Vitamin D and left ventricular dysfunction in pediatric dialysis patients; a tissue doppler study.

BACKGROUND: Assessment of the left ventricular function in the dialysis children and explore its association with vitamin D level and markers reflecting calcium and phosphate metabolism. METHODS: In this case-control study, we enrolled forty children on regular hemodialysis and forty healthy controls from July 2019 to March 2020 at the pediatric dialysis unit. Echocardiographic evaluation using both conventional and Tissue Doppler Imaging (TDI) was done for all subjects. Vitamin D and its markers were analyzed to assess its association with ventricular dysfunction. RESULTS: Diastolic function in children on hemodialysis was significantly impaired as evidenced by lower Mitral E/A velocity ratio (E/A), lower early diastolic velocity (E'), and higher E/E' ratio (Ratio of early diastolic mitral inflow velocity (measured by pulsed wave traditional Doppler) to early diastolic mitral annular velocity (measured by Tissue Doppler). in comparison with the controls. Most end stage renal disease (ESRD) participants had vitamin D deficiency. There was an important correlation between left ventricular (LV) dysfunction and both Vitamin D deficiency and hyperparathyroidism. Although our patients had normal systolic function by conventional and Tissue Doppler echocardiographic study, mean values of TDI- MPI (Mean Performance Index) in the haemodialysis group were significantly higher than in the control group, which indicates impaired global cardiac systolic and diastolic function. CONCLUSIONS: Tissue Doppler Imaging (TDI) provides a good reflection of the LV diastolic function. As vitamin D deficiency has been substantially associated with worsening of LV dysfunction, we suggest that TDI and Vitamin D might be included in the routine follow-up of pediatric dialysis patients.

Association of IL-10 gene polymorphisms and susceptibility to Juvenile Idiopathic Arthritis in Egyptian children and adolescents: a case-control study.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children worldwide. Among anti-inflammatory cytokines, interleukin-10 (IL-10) is a key immunosuppressive cytokine involved in the pathogenesis of JIA. To date, only a few studies concerned the association of interleukin-10 gene polymorphisms with JIA. In this study, we aimed to investigate 3 cytokine single-nucleotide polymorphisms situated at positions -1082(G/A), -819(C/T), and -592(C/A) in the promoter region of the IL-10 gene to determine whether this polymorphism could be a marker of susceptibility to JIA in Egyptian children and adolescents. We also measured the serum level of IL-10 to assess its relation to such polymorphism. METHODS: This was a case-control study included 100 patients diagnosed with JIA, and matched with age, gender, ethnicity 100 healthy control subjects. Interleukin-10 -1082(G/A), -819(C/T), and -592(C/A) polymorphisms were genotyped by amplification refractory mutation system- polymerase chain reaction (ARMS)-PCR methodology, while the serum IL10 levels were measured by ELISA method. RESULTS: Compared to the controls subjects, the frequency of IL-10- AA genotype and A allele at the -1082 position were overrepresented in patients with JIA (OR = 2.7; 95% CI: 1.1-6.4 for the AA genotype; P <0.05 and OR: 1.5; 95% CI: 1.03-2.3 for the A allele; P <0.05 respectively). On the other hand, no significant differences were found between the 2 groups in the genotype or allele frequencies for the -819 and -592 positions. Of note, we found a significant positive association between the IL-10 (-1082) AA genotype and susceptibility to polyarticular JIA (OR: 4.3; 95% CI: 1.5-12.7; P <0.01). We observed that patients with the IL-10 (-1082) AA genotype had significantly lower serum IL-10 levels (2.3 ± 0.9 pg/ml) compared to those with AG genotype (7.6 ± 1.5 pg/ml) and GG genotype (9.5 ± 1.2 pg/ml); P < 0.01, respectively. CONCLUSION: We demonstrate for the first time, to the best of our knowledge, that the presence of an A allele or AA gene variant at the -1082 position of the promoter region of the interleukin-10 gene may constitute risk factors for developing JIA in Egyptian children and adolescents. Moreover, we observed a significant positive association between the IL10 -1082 AA gene variant and susceptibility to polyarticular JIA.

Vitamin D receptor gene BsmI polymorphisms in Egyptian children and adolescents with systemic lupus erythematosus: A case-control study.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease. The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. To date, only a few studies concerned the association of the VDR gene polymorphisms with childhood-onset SLE.In this study, we aimed to investigate the BsmI polymorphisms in the VDR gene, for the first time in Egyptian children and adolescents with SLE, to determine whether this polymorphism could be a marker of susceptibility to or severity of SLE and we also measured the serum level of 25-hydroxyvitamin D (25[OH] D) to assess its relation to such polymorphism.This was a case-control study including 100 patients with SLE and matched with age, sex, and ethnicity and 100 healthy controls. All subjects were genotyped for the VDR gene BsmI polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), whereas the serum 25(OH) D levels were measured by enzyme-linked immunosorbent assay method.Compared to the contros subjects, the VDR BsmI BB genotype and B allele were overrepresented among SLE patients (odda ratio [OR]: 5.5; 95% confidence interval [CI]: 1.9-15.9; P = 0.002 and OR: 1.84; 95% CI: 1.21-2.80; P = 0.003; respectively). We found a significant association between VDR BsmI BB genotype with lupus nephritis (OR: 6.8; 95% CI: 1.18-50.5; P = 0.001). However, we did not observe any significant association of studied polymorphisms with other clinical manifestations, laboratory profiles of SLE, or disease activity score. Our data revealed no association between VDR BsmI genotypes or alleles and serum 25-hydroxyvitamin D levels among studied patients with SLE (all P > 0.05).We demonstrate for the first time, to the best of our knowledge, that the VDR BsmI gene polymorphisms may contribute to susceptibility to SLE in Egyptian children and adolescents. Moreover, we found that the BB genotype constituted a risk factor for the development of nephropathy among studied patients with SLE. However, we did not find any significant association of the VDR BsmI gene variants with other clinical manifestations, laboratory profiles of SLE, disease activity index score, or serum 25-hydroxyvitamin D levels.

Incidence of Philadelphia-chromosome in acute myelogenous leukemia and biphenotypic acute leukemia patients: And its role in their outcome.

BACKGROUND: Philadelphia-chromosome positive acute myeloid leukemia (Ph+ AML) is a rare entity and patient prognosis is poor, with short median survival. Biphenotypic acute leukemia (BAL) is a rare disorder that is difficult to diagnose and it displays features of both myeloid and lymphoid lineage. The aim of this study was to highlight the incidence of Philadelphia chromosome and its presence in cases of acute myeloid and biphenotypic leukemia and determine its role in the outcome of these leukemias. SUBJECTS AND METHODS: This study examined 464 subjects with newly diagnosed acute myeloid leukemia: 312 were males and 152 were females. All individuals were subjected to immunophenotyping and conventional karyotyping. FISH was used in failed cases of conventional cytogenetics analysis to quantify disease and to prove positive BCR-ABL fusion gene. RESULTS: the incidence of Ph+ chromosome was found to be higher in BAL (38.4%) than in AML (1.99%). There was statistically significant difference according to the age and the median survival time between the two groups. CONCLUSION: Detection of specific chimeric transcripts in AML and BAL at the time of diagnosis was crucial since it plays an important role for accurate risk stratification and treatment management.

Assessment of cell-free DNA with microvascular complication of type II diabetes mellitus, using PCR and ELISA.

In order to assess the potential biochemical markers in the development, diagnosis, and prognosis of diabetic patient with microvascular complication represented with retinopathy, we analyzed the levels of cell-free DNA by two different techniques. The levels of cell-free GAPDH assayed by quantitative PCR were significantly higher in the plasma samples of diabetic patients with and without diabetic retinopathy than in those of the control group; thus, it is a better biomarker than nucleosomes assayed by ELISA in patients with type 2 diabetes for the early detection of development of microvascular complications as retinopathy.

The Prognostic Impact of K-RAS Mutations in Adult Acute Myeloid Leukemia Patients Treated with High Dose Cytarabine.

UNLABELLED: Activating point mutation of the RAS gene has been generally accepted as an oncogenic event in a variety of malignancies. It represents one of the most common genetic alterations in acute myeloid leukemia (AML). However there is still controversy about its clinical relevance on the treatment outcome of this leukemia. OBJECTIVE: This study aimed to clarify the biologic and prognostic impact of K-RAS mutations in relation to the dose of cytarabine (ara-C) used in post induction consolidation chemotherapy in adult AML patients. PATIENTS AND METHODS: The study comprised 71de novo AML patients with a male: Female ratio of 1.4: 1; their ages ranged from 21-59 years with a median of 37 years. They were subjected to full clinical evaluation, routine laboratory investigations, cytogenetic studies by G banding and K-RAS mutation detection using realtime PCR. The patients were randomized into 2 groups (gps) according to the ara-C dose used in consolidation treatment, HDAC gp receiving 400 mg ara-C and LDAC gp receiving 100mg ara-C. They were followed over a period of 5 years. RESULTS: Mutations in the K-RAS gene (mutRAS) were detected in 23 patients (32%) with the remaining 48 patients (68%) having wild type RAS (wtRAS). Blast cell percentage was significantly lower in mutRAS compared to wtRAS patients (p≤0.001). The M4 subtype of AML and cases with Inv 16 showed significantly higher frequencies in mutRAS compared to wtRAS patients, (p=0.015, 0.003, respectively). The patients were followed up for a median of 43 months (range 11-57 months). There was no significant difference in overall survival (OS) between mutRAS and wtRAS patients (p=0.326). Within the mutRAS patients treated with HDAC, cumulative OS was significantly higher than those treated with LDAC (p=0.001). This was not the case in the wtRAS group (p=0.285). There was no significant difference in disease free survival (DFS) between mutRAS and wtRAS groups (p=0.923). MutRAS patients treated with HDAC had a statistically higher cumulative DFS than mutRAS patients treated with LDAC (p=0.001). Patients with wtRAS also benefited from HDAC but to a lesser extent. Among patients with wtRAS, those treated with HDAC showed higher cumulative and median DFS than patients treated with LDAC (p=0.031). CONCLUSION: Adult AML patients carrying mutations in the K-RAS gene benefit from higher cytarabine doses more than wtRAS patients, so pretreatment mutation detection could be an important predictor for treatment strategy and survival of adult AML patients. These findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies. KEY WORDS: K-RAS mutations - Acute myeloid leukemia - Cytarabine.