Whole Blood miR-210, miR-122, miR-223 Expression Levels and Their Relationship With Iron Status Parameters and Hypercoagulability Indices in Children With Iron Deficiency Anemia.

MicroRNAs have the potential to regulate systemic and cellular iron homeostasis at multiple points. In iron deficiency anemia (IDA), hypoxia, platelet reactivity, and potentially microRNAs play a role in the development of hypercoagulability. A total of 57 children diagnosed with IDA between October 2016 and October 2017 and 48 healthy children were included in this cross-sectional study. Blood count parameters, serum iron, transferrin saturation, ferritin level, maximum clot firmness (MCF), and clot formation time index, which are indicators of hypercoagulability in rotational thromboelastometry test, of the IDA and control groups obtained in our previous study were recorded. miR-210, miR-122, and miR-223 levels were analyzed. There was no difference in the miR-210, miR-122, and miR-223 levels between the IDA and control groups. Patients with hemoglobin (Hb) <8 g/dL had higher miR-210 levels than patients with Hb>8 g/dL (P<0.05). There was a negative correlation between miR-210 and Hb and ferritin levels, a positive correlation between miR-122 and ferritin levels, and a negative correlation between miR-223 and MCF index. In IDA, there is a close relationship between the severity of anemia and miR-210, and miR-210 expression is slightly increased in those with severe anemia. miR-210 and miR-122 collectively play a role in maintaining the iron balance. The correlation between miR-223, a platelet function regulator, and the MCF index, suggested that miR-223 has a role in the development of hypercoagulability in IDA.

Acute Sialadenitis in Children With Acute Leukemia During Chemotherapy: A Case Series Study.

Complications and toxicities of chemotherapy are the significant causes of morbidity and mortality during the treatment of childhood leukemias. Respiratory viral infections are the most common cause of febrile neutropenia episodes and rarely spread to the salivary glands. We submitted 4 patients with acute leukemia who got diagnosed with acute sialadenitis during their chemotherapy period.

Immunization status and re-immunization of childhood acute lymphoblastic leukemia survivors.

Intensive chemotherapy can cause long-lasting immunosuppression in children who survived cancer. The immunosuppression varies according to the type of cancer, intensity of chemotherapy and age of the patient. A sufficient immune reconstruction when has been completed in childhood cancer survivors, the re-vaccination program can achieve sufficient antibody levels for some of the life-threatening vaccine-preventable infectious diseases. This study evaluates the serological status of pediatric acute lymphoblastic leukemia (ALL) cases before and after the intensive chemotherapy treatment. Antibodies against measles, mumps, rubella, varicella, hepatitis A and B were tested with the enzyme-linked immunosorbent assay (ELISA) method. Antibody titers were measured firstly at the leukemia diagnosis time when the chemotherapy was not started. The second evaluation of antibody titers was studied at 6 months after the cessation of chemotherapy for all patients. Forty-six patients with the mean age of 6.1 ± 4.5 years were participated in this study. Changing to seronegative after treatment was significantly different in measles, rubella, hepatitis A and hepatitis B (p < .05). Seventy-eight (28%) antibody levels in the patients were non-protective for all diseases. Only three (7%) patients had protective antibody levels for all diseases in the sixth month of chemotherapy cessation. There was a negative correlation between patient's age and losing protective antibody levels for any vaccine-preventable disease (p < .05). Antibody levels against vaccine-preventable diseases have evident that reduced after ALL treatment at childhood. Pediatric ALL survivors must be re-vaccinated for vaccine-preventable diseases after achieving immune reconstruction.

A Case of Congenital Hepatoblastoma Coexisting with Pulmonary Hypertension.

Hepatoblastoma (HBL) is the most frequently detected malignant tumor of the liver in childhood. HBLs detected antenatally or up to 3 months after birth are considered congenital HBLs. We report a five-day-old female infant in whom a hepatic mass was detected at 20 weeks' gestation. At birth (36 weeks), the hepatic mass measured 12x6 cm, and she had respiratory distress. Pulmonary hypertension (PHT) was detected on echocardiographic evaluation. Despite dual medical therapy, her PHT did not improve. Histologically, the biopsy demonstrated a mixed epithelial-mesenchymal HBL with predominance of fetal morphology in the epithelial component. Chemotherapy was initiated on postnatal day 15; however, the baby died of respiratory failure on postnatal day 23. Conclusion: HBL is an embryonal tumor which can develop early in the intrauterine period. Although the mechanism is not known, it may cause PHT which would affect the prognosis negatively.

Erythrocyte Indices as Differential Diagnostic Biomarkers of Iron Deficiency Anemia and Thalassemia.

INTRODUCTION: The most common causes of microcytic anemia are iron deficiency anemia (IDA) and thalassemia trait (TT). This study investigated the reliability of erythrocyte indices and formulas as screening tests in the differential diagnosis of IDA and TT before performing detailed tests for definitive diagnosis. MATERIALS AND METHODS: In total, 50 children with ß-TT, 31 with α-TT, 50 with IDA were included. For the 8 erythrocyte indices and formulas (red blood cells [RBC], red blood cell distribution width [RDW], red blood cell distribution width index [RDWI], Mentzer index [MI], Shine and Lal index [S&L], England and Fraser [E&F], Green and King index [G&K], Srivastava index) the sensitivity, specificity, positive and negative predictive values (PPVs and NPVs, respectively) were calculated according to the cutoff values in the literature and recalculated revised cutoff values. RESULTS: According to the cutoff values in the literature for the differential diagnosis of IDA and TT, the ranking of sensitivity, specificity, PPVs, and NPVs from the highest to the lowest was RDWI, RBC, E&F, G&K, MI, Srivastava, RDW, S&L. The sensitivity, specificity, PPVs, and NPVs of all the indices according to the revised cutoff values were higher than those according to the cutoff values in the literature. CONCLUSIONS: According to both the cutoff values in the literature and revised cutoff values, the most reliable indices were RBC and RDWI.

A novel mutation in the GP1BA gene in Bernard-Soulier syndrome.

: The Bernard-Soulier syndrome (BSS) is a rare disease with a prevalence of 1/1000 000; it is characterized by macrothrombocytopenia. BSS develops as a result of a defect in the glycoprotein GPIb-IX-V complex on the platelet surface. In this article, we present a pediatric patient with the novel mutation that has been identified for the first time in BSS. A 13-month-old male patient was admitted with severe thrombocytopenia unresponsive to intravenous immunoglobulin in the neonatal period and recurrent mucocutaneous bleeding which initiated at 5 months of age. glycoprotein (GP) IX (CD42a) expression was normal as per flow cytometry results. Genetic analysis revealed a homozygous c.243C>A (p.Cys81) (p.C81) mutation. This novel mutation identified by us presents with severe thrombocytopenia and normal GPIX (CD42a) expression and is mistaken for immune thrombocytopenia in the neonatal period. This mutation creates an early stop codon and possibly leads to loss of function of the receptor.

Infantile hemangioma: Efficacy of low-dose propranolol and of intralesional bleomycin injection for propranolol non-response.

BACKGROUND: Infantile hemangioma (IH) is the most common form of benign childhood vascular tumor. Most resolve spontaneously, but treatment is recommended in patients who develop complication. Propranolol is recommended as the first-line therapy, while the treatment in the case of non-response to first-line therapy depends on the clinical experiences of each center. The aim of this study was to investigate the efficacy of low-dose propranolol in the treatment of IH, and the outcomes of percutaneous intralesional bleomycin injection (IBI) in patients unresponsive to propranolol. METHODS: Medical records of 104 children diagnosed with IH between June 2014 and June 2017 were reviewed retrospectively. RESULTS: Median patient age was 6 months (range, 3-12 months). Forty-five patients (43.3%) received therapy: 18 (40%) for cosmetic problems and 27 (60%) for lesion-related complications. The most common complications were hemorrhage (15.6%) and impairment in visual function (15.6%). All of the patients received propranolol 1 mg/kg/day as the first-line therapy. Response to treatment was excellent in 35 patients, good in four and poor in one, while five patients did not respond to therapy. The five unresponsive patients received percutaneous IBI at 0.3-0.5 mg/kg/dose as second-line therapy. The response to treatment was excellent in four patients, good in one. CONCLUSIONS: The majority of IH resolved spontaneously. In the patients who required treatment, low-dose propranolol was successful in most, and IBI was effective and safe in the remaining five patients who did not respond to propranolol.

Hemophagocytic Lymphohystiocytosis Associated With Type Ia Glycogen Storage Disease.

BACKGROUND: Hemophagocytic lymphohystiocytosis (HLH) is characterized by fever, splenomegaly, pancytopenia, and elevated levels of triglycerides and ferritin. These signs and symptoms are common to other metabolic diseases. OBSERVATION: A 5-month-old female infant, who presented with fever, respiratory distress, massive hepatomegaly, and bicytopenia, was diagnosed as having HLH and chemotherapy was initiated. The patient was negative for familial HLH gene mutations. Respiratory distress and laboratory findings improved rapidly after starting chemotherapy. However, there was no improvement in the massive hepatomegaly and she experienced hypoglycemic episodes. In addition, her family history included a cousin with glycogen storage disease (GSD). On the basis of the findings, the patient was diagnosed as having type Ia GSD. There are no previous reports of HLH secondary to GSD type Ia in the literature. CONCLUSIONS: Congenital metabolic diseases should be considered in the differential diagnosis of children with HLH.

The predictive value of procalcitonin, C-reactive protein, presepsin, and soluble-triggering receptor expressed on myeloid cell levels in bloodstream infections in pediatric patients with febrile neutropenia.

Özdemir ZC, Düzenli-Kar Y, Canik A, Küskü-Kiraz Z, Özen H, Bör Ö. The predictive value of procalcitonin, C-reactive protein, presepsin, and soluble-triggering receptor expressed on myeloid cell levels in bloodstream infections in pediatric patients with febrile neutropenia. Turk J Pediatr 2019; 61: 359-367. The present study investigates the predictive value of procalcitonin (PCT), C-reactive protein (CRP), presepsin (PRE-SEP) and soluble-triggering receptor, as expressed on myeloid cells (sTREM-1) levels in bloodstream infections in pediatric patients with febrile neutropenia. A total of 47 episodes of febrile neutropenia that developed in 30 children with malignancy were analyzed in this study, while the control group comprised 27 children who had undergone chemotherapy for malignancy (completed ≥2 years ago) without neutropenia, fever or drug use. Median PCT, CRP, PRE-SEP and sTREM-1 levels on admission were found to be significantly higher in the patient group than in the control group, while in the blood cultures, the microbiological agent was isolated in 13 (27.7%) of the 47 episodes. Median PCT and CRP levels on days 1, 2 and 7 were higher in the blood culture-positive episodes than in the blood culture-negative episodes. There was no significant difference in the PRE-SEP and sTREM-1 levels on days 1, 2 and 7 between the blood culture-positive and blood culture-negative episodes. The results of the study suggest that PRESEP and sTREM-1 are at measurable levels upon admission in children with febrile neutropenia, but that these markers may not be appropriate for the predicting of bloodstream infections, although CRP and PCT levels within the first 24 hours may serve as a guide for clinicians.

The Frequency of Metabolic Syndrome and Serum Osteopontin Levels in Survivors of Childhood Acute Lymphoblastic Leukemia.

PURPOSE: Metabolic syndrome (MetS) and obesity have increasingly been reported in survivors of childhood cancer. Osteopontin (OPN) is primarily synthesized in adipose tissue and is thought to have a role in obesity and the development of insulin resistance (IR). The aim of this study was to investigate the frequency of MetS in survivors of acute lymphoblastic leukemia (ALL) and to establish the relationship between serum OPN levels and anthropometric measurements and glucose metabolism. METHODS: A total 50 survivors of ALL (median age: 10.5 years; post-treatment interval 4.54 ± 2.48 years), and 20 healthy children (median age: 11 years) were included in the study. Anthropometric measurements were taken, and serum glucose, insulin, homeostasis model assessment and IR index (HOMA-IR index), lipoprotein, thyroid hormone levels, and OPN levels were measured. RESULTS: Twenty-one (42%) survivors were overweight/obese, 2 (5.1%) survivors had MetS, 7 (14%) survivors had IR, and 19 (38%) survivors had dyslipidemia. Fasting insulin levels and HOMA-IR of the overweight/obese survivors were significantly higher than those of the normal-weight survivors (p < 0.05 and p < 0.01) and control group (p < 0.01 and p < 0.01). The serum OPN level was significantly lower in the overweight/obese survivor than in the normal-weight survivor and control group (37.42 ng/mL [range, 27.32-62.07], 69.02 ng/mL [range, 40.29-88.21], and 85.7 ng/mL [range 67.7-102.3]; p < 0.01, p < 0.001, respectively). Serum OPN levels were inversely correlated with anthropometric measurements and HOMA-IR index in all the subjects. CONCLUSION: Our results showed that obesity and IR are associated with decreased serum OPN levels in childhood survivors of ALL.

Evaluation of hypercoagulability with rotational thromboelastometry in children with iron deficiency anemia.

OBJECTIVE: Iron deficiency anemia (IDA) has been demonstrated to be a risk factor for thromboembolic events, although the pathogenesis of the development of thromboembolism in IDA is as yet unclear. The likelihood of children with IDA contracting hypercoagulability was evaluated in this cross-sectional study using rotational thromboelastometry (ROTEM). MATERIAL AND METHOD: A total of 57 children with IDA (median age 11 years; 37 female, 20 male) and 48 healthy children (median age 9.9 years; 23 female, 25 male) were enrolled in the study. Whole blood count, serum iron, transferrin saturation, ferritin level, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen levels were ascertained, while ROTEM assays [intrinsic TEM (INTEM) and extrinsic TEM (EXTEM)] were used to measure and analyze coagulation time (CT), clot formation time (CFT), maximum clot firmness (MCF) and rate of maximum lysis (ML60%). This study conforms to ethical standards, has been approved by the appropriate Institutional Review Board. RESULTS: Hemoglobin, serum iron, transferrin saturation and ferritin levels were lower in the IDA group than in the control group (p < 0.001, for all), while the EXTEM and INTEM CT in the two groups were similar (p > 0.05). The EXTEM and INTEM MCF in the IDA group was higher than in the control group, while the INTEM CFT and rate of ML60% were lower than in the control group (p < 0.001, p < 0.001, p < 0.05, p < 0.001, respectively). CONCLUSION: The ROTEM results suggest that although the platelet count and coagulation tests were within normal ranges in IDA, the tendency to coagulate may have been increased.

Fatal course of Saprochaete capitata fungemia in children with acute lymphoblastic leukemia.

Saprochaete capitata (S. capitata) is a very rare fungal pathogen that causes disseminated opportunistic infections in patients with hematologic malignancies. Fever resistant to broad-spectrum antibiotic and antifungal treatment is common in the presence of fungemia during the period of profound neutropenia. We describe three cases of leukemic children who died from S. capitata fungemia following a first febrile neutropenic episode after the induction of chemotherapy. S. capitata fungemia is an emergent infection associated with high mortality and low susceptibility to fluconazole and echinocandins. Awareness of this emergent infection is needed to ensure that it can be properly treated.

Beta blocker and steroid therapy in the treatment of infantile hepatic hemangioendothelioma.

Infantile hepatic hemangioendothelioma (IHHE) is the most common benign vascular liver tumor and typically occurs during the first 6 months of life. A 4-month-old male patient presented with abdominal distention. A physical examination revealed massive hepatomegaly. Liver enzyme levels were normal. The alpha fetoprotein level was 1,323 mg/dL (6-1,000). Abdominal magnetic resonance imaging (MRI) showed multiple, well-defined and hyperintense nodular lesions in the liver. MRI findings suggested IHHE. The thyroid stimulating hormone (TSH) level was high (177.2 µU/mL). He was started on sodium levothyroxine 50 µg daily. The patient has hypoxemia due to abdominal distention during the follow-up period. Oral methylprednisolone therapy was started at a dose of 2.5 mg/kg/dose, and propranolol at a dose of 1 mg/kg/dose, bid. Fifteen days later his TSH level remained elevated at 212.3 µU/mL despite repeatedly increasing the dose of levothyroxine up to 200 µg/daily. One month after the initial presentation, his TSH level was reduced to 11.28 µU/mL. We observed a marked improvement in abdominal distention and respiratory distress within 15 days and an average reduction of 50% in the lesion diameters after a month. Despite its benign nature, IHHE may lead to development of complications. Steroid and propranolol treatment may be useful in in the management of emergency complications.

The frequency of hepatotoxicity and myelotoxicity in leukemic children with different high doses of methotrexate.

BACKGROUND AND OBJECTIVES: Methotrexate (MTX) is a chemotherapeutic agent that functions as a folic acid antagonist. The frequency of high dose methotrexate (HDMTX)-associated toxicity is variable. In this study, we investigated the frequency of myelotoxicity and hepatotoxicity 7 days after HDMTX infusion. PATIENTS AND METHODS: This study included children diagnosed with acute lymphoblastic leukemia (ALL) between January 2010 and April 2015. The patient blood counts and biochemical parameters measured before and after 7 days of HDMTX infusion were retrospectively recorded. We assessed HDMTX infusions for 48 children. The number of patients and drug doses included the following: 17 children receiving 1 g/m2 (68 infusions), 14 children receiving 2 g/m2 (56 infusions), and 17 children receiving 5 g/m2 (68 infusions). The classification of toxicity was made based on the Common Terminology Criteria for Adverse Events (CTCAE) 2010 criteria. Myelotoxicity was defined as a hemoglobin level <10 g/L and absolute neutrophil count <1 × 109/L or platelet count <75 × 109/L. The presence of transaminase levels ≥5 times the upper limit was considered to be hepatotoxicity grade ≥3. The MTX levels at 42 h in patients with and without toxicity were compared to evaluate the correlation between MTX levels, hematologic parameters, and transaminase levels. RESULTS: Myelotoxicity was observed in 35.2%, 37.5%, and 33.8% of the infusions, and hepatotoxicity grade ≥3 was detected in 13.2%, 12.5%, and 11.7% of the infusions in patients receiving 1, 2 and 5 g/m2 HDMTX after 7 days, respectively. There was no statistically significant difference between MTX levels at 42 h in patients with and without toxicity (P > .05, for all). There was no correlation between hematologic parameters and transaminase levels and MTX levels at 42 h. CONCLUSION: Hematologic toxicity was the most common toxicity observed. The data indicate the hematologic toxicity increased after repeated cycles in patients receiving 5 g/m2. However, the hepatic toxicity decreased with additional cycles. Our results show the level of MTX at 42 h is not effective to identify toxicity.