Isocitrate Dehydrogenase 1 and 2 Mutations in Pediatric Neuroblastoma Patients.

Objective: Neuroblastoma is one of the common tumors of childhood. The demonstration of new factors such as isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations will be important in the diagnosis and treatment. IDH1 and IDH2 mutations have been found in many types of cancer, such as malignant gliomas, acute myeloid leukemias, chondrosarcoma, and thyroid carcinoma. This study aimed to investigate the presence of IDH1 or IDH2 mutations in patients with neuroblastoma and to determine whether these mutations were different in terms of age, clinical findings, and response to treatment. Methods: Biopsy specimens of 25 patients with pediatric neuroblastoma patients were evaluated for IDH mutations. The clinical and laboratory features of the patients with/without mutation were retrospectively analyzed from a hospital database. Results: A total of 25 patients for whom genetic analysis could be performed were included in the study (60% male, n=15). The mean age was 32.2±25.9 months (3 days-96 months). IDH1 mutation was detected in 8 (32%) and IDH2 mutations in 5 (20%) patients. These mutations showed no statistically significant relationship with age, tumor localization, laboratory results, stage, and prognosis. However, in the case of IDH mutation, patients were diagnosed at the advanced stage. Conclusions: This study demonstrated the relationship between neuroblastoma and IDH mutation for the first time. Because to the fact that the mutation is very heterogeneous, it would be appropriate to conduct a larger series of patients in terms of the impact of the clinical significance of each mutation on the diagnosis and prognosis.

Can Propranolol Affect Platelet Indices in Infantile Hemangioma?

INTRODUCTION: Propranolol, a nonselective beta-blocker used in the medical treatment of infantile Hemangioma (IH), has been shown to decrease the levels of vascular endothelial growth factor and reduce angiogenesis with its antiproliferative and antiangiogenetic effects. MATERIALS AND METHODS: It has been reported that the storage, transport, and secretion of vascular endothelial growth factor (VEGF) are associated with platelet volume indices (PVI). We aimed to investigate the effect of propranolol on PVI in IH patients. Propranolol treatment was started on 22 IH patients. Platelets, mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit values in the follow-ups at months 0, 1, and 2 were compared between 22 patients who received treatment and 25 patients who did not. RESULTS: While a statistically significant difference between months 0, 1, and 2 in PDW and MPV values was detected in the treated group, it was not detected in the untreated group. Taking into consideration that VEGF levels were higher at the beginning of the treatment in the pathophysiology of the disease, it was thought that the decrease in VEGF levels by propranolol may have led to a decrease in MPV and PDW levels in the treatment group. CONCLUSION: Consequently, in IH cases, propranolol response follow-up can be evaluated with PVIs, especially MPV and PDW, and it may facilitate clinicians' monitoring of the disease after propranolol administration.

Thiol disulfide homeostasis in ionizing radiation and chemotherapeutic drug exposure.

OBJECTIVE: This study aims to reveal the oxidant and antioxidant status in nurses with chemotheropathic drug exposure and radiology unit workers exposed to ionizing radiation (IR). METHODS: Nineteen radiology unit workers, 14 nurses, and 15 controls were included the study. All of the participants using antioxidants, vitamin supplements, smokers, any therapeutic drugs, and exposed therapeutic or diagnostic X-ray or chemotherapeutic drugs in 12 months were excluded from the study. Total and native thiols, disulfide/native thiol percent ratios (SS/SH), disulfide/total thiol percent ratios, disulfide amounts, and native thiol/total thiol percent ratios, ischemia-modified albumin (IMA) were determined. RESULTS: Disulfide levels, disulfide/total thiol ratio, and disulfide/native thiol ratio of serum samples of both radiology unit workers and nurses were significantly higher and ratio of native thiol/total thiol was lower than the control group. The radiation dose in radiology unit workers was mean±SD: 0.02±0.009, median (min-max): 0.02 (0.001-0.04). Thiol-disulfide homeostasis was disturbed and the balance shifted in the direction of oxidant damage, even at low-dose IR exposure and normal range. CONCLUSION: As far as we know, the current findings first demonstrate an apparent chronic oxidative stress in the subjects who were occupationally exposed to antineoplastic drugs and radiation even if annual radiation exposure dose measurements are normal.

Intrauterine Growth Retardation is a Risk Factor for Anthracycline Toxicity.

BACKGROUND: Anthracycline chemotherapy is used to treat a variety of cancers. However, late cardiac effects of anthracycline chemotherapy, such as subclinical left ventricular dilatation and/or dysfunction, have been observed in more than half of long-term survivors of childhood cancers. A major risk factor for anthracycline cardiotoxicity is intrauterine growth restriction (IUGR). We assessed the significance of IUGR as an important risk factor for late cardiotoxic effects of anthracycline therapy in asymptomatic long-term survivors of childhood cancers. MATERIALS AND METHODS: The study included 61 survivors of childhood cancers. Cardiac functions were prospectively studied using both conventional and non-conventional echocardiographic methods (two-dimensional speckle tracking echocardiography) after completion of the treatment. The patients were divided into two groups based on their birth weights: Group 1 (patients with IUGR) and Group 2 (patients with normal birth weight). RESULTS: Conventional echocardiography revealed a similar and normal range of left ventricle systolic and diastolic functions in both groups. However, global longitudinal and circumferential strain values demonstrated subclinical left ventricular systolic dysfunction in both groups as compared with normal reference strain values. Furthermore, Group 1 patients had significantly lower global longitudinal and circumferential strain and strain rate values than those in Group 2 patients. CONCLUSION: Asymptomatic long-term survivors of childhood cancers with a history of IUGR may have an increased risk of anthracycline cardiotoxicity due to the low content of mitochondrial DNA (mtDNA). IUGR is a risk factor for late anthracycline cardiotoxicity.

Successful Treatment With Bortezomib for Refractory and Complicated Acquired Thrombotic Thrombocytopenic Purpura in an Adolescent Girl.

Thrombotic thrombocytopenic purpura (TTP) is a rare, dangerous, life-threatening disease characterized by microangiopathic hemolytic anemia and thrombocytopenia, along with organ dysfunction due to microangiopathy-related ischemia. Plasma exchange and steroids are used for initial treatment, and rituximab is often used in refractive patients. Caplacizumab, cyclophosphamide, and splenectomy are among other treatment options. It has been reported that bortezomib, a proteasome inhibitor, can be used in the management of refractory acquired TTP. Herein, we present a 16-year-old female patient who was monitored for acquired TTP and treated with high-dose steroids, plasma exchange, rituximab, cyclophosphamide, and N-acetylcysteine but developed renal, cardiac, gastrointestinal, and neurologic complications. The girl was then successfully treated with bortezomib, and she has been monitored in remission for 6 months. We consider that bortezomib is a beneficial treatment, especially in patients with refractory TTP.

Chemotherapy-related fever or infection fever?

BACKGROUND: The present study investigates the reason for the onset of fever after chemotherapy (CT) for cancer with the aim of reducing unnecessary medical care. METHODS: A total of 37 consecutive cycles of CT for cancer were analyzed retrospectively from the files of patients. Fever was defined as a temperature of ≥ 38 °C lasting for 1 h. RESULTS: The study sample included 23 males and 14 females (aged 8.43 ± 5.04 [min-max]). Fever was observed in all 37 cycles of chemotherapy agent (CA), which included cytarabine (ARA-C), dacarbazine, cyclophosphamide, irinotecan, adriamycin, etoposide, ifosfamide, cisplatin, and methotrexate. Fever was recorded within the first 12 h following treatment with ARA-C (45.9%), dacarbazine (16.2%), or cyclophosphamide (8.1%). A physical examination of the patients yielded normal results, C-reactive protein (CRP) and procalcitonin (PCT) values were within the normal range, the median absolute neutrophil count (ANC) was 3200/uL (0.00-16.340/uL), and a median sedimentation (ESR) level of 10 mm/h (2-59) was determined. All fevers were accepted as having resulted from CT based on the above criteria. Paracetamol and diphenhydramine were administered and the patients' treatments were continued. CONCLUSION: Febrile episodes occurring within the first 6 h following treatment were considered to constitute an adverse drug reaction after CT for the treatment of cancer. While ARA-C fever has been previously reported on in the literature, it should be kept in mind that CT fever can be seen with different CA. Physicians should be aware of this aspect of chemotherapy-associated fever and avoid unnecessary examinations and treatments, including antibiotics.

Therapeutic effect of N-acetylcysteine on chemotherapy-induced liver injury.

BACKGROUND: N-acetylcysteine (NAC) may be useful in the management of chemotherapy-induced liver injury. AIMS: The present study evaluates the possible therapeutic effects of NAC on chemotherapy-induced hepatotoxicity. METHODS: A total of 102 patients' files who were diagnosed with cancer between 2015 and 2019 were evaluated retrospectively. Two patient groups with and without NAC were selected. NAC was administered in a 3-µg/kg IV dose in a 24-h infusion to 70 patients when any alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT) values reached three times the normal levels. The other group consisted of 32 patients who were not treated with NAC. Alanine aminotransferase and GGT values were recorded at pretreatment, and on the 1st, 3rd, 5th, and 7th days in both the NAC and non-NAC groups from files. RESULTS: In the NAC group, ALT and GGT values on day 1, 3, 5, and 7 differed from each other, decreasing from day 1 to day 7. A statistically significant difference was noted between the values in the NAC group (p < 0.001). In the non-NAC group, the ALT values on day 7 were lower than the ALT values on day 1. A comparison of the ALT and GGT values in the NAC and non-NAC groups found that the values in the NAC group decreased earlier than in the non-NAC group. CONCLUSIONS: This study shows that NAC has a therapeutic effect on hepatotoxicity in children being treated with chemotherapeutic agents due to underlying malign diseases. The early reduction in the results of liver function tests is important for the continuation of chemotherapy.

Cerebral neoplasm in L-2-hydroxyglutaric aciduria: two different presentations.

BACKGROUND: L-2-hydroxyglutaric aciduria (L2HGA) is a rare neurometabolic disorder characterized by a slowly progressive clinical course, psychomotor and mental retardation, macrocephaly, dysarthria, seizures, and cerebellar and extrapyramidal findings. The diagnosis depends on the presentation of increased levels of L-2-hydroxyglutaric acid in the urine, plasma, and cerebrospinal fluids. Patients with L2HGA have an increased risk for the development of cerebral neoplasms which, though rarely, can be the initial presentation of the disease. Moreover, patients with L2HGA have an increased risk for the development of cerebral neoplasms. CASES PRESENTATION: Although psychomotor and mental retardation, macrocephaly, dysarthria, seizures, and cerebellar and extrapyramidal findings are the most common characteristics of the disease, we present two rare cases admitted with tumoral symptoms. CONCLUSION: Patients with L2HGA have an increased risk for the development of cerebral neoplasms.

A case of acute lymphoblastic leukemia mimicking juvenile idiopathic arthritis.

Patients with leukemia can be presented with monoarthritis without any hematologic abnormalities. These patients may be misdiagnosed with juvenile idiopathic arthritis (JIA), and the main treatment can also be delayed. An 11-year-old girl was admitted to our pediatric rheumatology outpatient clinic with a 4-week history of swelling in the left ankle. JIA was considered as a preliminary diagnosis after the antinuclear antibody was found to be positive, and non-steroidal anti-inflammatory drug was started. Diffuse bony edema was observed in the talus, navicular, cuboid, and cuneiform bones in magnetic resonance imaging of the left ankle. Despite the treatments, the patient's joint pain increased. There were no abnormalities in repeated peripheral blood smears. On week 3 of follow-up, after bicytopenia was revealed in complete blood count, bone marrow biopsy was performed, and she was diagnosed with precursor B cell acute lymphoblastic leukemia. We presented this case to emphasize that malignancies must be evaluated in the differential diagnosis of patients with arthritis.

Asymmetric dimethylarginine levels and diabetes duration: Relationship with measures of subclinical atherosclerosis and cardiac function in children and adolescents with Type 1 diabetes.

AIMS: We aimed to evaluate asymmetric dimethylarginine levels in young patients with Type 1 diabetes mellitus according to diabetes duration and to examine the relationship between these levels and measures of atherosclerosis and myocardial function. MATERIALS AND METHODS: In total, 83 patients (8.5-22 years) with Type 1 diabetes mellitus were stratified by diabetes duration: 12-60 months (Group 1, n = 27), >60-120 months (Group 2, n = 29) and >120 months (Group 3, n = 27). Asymmetric dimethylarginine levels were assessed. Carotid intima-media thickness was measured. Myocardial function was assessed by M-mode, conventional Doppler and tissue Doppler echocardiography. RESULTS: Asymmetric dimethylarginine level was significantly higher in Group 1, while carotid intima-media thickness was significantly greater in Group 3 ( p < 0.05). Tissue Doppler echocardiography showed the ratio of peak early to peak late diastolic myocardial annular velocity decreased significantly in Groups 2 and 3 with a negative correlation with duration (r: -0.310, p = 0.004) and HBA1c levels (r = -0.391, p < 0.001). Myocardial performance index in all groups and isovolumic relaxation time in Group 3 increased significantly. Asymmetric dimethylarginine levels were negatively correlated with carotid intima-media thickness and isovolumic relaxation time ( p < 0.05). CONCLUSION: In contrast to adult diabetics, asymmetric dimethylarginine concentration decreases as diabetes duration increases in young Type 1 diabetic patients and is associated with worsening measures of cardiovascular risk and poorer diastolic function.

A Case of ALL Developing Posterior Reversible Encephalopathy Secondary to Hyponatremia.

Posterior reversible encephalopathy syndrome (PRES), may be due to different causes. It may develop secondary to hypertension, renal decompensation, electrolyte imbalance, and chemotherapeutic drugs. We describe a case of acute lymphoblastic leukemia in which PRES developed secondary to hyponatremia despite being normotensive during receipt of chemotherapy. Magnetic resonance imaging findings were suggestive of PRES. Partial diffusion restriction was observed in lesions in the bilateral occipitoparietal regions and the cerebellum. The patient was treated with appropriate medications with the resolution of his stroke-like symptoms. No neurological deficit was observed and clinical condition improved. The patient continued with chemotherapy. Early diagnosis and treatment of this syndrome is important in terms of preventing neurological sequelae. Cases of secondary PRES developing for several etiological reasons have been reported in induction therapy, but no pediatric cases of PRES developing secondary to hyponatremia despite being normotensive while receiving chemotherapy in acute lymphoblastic leukemia have previously been reported.

Diffuse Adenomyomatosis of the Gallbladder in a Child.

Adenomyomatosis of the gallbladder (ADMG) is characterized by proliferation of the mucosal epithelium and hypertrophy of the muscularis. ADMG is predominantly diagnosed by using ultrasonography. Although ADMG is benign in nature, lithiasis, and chronic inflammation secondary to it may lead to dysplastic changes and cancer. Mucosal invagination through the hypertrophied muscularis results in large intramural diverticula or sinus tracts which are visible at radiology, known as Rokitansky-Aschoff sinuses. Histologically, ADMG manifests with hyperplasia of the muscular layer and proliferation of mucosal glandular tissues. We describe a case of ADMG in an 8-year-old girl presenting with recurrent abdominal pain. Diagnosis was made using ultrasound, and the condition was successfully treated with open cholecystectomy. Ultrasound scanning in children presenting with recurrent abdominal pain may lead to more accurate diagnosis of ADMG during childhood.

Neonatal hyperbilirubinemia in a Turkish cohort: association of vitamin B12.

BACKGROUND: Deficiency of vitamin B12 (VitB12) causes failure of erytrocyte maturation leading to cell lysis. Red blood cell lysis causes excess heme production that ends with hyperbilirubinemia. In this study, we aimed to evaluate the role of VitB12 in neonatal hyperbilirubinemia (NNH) with prolonged jaundice and to compare patients with control group who did not develop hyperbilirubinemia. METHODS: A total of 20 patients (M/F = 13/7) with jaundice and 20 healthy controls (M/F = 11/9) were included in the study. RESULTS: The mean indirect bilirubin level of patient group was 9.91 ± 1.90 mg/dL (6.71 - 15.2 mg/dL) and control group was 3.18 ± 1.24 mg/dL (1.16 - 4.96 mg/dL). The mean VitB12 level of patient group was 119.9 ± 43.9 ng/L (42.35 - 178 ng/L) and the control group was 286.17 ± 97.43 ng/L (207.90 - 624.10 ng/L). There was a statistically significant difference in terms of VitB12 level (< 0.001) between the study groups. CONCLUSION: To our knowledge, this study is the first study showing that low VitB12 level has been observed as a risk factor in NNH for the first time in the literature. We suggest that prophylactic use of VitB12 by pregnant women so will greatly benefit to prevent VitB12 deficiency and its complications in the first years of life such as NNH.

Beliefs about medications in asthmatic children presenting to emergency department and their parents.

OBJECTIVE: The aim of our study was to assess the relationship of beliefs about medications questionnaire (BMQ) scores of asthmatic children presenting to the emergency department and their parents with asthma severity parameters. METHODS: Eighty children with asthma presenting to the emergency department with acute asthma findings and their mothers were enrolled in the study. BMQ was applied to all parents and children older than 7 years of age. Asthma severity clinical score was recorded. RESULTS: The mean age of children (39 males, 41 females) was 49.1 ± 42.8 months. Parent necessity and concerns scores were significantly correlated with their counterparts in children (r = 0.74 and r = 0.60, respectively). Difference between necessity and concerns scores was correlated between parents and children (r = 0.60, p = .002). Child's necessity score was significantly correlated with respiratory severity score (r = -0.43, p = .036). CONCLUSION: BMQ necessity and concerns scores of asthmatic children in the emergency department and their parents are correlated with asthma severity. Although not assessed in this study, this result may be attributed to the relationship of necessity and concerns with drug adherence. Therefore, increasing the knowledge about asthma medications in asthmatic children and their parents may contribute to asthma control and decrease their emergency visits with acute asthma findings.