Common viral respiratory infections in children with cancer during the COVID-19 pandemic: a multicenter study from Türkiye.

BACKGROUND: Microbiologic confirmation of respiratory tract infections gained importance during the coronavirus disease 2019 (COVID-19) pandemic. This study retrospectively evaluated seasonal distribution, clinical presentation, and complications of respiratory viral infections (RVIs) other than COVID-19 in children with cancer during and after the pandemic lockdown. METHODS: Two hundred and sixty-five inpatient and outpatient RVI episodes in 219 pediatric cancer patients confirmed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) panels from 13 centers were enrolled. RESULTS: Eighty-six (32.5%) of the total 265 episodes occurred in 16 months corresponding to the lockdowns in Türkiye, and the remaining 67.5% in 10 months thereafter. Human rhinovirus/enterovirus (hRE) (48.3%) was the most common agent detected during and after lockdown. Parainfluenza virus (PIV) (23.0%), influenza virus (9.8%), and respiratory syncytial virus (RSV) (9.1%) were the other common agents. The 28.7% of episodes were lower respiratory tract infections (LRTIs), and complications and mortality were higher than upper respiratory tract infections (URTIs) (25.0% vs 5.3%). Bacteremia was identified in 11.5% of culture-drawn episodes. Treatment delay in one-third and death within four weeks after RVI in 4.9% of episodes were observed. CONCLUSION: During the pandemic, fewer episodes of RVIs occurred during the lockdown period. Respiratory viruses may cause complications, delays in treatment, and even death in children with cancer. Therefore, increased awareness of RVIs and rapid detection of respiratory viruses will benefit the prevention and, in some cases, abrupt supportive and some antiviral treatment of RVI in children with cancer.

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.

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.

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.

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.

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.

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.

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.

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.

Assessment of cardiac and liver iron overload by magnetic resonance imaging in patients with thalassemia major: short-term follow-up.

OBJECTIVE: This study was performed to assess cardiac and hepatic iron overload in young patients with thalassemia. METHODS: We reviewed the medical records of patients with thalassemia at a pediatric hematology clinic who had recently undergone cardiac and hepatic magnetic resonance imaging. RESULTS: Eleven patients underwent cardiac and hepatic T2* imaging at a mean age of 13.9 ± 4.48 (range, 9-21) years. Three patients had cardiac iron overload and all patients had hepatic iron overload according to the magnetic resonance imaging scan. Ten patients underwent control imaging approximately 1 year later. The mean serum ferritin level at the initial imaging examination was 1820.87 ± 1275.22 (range, 634.04-4221.03) ng/mL. There was a strong negative correlation between the ferritin level and cardiac T2* time and between the blood hemoglobin level and hepatic T2* time. Among the 10 patients who underwent control imaging, the average hemoglobin and ferritin levels significantly decreased from the initial to control imaging examinations, but there was no significant increase in the cardiac and hepatic T2*times. CONCLUSIONS: Cardiac and hepatic T2* imaging is a feasible method of assessing cardiac and hepatic iron overload even before complications and clinical signs of iron overload appear.