior frontal gyrus. Weaker connections in ASD group with respect to TD are the intra-hemispheric R temporal fusiform cortex with the R hippocampus, and the L supramarginal gyrus with L planum polare. The results indicate that both under-and over-FC occurred in a selected cohort of ASD children relative to TD controls, and that these functional alterations are spread in different brain networks

Very Low Alcohol Consumption Is Associated with Lower Prevalence of Cirrhosis and Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease

The role of moderate alcohol consumption in the evolution of NAFLD is still debated. The aim of this study is to evaluate the impact of current and lifelong alcohol consumption in patients with NAFLD. From 2015 to 2020, we enrolled 276 consecutive patients fulfilling criteria of NAFLD (alcohol consumption up to 140 g/week for women and 210 g/week for men). According to their current alcohol intake per week, patients were divided in: abstainers, very low consumers (C1: <70 g/week) and moderate consumers (C2). We created a new tool, called LACU (Lifetime Alcohol Consuming Unit) to estimate the alcohol exposure across lifetime: 1 LACU was defined as 7 alcohol units per week for 1 drinking year. Patients were divided into lifelong abstainers and consumers and the latter furtherly divided into quartiles: Q1-Q4. Stratification according to alcohol intake, both current and cumulative as estimated by LACU, showed that very low consumers (C1 and Q1-Q3) displayed lower frequency of cirrhosis and hepatocellular carcinoma compared to abstainers and moderate consumers (C2 and Q4). We can speculate that up to one glass of wine daily in the context of a Mediterranean diet may be a long-term useful approach in selected NAFLD patients

Disentangling the initiation from the response in joint attention: an eye-tracking study in toddlers with autism spectrum disorders

Joint attention (JA), whose deficit is an early risk marker for autism spectrum disorder (ASD), has two dimensions: (1) responding to JA and (2) initiating JA. Eye-tracking technology has largely been used to investigate responding JA, but rarely to study initiating JA especially in young children with ASD. The aim of this study was to describe the differences in the visual patterns of toddlers with ASD and those with typical development (TD) during both responding JA and initiating JA tasks. Eye-tracking technology was used to monitor the gaze of 17 children with ASD and 15 age-matched children with TD during the presentation of short video sequences involving one responding JA and two initiating JA tasks (initiating JA-1 and initiating JA-2). Gaze accuracy, transitions and fixations were analyzed. No differences were found in the responding JA task between children with ASD and those with TD, whereas, in the initiating JA tasks, different patterns of fixation and transitions were shown between the groups. These results suggest that children with ASD and those with TD show different visual patterns when they are expected to initiate joint attention but not when they respond to joint attention. We hypothesized that differences in transitions and fixations are linked to ASD impairments in visual disengagement from face, in global scanning of the scene and in the ability to anticipate object's action