From variant of uncertain significance to likely pathogenic in two siblings with atypical RAG2 Deficiency: a case report and review of the literature.

BACKGROUND: Severe combined immunodeficiencies (SCIDs) are hereditary disorders characterized by impaired T and B cell function, resulting in significant immune system dysfunction. Recombination-activating gene (RAG) mutations account for a substantial proportion of SCID cases. Here, we present two sibling cases of SCID caused by a novel RAG2 gene mutation. CASE PRESENTATION: The index case was an 8-year-old boy who had a history of recurring infections. After a comprehensive immunological workup, the initial diagnosis of agammaglobulinemia was revised to combined immunodeficiency (CID). The patient underwent hematopoietic stem cell transplantation (HSCT) but succumbed to cytomegalovirus (CMV) infection. His brother, a 4-month-old boy, presented with CMV chorioretinitis. Leaky SCID was diagnosed based on genetic tests and immunological findings. The patient received appropriate treatment and was considered for HSCT. Both siblings had a homozygous RAG2 gene variant, with the first case classified as a variant of uncertain significance (VUS). The presence of the same mutation in the second brother, and the clinical phenotype, supports considering the mutation as likely pathogenic. CONCLUSIONS: This case report highlights a novel RAG2 gene mutation associated with CID. The classification of a VUS may evolve with accumulating evidence, and additional studies are warranted to establish its pathogenicity. Proper communication between genetic counselors and immunologists, accurate documentation of patient information, increased public awareness, and precise utilization of genetic techniques are essential for optimal patient management.

"Y" anastomosis, a solution in doubtful venous anastomosis: a case report and review of the literature.

BACKGROUND: Lower lip squamous cell carcinoma is a significant subtype of head and neck cancer, constituting about 25-30% of cases. Traditional surgical methods, like primary closure, have limitations in managing large resections of lip tumors. Recent advancements in surgical techniques, particularly free flaps, have shown promising results in addressing these challenges. The Y-shaped anastomosis is an innovative approach aimed at enhancing the efficiency of microvascular free flap surgeries for improved lip cancer reconstruction outcomes. CASE PRESENTATION: A 77-year-old Persian male with lower lip squamous cell carcinoma underwent tumor resection with a 2 cm safety margin, bilateral neck dissection, and lip reconstruction using the right radial forearm free flap. The surgery incorporated a Y-shaped anastomosis to improve venous pedicle outcomes. CONCLUSION: In this case, it was decided not to open the first anastomosis but to add the second end to the side one to provide two vascular supports for the venous anastomosis. Y anastomosis makes the surgery easier and decreases complications resulting from vascular size mismatch.

Assessment of global histone acetylation in pediatric and adolescent obesity: Correlations with SIRT1 expression and metabolic-inflammatory profiles.

BACKGROUND: Epigenetic modifications, particularly histone acetylation-deacetylation and its related enzymes, such as sirtuin 1 (SIRT1) deacetylase, may have substantial roles in the pathogenesis of obesity and its associated health issues. This study aimed to evaluate global histone acetylation status and SIRT1 gene expression in children and adolescents with obesity and their association with metabolic and anthropometric parameters. METHODS: This study included 60 children and adolescents, 30 with obesity and 30 normal-weight. The evaluation consisted of the analysis of global histone acetylation levels and the expression of the SIRT1 gene in peripheral blood mononuclear cells, by specific antibody and real-time PCR, respectively. Additionally, insulin, fasting plasma glucose, lipid profile and tumor necrosis factor α (TNF-α) levels were measured. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Metabolic syndrome was determined based on the diagnostic criteria established by IDF. RESULTS: Individuals with obesity, particularly those with insulin resistance, had significantly higher histone acetylation levels compared to control group. Histone acetylation was positively correlated with obesity indices, TNF-α, insulin, and HOMA-IR. Additionally, a significant decrease in SIRT1 gene expression was found among obese individuals, which was negatively correlated with the histone acetylation level. Furthermore, SIRT1 expression levels showed a negative correlation with various anthropometric and metabolic parameters. CONCLUSION: Histone acetylation was enhanced in children and adolescents with obesity, potentially resulting from down-regulation of SIRT1, and could play a role in the obesity-associated metabolic abnormalities and insulin resistance. Targeting global histone acetylation modulation might be considered as an epigenetic approach for early obesity management.

Programmed Death 1 (PD-1) Expression in Relapsing and Remitting Hodgkin Lymphoma as Prognostic Factor.

BACKGROUND: Programmed death ligand 1 (PD-L1) plays critical role in PD-1-dependent immunity suppress. Abnormal PD-L1 expression has shown to be directly related to poor prognosis and drug resistance in cancer patients. Hence, we aimed to evaluate PD-L1 expression in relapsing and remitting Hodgkin lymphoma (HL) as a prognostic factor. METHODS: In this cross-sectional study, 100 patients with HL between 2007 and 2015, were included. A thin section of tumor tissue fixed and processed on slides, stained by immunohistochemistry (IHC) PD-L1 specific antibodies. The clinical, imaging and pathology information of patients were obtained using case reading and by retrospective follow-up. The status of recurrence or improvement was determined after 5 years of diagnosis. GraphPad Prism v.8 was used for analysis. RESULTS: of 100 HL cases, the mean age of 33 relapsed group cases was significantly higher than remission group (p-value = 0.006), and gender was not significant however majority of cases in both groups were male. The frequency of PD-L1 expression found in 49% of all patients. A significant relationship was found between the expression of PD-L1 and disease progression, HL subtype, stage of tumor (p-value<0.05). High expression of PD-L1 found in majority of relapse group and low expression in remission group. CONCLUSION: PD-L1 expression assessment in HL patients is a valuable tool for prediction of the disease subtype, progression, stage, and treatment outcome. IHC method as an available, simple, rather cheap, and efficient tool could use for evaluation of PD-L1 expression and predicting the prognosis of HL disease, elsewhere.