Identification of the molecular etiology in rare congenital hemolytic anemias using next-generation sequencing with exome-based copy number variant analysis.

OBJECTIVES: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next-generation sequencing (NGS) and clinical-exome-based copy number variant (CNV) analysis in patients with CHA. METHODS: One hundred and forty-three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole-exome sequencing in nine patients. Exome-based CNV calling was incorporated into the traditional single-nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long-range polymerase chain reaction. RESULTS: Molecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR. CONCLUSIONS: In this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success.

The effect of early and long-term propranolol therapy on learning and memory in mice.

Propranolol is the treatment of choice for infantile hemangioma. We investigated the effects of long-term propranolol use in early infancy on learning and memory later in life in mice. At three weeks of age, mice were randomly divided into six experimental groups. Groups 1 and 2 (controls) received only saline for 21 days. Groups 3 and 4 received propranolol (2.5 mg/kg) for 21 days. Groups 5 and 6 received propranolol (5 mg/kg) for 21 days. Groups 1, 3 and 5 were tested at the end of 21 days of treatment (week 6). However, groups 2, 4 and 6 received a 2-week break and then (week 8) exposed to tests. In the Morris water maze test, propranolol (2.5 and 5 mg/kg) dose-dependently increased the time spent in the target quadrant in mice at weeks 6 and 8. However, propranolol did not affect the swimming speed in both time periods. There were no significant effects of propranolol on the number of errors evaluated during the radial arm maze tests. In conclusion, long-term use of propranolol in early infancy did not disrupt the learning and memory of mice.

Central nervous system thrombosis in pediatric acute lymphoblastic leukemia in Turkey: A multicenter study.

BACKGROUND: In patients with acute lymphoblastic leukemia (ALL), the risk of thromboembolism increases due to hemostatic changes secondary to the primary disease and due to treatment-related factors. In this multicenter study, we aimed to research the frequency of central nervous system (CNS) thrombosis occurring during treatment, hereditary and acquired risk factors, clinical and laboratory features of patients with thrombosis, treatment approaches, and thrombosis-related mortality and morbidity rates in pediatric ALL patients. PROCEDURE: Pediatric patients who developed CNS thrombosis during ALL treatment from 2010 to 2021 were analyzed retrospectively in 25 different Pediatric Hematology Oncology centers in Türkiye. The demographic characteristics of the patients, symptoms associated with thrombosis, the stage of the leukemia treatment during thrombosis, the anticoagulant therapy applied for thrombosis, and the final status of the patients recorded through electronic medical records were determined. RESULTS: Data from 70 patients with CNS thrombosis during treatment, out of 3968 pediatric patients with ALL, were reviewed. The incidence of CNS thrombosis was 1.8% (venous: 1.5 %; arterial: 0.03%). Among patients with CNS thrombosis, 47 had the event in the first 2 months. Low molecular weight heparin (LMWH) was the most commonly used treatment with a median of 6 months (min-max: 3-28 months). No treatment-related complications occurred. Chronic thrombosis findings occurred in four patients (6%). In five (7%) patients who developed cerebral vein thrombosis, neurological sequelae (epilepsy and neurological deficit) remained. One patient died related to thrombosis, and the mortality rate was 1.4%. CONCLUSION: Cerebral venous thrombosis and, less frequently, cerebral arterial thrombosis may develop in patients with ALL. The incidence of CNS thrombosis is higher during induction therapy than during other courses of treatment. Therefore, patients receiving induction therapy should be monitored carefully for clinical findings suggestive of CNS thrombosis.

Acquired Thrombotic Thrombocytopenic Purpura in a 5-Year-old Child With Wiskott-Aldrich Syndrome.

Thrombocytopenia is often seen as a laboratory finding during childhood. A supposed idiopathic thrombocytopenic purpura patient who was later diagnosed as Wiskott-Aldrich syndrome (WAS) and developed acquired thrombotic thrombocytopenic purpura (aTTP). Although autoimmune manifestations in WAS described, aTTP was reported just once. Five-year-old-boy was initially brought with cough, bloody stool (diarrhea), oral mucosal bleeding at 12th months of age. Following diagnosed with idiopathic thrombocytopenic purpura and receiving intravenous immunoglobulin, platelet count raised from 20,000 to 50,000/µL. One year after WAS diagnosis by mutation analysis, he presented with complaints of resistant fever, epistaxis, and melena. Hemoglobin decreased from 10 to 5.9 g/dL. Schistocytes in peripheral blood smear and high anti-ADAMTS-13 antibody level indicated development of aTTP.

Major and minor subgroup profile of blood in patients receiving multiple transfusions and donors.

OBJECTIVE: It was aimed to profile the blood subgroups of our region and to reveal the prevalence of auto/alloimmune sensitization in patients who had to undergo multiple erythrocyte transfusions and to establish the sensitization profile by screening major and minor subgroups. MATERIALS AND METHODS: In this study, the distribution of ABO and Rh system major subgroups was studied in 100 donor blood. As the patient group, 50 patients who received three or more red blood cell transfusions were included. In addition to this group, Kell, Lewis, Duffy blood group systems were studied. RESULTS: According to the ABO system, 35% of the donors were in O, 33% in A, 17% in AB, and 15% in B. According to the Rh system, 75% is Dvi positive. Rh system is 99% e positive and 33% E positive in major subgroups and Kell1 positivity is 8%. In the patient group, 22% D(-) was determined compared to Rh blood group. Among the major subgroups of Rh, C was 68%, E was 14%, c was 76%, and e positivity was found to be 100%. The Kell1 negativity rate is 96%. The highest negativity was found in 86% Lea antigen in Lewis system, in 36% S antigen in MNS system, 34% Fyb antigen in Duffy system, and 24% Jka antigen in Kidd system. When inappropriate blood is given for any antigen, a double population is formed. The double negativities we detected in our study occurred as follows according to blood group systems: E 18%, C 12%, c 8%, Cw 2%, Kell 1 2%, M 8%, N 4%, S 18%, s 6%, Fya 8%, Jka 6%, Jkb 22%. Indirect Agglutination Test (IAT) was negative in all patients. CONCLUSION: IAT negativity in all patient groups suggests that we do not develop alloimmunization, but the high rates of double population suggest a high risk of alloimmunization.

Design and Utilization of a Direct Methanol Fuel Cell.

This study introduces a step-by-step, summarized overview of direct methanol fuel cell (DMFC) fundamentals, thermodynamic-electrochemical principles, and system evaluation factors. In addition, a parametric investigation of a JENNY 600S DMFC is conducted to simulate cell performance behavior under varying operating conditions. The system is mathematically modeled and solved in MATLAB and accounts for multi-irreversibilities such as the activation and ohmic and concentration overpotentials. The performance of the modeled system was validated against theoretical and experimental results from the literature. The results indicated that increasing the fuel cell's operating temperature yields enhanced output cell voltages due to enhanced methanol oxidation reactions. Nevertheless, the maximum efficiency limits of the fuel cell tend to decrease with an increase in temperature. In addition, the model has also depicted that enhanced output cell voltages are associated with increased oxygen consumption, resulting in the lower exit flowrates of the reactants.

Epidural blockade for alternative management of priapism: A case report of child with T-cell acute lymphoblastic leukemia.

Priapism is a clinical condition that rarely presents with leukemia in childhood. Management of priapism treatment can become more complex and difficult when accompanied by acute leukemia. We presented a 16 years old child with t-cell acute lymphoblastic leukemia (ALL) who developed priapism. Due to the failure of conservative methods and intracavernosal drainage, we performed epidural blockade which has limited data reported with successful results in the literature before shunt surgery.

Evaluation of taste and smell disorders in pediatric COVID-19 Cases.

OBJECTIVE: Pediatric coronavirus disease 2019 (COVID-19) cases have a high risk of contagiousness, as they usually progress with asymptomatic or mild respiratory symptoms. Disorder in taste and/or smell has rarely been reported in pediatric cases. In our study, early diagnosis and isolation measures were emphasized by evaluating the clinical, laboratory, and radiological imaging findings of pediatric COVID-19 cases presenting with symptoms of taste and/or smell disorder. METHODS: Seven cases aged 0-18 years were included in the study. The severe acute respiratory syndrome coronavirus-2 polymerase chain reaction test was performed for the seven cases presented with taste and/or smell disorders. Clinical findings, laboratory tests, and radiological imaging of all the cases were evaluated on the day of admission and on the fifth day. RESULTS: Seven (5.7%) of 122 pediatric COVID-19 cases had disorder in taste and/or smell. In two cases, pneumonia findings were detected in thorax computed tomography imaging. It was observed that all the patients fully recovered at the latest on the 21st day. In the cranial diffusion magnetic resonance imaging of a case, diffusion restriction was detected in the corpus callosum splenium. CONCLUSION: Although less common than adults, children with COVID-19 may also have taste and smell disorders, and this may be accompanied by central nervous system imaging findings.

Thrombolysis with Systemic Recombinant Tissue Plasminogen Activator in Children: A Multicenter Retrospective Study

Objective: This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA). Materials and Methods: Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h. Results: Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p>0.05). Conclusion: Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.

Evaluation of taste and smell disorders in pediatric COVID-19 Cases

SUMMARY OBJECTIVE: Pediatric coronavirus disease 2019 (COVID-19) cases have a high risk of contagiousness, as they usually progress with asymptomatic or mild respiratory symptoms. Disorder in taste and/or smell has rarely been reported in pediatric cases. In our study, early diagnosis and isolation measures were emphasized by evaluating the clinical, laboratory, and radiological imaging findings of pediatric COVID-19 cases presenting with symptoms of taste and/or smell disorder. METHODS: Seven cases aged 0-18 years were included in the study. The severe acute respiratory syndrome coronavirus-2 polymerase chain reaction test was performed for the seven cases presented with taste and/or smell disorders. Clinical findings, laboratory tests, and radiological imaging of all the cases were evaluated on the day of admission and on the fifth day. RESULTS: Seven (5.7%) of 122 pediatric COVID-19 cases had disorder in taste and/or smell. In two cases, pneumonia findings were detected in thorax computed tomography imaging. It was observed that all the patients fully recovered at the latest on the 21st day. In the cranial diffusion magnetic resonance imaging of a case, diffusion restriction was detected in the corpus callosum splenium. CONCLUSION: Although less common than adults, children with COVID-19 may also have taste and smell disorders, and this may be accompanied by central nervous system imaging findings.