Background: Somatic mutations in the hotspot region of the DNA-methyltransferase 3A (DNMT3A) gene were recurrently identified in acute myeloid leukemia (AML). It is believed that DNMT3A mutations confer an adverse prognosis for AML patients. These lines of evidence support the need for a rapid and cost-efficient method for the detection of these mutations. The present study aimed to establish high resolution melting (HRM) curve analysis as a rapid and sensitive test to identify DNMT3A gene mutations in AML patients.
Materials and Methods: In this retrospective cohort study, a total of 220 AML patients who referred to hematology-oncology and stem cell transplantation centers (referral center) at Shariati hospital in Tehran, Iran, were included. AML-M3 and therapy-related AML patients were excluded. The HRM assay was used to identify R882 mutations in DNMT3A gene, and the results were compared with those of Sanger sequencing as the gold standard test for detection of such mutations.
Results: Among 220 samples from AML patients, Sanger sequencing detected 25 (11.4%) patients as having DNMT3A R882 mutations. HRM assay detected mutations in 23 (92%) samples and reported two false-negative results that were related to poor-quality DNA samples. There was an overall good agreement between direct sequencing and HRM assay (kappa value of 0.95) (p<0.001). Sensitivity assay showed that the analytical detection limits for HRM were 10% for the detection of R882H mutation compared with Sanger sequencing at 25%. Both Sanger sequencing and HRM assay reported no false-positive results.
Conclusion: HRM curve analysis can be considered as a sensitive, fast, and high-throughput method for the detection of DNMT3A R882 mutation in AML patients. These results validate HRM analysis as an alternative method to Sanger sequencing because of its simplicity along with the lower cost and less required time.

Pediatric palliative care is a holistic caring approach for children and families that begins with diagnosis of a life-threatening illness and continues until death; it aimed to relieve pain and other symptoms in physical, mental, social and spiritual aspects. In spite of available evidence concerning optimal outcomes of the provision of palliative care, establishment of a palliative care system for children has hardly been feasible so far due to a number of challenges. Therefore, this review study aimed at identifying the challenges of the provision of pediatric palliative care along with the relevant solutions. The identified challenges were classified into two categories including structure-based challenges (i.e. lack of a clear structure in the health system and classification of services, shortage of specialized staff, insufficient home care services, absence of health care tariffs along with insurance coverage of palliative care services) and process-based challenges (i.e. absence of guidelines, lack of educational programs for family, family attitudes and beliefs, communication barriers, and lack of access to opioids). Thereafter, the solutions for each challenge are provided in accordance with the available literature separately. Given the significance of palliative care for children with cancer and in order to improve the quality of life of the children and the families, it appears necessary that policymakers and managers take account of the challenges as well as the feasibility and the implementation of provided solutions.
 

Background: The changes of platelet parameters can be a useful index for rapid diagnosis of urinary tract infection (UTI), since platelet changes are routinely determined through complete blood count (CBC) test. The correlation between platelet indices, included number (PLTs), mean platelet volume (MPV) and platelet distribution width (PDW), which are the indicators of production and function of platelets, with UTI was evaluated in this study.        
Materials and Methods: In this descriptive-analytical study, 97 patients with UTI (patient group) and 117 healthy people (control group). The average age for the patient and the control group was 10.84±6.68 and 11.34±7.1 years old, respectively. This study was done during 2016-2018 in Imam Reza Hospital, Kermanshah, west of Iran. The PLT, MPV, PDW, and other inflammatory indices, including white blood cell, neutrophils, lymphocytes, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were evaluated. The diagnosis of bacteria was done using routine microbiological and biochemical methods. The platelet indices were statistically compared between the patients and the control groups (T test and Chi square test).
Results: The most common isolated gram negative and gram positive bacteria were E. coli, Citrobacter, and Staphylococcus aureus, respectively. In the patient group, PLT number was significantly higher than that in the control group (p=0.0007), while difference of other indices such as MPV, PDW, neutrophils, lymphocytes, CRP, and ESR were not statistically significant between the two groups. In case of UTI with gram positive bacteria, PLT number (p=0.05) was lower but MPV (p=0.02) and PDW (p=0.045) was higher compared to the UTI with gram negative bacteria.
Conclusion: The results of this study showed that the platelet number could be a useful diagnostic index for urinary tract infection. However, more studies need to be done with higher number of patients to evaluate the more details of platelet changes during UTIs.

Background: Frequent blood transfusion can lead to iron overload which is potentially dangerous for the heart and liver. Silymarin has well-documented protective effects on hepatocytes. The purpose of this study was to evaluate the hepatoprotective effects of silymarin addition to iron chelators in children with thalassemia.
Materials and Methods: This randomized, double-blinded, and placebo-controlled trial was performed on 40 subjects with thalassemia major and intermedia in Amir Kabir Hospital, Arak, Iran. Subjects were randomized 1:1 oral to 30 mg/kg deferasirox plus placebo, or deferasirox plus oral 70-140 mg silymarin (twice daily) for 6 months. Cardiac and hepatic iron levels and levels of Gamma-glutamyltransferase (GGT), Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin, albumin, total protein, and total cholesterol were measured at baseline and after 6 months of treatment.
Results: The mean age of patients was 16 years and 60% of patients were female. After 6 months, there were significant increases in the levels of ALT, AST, GGT, and TG in the placebo group as compared to the silymarin group (P < 0.05). In contrast, ALT, AST, and GGT had significant reductions compared to the silymarin group (P =0.05). Patients in the placebo group had a rise in total bilirubin (P = 0.07), but total protein and albumin did not have significant changes in the silymarin group (P > 0.05). Finally, a significant improvement was noted in cardiac iron values in patients using silymarin; 22.2 ± 6.6 ms at baseline vs 26.9 ± 7.1 ms at 6 months (P < 0.05).
Conclusion: This study suggests that twice-daily addition of silymarin to deferasirox could improve liver function in children with thalassemia major and intermedia. Silymarin seems safe in pediatrics.

Background: Nausea and vomiting are among the most important side-effects associated with chemotherapy in children with cancer, affecting the quality of their lives. Clinical guidelines for selecting antiemetics are effective in reducing acute chemotherapy-induced nausea and vomiting (CINV).
Materials and Methods: The present quasi-experimental study compared the effectiveness of the Pediatric Oncology Group of Ontario (POGO) CINV guideline with that of conventional arbitrary therapies for CINV in 82 children aged 6 months to 16 years old. Out of 177 cycles of chemotherapy, in 101 cycles patients were treated according to POGO-CINV Guideline; in the other 76 cycles, patients were treated with arbitrary types and doses of antiemetics. Then, vomiting in the first 24 hours after chemotherapy in both groups was measured and compared.
Results: In this study, 82 patients hospitalized in the Hematology Department of Dr. Sheikh Children’s Hospital were enrolled, of whom 48 patients (58.7%) were boys and 34 (41.3%) were girls. The mean age of patients was 6.24±4.47 years (6 months to 16 years). The results of the current study showed that using a protocol for the prevention of vomiting based on the patient’s age and the type of chemotherapy is superior to conventional management of CINV. Findings showed that the frequency of nausea and vomiting in the protocol group was significantly reduced in comparison with the control group (p˂0.005). Moreover, a reduction in the frequency of nausea and vomiting was quite significant in the sub-categories of the protocol group who had received high-risk or moderate-risk emetogenic drugs (p˂0.005).
Conclusion: The results of the current study showed that using the POGO guideline, which takes into account the patient’s age and the type of chemotherapy, is more effective than arbitrary management of CINV, particularly in children.

Background: Lymphadenopathy is an enlargement of a lymph node. Pathologic Lymphadenopathy is when there is a symptom of infectious and noninfectious abnormalities or malignant diseases. Most Lymphadenopathies are benign and are associated with a short period of symptoms. Concerning diagnosis and management of adenopathy, especially in the case of children, research is still underway. For this reason, our study investigated and analyzed the causes of lymphadenopathy in children.
Materials and Methods: This is a retrospective study conducted at the Pediatric Department of children's medical center of Tehran University of medical science. In this study, 130 children with cervical lymphadenopathy aged under 12 years underwent lymph node biopsy. Then under general anesthesia and evaluation of a senior pathologist, the lymph node was excised and biopsied.
Results: During the study, twenty-five cases were excluded. Fifty-three patients (50.47%) demonstrated infection history, 22 cases (21%) had neoplasia, and reactive inflammatory changes with nonspecific origin were seen in 42 cases (40.0%). We observed chronic lymphadenitis in 3(2.9%) cases, and finally, 1(1.0%) case was metastatic. Mean lymph node size proved to be greater than two cm in metastatic (2.22cm), lymphoma (2.33cm), and granulomatous (3.17cm) lymphadenopathies. The average lymph node size turned out to be 1.53 cm in reactive lymph nodes (P =0.021). The diagnosis was obtained by excisional biopsy and histopathology.
Conclusion: Acute infections are the most common reason for lymphadenopathy in pediatric conditions. It is better to be suspicious of malignancy with a high index in cases of cervical lymphadenopathy, especially if the lymph node size is higher than 2 cm. History, clinical features, and paraclinical tests can be used for lymphadenopathy in children.

Background: β-thalassemia is the most common hereditary disease in Iran, and more than 2 million carriers of β-thalassemia live in Iran. On the other hand, our country is located in the thalassemia belt, and no comprehensive study has been conducted regarding the effect of erythropoietin on blood parameters in thalassemia intermedia patients in our region. Therefore this study aimed to investigate the effect of erythropoietin on blood parameters of thalassemia intermedia patients.
Materials and Methods: This prospective cross-sectional study was conducted on all patients suspected of thalassemia intermedia in Shahid Sadoughi hospital from March 2021 to M 2022.  In the case of diagnosis of microcytic anemia, an electrophoresis test was performed, and people diagnosed with thalassemia intermedia entered the study. Then patients were divided into two groups (the intervention and control groups). The erythropoietin dose was 50-100 units/ kilogram (body weight) three times a week for six months. The measurement of hematocrit and hemoglobin were done using CBC cell counter (Sysmex KX21). Other data were extracted from medical records.
ResultL: In the current study, the mean age of patients in the intervention and control groups was 9.15±1.53 and 8.35± 6.90 years old, respectively (p=0.9). The mean hematocrit level in the intervention and control groups was 28.05± 4.06 and 23.45± 3.22 %, respectively (P<0.001). The mean hemoglobin level in the two groups was 9.15± 1.53 and 7.65± 1.23 g/dL respectively (p=0.002). The mean hematocrit level before and after the intervention was 25±3.71 and 28.05±4.06 %, respectively. The mean hemoglobin levels before and after therapy were 7.9±1.52 and 9.15±1.53 g/dL, respectively.
Conclusion: According to the findings, hemoglobin and hematocrit increased in thalassemia intermedia patients taking erythropoietin. Therefore it seems that recombinant erythropoietin can be helpful in these patients.

Background: Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma, characterized by abnormal B-cell growth within the germinal center. Research has shown the role of genes and molecular pathways in the pathogenesis of FL. However, the main factor of pathogenesis has not been determined. Therefore, in this study, the genes and molecular pathways related to the pathogenesis of FL were evaluated using a systems biology approach.
Materials and Methods: In this study (bioinformatics analysis), the GSE32018 database was used for data analysis. This database was extracted from Gene Expression Omnibus (GEO). The sample of this database was 36, which included normal and FL samples. For this purpose, 23 cases were FL and 13 were healthy samples. Protein-protein interaction (PPI) is performed to show the interaction between DEGs. STRING software is used for this purpose. Associations between the hub genes, transcription factors, and microRNAs were assessed using the miRTarBase and TRRUST databases. The criteria used for data analysis included log fold change greater than one and p < 0.05.
Results: After evaluating and analyzing the data, the results showed that 866 DEGs were identified between the control and FL samples. Of this population, 231 cases of UP regulation and 635 cases of downregulation were in FL samples compared to control samples. PPI network and hub gene analyses identified 7 hub genes, including RPL37A, MRPS7, RPS14, RPS28, RPL34, RPS20, and RPS3. According to the results, hsa-miR-191-5p has the highest interactions with hub genes among miRNAs, and KDM5A has the most interactions among TFs. Conclusion: Identifying genes and molecular pathways can be effective in designing therapeutic strategies and preventing the proliferation of FL cells, thereby increasing patients’ survival.