Emine Zengin

MONOTHERAPY WITH PIPERACILLIN/TAZOBACTAM VERSUS CEFEPIME AS EMPIRICAL THERAPY FOR FEBRILE NEUTROPENIA IN PEDIATRIC CANCER PATIENTS: A Randomized Comparison

The purpose of this study was to compare the efficacy, safety, and cost of piperacillin/tazobactam with cefepime monotherapy in children with febrile neutropenia. A prospective randomized study in children and adolescent with cancer was conducted. Patients were randomly assigned to receive either 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 h (maximum 4.5 g/dose) or cefepime 50 mg/kg every 8 h (maximum 2 g/dose). Treatment modification was defined as all the changes in the empirical antimicrobials after the first 96 h. Overall treatment success was defined as cure of febrile episode with or without modification. Cost of hospitalization, antimicrobial drugs, and supportive therapy were calculated. Fifty febrile netropenic episodes (25 in the piperacillin/tazobactam group, 25 in the cefepime group) in 27 pediatric cancer patients were evaluated. The groups were comparable in terms of age, gender, body weight, primary diagnosis, disease status, initial neutrophil count, and duration of neutropenia. Microbiologically and clinically documented infection rate was 46%. There was no infection-related mortality in the study period. The treatment success of initial empirical therapy without modification was not different in the 2 groups (56% in piperacillin/tazobactam group and 48% in cefepime group). Anti-anaerobic drugs were added more frequently in the cefepime group. Duration of fever, neutropenia, treatment, and cost of therapy were not different in the treatment groups. Piperacillin/tazobactam monoterapy is as effective as cefepime monotherapy in febril neutropenia of pediatric cancer patients.

Clinical manifestations of infants with nutritional vitamin B12 deficiency due to maternal dietary deficiency

Aim: In developing countries, nutritional vitamin B12 deficiency in infants due to maternal diet without adequate protein of animal origin has some characteristic clinical features. In this study, haematological, neurological and gastrointestinal characteristics of nutritional vitamin B12 deficiency are presented.

Cord Blood Cardiac Troponin I as an Early Predictor of Short-Term Outcome in Perinatal Hypoxia

BACKGROUND In most perinatal-hypoxia survivors, myocardial dysfunction can be reversed with appropriate inotropic support and oxygenation. The main problem related to outcome is cerebral damage. OBJECTIVE We tested the hypothesis that cardiac troponin I (cTnI), a known marker of myocardial injury, is also an early predictor of severity of cerebral damage and mortality in intrauterine hypoxia. METHODS Venous and arterial cord blood samples were collected at delivery from 54 consecutive newborns with hypoxic-ischemic encephalopathy and from 50 consecutive healthy controls. Arterial blood gas analysis was performed and levels of cTnI, creatine kinase and creatine kinase-MB in venous cord blood were measured. The same serum parameters were also measured on the 3rd and 7th day of life. RESULTS Infants with hypoxia had a significantly higher cord blood cTnI levels than controls (p < 0.0001). Cord blood and 3rd and 7th day serum cTnI values showed a significant increase with severity of HIE (p < 0.0001). In non-survivors cord blood cTnI levels were significantly higher than the survivors (5.9 ng/ml, range 2.1-12.8, and 1.6 ng/ml, range 0.4-5.8, respectively; p < 0.0001). Receiver-operator curve analysis revealed cord cTnI as the most sensitive factor for predicting early death (area under curve = 0.956; SE: 0.028; 95% CI: 0.9-1.01). Cord blood cTnI of 4.6 ng/ml was identified as the optimal cut-off level for predicting serious risk of early mortality. CONCLUSION The results suggest that significant elevation of cord cTnI is an excellent early predictor of severity of hypoxic-ischemic encephalopathy and mortality in term infants.

Humoral immunity to diphtheria, tetanus, measles, and hemophilus influenzae type b in children with acute lymphoblastic leukemia and response to re-vaccination

Loss of immunity to previous vaccination and timing of re‐vaccination in children receiving chemotherapy remains controversial. The aim of this study was to investigate the immunity to vaccine preventable diseases in children with acute lymphoblastic leukemia (ALL).

EVALUATION OF ANTHRACYCLINE-INDUCED EARLY LEFT VENTRICULAR DYSFUNCTION IN CHILDREN WITH CANCER: A Comparative Study with Echocardiography and Multigated Radionuclide Angiography

The study aimed to compare diastolic and systolic dysfunctions detected by echocardiography (ECHO) and multigated radionuclide angiography (MUGA) in patients with cancer in the first 3 months after anthracycline-comprising chemotherapy. Children with leukemia and solid tumors who had anthracycline-comprising chemotherapy were enrolled in the study. ECHO and MUGA were performed in all patients before the first chemotherapy course and in the first 3 month of completing anthracycline-comprising chemotherapy. Cumulative anthracycline doses per body surface were calculated. Left ventricular systolic and diastolic functions were measured by both techniques. Twenty-one patients with a median age of 6.9 ± 3.6 years were enrolled in the study. Mean cumulative anthracycline doses were equivalent to 276 ± 83 mg/m2 doxorubicin. After anthracycline chemotherapy, cardiac dysfunction was detected in 14 and 48% of the patients by ECHO and MUGA, respectively. All dysfunctions detected by ECHO were systolic, whereas 29% of the patients had diastolic and 38% of the patients had systolic dysfunction in MUGA study. Although the study group is small, MUGA seems more sensitive in detecting anthracycline-induced systolic and diastolic cardiac dysfunctions compared to ECHO.

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia

WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated β-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When β-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL.

Hemophilia-Specific Quality of Life Index (Haemo-QoL and Haem-A-QoL questionnaires) of children and adults: result of a single center from Turkey.

The aim of this study is to describe the health status, health care received, and their impact on the quality of life in patients with hemophilia. Patients with severe factor VIII or IX deficiency without inhibitors or other chronic disease were enrolled. Turkish version of the Hemophilia-Specific Quality of Life Index (Haemo-QoL) questionnaire was administered to the pediatric patients aged 4 to 16 years and Haem-A-QoL to the adult patients. Joints were evaluated according to the World Federation of Hemophilia (WFH) orthopedic joint scores.Thirty-nine children/adolescents and 31 adult patients were enrolled. Mean Haemo-QoL scores were 39.6 ± 15.0 for the children and mean Haem-A-QoL 47.4 ± 14.1 for the adult patients, respectively. Internal consistency reliability was generally sufficient. Total Cronbachs alpha coefficient was >.70 (range .77–.96) in all the age groups. Mean total WFH orthopedic joint scores were 1.83 ± 2.7, 4.9 ± 4.96, and 6.94 ± 6.15 in 4–7, 8–12, and 13–16-year-old groups, respectively. They were more impaired in the adult patients (16.23 ±14.12). These results show that the Turkish version of the Haemo-QoL and Haem-A-QoL are reliable instruments to measure the quality of life in the pediatric and adult patients with severe hemophilia. When compared to the Haemo-QoL scores of an international multicenter West European study of children, quality of life in the Turkish patients were more impaired in the subscales of physical health, feeling, view, school and sport, and treatment as well as more impaired WFH joint scores. The authors recommend primary factor prophylaxis and encouraging the patients to learn home treatment to improve joint scores and quality of life.

The effect of blood gas and Apgar score on cord blood cardiac troponin I.

OBJECTIVES The aims of this study were to (a) establish a reference range for cardiac troponin I (cTnI) in the cord blood of healthy infants, and (b) investigate the effect of Apgar score, cord blood gas, gestational age, and creatine kinase (CK) and creatine kinase MB (CK-MB) fraction levels on cord blood cTnI levels. METHODS 112 perinatal hypoxic and 84 control newborns without perinatal hypoxia were enrolled in this study. Cord blood samples were collected from the babies for arterial blood gas analysis, cTnI, CK and CK-MB measurements. Gestational age, birth weight, sex, Apgar score and history of fetal distress were recorded. Hypoxic ischemic encephalopathy (HIE) group, hypoxic but without HIE group and control groups were identified according to clinical observations during the first 72 h in the newborn unit. RESULTS HIE and perinatal hypoxic without HIE groups had a significantly higher cord blood cTnI level according to the control group (1.8 ng/mL (0-13), 0 ng/ml (0-1.1) and 0 ng/ml (0-0.3) respectively). Cord blood cTnI level did not have a correlation with birth weight and gestational age (r = -0.02, p > 0.05 and r = 0.08, p > 0.05 respectively). Cord blood cTnI level also had a negative correlation with pH, bicarbonate, base deficit, and Apgar score (r = -0.40, p < 0.001; r = -0.39 p < 0.001; r = -0.45 p < 0.001; r = -0.41, p < 0.001) respectively). Cord blood cTnI level showed a positive correlation with CK and CK-MB levels (r = 0.45, p < 0.001 and r = 0.37, p < 0.001 respectively). Receiver operator curve analysis revealed that the most sensitive factor for prediction of perinatal hypoxia is cord cTnI value [area under curve = 0.929]. The optimal cut-off value of cord cTnI was 0.35 ng/ml for hypoxia. CONCLUSION cTnI levels in the cord blood are not affected by gestational age and birth weight. cTnI together with CK and CK-MB has been found to be elevated in hypoxic infants compared to normal infants. Therefore cTnI may be an indicator for perinatal hypoxia in neonates.

Screening Survivors of Childhood Acute Lymphoblastic Leukemia for Obesity, Metabolic Syndrome, and Insulin Resistance

Acute lymphoblastic leukemia (ALL) survivors were screened for risk factors of cardiovascular disease. Forty-four ALL survivors in first remission were enrolled. Twenty-six also received 12–18 Gy cranial radiotherapy (RT). Patients’ body mass indexes (BMIs) at dignosis and during the study were compared. Metabolic syndrome (MS) evaluation was performed in patients, parents, and siblings older than 6 years. Homeostasis Model Assessment (HOMA) index of the survivors was also calculated. In survivors with impaired fasting glucose levels, oral glucose tolerance test (OGTT) was performed. Thyroid functions and IGF-1 and/or IGFBP-3 levels of the survivors who received cranial RT were evaluated. Median age of the survivors was 11.5 years (6–23). At diagnosis, mean BMI percentile was 46.7 (3–95) and mean z-score was −0.09 ± 1.14; during the study, these values rose to 71.1 ± 25.6 (3–100) and 0.8 ± 0.94, respectively (P < .001). One patient (2.2%) and nine survivors (20%) were obese at diagnosis and during the study, respectively (P = .005). Survivors had significantly higher BMI percentile and BMI z-score compared to their siblings (P = .006 and P = .011, respectively). The study group was small and we could not show a correlation of the patients’ obesity with RT, thyroid functions, IGF-1, and IGFBP-3 levels. In three survivors (6.8%), there was MS. Maternal and paternal MS was not found as a risk factor for MS of the survivors (P = .1, P = .5, respectively). The HOMA index revealed insulin resistance (IR) in 12 (27.2%) of the survivors, whereas OGTT revealed abnormal glucose regulation and/or IR in four. As a conclusion, ALL survivors have high risk for obesity and MS.

A child with severe form of dyskeratosis congenita and TINF2 mutation of shelterin complex

A 26‐month‐old male presented with bone marrow failure and dystrophic nail lesions mimicking onychomycosis. There was no skin finding. Treatment with androgen and methylprednisolone was started due to unavailability of a matched‐related hematopoietic stem cell donor. After 30 months, transfusion support was required. TINF2 mutation was identified at the age of five and dyskeratosis congenita (DC) was confirmed. TIN2 mutation analysis must be carried out in patients younger than 10 years presenting with bone marrow failure even if characteristic physical anomalies of DC is missing. Genetic confirmation of DC prevents ineffective immunotherapy with misdiagnosis of acquired aplastic anemia. Pediatr Blood Cancer. 2010;55:1185–1186.