Two siblings with Fanconi anemia (FANCQ, ERCC4/XPF) presenting with tumor-mimicking lesions in the brain and acute neurological deterioration.

The complementation Q group (FANCQ) subtype of Fanconi anemia (FA) caused by the ERCC4/XPF mutation is very rare. Two siblings, aged 13 and 10 with Fanconi phenotypic features, presented with right hemiparesis and focal-onset seizures. In both cases, cranial magnetic resonance imaging (MRI) showed mass-like lesions accompanied by peripheral edema and calcification. In one case, oral steroid treatment and surgical excision were performed, while in the other case, the cranial lesion regressed just with steroid treatment and without surgery. Both siblings remained wheelchair-bound due to neurological dysfunction. One case died due to hepatocellular carcinoma. ERCC4/XPF gene mutation was detected in both siblings.

Thrombin generation assay in platelet-poor plasma in children with iron deficiency anemia.

OBJECTIVES: Iron deficiency anemia (IDA) is the most common type of anemia in childhood and it leads to a hypercoagulable state. We investigated endogenous thrombin production in platelet-poor plasma before and after oral iron replacement in children with IDA using the thrombin generation assay (TGA). METHODS: A total of 72 children diagnosed with IDA (IDA group) and 60 healthy children (control group) were included in the study. Blood samples were collected from the patients before and 1 month after oral iron replacement. TGA parameters [lag time, time to peak, peak height, endogenous thrombin potential (ETP)] were studied. RESULTS: In the IDA group, the lag time and time to peak decreased by 8.3% and 10.6%, respectively, and the endogenous thrombin potential (ETP) and peak height both increased by 30% compared to those of the control group. Compared to the values before iron replacement, 1 month after iron replacement, the lag time and time to peak increased by 8.7% and 5%, respectively, and the ETP and peak height decreased by 31% and 31.3%, respectively, and became similar to those of the control group. CONCLUSION: Children with IDA have increased endogenous thrombin production in platelet-poor plasma and a tendency for hypercoagulability. These changes are reversible, and the ETP values become similar to those of healthy children 1 month after iron replacement.

Clinical and laboratory responses to tigecycline in children.

WHAT IS KNOWN AND OBJECTIVE: The frequency of multidrug-resistant bacterial infections is increasing worldwide. Tigecycline may be an important option for children with life-threatening nosocomial infections due to multidrug-resistant bacteria. However, there are few published data on the use of tigecycline in paediatric patients. By examining the results of tigecycline use in children, we aimed to draw attention to the fact that tigecycline may be an alternative in the treatment of resistant infections in children. METHODS: Paediatric patients treated with tigecycline from 1 January 2010 to 31 October 2018 at Eskisehir Osmangazi University Medical Faculty, which is a tertiary hospital, were analysed retrospectively to assess the efficacy and safety of tigecycline treatment in children. Patients using tigecycline were identified using the pharmacy database. Clinical and laboratory data were obtained from the files. RESULTS AND DISCUSSION: This study included 91 children aged 7 months to 17.5 years; 52 were female (57.1%). At least one predisposing factor was present in 98.9% of the patients. Fifty-one bacteria were isolated from 44 patients. The tigecycline resistance rate was 3.9%. Only 2 of 91 patients experienced one or more side effects of tigecycline. Tigecycline can be used as salvage therapy in resistant infections where options are limited, although definitive conclusions about the efficacy and safety of tigecycline in children cannot be reached. WHAT IS NEW AND CONCLUSION: Tigecycline may be a safe and important option in paediatric nosocomial infections due to resistant bacteria. Resistant bacterial infections have become more common in recent years, its treatment becomes a difficult problem. Tigecycline has a broad-spectrum antibacterial activity including resistant pathogens.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

The effects of N-acetylcysteine on experimentally created l-asparaginase-induced liver and pancreatic damage in rats.

In this study, oxidative stress marker (malondialdehyde, MDA) and antioxidant enzymes (glutathione (GSH), catalase (CAT)) levels in the liver and pancreas tissue and the histopathological effects of N-acetylcysteine (NAC) were investigated in l-asparaginase (l-ASP) induced liver and pancreatic damage in rats. Forty male albino rats were divided into four groups. The control group was intraperitoneally injected physiological saline (0.02 mL/g); NAC group was injected NAC (200 mg/kg, five days); l-ASP group was injected single-dose l-ASP (10,000 U/kg), and l-ASP + NAC group was injected NAC for five days following single-dose l-ASP (10,000 U/kg). The surgical operation was performed on all animals on the fifth day. There was no difference between the groups regarding tissue MDA, GSH, and CAT levels (p>.05, for all). In the group receiving NAC after l-ASP, there was a significant improvement in the liver and pancreas damage score than the l-ASP group. NAC was effective in reducing organ damage caused by l-ASP.

Hepatitis-Associated Aplastic Anemia: Etiology, Clinical Characteristics and Outcome.

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were <3 to 5×upper limit of normal (ULN) in 2 patients, <5 to 10×ULN in 2 patients, and >10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed.

A Case Report of Congenital Thrombotic Thrombocytopenic Purpura: The Peripheral Blood Smear Lights the Diagnosis.

We report on a 12-year-old boy with congenital thrombotic thrombocytopenic purpura, on who had an erroneous diagnosis as chronic immune thrombocytopenia. The patient presented with complaints of jaundice and skin rash. Laboratory analysis showed nonimmune hemolytic anemia and severe thrombocytopenia. Peripheral blood smear showed 8% schistocytes, polychromasia, and anisocytosis. The ADAMTS13 antigen and activity were suspected to be lower than 5% with any antibodies against the enzyme. The DNA sequence analyses resulted in compound heterozygosity consisting of c.291_391del in exon 3 and c.4143dupA in exon 29. Schistocyte (fragmented erythrocytes) on the peripheral blood smear is a light that illuminates the diagnosis. Early recognition of the disease can prevent inappropriate treatments and morbidities due to organ damage.

Etiological causes and prognosis in children with neutropenia.

OBJECTIVE: Neutropenia is defined as an absolute neutrophil count (ANC) below 1500/mm3 in the peripheral blood and is a common condition in childhood. In this study, underlying etiological causes and prognoses in children in follow-up due to neutropenia were analyzed to form a guide for physicians working in primary health care institutions. METHODS: The medical records of pediatric patients who were followed up as an inpatients or outpatients due to neutropenia between October 2014 and October 2017 were reviewed retrospectively. RESULTS: A total of 94 patients were included in the study with a median age of 24 (8-77) months. The median ANC at the time of admission was 600 (300-970)/mm3. The ANC was 0-500/mm3 in 34 patients (36.2%), 500-1000/mm3 in 36 patients (38.3%), and 1000-1500/mm3 in 24 patients (25.5%). Of the total, 43 patients (45.7%) were followed up as inpatients and 51 (54.3%) were followed as outpatients. Fifty-five patients (58.5%) were diagnosed with post-infectious neutropenia. The most common focus of infection was the upper respiratory airway (38.4%). The etiological cause could not be identified in 23 (24.6%) patients, neutropenia developed during drug use in 6 patients (6.3%), 5 patients (5.3%) were diagnosed with Vitamin B12 deficiency (Vitamin B12 level: 168 [129-174] pg/ml, the levels were studied in 48 patients), 2 patients (2%) were diagnosed with chronic benign neutropenia, 1 patient (1.1%) was diagnosed with immune deficiency, 1 patient (1.1%) was diagnosed with autoimmune lymphoproliferative syndrome, and 1 patient (1.1%) was diagnosed with hemophagocytic lymphohistiocytosis secondary to a previous infection. No patient was diagnosed with congenital neutropenia. A total of 91 patients (96.8%) recovered from the neutropenia. Neutropenia did not improve in 3 patients (3.2%). One patient was lost due to infection. CONCLUSION: Etiological cause can be shown in approximately 75% of neutropenic children. The most common etiological cause is infection. Drug use, nutritional deficiencies, and chronic benign neutropenia are less common causes of neutropenia. The clinical course is largely benign and the mortality rate is very low.

Assessment of respiratory tract viruses in febrile neutropenic etiology in children and comparison with healthy children with upper/lower respiratory tract infection.

OBJECTIVE: This study aims to compare the frequency of respiratory viruses using real-time and multiplex polymerase chain reaction technology and nasopharyngeal swabs taken during exacerbation of patients aged 0-18 years followed for febrile neutropenia (FN) with non-FN children. METHODS: This prospective study included a total of 40 patients with FN and malignancies followed at Eskisehir Osmangazi University, Department of Pediatric Hematology and Oncology. The control group (n=76) consisted of age-matched patients with upper respiratory tract infections (URTIs) or lower respiratory tract infections (LRTIs) who were admitted to the emergency service due to fever. RESULTS: Viral agents were detected in 16 of 53 FN attacks (30.1%). The most commonly isolated viruses were coronavirus (23.7%, n=9), influenza B (18.4%, n=7), and adenovirus (18.4%, n=7). Of 76 children diagnosed with URTI with fever (52.6%) had viral agents, and only 28 of them had a single agent. The most commonly isolated virus was adenovirus (28.6%, n=14). Viral factors were found in 32 of 42 patients (76.1%) patients diagnosed with LRTI, while respiratory syncytial virus was the most common virus in 27 patients (21.7%, n=5). CONCLUSION: Our study results show that viral agents play an important role in the etiology of FN. This is the first study to show that viral agents play an important role in the etiology of this disease and viral factors in non-neutropenic febrile children at the same time period by detecting respiratory viruses in 30% of FN cases. More similar studies provide antiviral therapy in selected patients, as well as these studies lead to reduce the use of antimicrobial agents or allow more selective use of antibiotics and/or the earlier discontinuation of these antibiotics in febrile neutropenic children who have been shown to have viral cause of respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria.

A pediatric BAL case with double Ph chromosomes and trisomy 5.

Biphenotypic acute leukemias (BAL) are known as a type of leukemia involving cells with myeloid and along with lymphoid origin, in which genomic changes are detected. It has been stated that the most common genomic changes in BAL are t(9;22) and the translocations of the 11q23 region, these anomalies cause poor prognostic effects. We detected trisomy 5 (+5) in addition to the double Ph chromosome in a case where we investigated the genomic changes using molecular and conventional cytogenetic methods. Bone marrow transplantation was planned due to the poor response to prednisone. According to the information we have obtained, our report will be the first article to discuss the aberrations found in addition to the Ph chromosome in BAL and the effect of these aberrations on prognosis. However, the double observation of the Ph chromosome, which has a poor prognostic effect, is expected to affect the prognosis more negatively, this case will contribute to the literature in terms of trisomy 5. We think that more case reports are needed to reveal the anomalies and their prognostic significance in BAL.

Relationship between oxidant-antioxidant status and hypercoagulobility indices in children with iron deficiency anaemia.

Oxidative stress is a potential mechanism involved in the pathogenesis of iron deficiency anaemia (IDA). Although a tendency for hypercoagulability has been reported in IDA, its underlying mechanism is yet to be elucidated. This study investigated the probable relationship between oxidative stress and hypercoagulability in children with IDA. This study included 57 children diagnosed with IDA (IDA group) between October 2016 and October 2017 in addition to 48 healthy children (control group). The maximum clot firmness (MCF) index, and clot formation time (CFT) index, which are indicators of hypercoagulability in rotational thromboelastometry assays [intrinsic TEM (INTEM) and extrinsic TEM (EXTEM)] derived from our previous study, were recorded. Total oxidant status (TOS), total antioxidant capacity (TAC) and oxidative stress index (OSI) were analysed from serum samples of the individuals. In IDA group, OSI and TOS levels were higher and TAC level was lower compared to the control group (P < 0.001, for all). The EXTEM and INTEM MCF in the IDA group was higher than in the control group, while the INTEM CFT was lower than in the control group (P < 0.001, P < 0.001, P < 0.05, published data).TOS and OSI had a negative correlation with INTEM CFT (r:-0.361, P < 0.001 and r:-0.333, P = 0.001) and a positive correlation with INTEM MCF (r:+0.420, P < 0.001 and r:+0.367, P < 0.001) and EXTEM MCF (r:+0.476, P < 0.001 and r:+0.403, P < 0.001). However, TAC demonstrated no correlation with CFT and MCF index. The oxidant-antioxidant balance is disrupted in favour of oxidative stress in children with IDA. In addition, TOS and OSI, which are parameters of oxidative stress, are correlated with CFT and MCF indices. Oxidative stress appears to be an important factor for the development of tendency to hypercoagulability in IDA.

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.

Rotational Thromboelastometry Profile in Children With Chronic Spontaneous Urticaria.

The pathogenesis of chronic spontaneous urticaria (CSU) is incompletely understood. There is a growing interest in the role of the coagulation cascade in chronic urticaria. Rotational thromboelastometry (ROTEM) assay enables the global assessment of coagulation status. In the present study, we aimed to test the coagulation profile in children with CSU using ROTEM and correlate these parameters with those of a healthy group. A total of 24 children with active CSU (11 girls and 13 boys) 8 to 17 years of age and age-matched and sex-matched 30 healthy control participants were enrolled in the study. ROTEM assays (intrinsic thromboelastometry and extrinsic thromboelastometry) were used to measure and analyze coagulation time, clot formation time, and maximum clot firmness. The CSU patients and controls did not differ in age, sex, erythrocyte, neutrophil, and platelet counts. Also, ROTEM parameters did not show any difference between the 2 groups. ROTEM is increasingly being used as a tool for monitoring coagulation status. In this study, ROTEM parameters did not show any difference between CSU patients and the healthy group. Further studies are needed to confirm our findings on a larger number of CSU patients.

Thiol / disulfide balance and oxidative stress parameters in pediatric patients diagnosed with acute and chronic idiopathic thrombocytopenic purpura.

BACKGROUND: Changes in oxidative stress and thiol / disulfide balance are thought to play a role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP). Our study investigates total oxidant level (TOS), total antioxidant level (TAS), oxidative stress index (OSI) levels and thiol / disulfide balance in pediatric patients with acute and chronic ITP. METHODS: Thirty four patients with acute ITP, eighteen patients with chronic ITP and thirty three healthy children (control) were included. TOS, TAS, OSI, thiol / disulfide balance were analyzed. RESULTS: In acute ITP, TAS levels were lower than chronic ITP and control, TOS and OSI levels were higher than control, and native thiol level was lower than chronic ITP (p < 0.05). In acute ITP; disulfide level, disulfide / native thiol and disulfide / total thiol ratios were higher than chronic ITP and control, and native thiol / total thiol ratio was lower than chronic ITP and control group (p = 0.038, p = 0.018, respectively). TOS and OSI levels of the chronic ITP were higher than the control group (p < 0.05). CONCLUSIONS: The results of this study have shown that oxidative stress increases in children with acute ITP and chronic ITP, that thiol / disulfide balance is disrupted in favor of disulfide in acute ITP, and that thiol / disulfide balance isn`t disrupted in chronic ITP patients whose platelet count is close to normal and who don`t require treatment.

Cerebral sinovenous thrombosis in children: clinical presentation, locations, and acquired and inherited prothrombotic risk factors.

BACKGROUND: Cerebral sinovenous thrombosis (CSVT) in children is a rare and life-threatening cerebrovascular disease. Hence, we evaluated its clinical presentations, inherited and acquired prothrombotic risk factors along with the accompanying diseases, the thrombosis locations as well as the outcomes of anticoagulant therapy in children with CSVT. METHODS: The medical records of pediatric CSVT patients treated between January 2011 and September 2018 were analyzed retrospectively. RESULTS: The study included 29 children, 15 boys (51.7%) and 14 girls (48.3%), with the median age being 11 years (range:3 days-17 years). The most commonly presented complaint in neonates was seizures and in the non-neonatal age groups was a headache. Also, at least one acquired and/or inherited thrombophilic risk factor was identified in 89.7% of the patients. The most commonly acquired prothrombotic risk factors along with the accompanying diseases included infections, central venous catheter, and dehydration, while the most commonly inherited thrombophilic risk factors included heterozygous factor-V Leiden mutation and elevated lipoprotein (a). The most common thrombosis location was found to be the transverse sinus. Also, none of the patients died due to the thrombotic episode. Complications included epilepsy in five patients, hydrocephalus in one patient, and intracranial hypertension in another patient. CONCLUSIONS: Clinicians need to be well aware of the inherited and acquired prothrombotic risk factors in CSVT. It should also be kept in mind that at-risk patients may also present with nonspecific signs and symptoms with no apparent neurological manifestation. The risk of acute complications and long-term sequelae can be substantially reduced if diagnosed early and initiated with appropriate treatment at the early stages.

Evaluation of Cardiotoxic Effects of Anthracyclines by Tissue Doppler Imaging in Survivors of Childhood Cancer.

BACKGROUND: Childhood cancer survivors (CCSs) are at risk for anthracycline-induced cardiotoxicity which tends to be more prominent long after completion of the chemotherapy. The aim of this study was to examine echocardiographic parameters of anthracycline-induced subclinical cardiotoxicity in children who had received chemotherapy. MATERIALS AND METHODS: A cross-sectional single-center study was conducted in a tertiary level university hospital in Eskisehir, Turkey. A total of 50 CCSs and 40 healthy peers were included. The CCSs were divided into 3 subgroups according to cumulative anthracycline dose (100-200 mg/m2, 201-299 mg/m2, and ≥ 300 mg/m2). Biventricular cardiac examination was performed with conventional echocardiography and tissue Doppler echocardiography imaging (TDI). RESULTS: The mean duration from termination of chemotherapy to echocardiographic assessment was 3.9 ± 2.2 years. The mean age of the CCSs was 11.6 ± 3.9 years. TDI-derived mitral annular isovolumetric relaxation time (IVRT) and myocardial performance index (MPI) were higher in the high-dose group of CCSs than in controls (P = .006, P = .007, P < .001, P = .0014, respectively). IVRT was also higher in patients with ≥ 300 mg/m2 cumulative dose than in those with < 200 mg/m2 (P = .007). TDI-derived mitral annular MPI and IVRT were significantly associated with cumulative anthracycline dose (r = 0.288, P = .006, r = 0.340, P = .001). CONCLUSION: A cumulative anthracycline dose > 300 mg/m2 may lead to subclinical cardiotoxicity, and is therefore a potential risk factor for late onset cardiac failure. TDI-derived MPI can be a sensitive tool to reveal subtle signs of myocardial damage, which may facilitate implementation of preventive therapies for patients suspected to be at risk.