Necroptosis is a novel form of programmed necrotic cell death involved in various autoimmune diseases. The potential role of necroptosis in primary immune thrombocytopenia (ITP) and the possible interlink with autophagy have not been fully investigated. The gene expression of mixed lineage kinase-like domain (MLKL), receptor-interacting protein kinase 3 (RIPK3) and Beclin-1 were quantified in peripheral blood of 45 ITP patients and 20 healthy controls. Their associations with clinical, laboratory parameters and response to steroid therapy in ITP patients were evaluated. RIPK3, MLKL, and Beclin-1 were significantly upregulated in ITP patients than in healthy controls (P < 0.001). Beclin-1 mRNA levels were positively correlated with both RIPK3 and MLKL mRNA levels in ITP patients (P < 0.0001). In addition, MLKL, RIPK3, and Beclin-1 mRNA levels were inversely correlated with platelet count (r = −0.330, −0.527 and −0.608, respectively). On the hand, positive correlations between MLKL (P = 0.01), RIPK3 (P = 0.005), Beclin-1 (P = 0.002) mRNA levels and severity of bleeding in ITP patients were reported. Steroid responders (n = 18, 40%) had significantly lower MLKL, RIPK3, Beclin-1 mRNA expression levels than their levels in the non-responders (n = 27, 60%). Necroptosis may play a critical role in the pathogenesis of ITP and provide both novel therapeutic targets and promising biomarkers for the prediction of bleeding severity and treatment response in ITP patients. Additionally, this study highlighted the crosstalk between autophagy and necroptosis in ITP patients. Graphical abstract

Background: Primary refractory acute myeloid leukemia (AML) represents a continuing obstacle in clinical management. The Runtrelated transcription factor 1 (RUNX1) gene is a relatively uncommon mutational target in AML cases. Aim: to investigate the role of RUNX1 mutation in newly diagnosed refractory AML patients receiving first-line induction chemotherapy. Methods: Our research involved 50 newly diagnosed Egyptian AML patients; As a control group, 20 newly diagnosed AML patients who received the conventional first induction chemotherapy with complete remission (CR) and 30 newly diagnosed AML patients who received the same conventional first induction chemotherapy protocols but did not respond to the treatment.Results: 13.3% of the examined cases group had RUNXI mutations found, compared to 5% of the control group, RUNXI mutation was found statistically significant with cases group (P=0.01) and RUNX1 mutation and OS were significantly correlated (P=0.05). Conclusion: RUNX1 mutation have a role in resistance totreatment and prognosis in AML. Therefore, measurement of RUNX1 level provides a new strategy to more aggressive treatments for primary refractory AML cases.

Background: About one-fifth of the adult population has end-stage renal disease (ESRD), which is associated with an elevated risk of illness and death. To remove excess sodium from the body, hemodialysis treatments using dialysate sodium (D-NA) with a concentration of 120 mEq/L have been utilized for decades. Higher D-Na (around140 mEq/L) has been employed for dialysis hemodynamic stability over time. Objective: To determine the impact of decreased dialysate Na (equal to or less than 135 mEq/L) on cardiac functions and different echocardiographic parameters in prevalent hemodialysis patients. Patients and Methods: At Rod Elfarag Hospital's Dialysis Unit, 45 patients on regular hemodialysis underwent a 6month prospective study. Results: This study found a significant difference between baseline and six-month lab results in terms of hemoglobin, WBCs, platelets and Ht/URR as well as serum albumin and Ca/Na/phosphorus and BNP (p < 0.001). We discovered a highly statistically significant variation in PR interval, QRS duration, and QT interval between the baseline and followup ECGs after six months (p < 0.001). There was high statistically significant difference between baseline echocardiography and after 6 months echocardiography as regard left atrium diameter, ejection fraction (EF%), diastolic blood pressure (DBP) and systolic BP (p < 0.001). Conclusion:Our results showed that the PR interval, QRS duration, and QT interval at baseline were all statistically significantly different from those after six months of treatment. DBP couldn't be lowered in this short time frame at all. This strategy's impact should be investigated in depth over an extended period of time.

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Background: Osteoblasts, the cells that make up bone, produce and secrete fibroblast growth factor 23 (FGF23). People with chronic renal disease had a higher-than-normal levels of FGF23 in their blood. Objective: The goal of this study was to examine FGF23's possible predictive function for renal impairment (RI) in patients with multiple myeloma (MM). Patients and Methods: Intact FGF23 serum levels were measured in four groups of patients: 1 st Group: 20 MM patients with RI either on dialysis or not; 2 nd Group: 20 MM patients without RI; 3 rd Group: 30 healthy individuals; 4 th Group: 10 RI patients without MM. ResultsIn this study, we found that both MM patients with and without RI had elevated levels of FGF23 (mean=158.50 and 94.75, respectively) than in healthy individuals (mean=25.17). The difference in results between the MM and healthy individual groups was highly significant (p<0.01). Patients with MM and RI have greater serum iFGF23 levels compared to those with MM and no RI (p<0.05). Significant direct link exists between iFGF23 and creatinine (p<0.01), (r=0.689). There is a strong inverse correlation between eGFR and iFGF23 in the serum (p<0.01). Conclusion: FGF23 levels increase significantly in MM with RI patients and are higher in MM patients with RI than those without RI. Renal impairment in MM may be diagnosed and predicted with the help of FGF23.

Background: Chronic myeloid leukaemia (CML) is a clonal disease of a hematopoietic stem cell. The incidence of this disease is about 15% of leukemias and may be present at any age. The presence of the Philadelphia (Ph) chromosome confirms the diagnosis of CML. The expression of the Patched homolog 1 gene (PTCH1) has been proposed as a prognostic marker of imatinib response in chronic phase chronic myeloid leukaemia (CP-CML) patients. Aim: This study aimed to measure the level of PTCH1 protein in newly diagnosed CP-CML and to find correlation between its level in those patients and response to first line of treatment, imatinib and other prognostic factors.Patients and Methods: Our study enrolled 50 patients of newly diagnosed CP-CML. We have measured the level of PTCH1 protein initially once the patient diagnosed and after 6 months of treatment with imatinib by ELISA test. Results: There was highly significant difference between initial PTCH1 level and its level after 6 months of imatinib treatment (P=0.000). The level of PTCH 1 was correlated significantly with the molecular response both at the beginning of treatment with imatinib and six months later. (P=0.002), (p=0.001) respectively. Conclusion:To the best of our knowledge that we are the first to report on PTCH1 protein as a new diagnostic and prognostic marker in CP-CML patients.