Central retinal artery occlusion in a young child affected by COVID-19: a first case report.

BACKGROUND: Central retinal artery occlusion (CRAO) is an ophthalmic emergency, and its etiology is generally ascribed to vessel occlusion by a thrombus or embolus, eventually due to a hypercoagulable state. CRAO occurrence is described even in the pediatric population, but its incidence is very rare. SARS-CoV-2 infection has a multitude of presentations, and almost any organ may be involved including the ocular district. Cases of CRAO in patients affected by COVID-19 are reported in the literature in the adult population, but not in the pediatric one. CASE PRESENTATION: We describe the case of a six-year-old otherwise healthy girl, who presented a sudden and complete bilateral vision loss after a one-day fever. All the clinical, ophthalmological, laboratory and instrumental investigations led to the diagnosis of a right CRAO and the suspicion of a contralateral posterior optic nerve affection. These manifestations could not be ascribed to any etiological condition apart from the documented ongoing mild SARS-CoV-2 infection. Treatment with anticoagulants and steroids was tried but the visual outcome was poor during the one-month hospitalization and at the last follow-up. CONCLUSIONS: To the best of our knowledge, this is the first report of CRAO in the course of SARS-CoV-2 infection in the pediatric age. In our review of the literature, we found few cases of CRAO in adults with COVID-19; we highlighted differences in anamnestic, clinical, and interventional aspects and therefore we tried to summarize the state of the art on this topic to facilitate further studies. Even if rare, the prognosis of CRAO is poor and the thrombolytic treatment could be effective only if rapidly administered, so the disease suspicion should be high in a patient with sudden vision loss, also in pediatric age.

Immunosuppressive Treg cells acquire the phenotype of effector-T cells in chronic lymphocytic leukemia patients.

BACKGROUND: In chronic lymphocytic leukemia (CLL) disease onset and progression are influenced by the behavior of specific CD4+ T cell subsets, such as T regulatory cells (Tregs). Here, we focused on the phenotypic and functional characterization of Tregs in CLL patients to improve our understanding of the putative mechanism by which these cells combine immunosuppressive and effector-like properties. METHODS: Peripheral blood mononuclear cells were isolated from newly diagnosed CLL patients (n = 25) and healthy volunteers (n = 25). The phenotypic and functional characterization of Tregs and their subsets was assessed by flow cytometry. In vitro analysis of TH1, TH2, TH17 and Tregs cytokines was evaluated by IFN-γ, IL-4, IL-17A and IL-10 secretion assays. The transcriptional profiling of 84 genes panel was evaluated by RT2 Profiler PCR Array. Statistical analysis was carried out using exact non parametric Mann-Whitney U test. RESULTS: In all CLL samples, we found a significant increase in the frequency of IL-10-secreting Tregs and Tregs subsets, a significant rise of TH2 IL-4+ and TH17 IL-17A+ cells, and a higher percentage of IFN-γ/IL-10 and IL-4/IL-10 double-releasing CD4+ T cells. In addition, we also observed the up-regulation of innate immunity genes and the down-regulation of adaptive immunity ones. CONCLUSIONS: Our data show that Tregs switch towards an effector-like phenotype in CLL patients. This multifaceted behavior is accompanied by an altered cytokine profiling and transcriptional program of immune genes, leading to a dysfunction in immune response in the peripheral blood environment of CLL patients.

A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review.

INTRODUCTION: Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease, whose clinical phenotype was expanded since the first cases, originally described as mimicker of polyarteritis nodosa, with immunodeficiency and early-onset stroke. METHODS: A systematic review according to PRISMA approach, including all articles published before the 31st of August 2021 in Pubmed and EMBASE database was performed. RESULTS: The search identified 90 publications describing 378 unique patients (55.8% male). To date 95unique mutations have been reported. The mean age at disease onset was 92.15 months (range 0-720 months), 32 (8.5%) showed an onset of the first signs/symptoms after 18 years old and 96 (25.4%) after 10 years old. The most frequent clinical characteristics described were cutaneous (67.9%), haematological manifestations (56.3%), recurrent fever (51.3%), neurological as stroke and polyneuropathy (51%), immunological abnormalities (42.3%), arthralgia/arthritis (35.4%), splenomegaly (30.6%), abdominal involvement (29.8%), hepatomegaly (23.5%), recurrent infections (18.5%), myalgia (17.9%), kidney involvement (17.7%) etc. Patients with skin manifestations were older than the others (101.1 months SD ± 116.5, vs. 75.3 SD ± 88.2, p 0.041), while those with a haematological involvement (64.1 months SD ± 75.6 vs. 133.1 SD ± 133.1, p < 0.001) and immunological involvement (73.03 months SD ± 96.9 vs. 103.2 SD ± 112.9, p 0.05) are younger than the others. We observed different correlations among the different clinical manifestations. The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) has improved the current history of the disease. CONCLUSION: Due to this highly variable phenotype and age of presentation, patients with DADA2 may present to several type of specialists. Given the important morbidity and mortality, early diagnosis and treatment are mandatory.

Neurological Involvement in Children with COVID-19 and MIS-C: A Retrospective Study Conducted for More than Two Years in a Pediatric Hospital.

This study aimed to evaluate the type and severity of neurological involvement in children with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) and compare these findings between the two groups. Children hospitalized with the diagnosis of COVID-19 or MIS-C at Meyer Children's Hospital between February 2020 and June 2022 were retrospectively studied. One hundred twenty-two patients were enrolled, 95 in the COVID-19 group and 27 in the MIS-C group. In the COVID-19 group, impairment of consciousness was found in 67.4% of patients, headache in 18.9% and about 16.8% of patients experienced seizures. In this group, three patients were diagnosed with arterial ischemic stroke and one patient was diagnosed with Guillain-Barré syndrome (GBS). In the MIS-C group, about 70% of patients experienced consciousness impairment, about 20% behavioral changes, and another 20% mood deflection. Neurological symptoms and signs were highly heterogeneous and could be differentiated in COVID-19 and MIS-C. Consciousness impairment remained the most frequent manifestation in both groups, potentially underlying an encephalopathy. We also highlight the importance of considering psychiatric symptoms in children with COVID-19 and/or MIS-C. Most neurological manifestations were mild in our series; however, severe complications such as ischemic stroke and GBS are worthy of note.

Pelvic Pyomyositis in Childhood: Clinical and Radiological Findings in a Tertiary Pediatric Center.

Pyomyositis (PM) is an infrequent but increasing bacterial infection of the skeletal muscle, with muscles of the pelvis and thigh frequently involved. The diagnosis is often challenging, especially when a deep muscle is affected. We present a single-center pediatric cohort affected by pelvic PM. A retrospective analysis was performed, including children admitted to Meyer Children's Hospital between 2010 and 2020. Demographic, anamnestic, clinical, laboratory, radiological and management data were collected. Forty-seven patients (range 8 days-16.5 years, 66% males) were selected. Pain (64%), functional limitations (40%) and fever (38%) were the most common presenting symptoms; 11% developed sepsis. The median time to reach the diagnosis was 5 days (IQR 3-9). Staphylococcus aureus was the most common organism (30%), Methicillin-Resistant S aureus (MRSA) in 14%. PM was associated with osteomyelitis (17%), arthritis (19%) or both (45%). The infection was multifocal in 87% of children and determined abscesses in 44% (40% multiple). Pelvic MRI scan, including diffusion-weighted imaging (DWI), always showed abnormalities when performed. Clinical and laboratory findings in pelvic PM are unspecific, especially in infancy. Nevertheless, the infection may be severe, and the suspicion should be higher. MRI is the most useful radiological technique, and DWI sequence could reveal insidious infections.

Early anti IL-1 treatment replaces steroids in refractory Kawasaki disease: clinical experience from two case reports.

Refractory Kawasaki disease (KD) is related to a major risk of coronary arteries abnormalities and its treatment is not standardized. In this regard, anakinra (ANA), an interleukin (IL)-1 receptor antagonist, represents an emerging therapeutic option. We report two cases of children, diagnosed with KD, nonresponsive to two doses of intravenous immunoglobulins, successfully treated with ANA, without a prior use of steroids. Patient 2 developed a coronary dilatation, that improved significantly after ANA therapy. Our experience highlights IL-1 blockade effectiveness in reducing KD inflammation and suggests ANA adoption as second-line therapy, with a timesaving and steroid-sparing strategy. Our results, combined with the evidence of the IL-1 key role in KD and coronary arteritis pathogenesis and to the recent clinical evidence reported by the KAWAKINRA trial, encourage an earlier recourse to ANA in patients with refractory KD, in order to fight inflammation, and to treat and prevent the development of coronary artery aneurysms. Further studies are needed to better define the place of IL-1 blockade in KD step-up treatment.

Kevetrin induces apoptosis in TP53 wild­type and mutant acute myeloid leukemia cells.

Tumor protein p53 is a key regulator of several cellular pathways, including DNA repair, cell cycle and angiogenesis. Kevetrin exhibits p53­dependent as well as­independent activity in solid tumors, while its effects on leukemic cells remain unknown. The aim of the present study was to analyze the response of acute myeloid leukemia (AML) cell lines (TP53 wild­type: OCI­AML3 and MOLM­13; and TP53­mutant: KASUMI­1 and NOMO­1) to kevetrin at a concentration range of 85­340 µM. The cellular and molecular effects of the treatment were analyzed in terms of cell growth, viability [Annexin V­propidium iodide (PI) staining] and cell cycle alterations (PI staining). Gene expression profiling, western blotting and immunofluorescence were performed to elucidate the pathways underlying kevetrin activity. Pulsed exposure exerted no effect on the wild­type cells, but was effective on mutant cells. After continuous treatment, significant cell growth arrest and apoptosis were observed in all cell lines, with TP53­mutant models displaying a higher sensitivity and p53 induction. Kevetrin also displayed efficacy against TP53 wild­type and mutant primary AML, with a preferential cytotoxic activity against blast cells. Gene expression profiling revealed a common core transcriptional program altered by drug exposure and the downregulation of glycolysis, DNA repair and unfolded protein response signatures. These findings suggest that kevetrin may be a promising therapeutic option for patients with both wild­type and TP53­mutant AML.

Cauliflower Mosaic Virus TAV, a Plant Virus Protein That Functions like Ribonuclease H1 and is Cytotoxic to Glioma Cells.

Recent comparisons between plant and animal viruses reveal many common principles that underlie how all viruses express their genetic material, amplify their genomes, and link virion assembly with replication. Cauliflower mosaic virus (CaMV) is not infectious for human beings. Here, we show that CaMV transactivator/viroplasmin protein (TAV) shares sequence similarity with and behaves like the human ribonuclease H1 (RNase H1) in reducing DNA/RNA hybrids detected with S9.6 antibody in HEK293T cells. We showed that TAV is clearly expressed in the cytosol and in the nuclei of transiently transfected human cells, similar to its distribution in plants. TAV also showed remarkable cytotoxic effects in U251 human glioma cells in vitro. These characteristics pave the way for future analysis on the use of the plant virus protein TAV, as an alternative to human RNAse H1 during gene therapy in human cells.