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.

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.

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.

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.

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.

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.

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.

Evaluation of the Coagulation Profile With Rotational Thromboelastometry in Children With Hereditary Spherocytosis.

Hereditary spherocytosis (HS) is a familial hemolytic disorder associated with a variety of mutations that lead to defects in red blood cell (RBC) membrane proteins. There is increasing evidence that hypercoagulability occurs in chronic hemolytic anemia. In this study, changes in the coagulation profile in children with HS were investigated using rotational thromboelastometry. A total of 21 children with HS and 28 healthy children were enrolled in the study between October 2010 and October 2018. Complete blood count, prothrombin time, activated partial thromboplastin time, and fibrinogen level were ascertained, while rotational thromboelastometry assays were used to measure and analyze coagulation time, clot formation time, and maximum clot firmness. There was no difference between the 2 groups in terms of age and sex. The values of hemoglobin and RBC in the patient group were statistically significantly lower than those in the control group (P<0.01, <0.0001, respectively), and the values of platelet count, mean corpuscular hemoglobin concentration, and RBC distribution width were statistically significantly higher than those in the control group (P<0.05, 0.001, <0.0001, respectively). There was no statistically significant difference between the 2 groups in terms of prothrombin time, activated partial thromboplastin time, fibrinogen levels, coagulation time, clot formation time, and maximum clot firmness values. In contrast to other chronic hemolytic anemias, no predisposition to hypercoagulability has been shown in the coagulation profile of children with HS without splenectomy.

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.

Hemotologic Indices for Predicting Internal Organ Involvement in Henoch-Schönlein Purpura (IgA vasculitis).

Henoch-Schönlein purpura is the most common vasculitis of childhood. This study investigated the values of hematologic indices that can help predict internal organ involvement. The study included 112 patients followed up between January 2007 and May 2017 and 81 healthy children. Leukocyte, neutrophil, monocyte, lymphocyte and platelet counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels were compared between patients with and without internal organ involvement. Overall, 57 (50.8%) patients had internal organ involvement. Leukocyte, neutrophil, and monocyte counts, NLR, and CRP levels were significantly higher in patients with internal organ involvement than in patients without internal organ involvement. There was no difference between the groups in terms of lymphocyte count, platelet count, and PLR. The cutoff values were found to be ≥10.8×10/L [area under the curve (AUC), 0.734] for leukocyte, ≥6.0×10/L (AUC, 0.665) for neutrophil, ≥0.710×10/L (AUC, 0.681) for monocyte, ≥3.95×10/L (AUC, 0.609) for NLR, and 2.41 mg/dL (AUC, 0.635) for CRP. Logistic regression analysis revealed that leukocyte count is a risk factor for internal organ involvement. Leukocyte, neutrophil, monocyte counts, NLR, and CRP levels are useful in predicting internal organ involvement in the acute phase of Henoch-Schönlein purpura. Leukocyte count is an important risk factor for internal organ involvement and its predictive value is more reliable than the other hematologic indices.

Cytokine Profile, Apoptosis, Glucocorticoid Receptor, and P-glycoprotein Expression Before and After Megadose Methylprednisolone Treatment in Children With Acute Immune Thrombocytopenia.

OBJECTIVE: Immune thrombocytopenia (ITP) is an autoimmune disease, and it has become evident that T lymphocytes play an important role in the pathogenesis of ITP. We investigated the role of T helper (Th) intracellular IL-2, IL-4, IL-6, IFN-γ, and T lymphocyte apoptosis in the pathogenesis of acute ITP and the effect of glucocorticoid treatment on cytokine profile. We investigated also P-glycoprotein (P-gp) and glucocorticoid receptor (GCR) expression as a possible mechanism for glucocorticoid resistance. MATERIAL AND METHODS: The study includes 20 children with acute ITP having a platelet count <20,000/mm and 20 healthy children as a control group. Patients with acute ITP were treated with megadose methylprednisolone (MDMP) (MDMP in the dose of 30 mg/kg/d between day 1 and 3 and 20 mg/kg/d between day 4 and 7). Th intracellular IL2, IL-4, IL-6, and IFN-γ percentages, T-cell P-gp expression, T-cell and monocyte GCR expression, and T-cell apoptosis were evaluated before and after treatment in acute ITP patients and in the control group. RESULTS: Acute ITP patients had significantly higher Th IL-2, IL-4, IL-6, and IFN-γ percentages compared with the control group (P<0.05). Th IL-2 and IFN-γ percentages were significantly lowered with MDMP treatment (P<0.05). IFN-γ/IL-4 ratio was also lowered with the MDMP treatment (P<0.05). T-lymphocyte P-gp expression and T lymphocyte and monocyte GCR expression were all similar between acute ITP pretreatment and control groups (P>0.05). T-lymphocyte P-gp expression was higher in the posttreatment group than in the pretreatment group (P<0.05). Both T lymphocyte and monocyte GCR expression percentages were not different in the pretreatment and posttreatment groups (P>0.05). Early apoptosis in T lymphocytes was significantly lower in the pretreatment acute ITP group than in the control group (P<0.05). Necrotic apoptosis in T lymphocytes was significantly increased with MDMP treatment (P<0.05). CONCLUSIONS: Th1 and Th2 cytokine profile is observed in acute ITP pathogenesis, and MDMP treatment causes Th1 to Th2 cytokine profile shift and induction of T-lymphocyte apoptosis. There is a need to have a greater number of resistant cases in order to better evaluate the P-gp and GCR expression in glucocorticoid resistance in acute ITP.

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.

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.

Comparison of Methods Used for the Diagnosis of Epstein-Barr Virus Infections in Children.

The accurate diagnosis of Epstein-Barr virus (EBV) infections is important, as many other infectious agents or diseases can cause similar symptoms. In this study, sera of pediatric patients who were suspected to have an EBV infection, were sent to Eskisehir Osmangazi University Faculty of Medicine, Department of Clinical Microbiology, and investigated by IFA, ELISA, immunoblotting and Real-time PCR. The performances of these tests were compared with IFA. The rates of agreement between ELISA and IFA were found as 100% for seronegative, 100% for acute primary infection, 22.2% for late primary infection, 92.1% for past infection. The rates of agreement between immunoblotting and IFA were found as 80.8% for seronegative, 68.8% for acute primary infection, 55.6% for late primary infection, 86.6% for past infection. The sensitivity of immunoblotting for anti-VCA IgM was identical with ELISA, and higher for anti-VCA IgG, anti-EBNA IgG, anti-EA antibodies, while the specificity of immunoblotting for these antibodies were found to be lower. The sensitivity and specificity of Real-time PCR for detection of viremia in acute primary infection were found as 56.25% (9/16) and 97.89% (139/142), respectively. The diagnostic methods should be chosen by evaluating the demographic characteristics of patients and laboratory conditions together.

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.

Ptosis during hematologic malignancy in children.

Neurological symptoms such as ptosis may develop due to either chemotherapeutic agents or involvement of the central nervous system (CNS) during hematologic malignancy. It is difficult to make this distinction according to clinical symptoms and magnetic resonance imaging findings. If the neurologic symptoms are increased, it is a warning of CNS involvement. Herein are described the clinical and neuroimaging features of three patients with hematologic malignancy who presented with ptosis.

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.

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.

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.