TNFα-308G>A Polymorphism and Susceptibility to Immune Thrombocytopenia Purpura (ITP): Evidence From a Systematic Review and Meta-analysis.

BACKGROUND: Relation between the emergence of ITP and the presence of TNFα 308G/A polymorphism in the involved individuals has been studied by previous researchers in different ethnicity, but a definite result was not gained. So, this meta-analysis was performed to find an absolute answer to the question whether TNF-α-308G/A polymorphism is a susceptibility factor for ITP or not? METHODS: Electronic databases including PubMed, Google scholar, and Science Direct were searched and case control studies compatible to the defined inclusion criteria were selected; their references were also evaluated manually. Pooled OR with 95 % confidence intervals (CIs) as a strength of association between TNF-α-308G/A polymorphism and risk of ITP were calculated using a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. RESULTS: Totally, 16 eligible articles were found involving 1470 ITP cases and 2324 healthy controls. The Meta-results revealed that TNFα 308G/A polymorphism is associated with increased risk of ITP under the genetic models of recessive (OR: 1.54, 95 % CI: 1.03-2.29), dominant (OR: 2.29, 95 % CI: 1.44-3.64), and the heterozygote (OR: 2.46, 95 % CI:1.49-4.6). Subgroup analysis suggested a remarkable role for this SNP as a risk factor in the Caucasian ethnicity and the chronic subtype. CONCLUSION: TNFα 308G/A polymorphism can be an ITP susceptibility factor in the Caucasian population and the chronic subtype. Although more studies in large scale are needed for clinical decision but this finding can be used in the clinical trials to prevent the ITP consequences in the involved individuals.

Frequency of Kell and Rh alloantibodies in Iranian Thalassemia Patients in Khorasan Razavi Province, Iran.

Background: Thalassemia is an inherited disease with anemia and hemolysis. Blood transfusion is a routine treatment for thalassemia patients; alloimmunization is one of the complications of blood transfusion, which is very serious for these patients, especially girls and young women. Materials and Methods: In this cross-sectional study, 446 thalassemia patients were examined. Demographic information of patients was extracted and recorded. The phenotype of ABO, Rh, and Kell antigens (tube method) with antisera from IMMUNDIANOSTICA Company (Germany) and the frequency of alloantibodies were determined. Results: 55.8% of the studied individuals were male, and 44.2% were female. Mean age of the studied patients was 19.94±10.63. The alloantibodies were detected in 7.5% of cell-pack receivers. The most prevalent phenotype of the ABO system was the O blood group (37.4%), and the most abundant antigen of the Rh group was 'e', which was found in 99.8% of the studied population. The most common alloantibody detected was Anti K (38.2%); concerning kell phenotype, (K_k+) and (K+k+) were found in 99.3% and 0.7% of patients, respectively. The frequency of Anti-D, Anti-C, Anti-c, and Anti-E was 23.5%, 14.7%, 2.9%, and 14.7%, respectively. Conclusion: According to the results of this paper, finding the compatible packed cells in terms of Kell and Rh systems antigens in addition to the ABO blood group is recommended to decrease the rate of alloantibodies in thalassemia patients.

Evaluation of FLT3-ITD Mutations and MDR1 Gene Expression in AML Patients.

Background & Objective: Acute myeloid leukemia (AML) is a hematopoietic malignancy caused by genetic abnormalities. Currently, molecular and genetic factors are routinely used as diagnostic and prognostic markers. FLT-3 is one of the most known diagnostic factors in AML. MDR1 gene belongs to the ATP binding cassette family; it is known as one of the chemotherapy-resistant causes of AML. We aimed to study FLT-3ITD mutations and their association with MDR1 gene expression in AML individuals. Methods: For investigation, 80 AML individuals and 20 healthy controls were selected. This study was done in the Cancer molecular Pathology Research Center of Mashhad University of Medical Sciences (MUMS), Iran during 2017-2019. FLT3-ITD mutation was assessed by polymerase chain reaction (PCR); Real-time quantitative PCR was performed to measure the amount of MDR1 gene expression. Bone marrow and blood smears of patients were evaluated in terms of morphology. SPSS 16.0 was used for data analysis. Results: FLT3-ITD mutation and MDR1 overexpression were found in 18.8% and 23.8% of AML patients, respectively. Statistical analysis did not show any relationship or association between these two markers. Cuplike morphology was observed in blast cells in 21.25% of AML cases, which was associated with the presence of FLT3-ITD mutation. Conclusion: FLT-3 and MDR1 function independently. Survival studies to determine the exact role of MDR1 overexpression in drug resistance issues would be suggested.

Incidence and risk factors of common viral infections among renal transplant recipients during the first year post-transplant in North-eastern Iran.

Despite major therapeutic advances, management of viral infections in renal transplant recipients is still a major challenge. Hence, it is urgently needed to establish protocols for appropriate control and the prevention of viral infection. We evaluated demographic/clinical characteristics, frequency, and risk factors of symptomatic viral infections in renal transplant recipients during the 1st year posttransplant, in northeastern Iran. We retrospectively reviewed medical files of 247 patients including 146 males and 101 females who had undergone renal transplantation at Montaserie organ transplantation hospital of Mashhad during 2012-2014. These patients were followed up for one year after transplantation for the detection of any symptomatic viral infection. Demographic and clinical characteristics of recipients were collected and analyzed using the Statistical Package for Social Sciences version 18 software; P < 0.05 was considered as statistically significant. Data were presented using descriptive statistics. Furthermore, logistic regression analysis was used to determine risk factors for infection. The mean age of the patients was 34.94 ± 13.89 years. During the 1st year posttransplant, 68 episodes of viral infections were detected in 64 patients (25.9%). Cytomegalovirus (CMV, 21.9%), Varicella Zoster virus (2.8%), herpes simplex virus (2.0%), and human polyomavirus BK virus (0.8%) were the most common symptomatic viral infections found. Age of the patients was the only significant risk factor for viral infections (odds ratio = 1.066; 95% confidence interval: 1.002-1.134; P = 0.042). The incidence of symptomatic viral infections, particularly CMV disease, is high in our center. Hence, it is recommended to use appropriate prophylaxis and monitor the patients during the first six months post-transplant.

KRAS Codon 12 and 13 Mutations in Gastric Cancer in the Northeast Iran.

BACKGROUND & OBJECTIVE: KRAS mutations are reported in many types of cancers including pancreas, lung, colon, breast,and gastric (GC). High frequency of KRAS mutation is observed in the pancreas,colon, and lung cancers; they commonly arise in codon 12 and 13 of exon 2. Due to the lack of information about the frequency of KRAS mutations in the Northeast of Iran, the currentstudy aimed at evaluating KRAS frequency in cases with GC in this region. METHODS: A total of120 formalin-fixed, paraffin-embedded blocks of patients with GC were assessed. The assays to detect KRAS in codon 12 and13 were obtained through the peptide nucleic acid (PNA)-clamp. RESULTS: Totally 87 male and 33 female patients were analyzed in the current study. The mean age of the subjects was 55years.The most common tumoral fragment was located on the body with 48 cases (40%) and the less frequent was related to fondues with six cases (5%).Of the 120 GC samples, 16(13.3%) caseshad codon 12 KRAS mutation, and 16.7% had codon 13 mutations. There were no significant relationships between gender,age, and KRAS mutations in the studied specimens. CONCLUSION: In conclusion, the overall frequency of KRAS codon 12 and 13 mutations in GC was 30% in the current study population.Frequency of KRAS codon 12 and 13 mutations hadsignificant correlation with tumors location. Different pathogenic mechanismsare suggested for GC according to tumor location. The current study resultsmay be an important diagnostic tool for physicians managing atrophic gastritis.

Prevalence of MPL (W515K/L) Mutations in Patients with Negative-JAK2 (V617F) Myeloproliferative Neoplasm in North-East of Iran.

BACKGROUND AND OBJECTIVE: Janus kinase 2 (JAK2) and Myeloproliferative Leukemia (MPL) mutations are confirmatory indicators for Myeloproliferative Neoplasm (MPN). The current study was performed to determine the frequency of MPL mutation in MPN patients without JAK2 mutation, in order to assign MPL mutation frequency in North-East of Iran. METHODS: Total of 105 negative JAK2 cases including 5 Myeloproliferative Disorders (MPD), 15 Polycytemia Vera (PV) and 15 Essential Thrombocytosis (ET) who referred to Qaem Medical Center were assigned to this study. ARMS-PCR was carried out for measuring MPL mutations. RESULTS: A significant difference was observed between MPL mutant and non-mutant groups from overview of MPL mutation (P=0.00001). From the total studied population, 14.28% were ET cases and 4.71% of them had splenomegaly. About 66.66% had thrombocytosis and 33.33% of all the individuals had leukocytosis according to WHO criteria, and 4.76% of non-MPL mutant individuals had splenomegaly (P=1).This mutation was reported in 4-6% of ET and PMF individuals. In this research, 4.76 % of studied individuals had MPL (W515L/K) mutation, which were diagnosed with ET. CONCLUSION: Generally, the presence of JAK2 and MPL mutations are the most important criteria for MPN diagnosis. The obtained frequency of MPL mutation was similar to previous studies. Despite the high frequency of JAK2 and Philadelphia abnormality, MPL mutation was rare in myeloprolifrative disorders. Further studies are suggested to investigate its prognostic effects for these diseases.

Molecular Status of BRAF Mutation in Prostate Adenocarcinoma: The Analysis of 100 Cases in North-East of IRAN.

BACKGROUND AND OBJECTIVE: BRAF mutations were studied in various populations for prostate carcinoma (PC); however, mutations in BRAF gene are unusual compared to KRAS. Oncogenic activating of BRAF mutations were studied lately in almost 0%10% of prostate cancer cases. METHODS: In this retrospective study, we gathered 100 formalin-fixed paraffin-embedded samples of prostate adenocarcinoma. A hundred archived samples of adjacent benign prostatic hyperplasia were chosen as normal control. This study was done in pathology laboratory of Qaem Hospital during 2013-2015. RESULTS: Total number of 200 PC and normal cases was investigated for BRAF V600E mutation. The BRAF V600E mutation was found in only 4 patients but it was not detected in normal cases. There were no significant differences between patient and control groups for this mutation (P>0.99). The frequency of BRAF V600E mutation was not significant in different age groups (P>0.285); the most frequency was related to the age range of 71-80. No significant difference was observed between tumor grade and BRAF mutation (P=0.21). CONCLUSION: According to our findings, BRAF gene mutations did not play essential role in PC. Therefore, anti-BRAF (V600E) could not be considered as a proper target for therapy.

Cytogenetic Abnormalities with Interphase FISH Method and Clinical Manifestation in Chronic Lymphocytic Leukemia Patients in North-East of Iran.

Background: Chronic lymphocytic leukemia (CLL) is one of the most prevalent adult leukemias. This malignancy is known by lymphocytosis for a duration of more than 3 months. In fact, it is a heterogeneous clinical disease with changeable progression. Chromosomal aberrations are significant parameters to predict result and survival rate and find treatment strategies for each patient. Cytogenetic methods are known as sensitive and relatively new procedures to detect abnormalities in genome. Materials and Methods: In order to identify CLL-related chromosomal abnormalities, 48 CLL patients included 38 Men and 10 Women with mean age of 58.25±36 were enrolled in this case series study.The survey was done at Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences. Interphase fluorescent in situ hybridization (I-FISH) was done on unstimulated peripheral blood or bone marrow samples, which were cultured in whole medium culture; it was used to detect chromosomal abnormalities such as 11q- , 13q14-, 17p- , 6q- and trisomy 12 in CLL patients. Results: Analysis demonstrated that 45.5% of CLL cases had chromosomal abnormalities; 13.63% haddel 17p, 40.90% had del 13q14 and 9.09% had del 11q. Statistical analysis of data revealed a significant relevancy between age variable and splenomegaly occurrence (P value<0.05). The younger the patients were, the less the splenomegaly occurrence. Conclusion: Laboratory findings were correlated with clinical data.

Quantitative assessment of Wilms tumor 1 expression by real-time quantitative polymerase chain reaction in patients with acute myeloblastic leukemia.

BACKGROUND: The Wilms tumor 1 (WT1) gene is originally defined as a tumor suppressor gene and a transcription factor that overexpressed in leukemic cells. It is highly expressed in more than 80% of acute myeloid leukemia (AML) patients, both in bone marrow (BM) and in peripheral blood (PB), and it is used as a powerful and independent marker of minimal residual disease (MRD); we have determined the expression levels of the WT1 by real-time quantitative polymerase chain reaction (RQ-PCR) in PB and BM in 126 newly diagnosed AML patients. MATERIALS AND METHODS: This study was done in molecular pathology and cancer research center from April 2014 to June 2015, RQ-PCR method was used to determine the WT1 gene expression in BM and/or PB samples from 126 patients of AML, we cloned both WT1 and ABL genes for creating a standard curve, and we calculate copy number of WT1 genes in patients. RESULTS: A total of 126 AML patients consist of 70 males (55.6%) and 56 females (44.4%), with a median age of 26 years; 104 (81%) patients out of 126 show overexpression of WT1 gene. We also concomitant monitoring of fusion transcripts (PML RARa, AML1-ETO, MLL-MLL, CBFb-MYH11, or DEK-CAN) in our patients, the AML1-ETO group showing remarkably low levels of WT1 compared with other fusion transcript and the CBFB-MYH11 showing high levels of WT1. CONCLUSION: We conclude that WT1 expression by RQ-PCR in AML patients may be employed as an independent tool to detect MRD in the majority of normal karyotype AML patients.

Urinary tract infections in kidney transplant recipients 1st year after transplantation.

BACKGROUND: One of the main causes of adverse complications following kidney transplantation is urinary tract infection (UTI). This study was done to define the incidence rate, clinical profiles, causative microorganisms, and UTI risk factors among kidney transplant recipients in Mashhad city. MATERIALS AND METHODS: In this retrospective study, we perused medical files of 247 kidney recipients who underwent transplant surgery at Mashhad University Montaserie Hospital, during 2012-2014. All patients were followed for UTI during the 1st year after surgery. RESULTS: 75 episodes of UTI developed by 152 pathogens in 56 (22.7%) of patients during 1-year follow-up. 26.6% of total UTIs were diagnosed within the 1st month after transplantation. The most frequently isolated uropathogens were Escherichia coli (55.3%, n = 84). The high rate of candiduria (8.5%) was observed, too. CONCLUSION: UTI is known as one of the hospitalization reasons in kidney transplantation recipients. Defining appropriate antibiotic prophylaxis against bacterial and fungal agents and early removal of urethral catheter are suggested to decrease posttransplantation complications.

Epidemiology of Infectious Complications in Renal Allograft Recipients in the First Year After Transplant.

OBJECTIVES: Renal transplant is one of the best ways to extend life of patients in the end stage of renal disease. Infections are significant causes of morbidity and mortality after renal transplant. The aim of this study was to evaluate frequency, risk factors, causative pathogens, and clinical manifestations in renal transplant recipients from Mashhad City during the first year after transplant. MATERIALS AND METHODS: This research was conducted at Montaserie Hospital of Mashhad University of Medical Sciences from March 2013 to July 2015. All studied cases were followed for 1 year. In this retrospective study, our study cohort comprised 193 kidney transplant recipients, including 118 male (61.1%) and 75 female (38.9%) patients, with mean age of 34.4 ± 12.2 years. Of the total patients, 58 received kidneys from living donors (30.1%) and 135 received kidneys from deceased donors (69.9%). RESULTS: We found that 151 infectious episodes had occurred in 96 patients. The most common infectious site involved the urinary tract (39.1%). Escherichia coli was the most frequently isolated pathogen. The only significant infection risk factor to affect transplant outcomes during the first year was age. CONCLUSIONS: Infections are highly prevalent during the first year after transplant. Prevention and effective antibiotic therapy can reduce the related adverse effects.

Prognostic Importance of C-KIT Mutations in Core Binding Factor Acute Myeloid Leukemia: A Systematic Review.

OBJECTIVE/BACKGROUND: Acute myeloid leukemia (AML) is defined as leukemic blast reproduction in bone marrow. Chromosomal abnormalities form different subgroups with joint clinical specifications and results. t(8;21)(q22;q22) and inv(16)(p13;q22) form core binding factor-AML (CBF-AML). c-kit mutation activation occurs in 12.8-46.1% of adults with CBF leukemia. These mutations occur in 20-25% of t(8;21) and 30% of inv(16) cases. METHODS: In this systematic review, we searched different databases, including PubMed, Scopus, and Embase. Selected articles were measured based on the inclusion criteria of this study and initially compared in terms of titles or abstracts. Finally, articles relevant to the subject of this review were retrieved in full text. Twenty-two articles matched the inclusion criteria and were selected for this review. RESULTS: In this study, c-kit mutations were associated with poor prognosis in AML patients with t(8;21) and inv(16). In addition, these mutations had better prognostic effects on AML patients with inv(16) compared with those with t(8;21). CONCLUSION: According to the results of this study, c-kit mutations have intense, harmful effects on the relapse and white blood cell increase in CBF-AML adults. However, these mutations have no significant prognostic effects on patients.

Chromogenic in situ Hybridization Compared with Real time Quantitative Polymerase Chain Reaction to Evaluate HER2/neu Status in Breast Cancer.

BACKGROUND AND OBJECTIVE: The assessment of human epidermal growth factor receptor 2 (HER2) status has become of great importance in the diagnosis of breast cancer. The aim of this study was to investigate the diagnostic value of quantitative Polymerase Chain Reaction (qPCR) and Chromogenic In Situ Hybridization (CISH) to assess HER2 status of biopsy specimens. METHODS: To elucidate the status of HER2 gene amplification, biopsies of breast carcinoma from 120 patients with 2+ IHC status were analyzed by qPCR and CISH. RESULTS: The results of the two experiments were compared, and it was depicted that the concordance rate between CISH and qPCR assays was 88.1%.The quantification of HER2 gene with CISH and qPCR showed that there was a significant correlation (p value= 0.0001 and r= 0.808). CONCLUSION: The results of this research support the idea that qPCR is a precise and reproducible technique, which can be employed as a supplementary method to evaluate HER2 status.

Evaluation of BAALC gene expression in normal cytogenetic acute myeloid leukemia patients in north-east of Iran.

Background: Acute myeloid leukemia (AML) is known as one of the most common leukemia among adults. Environmental and different genetic factors affect disease process, prognosis and treatment. Among different genetic factors NPM1, FLT3, MLL and BAALC genes are the most effective on patient's survival rate. The aim of this study was to assess amount of BAALC gene expression in AML patients, and its relation to survival rate. Methods: In this case-control study, from all 94 individuals referred to Ghaem Medical Center during 2012-2015, 47 cases were normal cytogenetic AML and others were healthy individuals that were studied as control group. Real-time PCR method was applied for gene expression evaluation. Other information of patients was extracted from medical documents. SPSS v.21 was used for data processing. Results: Mean age of studied cases was 31.50 years. The most of BAALC gene expression was seen in M1 and M2 subtypes, and the less was in M5. A significant relation was found between amount of gene expression and patient's survival rate. Conclusion: BAALC gene expression was increased significantly in AML cases. BAALC expression had reverse relation with patients' survival rate in North-East of Iran.