Atypical Huntington's disease with the clinical presentation of behavioural variant of frontotemporal dementia.

Huntington's disease is an incurable, adult-onset, autosomal dominant inherited disorder caused by an expanded trinucleotide repeat (CAG). In this study, we describe a Huntington's disease patient displaying clinical symptoms of the behavioural variant of frontotemporal dementia in the absence of tremor and ataxia. The clinical onset was at the age of 36 years and the disease progressed slowly (18 years). Genetic testing revealed expanded trinucleotide CAG repeats in the Huntingtin gene, together with a Glu318Gly polymorphism in presenilin 1. Neuropathological assessment revealed extensive amyloid ß (Aß) aggregates in all cortical regions. No inclusions displaying hyperphosphorylated tau or phosphorylated transactive response DNA-binding protein 43 (TDP43) were found. A high number of p62 (sequestosome 1) immunopositive intranuclear inclusions were seen mainly in the cortex, while subcortical areas were affected to a lesser extent. Confocal microscopy revealed that the majority of p62 intranuclear lesions co-localised with the fused-in-sarcoma protein (FUS) immunostaining. The morphology of the inclusions resembled intranuclear aggregates in Huntington's disease. The presented proband suffered from Huntington's disease showed atypical distribution of FUS positive intranuclear aggregates in the cortical areas with concomitant Alzheimer's disease pathology.

Anti-SARS-CoV-2 Antibody Status at the Time of Hospital Admission and the Prognosis of Patients with COVID-19: A Prospective Observational Study.

The association between COVID-19 severity and antibody response has not been clearly determined. We aimed to assess the effects of antibody response to SARS-CoV-2 S protein at the time of hospital admission on in-hospital and longitudinal survival. Methods: A prospective observational study in naive hospitalised COVID-19 patients. The presence of anti-S SARS-CoV-2 IgM and IgG was evaluated using a lateral flow assay at the time of admission. The patients were followed up for 8-30 months to assess survival. We recruited 554 patients (330 men and 224 women). Overall, 63.0% of the patients had positive IgG or IgM anti-S SARS-CoV-2 antibodies at the time of hospital admission. In the univariate analysis, the patients with negative anti-S SARS-CoV-2 IgM and IgG antibodies were referred to the hospital sooner, had lower CRP and D-dimer concentrations, and were hospitalised longer. They were also more likely to be admitted to an intensive care unit and more often received baricitinib treatment. During their hospital stay, 8.5% of the antibody-positive and 22.3% of the antibody-negative patients died (p = 0.0001). The median duration of the follow-up was 21 months. During the follow-up after hospital discharge, 3.6% of antibody-positive and 9.1% of antibody-negative patients died (p = 0.027). In the multivariate analysis, the negative anti-S SARS-CoV-2 antibodies were associated with a higher risk of in-hospital death (OR 3.800; 95% CI 1.844-7.829; p = 0.0001) and with a higher risk of death during follow-up (OR 2.863; 95% CI 1.110-7.386; p = 0.030). These associations were independent of age, the time from symptom onset to hospital admission, CRP, D-Dimer, the number of comorbidities, disease severity at the time of hospital admission, and baricitinib therapy. Our study concludes that negative anti-S SARS-CoV-2 IgM and IgG at the time of admission are associated with higher in-hospital mortality and cause a higher risk of all-cause death during follow-up after discharge.

Intrauterine Fetal Demise After Uncomplicated COVID-19: What Can We Learn from the Case?

BACKGROUND: SARS-CoV-2 infection in pregnant women can lead to placental damage and transplacental infection transfer, and intrauterine fetal demise is an unpredictable event. CASE STUDY: A 32-year-old patient in her 38th week of pregnancy reported loss of fetal movements. She overcame mild COVID-19 with positive PCR test 22 days before. A histology of the placenta showed deposition of intervillous fibrinoid, lympho-histiocytic infiltration, scant neutrophils, clumping of villi, and extant infarctions. Immunohistochemistry identified focal SARS-CoV-2 nucleocapsid and spike protein in the syncytiotrophoblast and isolated in situ hybridization of the virus' RNA. Low ACE2 and TMPRSS2 contrasted with strong basigin/CD147 and PDL-1 positivity in the trophoblast. An autopsy of the fetus showed no morphological abnormalities except for lung interstitial infiltrate, with prevalent CD8-positive T-lymphocytes and B-lymphocytes. Immunohistochemistry and in situ hybridization proved the presence of countless dispersed SARS-CoV-2-infected epithelial and endothelial cells in the lung tissue. The potential virus-receptor protein ACE2, TMPRSS2, and CD147 expression was too low to be detected. CONCLUSION: Over three weeks' persistence of trophoblast viral infection lead to extensive intervillous fibrinoid depositions and placental infarctions. High CD147 expression might serve as the dominant receptor for the virus, and PDL-1 could limit maternal immunity in placental tissue virus clearance. The presented case indicates that the SARS-CoV-2 infection-induced changes in the placenta lead to ischemia and consecutive demise of the fetus. The infection of the fetus was without significant impact on its death. This rare complication of pregnancy can appear independently to the severity of COVID-19's clinical course in the pregnant mother.

Use of Advanced Artificial Intelligence in Forensic Medicine, Forensic Anthropology and Clinical Anatomy.

Three-dimensional convolutional neural networks (3D CNN) of artificial intelligence (AI) are potent in image processing and recognition using deep learning to perform generative and descriptive tasks. Compared to its predecessor, the advantage of CNN is that it automatically detects the important features without any human supervision. 3D CNN is used to extract features in three dimensions where input is a 3D volume or a sequence of 2D pictures, e.g., slices in a cone-beam computer tomography scan (CBCT). The main aim was to bridge interdisciplinary cooperation between forensic medical experts and deep learning engineers, emphasizing activating clinical forensic experts in the field with possibly basic knowledge of advanced artificial intelligence techniques with interest in its implementation in their efforts to advance forensic research further. This paper introduces a novel workflow of 3D CNN analysis of full-head CBCT scans. Authors explore the current and design customized 3D CNN application methods for particular forensic research in five perspectives: (1) sex determination, (2) biological age estimation, (3) 3D cephalometric landmark annotation, (4) growth vectors prediction, (5) facial soft-tissue estimation from the skull and vice versa. In conclusion, 3D CNN application can be a watershed moment in forensic medicine, leading to unprecedented improvement of forensic analysis workflows based on 3D neural networks.

Challenging management of severe chronic disorders in acute pandemic situation: Chronic liver disease under COVID-19 pandemic as the proof-of-principle model to orchestrate the measures in 3PM context.

Chronic liver disease management is a comprehensive approach requiring multi-professional expertise and well-orchestrated healthcare measures thoroughly organized by responsible medical units. Contextually, the corresponding multi-faceted chain of healthcare events is likely to be severely disturbed or even temporarily broken under the force majeure conditions such as global pandemics. Consequently, the chronic liver disease is highly representative for the management of any severe chronic disorder under lasting pandemics with unprecedented numbers of acutely diseased persons who, together with the chronically sick patient cohorts, have to be treated using the given capacity of healthcare systems with their limited resources. Current study aimed at exploring potentially negative impacts of the SARS CoV-2 outbreak on the quality of the advanced chronic liver disease (ACLD) management considering two well-classified parameters, namely, (1) the continuity of the patient registrations and (2) the level of mortality rates, comparing pre-COVID-19 statistics with these under the current pandemic in Slovak Republic. Altogether 1091 registrations to cirrhosis registry (with 60.8% versus 39.2% males to females ratio) were included with a median age of 57 years for patients under consideration. Already within the very first 3 months of the pandemic outbreak in Slovakia (lockdown declared from March 16, 2020, until May 20, 2020), the continuity of the patient registrations has been broken followed by significantly increased ACLD-related death rates. During this period of time, the total number of new registrations decreased by about 60% (15 registrations in 2020 versus 38 in 2018 and 38 in 2019). Corresponding mortality increased by about 52% (23 deaths in 2020 versus 10 in 2018 and 12 in 2019). Based on these results and in line with the framework of 3PM guidelines, the pandemic priority pathways (PPP) are strongly recommended for maintaining tertiary care uninterrupted. For the evidence-based implementation of PPP, creation of predictive algorithms and individualized care strategy tailored to the patient is essential. Resulting classification of measures is summarized as follows:The Green PPP Line is reserved for prioritized (urgent and comprehensive) treatment of patients at highest risk to die from ACLD (tertiary care) as compared to the risk from possible COVID-19 infection.The Orange PPP Line considers patients at middle risk of adverse outcomes from ACLD with re-addressing them to the secondary care. As further deterioration of ACLD is still probable, pro-active management is ascertained with tertiary center serving as the 24/7 telemedicine consultation hub for a secondary facility (on a physician-physician level).The Red PPP Line is related to the patients at low risk to die from ACLD, re-addressing them to the primary care. Since patients with stable chronic liver diseases without advanced fibrosis are at trivial inherent risk, they should be kept out of the healthcare setting as far as possible by the telemedical (patient-nurse or patient- physician) measurements. The assigned priority has to be monitored and re-evaluated individually-in intervals based on the baseline prognostic score such as MELD. The approach is conform with principles of predictive, preventive and personalized medicine (PPPM / 3PM) and demonstrates a potential of great clinical utility for an optimal management of any severe chronic disorder (cardiovascular, neurological and cancer) under lasting pandemics.