Clinical features and radiological manifestations of COVID-19 disease

Coronavirus disease 2019 (COVID-19) was discovered after unusual cases of severe pneumonia emerged in December 2019 in Wuhan Province (China). Coronavirus is a family of single-stranded RNA viruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted from person to person. Although asymptomatic individuals can transmit the virus, symptomatic patients are more contagious. The incubation period ranges from 3-7 d and symptoms are mainly respiratory, including pneumonia or pulmonary embolism in severe cases. Elevated serum levels of interleukins (IL)-2, IL-6, IL-7 indicate the presence of cytokine release syndrome, which is associated with disease severity. The disease has three main phases: Viral infection, pulmonary involvement, and hyperinflammation. To date, no treatment has proved to be safe or effective. Chest X-ray and computed tomography (CT) are the primary imaging tests for diagnosis of SARS-CoV-2 pneumonia, follow-up, and detection of complications. The main radiological findings are ground-glass opacification and areas of consolidation. The long-term clinical course is unknown, although some patients may develop pulmonary fibrosis. Positron emission tomography-computed tomography (PET-CT) is useful to assess pulmonary involvement, to define the affected areas, and to assess treatment response. The pathophysiology and clinical course of COVID-19 infection remain poorly understood. However, patterns detected on CT and PET-CT may help to diagnose and guide treatment. In this mini review, we analyze the clinical manifestations and radiological findings of COVID-19 infection.     

Analysis of a cell line derived from a chicken hepatoma induced by virus MC29

A cell line derived from a transplantable chicken hepatoma induced by virus MC29 was established. This cell line grew permanently over 2 years and could be easily recovered from frozen state. Morphology of cells did not change during the period of cultivation. Karyological analysis revealed the hypodiploid stemline with reduced numbers of microchromosomes. The cell line was not transplantable in 1-day-old chicks, but induced multiple tumour nodules in the mesenterium and liver about 8 weeks postinoculation. The cell line is virus productive. The analysis of viral proteins with the gag specific determinants showed the presence of pr76 and p110.     

MSH6 mutation in a family affected by Muir-Torre syndrome

Muir-Torre syndrome (MTS), a phenotypic variant of the more common hereditary nonpolyposis colorectal cancer syndrome, or Lynch syndrome, is an autosomal dominantly inherited condition that combines at least one cutaneous sebaceous neoplasm and at least one visceral malignancy. Most patients (~90%) with MTS carry mutations in the MSH2 gene; less than 10% of the cases are associated with a mutation MLH1 gene, and only 3 MTS patients with a pathogenic MSH6 mutation have been previously documented. We report a family affected with MTS in which 3 members (father and 2 sons) were found to harbor a missense mutation c.2633T>C (p.V878A) in exon 4 of the MSH6 gene.     

Rufinamide for pediatric patients with Lennox-Gastaut syndrome: a comprehensive overview

Rufinamide is a triazole derivative with broad-spectrum antiepileptic effects that is unrelated to any antiepileptic drug currently on the market. The European Commission and the US FDA approved rufinamide in 2007 and 2008, respectively, for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children 4 years of age or older and adults. The mechanism of action of rufinamide is not completely understood but it is believed to prolong the inactive state of sodium channels, therefore limiting excessive firing of sodium-dependent action potentials. Rufinamide is well absorbed when taken with food, with an absolute bioavailability between 70% and 85%. The elimination half-life of the drug is around 6-10 hours, with a time to maximum plasma concentration (C(max)) of approximately 4-6 hours. The C(max) at a dosage of 10?mg/kg/day and 30?mg/kg/day is 4.01?μg/mL and 8.68?μg/mL, respectively, and the area under the plasma concentration-time curve from time 0 to 12 hours was 37.8?±?47?μg?·?h/mL and 89.3?±?58?μg?·?h/mL, respectively. Rufinamide exerts non-linear pharmacokinetics with increasing doses. The volume of distribution in children is similar to that in adults (0.8-1.2?L/kg) and the drug binds rather poorly to plasma protein (26.2-34.8%). Rufinamide is mainly metabolized by carboxylesterases to an inactive metabolite (CGP 47292), and the majority of the metabolites are excreted in the urine (91%). No dosage adjustment is required in patients with renal dysfunction. Rufinamide does not affect the plasma concentration of other antiepileptics, but phenytoin, phenobarbital, valproate, and primidone affect the clearance of rufinamide. In a clinical study of 138 patients averaging 12 years of age, rufinamide used as an adjunctive therapy (with an initial dosage of 10?mg/kg/day up to a target dosage of 45?mg/kg/day) in patients with Lennox-Gastaut syndrome reduced the median total seizure frequency by 32.7% versus 11.7% in the placebo group (p?=?0.0015). Similar reduction in total seizure frequency was maintained in the extension phase of this study. In other studies, rufinamide also seemed to provide improvement in both partial seizures and refractory epilepsy, but further studies need to validate this observation and to identify its clinical significance. Rufinamide is usually started orally at 10?mg/kg/day, titrating up by 10?mg/kg/day every 2 days to a target dosage of 45?mg/kg/day divided twice daily (maximum dosage of 3200?mg/day). Dosing of rufinamide has not been established in patients <4 years of age. Rufinamide is available as 100, 200, and 400?mg tablets in Europe, and 200 and 400?mg tablets in the US; a suspension of 40?mg/mL can be prepared extemporaneously. Rufinamide is well tolerated, with the most common adverse effects being dizziness, fatigue, nausea, vomiting, diplopia, and somnolence. From the current data, rufinamide serves as an adjunctive therapy in the management of Lennox-Gastaut syndrome. Further studies need to evaluate its efficacy as a first-line agent in the management of this neurologic disorder.     

Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis

Administration of daclizumab, a humanized mAb directed against the IL-2Ralpha chain, strongly reduces brain inflammation in multiple sclerosis patients. Here we show that daclizumab treatment leads to only a mild functional blockade of CD4(+) T cells, the major candidate in multiple sclerosis pathogenesis. Instead, daclizumab therapy was associated with a gradual decline in circulating CD4(+) and CD8(+) T cells and significant expansion of CD56(bright) natural killer (NK) cells in vivo, and this effect correlated highly with the treatment response. In vitro studies showed that NK cells inhibited T cell survival in activated peripheral blood mononuclear cell cultures by a contact-dependent mechanism. Positive correlations between expansion of CD56(bright) NK cells and contraction of CD4(+) and CD8(+) T cell numbers in individual patients in vivo provides supporting evidence for NK cell-mediated negative immunoregulation of activated T cells during daclizumab therapy. Our data support the existence of an immunoregulatory pathway wherein activated CD56(bright) NK cells inhibit T cell survival. This immunoregulation has potential importance for the treatment of autoimmune diseases and transplant rejection and toward modification of tumor immunity.     

Extra nuchal-type fibroma associated with elastosis, traumatic neuroma, a rare APC gene missense mutation, and a very rare MUTYH gene polymorphism: a case report and review of the literature*

We report a case of an extra nuchal-type fibroma in a 51-year-old male suspected to have attenuated familial adenomatous polyposis (Gardner's syndrome), who presented with a longstanding buttock mass excised due to enlargement and pain. Histopathologically, lobules of haphazard, hypocellular, hyalinized collagen bundles replaced the dermis and subcutis and entrapped nerve bundles, mimicking Morton neuroma. Ramifying nerve twigs found around larger nerve fascicles showed the co-existence of traumatic neuroma. Elastic tissue stain revealed elastosis characterized by large, arborizing fibers lying between and within the hyalinized collagen bundles. Modified Masson's trichrome stain showed light blue staining of collagen bundles producing the hyalinized nodules with irregular, light red staining of collagen bundles at their periphery and within tumor collagen. Compression and/or degeneration of collagen and secondary elastosis with later entrapment by tumor collagen could explain this microscopic phenotype. By immunohistochemistry, tumor spindle cells expressed nuclear β-catenin and cyclin D1, mostly within regions of fibrosis implicating activation of the adenomatous polyposis coli (APC)-Wnt pathway. Genetic analysis showed a missense mutation in APC gene (c.7504G>A, p.G2502S in exon 15) and a functional homozygous polymorphism in the MUTYH gene (c.36+325G>C, (IVS1+5G/C)). Nuchal-type fibroma has been associated with Gardner's syndrome and trauma. In this patient, genetic predisposition coupled with repetitive, localized trauma and collagen degeneration may have provided the stimulus for the development of extra nuchal-type fibroma.