Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms in a cohort of Egyptian patients with immune thrombocytopenia (ITP).

BACKGROUND: Immune thrombocytopenia (ITP) is characterized by immune response dysregulations. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a central role in immune checkpoint pathways and preventing autoimmune diseases by regulating immune tolerance. We aimed to explore the potential association between CTLA-4 gene polymorphisms and ITP as well as study their impact on the response to therapy. METHODS: We investigated two CTLA-4 single-nucleotide polymorphisms (SNPs; rs: 231775 and rs: 3087243) using real-time PCR as well as the plasma levels of CTLA-4 by ELISA in 88 patients with ITP and 44 healthy participants (HC). RESULTS: CTLA-4 (rs: 3087243) A > G polymorphism analysis showed most HC had the homozygous AA genotype, which was statistically significant compared to patients with ITP. Plasma levels of CTLA4 were statistically lower in patients with acute ITP. There was no correlation between CTLA-4 (rs: 231775 and rs: 3087243) A/G SNPs were not correlated to the response to all lines of therapy assessed (corticosteroids, thrombopoietin receptor agonists, splenectomy, and rituximab). CONCLUSION: CTLA-4 CT 60 A/G may affect the susceptibility of ITP, but both CTLA-4 + 49 A/G and CT60 A/G did not impact the response of patients with ITP to different lines of therapy.

The effect of a distance education training program on nurse Interns' readiness for distance education and their perceptions of lifelong learning.

AIM: The purpose of this study is to assess the effect of a distance education training program on nurse interns' readiness for distance education and their perceptions of lifelong learning. DESIGN: A quasi-experimental research approach with one-group, pre/post-test was used. METHODS: The study used a quasi-experimental research approach and was carried out at Damanhour University's Faculty of Nursing. A study was carried out on 345 interns' students. All nursing interns enrolled in the 2020-2021 internship training year. The researchers employed a program that contained a distance education readiness assessment as well as a questionnaire about the perceived advantages of lifelong learning. RESULTS: The majority (99.7%) of nurse interns were highly ready for distance education, whereas only 0.3 percent were moderately ready following the training program implementation immediately. In comparison to pre-training, the majority (91.9%) of them were somewhat ready for distance education, while just 7.2 percent were highly prepared. Furthermore, the majority (97.1%) of them had high total skills of distance education after implementation of the training program by 3 months, and 95.4 percent had high total skills of learning immediately after the training program, whereas 26.1% of nurse interns had high total skills before the training program, at p value 0.01.

Therapeutic Outcomes of High Dose-Dexamethasone versus Prednisolone + Azathioprine, Rituximab, Eltrombopag, and Romiplostim Strategies in Persistent, Chronic, Refractory, and Relapsed Immune Thrombocytopenia Patients.

BACKGROUND: Primary immune thrombocytopenia (ITP) is an inflammatory autoimmune disease that can be managed with several treatment options. However, there is a lack of comparative data on the efficacy of these options in different phases of the disease. AIM OF THE STUDY: This study aimed to evaluate the efficacy of high-dose Dexamethasone (HD-DXM), Prednisolone + Azathioprine, Rituximab, Eltrombopag, and Romiplostim schedules in persistent, chronic refractory or relapsed Egyptian ITP patients with a platelet count ≤30 × 109/L. The primary outcome measure was a sustained increase in platelet counts over 50 × 109/L for an additional 12 months without additional ITP regimens. The study also aimed to identify a suitable treatment regimen with a long remission duration for each phase of ITP. RESULTS: Prednisolone + Azathioprine was significantly more effective in achieving an overall response in persistent patients than Romiplostim, high-dose Dexamethasone, and Rituximab. (90.9% vs. 66.6, [Odds ratio, OR: 5; confidence interval, CI 95% (0.866-28.86)], 45%, [OR: 0.082, CI 95% (0.015-0.448)] and, 25%, [OR: 30, CI 95% (4.24-211.8)], respectively, p-value < 0.01). Eltrombopag was significantly more effective in achieving a durable response in refractory ITP than HD-DXM, Rituximab, and Prednisolone; (80% compared to 32.2% [OR: 0.119, CI 95% (0.035-0.410)], 22.2% [OR:0.071, CI 95% (0.011-0.455)], and 18.1% [OR: 0.056, CI 95% (0.009-0.342)], respectively, p-value < 0.01). CONCLUSIONS: Finally, Eltrombopag following HD-DXM showed the highest percentage of patients with complete treatment-free survival times of at least 330 days. These findings could help clinicians choose the most appropriate treatment for their patients with ITP based on the phase of the disease. This trial is registered in clinicaltrials.gov with registration number NCT05861297.

Clinical Care Team's Guide for Awareness on Risk Assessment of Eltrombopag Complicating Acute Kidney Injury in Relapsed Immune Thrombocytopenic Patients: A Case Report.

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by antigen-specific T cells and antiplatelet autoantibodies that inhibit platelet production in the bone marrow or destroy platelets in the spleen. ITP is a form of autoimmunity and is closely associated with inflammation. Corticosteroids are the first-line therapy for ITP, with a total response rate of 53-80%. However, corticosteroid therapy is associated with significant side effects and is often ineffective in patients with corticosteroid-resistant or -intolerant disease. Eltrombopag has been validated as a second-line option in ITP therapy. Despite several studies demonstrating the efficacy and safety of Eltrombopag in immune thrombocytopenia patients, the prevalence of Eltrombopag-induced acute kidney injury has been observed. This case report describes a patient who experienced acute kidney injury during Eltrombopag therapy. A sudden increase in serum creatinine to 6.7 mg/dL and metabolic acidosis occurred after eight weeks of Eltrombopag. The patient's renal failure had worsened, proteinuria was detected, and emergency hemodialysis was initiated. With vigilant kidney function screening and prompt treatment, the patient's renal function improved remarkably following cessation of Eltrombopag and initiation of hemodialysis. This case highlights the importance of comprehensive medication history-taking and vigilant kidney function screening in patients receiving Eltrombopag.

The Outcomes and Adverse Drug Patterns of Immunomodulators and Thrombopoietin Receptor Agonists in Primary Immune Thrombocytopenia Egyptian Patients with Hemorrhage Comorbidity.

Immune thrombocytopenia (ITP) treatment has evolved recently. However, none of the treatments have only benefits without drawbacks. This study aimed to compare the clinical outcomes and adverse drug patterns of Eltrombopag, Romiplostim, Prednisolone + Azathioprine, High Dose-dexamethasone (HD-DXM) (control group), and Rituximab in primary ITP Egyptian patients. All patients were initiated with corticosteroids, HD-DXM, as a first-line treatment for the first month immediately following diagnosis. Four hundred sixty-seven ITP patients were randomly assigned to five groups. The outcome measures were judged at baseline, at the end of treatment (6 months), and after an additional 6-month free treatment period. The follow-up period for which relapse is noted was 6 months after the end of treatment. Eltrombopag and Romiplostim resulted in a significantly higher incidence of sustained response than Rituximab, HD-DXM, and Prednisolone + Azathioprine (55.2% and 50.6% vs. 29.2%, 29.1%, and 18%, respectively; p-value < 0.001). More patients on immunomodulators (Prednisolone+ Azathioprine, HD-DXM, and Rituximab) relapsed than those on Romiplostim and Eltrombopag (81.9%, 70.8%, and 70.7% vs. 49.3%, and 44.7%, respectively; p-value < 0.01). We also describe 23 reports of pulmonary hypertension with Prednisolone+ Azathioprine and 13 reports with HD-DXM. The thrombotic events occurred in 16.6% and 13% of patients who received Eltrombopag and Romiplostim treatment, respectively. Most patients had at least one or two risk factors (92.8% of cases). Corticosteroids are effective first-line therapy in primary ITP patients. However, relapse is frequent. Eltrombopag and Romiplostim are safer and more effective than Prednisolone, HD-DXM, and Rituximab. They might be reasonable beneficial options after a one-month HD-DXM regimen.

IL-4Rα (rs1801275) A>G polymorphism in Egyptian immune thrombocytopenia (ITP) patients: a single center experience.

INTRODUCTION: Chronic immune thrombocytopenia (cITP) is characterized by dysregulation of the immune response. Until recently, the role of Th2-related cytokine gene polymorphisms was unclear. Interleukin 4 (IL-4) exerts its functions by binding to three types of IL-4 receptor (IL-4R) complexes. We aimed to explore the potential association between the gene polymorphism of IL-4Rα and cITP. METHODS: We investigated the clinical impact of the IL-4Rα (rs1801275) A>G single nucleotide polymorphism (SNP) using the polymerase chain reaction (PCR) followed by the restriction fragment length polymorphism (RFLP) method in 82 cITP patients and 60 healthy controls (HCs). RESULTS: The IL-4Rα (rs1801275) A>G polymorphism analysis showed the mutant GG genotype was significantly higher in control females (p = 0.033). The wild AA genotype had a higher bleeding score (p = 0.02) in the adulthood onset group. Furthermore, the wild AA genotype in the cITP childhood onset group was significantly associated with the disease severity, as well as the response to treatment (p = 0.040). CONCLUSION: The mutant G allele is protective against the susceptibility to cITP in the Egyptian females. The IL-4Rα (rs1801275) A>G polymorphism may affect the clinical severity of cITP and treatment response in the Egyptian population.

Acquired hemophilia A (AHA): underreported, underdiagnosed, undertreated medical condition.

BACKGROUND: Acquired hemophilia A (AHA) is a rare acquired bleeding disorder occurred due to the formation of inhibitory antibodies neutralizing endogenous factor VIII. MAIN BODY: About half the cases are idiopathic. Symptoms include severe and unexpected bleeding that could be life-threatening. High index of suspicion should be raised when unexplained subcutaneous or post-surgical bleeding with isolated prolonged APTT. CONCLUSIONS: Acquired hemophilia A is a rare underdiagnosed underreported acquired hemostatic disorder that presents with sudden usually life-threatening bleeding; it is crucial to raise awareness and suspicion index of clinicians for early diagnosis and treatment to avoid morbidity and mortality.

The Association of Pre-diagnostic Inflammatory Markers and Adipokines and the Risk of Non-Hodgkin Lymphoma Development in Egypt.

Non-Hodgkin lymphoma (NHL) is an etiologically, clinically, and histologically heterogeneous group of lymphoproliferative disorders. Immune dysfunction is a well-known risk factor and dysregulation of cytokines may mediate disease progression. Obesity is one of the important relations connecting immune system abnormalities and lymphomagenesis. We conducted a study to find out the association between obesity as measured by body mass index (BMI), and risk of non-Hodgkin lymphoma (NHL) development by assessment the of inflammatory cytokines levels, (IL-6, IL-10, IFN-gamma and CRP) and adipokines levels (leptin and adiponectin). Also, to predict the effect of higher BMI on the incidence of NHL. The study included 180 NHL patients and 172 healthy controls. The inflammatory markers (IL-6, IL-10, IFN-γ & CRP) together with adiponectin were assessed by ELISA technique. IL-6, IL-10, CRP, IFN-γ and Adiponectin were statistically higher in cases than control. A positive significant difference of Leptin (p-value 0.001) was found with higher levels in patients with BMI (≥ 25 kg/m2) than in patients with < 25 kg/m2. IL-6, IL-10, CRP, IFN-γ and Adiponectin could be implicated in lymphomagenesis in Egyptian NHL. The study results support the hypothesis that obesity has a major role in the development of NHL. An association between Leptin and NHL risk with higher levels in patients with BMI (≥ 25 kg/m2) was proved.

Assessment of Atherosclerosis in Peripheral and Central Circulation in Adult ß Thalassemia Intermedia Patients by Color Doppler Ultrasound: Egyptian Experience.

BACKGROUND: Atherosclerosis has been extensively studied in thalassemia major (TM) and sickle cell disease but not yet in ß thalassemia intermedia (TI). Previous studies concerned with TM were performed in children. TI patients usually live longer and, thus, are more prone to complications of atherosclerosis. AIM: In our study, we applied color Doppler for the determination of arterial conduit and flow velocities in ß TI patients. METHODS: For central circulation, we measured right and left middle cerebral arteries (MCAs) and basilar artery (BA) mean flow velocity (MFV), pulsatility index (PI), and peak systolic velocity (PSV) as well as carotid intimal media thickness, and to assess peripheral circulation, we studied ankle/brachial index and posterior and anterior tibial arteries' (ATA, PTA) pressure and PSV. This was applied for 30 adult TI patients and 20 age-, sex-, and ethnic group-matched controls. RESULTS: Transcranial Doppler findings among cases and controls showed that the MFV, PSV of MCAs, and PSV, PI, and MFV of the BA were statistically higher in cases than controls. A comparison between splenectomized and nonsplenectomized patients showed that total leukocyte count, platelet count, lactate dehydrogenase, ferritin, PSV and MFV of the left MCA were all statistically higher in splenectomized cases. Differences between males and females with TI with respect to laboratory and Doppler findings were all statistically insignificant except for intima media thickness, PTA pressure, ATA pressure, and PSV. CONCLUSION: More than one parameter should be applied to assess atherosclerosis in TI. There is evidence of an increased risk of central ischemia rather than peripheral ischemia in these patients.

Role of physical function in predicting short-term treatment outcome in Egyptian acute myeloid leukemia patients: a single center experience

Abstract Background Acute myeloid leukemia (AML) is a potentially fatal hematological disease. Along with disease-related factors, patient-related factors, in particular age, are a strong predictor of outcome that influence treatment decisions. Many acute myeloid leukemia risk stratification models have been developed to predict the outcome of intensive chemotherapy. However, these models did not include physical function assessments. Methods This study investigated the impact of several factors, namely the performance status, physical function and age on the short-term outcomes of intensive chemotherapy in a cohort of 50 Egyptian patients with de novo acute myeloid leukemia. Results Complete remission after intensive chemotherapy in these myeloid leukemia patients at Day 28 was 56% and the mortality rate was 12% and 34% at Day 28 and Day 60, respectively. The pretreatment Eastern Cooperative Oncology Group score was significantly correlated with outcomes on Day 28 and Day 60 (p-value = 0.041 and p-value = 0.032, respectively). There were significant correlations between the two-minute walk test and outcomes of therapy on Day 28 and 60 (p-value = 0.032 and p-value = 0.047, respectively) and between grip strength test and outcomes of therapy on Day 28 and 60 (p-value = 0.046 and p-value = 0.047 respectively). Furthermore, there was a significant correlation between chair stand test and outcome of therapy on Day 28 (p-value = 0.023). Conclusion Performance status and physical function assessments were strong predictors of outcome of intensive chemotherapy in acute myeloid leukemia and we recommend the incorporation of these variables in risk stratification models for the personalization of therapy before treating acute myeloid leukemia patients with intensive chemotherapy.

Role of physical function in predicting short-term treatment outcome in Egyptian acute myeloid leukemia patients: a single center experience.

BACKGROUND: Acute myeloid leukemia (AML) is a potentially fatal hematological disease. Along with disease-related factors, patient-related factors, in particular age, are a strong predictor of outcome that influence treatment decisions. Many acute myeloid leukemia risk stratification models have been developed to predict the outcome of intensive chemotherapy. However, these models did not include physical function assessments. METHODS: This study investigated the impact of several factors, namely the performance status, physical function and age on the short-term outcomes of intensive chemotherapy in a cohort of 50 Egyptian patients with de novo acute myeloid leukemia. RESULTS: Complete remission after intensive chemotherapy in these myeloid leukemia patients at Day 28 was 56% and the mortality rate was 12% and 34% at Day 28 and Day 60, respectively. The pretreatment Eastern Cooperative Oncology Group score was significantly correlated with outcomes on Day 28 and Day 60 (p-value = 0.041 and p-value = 0.032, respectively). There were significant correlations between the two-minute walk test and outcomes of therapy on Day 28 and 60 (p-value = 0.032 and p-value = 0.047, respectively) and between grip strength test and outcomes of therapy on Day 28 and 60 (p-value = 0.046 and p-value = 0.047 respectively). Furthermore, there was a significant correlation between chair stand test and outcome of therapy on Day 28 (p-value = 0.023). CONCLUSION: Performance status and physical function assessments were strong predictors of outcome of intensive chemotherapy in acute myeloid leukemia and we recommend the incorporation of these variables in risk stratification models for the personalization of therapy before treating acute myeloid leukemia patients with intensive chemotherapy.

Multifocal avascular necrosis in a patient with refractory immune thrombocytopenia and antiphospholipid antibodies; case report and review of literature.

Avascular necrosis (AVN) is a devastating condition that is rarely reported in patients with immune thrombocytopenia (ITP). Treatment with steroids remains a major risk factor for developing AVN. However, the incidence of AVN in patients with ITP requiring corticosteroid therapy is much less than that observed with other clinical conditions requiring corticosteroids. ITP is a bleeding disorder but can be also be a pro-thrombotic state via different mechanisms and thus could result in AVN. Among the possible causes of this pro-thrombotic state is the presence of antiphospholipid antibodies (aPLs). In this case, we report a patient with refractory ITP who developed multifocal AVN around the time she acquired new aPLs. We also discuss different mechanisms by which risk of thrombosis is increased in ITP and the relationship between ITP, aPLs and antiphospholipid syndrome.

Role of Granulocyte-Macrophage Colony-Stimulating Factor in Acute Myeloid Leukemia/Myelodysplastic Syndromes.

PURPOSE: Granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine stimulates growth, differentiation, and function of myeloid progenitors. We aimed to study the role of GM-CSF gene expression, its protein, and antibodies in patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) and their correlation to disease behavior and treatment outcome. The study included 50 Egyptian patients with AML/MDS in addition to 20 healthy volunteers as control subjects. PATIENTS AND METHODS: Assessment of GM-CSF gene expression was performed by quantitative real-time polymerase chain reaction. GM-CSF proteins and antibodies were assessed by enzyme-linked immunosorbent assay. RESULTS: There was significant decrease in GM-CSF gene expression ( P = .008), increase in serum level of GM-CSF protein ( P = .0001), and increase in anti-GM-CSF antibodies ( P = .001) in patients with AML/MDS compared with healthy control subjects. In addition, there was a significant negative correlation between serum levels of GM-CSF protein and initial peripheral blood blasts, percentage as well as response to therapy. CONCLUSION: Any alteration in GM-CSF gene expression could have implications in leukemogenesis. In addition, GM-CSF protein serum levels could be used to predict outcome of therapy. GM-CSF antibodies may also play a role in the pathogenesis of AML/MDS. The use of these GM-CSF parameters for disease monitoring and as markers of disease activity needs further research.

The Effect of Monophosphoryl Lipid A on Maturation of DCs from Patients with Acute Myeloid Leukaemia.

BACKGROUND: Generation of monocyte-derived dendritic cells (MDDC) is induced in the presence of GM-CSF and IL-4, and a maturation stimulus is added to the monocyte culture to obtain mature Dendritic Cells (DCs) suitable for therapy. TNF-α is the most common cytokine used for activating DCs and generating mature MDDC either alone or in combination with other cytokines. OBJECTIVE: To compare effects of traditional cytokine cocktail (TNF-α + IL-1ß) versus TLR4-agonist monophosphoryl lipid A on the viability, phenotype, cytokine profile and functionality of MDDC. METHODS: The study included 32 individuals; twenty Acute Myeloid Leukaemia (AML) cases in complete remission and 12 healthy volunteers. They were divided into 3 groups: Group 1: control group: 12 subjects to measure the baseline levels of all markers in the monocytic preparation. Group 2: cytokine cocktail (TNF-α) group, which included 10 AML subjects. Group 3: MPLA group which included 10 AML subjects. RESULTS: TNF-α group showed higher expression of CD83 than MPLA group indicating higher capacity to induce DC maturation but both were similar in CD86, CCR7 and IL-10 expression. Preparation of dendritic cells from AML cases in remission and loading them with tumor peptides was successful. CONCLUSION: MPLA effect in DC maturation is comparable with traditional DC maturation cocktail.

Correlation between JAK2 allele burden and pulmonary arterial hypertension and hematological parameters in Philadelphia negative JAK2 positive myeloproliferative neoplasms. An Egyptian experience.

Myeloproliferative neoplasms are characterized by a common stem cell-derived clonal proliferation, but are phenotypically diverse. JAK2 is mutated (V617F) in more than 90 % of patients with polycythemia vera (PV) and approximately 60 % of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Pulmonary arterial hypertension (PAH) is a major complication of several hematological disorders. Chronic myeloproliferative disorders associated with PAH have been included in group five for which the etiology is unclear and/or multifactorial. The aim of this study is to screen Egyptian Philadelphia negative JAK2 positive myeloproliferative neoplasm patients for the presence of PAH and its correlation with JAK2 allele burden. We also made a review for correlation of JAK2 allele with hematological parameters comparing our results to others. We enrolled 60 patients with Philadelphia negative myeloproliferative neoplasms. All patients enrolled in the study were subjected to laboratory and imaging workup in the form of CBC, liver, kidney profile, bone marrow examination, abdominal ultrasonography, and transthoracic echocardiography. Our results revealed that 7 patients out of 60 (11.67 %) had pulmonary arterial hypertension, 3 patients with PMF, 2 patients with PRV, and 2 patients with ET, and its correlation with JAK2 allele burden was not statistically significant. Correlation analysis between JAK2 V617F allele burden and other parameters revealed: statistical significant correlation with age, HB, HCT, PLT, UA, LDH, and splenic diameter but insignificant correlation with WBCs and PAH. Pulmonary arterial hypertension prevalence in our study was 11.67 % and no significant correlation with JAK 2 allele burden. Our study is the largest one up to our knowledge that studies the association between its prevalence and JAK2 burden.