Thiamine status during treatment of diabetic ketoacidosis in children - tertiary care centre experience.

OBJECTIVES: There is a lack of information regarding thiamine status in children with diabetic ketoacidosis (DKA). This study was designed to assess the thiamine status upon admission and 24 h after treatment initiation of DKA, whether newly diagnosed children or with established T1DM diagnosis, who presented with DKA. METHODS: We enrolled 90 children (mean age, 9.8 ± 2.6 years; 58 females and 32 males) with type 1 diabetes mellitus (T1DM), whether newly diagnosed or with an established T1DM diagnosis (from 1 to 5.2 years ago), who presented with DKA. We observed the initial Glasgow Coma Scale (GCS) and recovery time. The whole blood thiamine diphosphate levels were measured upon admission (baseline point) and 24 h after initiation of the DKA treatment (second-time point). RESULTS: The mean blood thiamine levels at the second-time point (90.11 ± 15.76 nmol/L) significantly decreased compared with their levels at baseline (108.8 ± 17.6 nmol/L) (p<0.001). We compared thiamine levels with the initial GCS, patient's age, and recovery time. Thiamine levels at the second-time point were positively correlated with baseline thiamine levels (r=0.86, p=0.0001) and the initial GCS (r=0.68, p=0.001) but were negatively correlated with patient's age (r=-0.61, p=0.001) and recovery time (r=-0.724, p=0.001). Based on multiple regression analysis, thiamine levels at the second-time point were directly related to the initial GCS and inversely related to the patient's age. CONCLUSIONS: The current study indicates that blood thiamine diphosphate levels significantly decreased after 24 h of DKA treatment initiation compared to pre-treatment levels. After 24 h of treatment initiation, blood thiamine levels are directly related to the initial GCS and inversely related to the patient's age.

Prognostic Impact of Concurrent DNMT3A, FLT3 and NPM1 Gene Mutations in Acute Myeloid Leukemia Patients.

BACKGROUND: Acute myeloid leukemia (AML) is one of the rapidly progressing malignancies which is characterized by unregulated proliferation of hematopoietic precursors. Technological improvements enhanced the availability of genetic AML biomarkers. The clinical relevance of these molecular markers for AML diagnosis, planning of therapy and risk stratification are increasing evidently. METHODS: In current study, one hundred newly diagnosed AML patients before receiving induction chemotherapy were included, they were subjected to clinical examination, cytochemical and morphological analysis of blood cells, flow cytometric, cytogenetic and molecular genetic analysis for detection of NPM1, FLT3-ITD and DNMT3A mutations. Direct sequencing analysis for detection of NPM1 and DNMT3A genes mutations were done. FLT3 /ITD gene mutation was detected by gel electrophoresis after PCR amplification. RESULTS: According to genetic markers, our AML patients are classified in to further 8groups. AML patients with three DNMT3A/FLT3/NPM1 gene mutations (AML DNMT3A /FLT3/NPM1) this group of patients presented with a heavy disease burden, had an elevated WBC in comparison to other groups (70 vs. 41 × 103/µL; P = .019), and BM blast counts (71% vs. 55.6%, P < .02). When comparing eight groups for death event there were significant difference among groups; P = .005, group 1 (AML DNMT3A /FLT3/NPM1) showed rapid decline of the cumulative overall survival. There was a significant difference among 8 groups as regards response to treatment after 14 days (P = .02), group 7 AML with (DNMT3A +NMP1) gene mutations showed better response to treatment (100%), groups 1 and 3 AML with (NPM1+DNMT3A +NMP1) gene mutations and AML with isolated FLT3-ITD showed no response to treatment after 14 days. And as regards response to treatment after 28 days, the eight groups showed no significant difference (P = .14). CONCLUSION: Our study supports adverse prognostic effect of presence of DNMT3A gene mutation either alone or in the presence of FLT3 and/or NPM1 gene mutations.

Role of MicroRNA-155 as a Potential Biomarker for Allergic Rhinitis in Children.

Background: Allergic rhinitis (AR) is an inflammatory state categorized by a disturbance of immunoregulatory mechanisms. MicroRNA-155 (miRNA-155) has an essential role in regulating gene expression and can mediate the allergic TH2 process. Objective: In this study, we aimed to evaluate the role of miR-155 as a biomarker in AR and correlate its level with the total nasal symptom score (TNSS) and the levels of serum interleukin-4 (IL-4). Methods: This study included 90 children: 45 with pollen-induced AR and 45 healthy controls. Serum miR-155 expression levels were measured using quantitative real-time PCR. Human IL-4 ELIZA kits were used for the semiquantitative detection of the serum levels of IL-4. Receiver operating characteristic (ROC) curves were used to determine the best cutoff values for the studied parameters for the diagnosis of AR. Results: The demographic characteristics of the two groups were matched with respect to age and sex. The AR case group included 23 (51.1%) males and 22 (48.9%) females, while the control group included 24 (53.3%) males and 21 (46.7%) females. The miR-155 level was increased in the serum of children with pollen-induced AR compared with controls (mean difference = 2.8, p < 0.001). A significant positive correlation between the serum expression level of miR-155 and TNSS in children with AR was detected (r = 0.494, p < 0.001). However, no significant correlation was identified between the expression of miR-155 and that of IL-4. At a cutoff value of 1.09, the sensitivity of miR-155 as a biomarker for AR was 100%, and the specificity was 71.1%. Conclusion: MiR-155 expression levels were elevated in the serum of AR children. Therefore, miR-155 could be used as a biomarker in AR diagnosis.

C677T MTHFR Gene Polymorphism is Contributing Factor in Development of Renal Impairment in Young Hypertensive Patients.

Homocysteine concentration affected by the activities of the enzymes methylene tetra-hyrdofolate reductase (MTHFR). Polymorphisms in MTHFR gene associated with an impairment of MTHFR activity. Hyperhomocysteinemia is a result of single nucleotide polymorphisms (SNPs) in MTHFR 677 C>T that can cause homocysteine levels in the blood to increase. The purpose of this study is to investigate the relationships between MTHFR C677T (rs1801133) gene polymorphism, changes in homocysteine concentrations and progress of renal impairment in young adult hypertensive patients. Two hundred young hypertensive patients (age 21-24 years) were involved in this study; they were classified into patients with and without renal impairment in addition to 200 age and sex matched healthy controls. All participants were submitted to laboratory investigations as assay of MTHFR gene polymorphism C677T (rs1801133) by PCR/RFLP, determination of lipid profile, homocysteine and folic acid concentrations in addition to urinary albumin creatinine ratio (UACR). The levels of both homocysteine and UACR in the TT genotype patients were higher than those in the CC genotype group. Individuals who carry the T allele were more risky to hypertension and progress to early renal impairment in young age compared with those carrying the C allele [OR 2.02 (1.33-3.08), P < 0.001]. Genetic variants of C677T MTHFR gene and hyperhomocysteinemia may be responsible for rapid progress of renal impairment in Egyptian young age hypertensive patients. TT genotype or T allele may be considered as a predisposing factor for both elevated Hcy levels and the development of renal impairment. This study believed that lowering of homocysteine level can reduce renal impairment of hypertensive patients.