Early onset demyelinating Charcot‐Marie‐Tooth disease caused by a novel in‐frame isoleucine deletion in peripheral myelin protein 2

Peripheral myelin protein 2 (PMP2) is a small protein located on the cytoplasmic side of compact myelin, involved in the lipids transport and in the myelination process. In the last years few families affected with demyelinating Charcot‐Marie‐Tooth neuropathy (CMT1), caused by PMP2 mutations, have been identified. In this study we describe the first case of a PMP2 in‐frame deletion. PMP2 was analyzed by direct sequencing after exclusion of the most frequent CMT‐associated genes by using a next generation sequencing (NGS) genes panel. Sanger sequencing was used for family's segregation analysis. Molecular modeling analysis was used to evaluate the mutation impact on the protein structure. A novel PMP2: p.I50del has been identified in a child with early onset CMT1 and in three affected family members. All family members show an early onset demyelinating neuropathy without other distinguish features. Molecular modeling analysis and in silico evaluations do not suggest a strong impact on the overall protein structure, but a most likely altered protein function. This study suggests the importance to add PMP2 in CMT NGS genes panels or, at most, to test it after major CMT1 genes exclusion, due to the lack of diagnostic‐addressing additional features.     

Autoantibodies against the autophagic protein microtubule-associated light-chain 3 (LC3): Immunocharacterization of an atypical ANA pattern

Abstract

Autoantibodies to nuclear and cytoplasmic antigens are commonly detected by indirect immunofluorescence (IIF) on HEp-2 cells, and three major staining patterns (nuclear, cytoplasmic, and mitotic) are distinguished. Here, we report an atypical cytoplasmic pattern, not described so far, observed in the serum of a patient with a controversial diagnosis of systemic lupus erythematosus (SLE). Moreover, for the first time, we have revealed the presence of autoantibodies against the microtubule-associated light-chain 3 (LC3) protein, which plays a key role in the autophagic process. The target antigen has been identified in IIF by means of a competition test using purified anti-LC3 antibodies on HEp-2 cells, and confirmed by Western blot analysis using cellular or recombinant LC3 as antigen, immunoreacted with the patient’s serum. The identification of this atypical pattern and the related autoantibody-antigen system sheds new light on autophagy, which is increasingly considered to be involved in the etiopathogenesis of autoimmune disorders, and could contribute to select more personalized therapies.     

On the management of COVID-19 pandemic in Italy

The fast-moving coronavirus disease 2019 (COVID-19) called for a rapid response to slowing down the viral spread and reduce the fatality associated to the pandemic. Policymakers have implemented a wide range of non-pharmaceutical interventions to mitigate the spread of the pandemic and reduce burdens on healthcare systems. An efficient response of healthcare systems is crucial to handle a health crisis. Understanding how non-pharmaceutical interventions have contributed to slowing down contagions and how healthcare systems have impacted on fatality associated with health crisis is of utmost importance to learn from the COVID-19 pandemic. We investigated these dynamics in Italy at the regional level. We found that the simultaneous introduction of a variety of measures to increase social distance is associated with an important decrease in the number of new infected patients detected daily. Contagion reduces by 1% with the introduction of lockdowns in an increasing number of regions. We also found that a robust healthcare system is crucial for containing fatality associated with COVID-19. Also, proper diagnosis strategies are determinant to mitigate the severity of the health outcomes. The preparedness is the only way to successfully adopt efficient measures in response of unexpected emerging pandemics.     

Giant gastrointestinal stromal tumour of rare sarcomatoid epithelioid subtype:Case study and literature review

Gastrointestinal stromal tumours(GISTs) are the most common mesenchymal tumours of the gastrointestinal tract,but they represent less than 3% of all gastrointestinal tract malignancies.This is a detailed case study of a 52-yearold male patient treated for very uncommon histological subtype of gastric GIST with atypical clinical presentation,asymptomatic progress and late diagnosis.The resected tumour,giant in diameters,was confirmed to represent the most rare histopathologic subtype of GISTs- sarcomatoid epithelioid GIST.We report this case and review the literature with a special focus on pathomorphological evaluation,biological aggressiveness and prognostic factors.To our knowledge this is the first report of giant GIST of very uncommon sarcomatoid epithelioid subtype.It is concluded that clinicians should pay attention to the fact that initial diagnosis may be delayed due to mildly asymptomatic and non-specific clinical presentation.Asymptomatic tumours diagnosed at a late stage,which is often the case,can be large on presentation.Prognosis for patients diagnosed with GIST depend on tumour size,mitotic rate,histopathologic subtype and tumour location.That is why early diagnosis and R0 resection,which is usually feasible and safe even in giant gastric sarcomatoid epithelioid subtype of GISTs,are the key factors for further treatment and good prognosis.     

Early composite cranioplasty in infants with severe aplasia cutis congenita: a report of two cases.

OBJECTIVE: Severe cutis aplasia congenita has traditionally been treated with initial soft tissue coverage and delayed cranioplasty. We advocate the technique of early composite reconstruction of both bone and soft tissues. METHODS: Two cases of cutis aplasia congenita with large skull defects (6 x 10 cm, 8 x 8 cm) of superficial layers, skull, and dura are presented. In each case, composite reconstruction was undertaken before 2 weeks of age with restoration of bony and soft tissue coverage through autologous, full-thickness cranial bone grafts and scalp flaps. Both children have been followed up over 2 years with clinical examination and computed tomography (CT) scans. RESULTS: In both cases, defects were completely repaired postoperatively and remained closed 2 years later. Complete regeneration of calvarial bone graft donor sites were documented by CT scan. Head shape and circumference were normal at 2-year follow up.     

ASO Visual Abstract: Margin Management and Adjuvant Therapy for Phyllodes Tumors—Practice Patterns of the American Society of Breast Surgeons Members

Annals of Surgical Oncology -