Hepatitis A susceptibility parallels high COVID-19 mortality.

Background/aim: COVID-19 has become the biggest health problem of this century. It has been hypothesized that immunity against hepatitis A virus (HAV) may provide protection from COVID- 19. Materials and methods: As of 10June 2020, the infection had spread to 213 countries, with 7.3 million people infected and 413,733 dead. This data was combined with the World Health Organization susceptibility classification on the worldwide prevalence of HAV, and the relationship between HAV susceptibility and COVID-19 mortality were analyzed. Results: When the data from 213 countries were analyzed, it was found that there was a significant increasing trend in COVID-19 mortality rates by HAV susceptibility (P <0.001). Using a cut-off of 200/million population, the mortality risk associated with living in a more susceptible country (medium/high) was 27.8 times higher (95% CI for OR: 3.6­213.2) Conclusion: The results of this study showed that, despite confounding factors in different countries, hepatitis A susceptibility of the population may have been correlated with COVID-19 mortality. This observation needs to be confirmed by further studies.

Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations

Objective: Hemophilia A (HA) is the most severe X-linked inherited bleeding disorder caused by hemizygous mutations in the factor 8 (F8) gene. The aim of this study is to determine the mutation spectrum of the F8 gene in a large HA cohort from Turkey, and then to establish a phenotype-genotype correlation. Materials and Methods: All HA cases (270 patients) analyzed molecularly in the Ege University Pediatric Genetics Molecular Laboratory between March 2017 and March 2018 were included in this study. To identify intron 22 inversion (Inv22), intron 1 inversion (Inv1), small deletion/insertions, and point mutations, molecular analyses of F8 were performed using a sequential application of molecular techniques. Results: The mutation detection success rate was 95.2%. Positive Inv22 was found in 106 patients (39.3%), Inv1 was found in 4 patients (1.5%), and 106 different disease-causing sequence variants were identified in 137 patients (50.6%). In 10 patients (3.7%), amplification failures involving one or more exonic regions, considered to be large intragenic deletions, were identified. Of 106 different F8 mutations, 36 were novel. The relationship between F8 genotype and inhibitor development was considered significant. Conclusion: A high mutation detection rate was achieved via the broad molecular techniques applied in this study, including 36 novel mutations. With regard to mutation types, mutation distribution and their impact on clinical severity and inhibitor development were found to be similar to those previously reported in other hemophilia population studies.

Differences in Granule Morphology yet Equally Impaired Exocytosis among Cytotoxic T Cells and NK Cells from Chediak-Higashi Syndrome Patients.

Chediak-Higashi syndrome (CHS) is caused by autosomal recessive mutations in LYST, resulting in enlarged lysosomal compartments in multiple cell types. CHS patients display oculocutaneous albinism and may develop life-threatening hemophagocytic lymphohistiocytosis (HLH). While NK cell-mediated cytotoxicity has been reported to be uniformly defective, variable defects in T cell-mediated cytotoxicity has been observed. The latter has been linked to the degree of HLH susceptibility. Since the discrepancies in NK cell- and T cell-mediated cellular cytotoxicity might result from differences in regulation of cytotoxic granule release, we here evaluated perforin-containing secretory lysosome size and number in freshly isolated lymphocytes from CHS patients and furthermore compared their exocytic capacities. Whereas NK cells from CHS patients generally contained a single, gigantic perforin-containing granule, cytotoxic T cells predominantly contained several smaller granules. Nonetheless, in a cohort of 21 CHS patients, cytotoxic T cell and NK cell granule exocytosis were similarly impaired upon activating receptor stimulation. Mechanistically, polarization of cytotoxic granules was defective in cytotoxic lymphocytes from CHS patients, with EEA1, a marker of early endosomes, mislocalizing to lysosomal structures. The results leads to the conclusion that lysosome enlargement corresponds to loss of distinct organelle identity in the endocytic pathway, which on a subcellular level more adversely affects NK cells than T cells. Hence, vesicular size or numbers do not per se dictate the impairment of lysosomal exocytosis in the two cell types studied.

Paracetamol infusion-related severe hypotension and cardiac arrest in a child.

Paracetamol (also known as Acetaminophen) is an antipyretic, non-opioid analgesic, and non-steroidal anti-inflammatory drug (NSAID), and is one of the most commonly used medications worldwide. In recent years, IV paracetamol has been frequently used in hospitalized patients to reduce fever and pain. Significant adverse reactions associated with intravenous paracetamol are extremely rare. Typically reported adverse events include hypotension, malaise, hypersensitivity reaction, liver enzyme elevation, and thrombocytopenia. We present herein a case of IV paracetamol infusion-related severe hypotension and cardiac arrest.

Molecular basis and bleeding manifestations of factor XI deficiency in 11 Turkish families.

Factor XI (FXI) deficiency is an autosomal bleeding disorder characterized by variable bleeding tendency. In the present study, the gene encoding FXI (F11) was analyzed by direct sequencing in 33 individuals belonging to 11 unrelated Turkish families, and the bleeding tendency was quantitatively assessed by means of a bleeding questionnaire in 27 individuals with low FXI clotting activity and/or mutated F11 gene. We identified 10 distinct mutations (five missense, three nonsense and two splice site), four of which were novel. No mutation was found in one family. Of the four novel mutations, homozygosity for a c.89T>C (p.Phe30Ser) mutation and compound heterozygosity for a c.646G>A (p.Asp216Asn) mutation with the known c.403G>T (p.Glu135) type II Jewish mutation were associated with severe deficiency, whilst heterozygosity for the novel c.1655A>C (p.His552Arg) and c.1627G>A (p.Glu543Lys) mutations was associated with partial deficiency. p.Glu135 was found in 19% (5/27) of the mutated alleles. Bleeding score was positive in 57% (4/7) of individuals with severe and 39% (7/18) of those with partial deficiency. It was significantly correlated with clinical severity of bleeding (r = 0.43, P = 0.02), but not with FXI clotting activity (P > 0.05). There was no optimal cut-off level of the bleeding score that could predict FXI deficiency. We conclude that the spectrum of mutations found in this study reflects the genetic heterogeneity of FXI deficiency in the Turkish population. Quantitative assessment of the bleeding symptoms by a bleeding questionnaire seems to be useful for evaluating the severity of bleeding episodes, but it can not be recommended as a screening tool for FXI deficiency.

Granulocyte Colony Stimulating Factor Induced Sweet's Syndrome Following Autologous Transplantation in a Child with Relapsed Acute Myeloblastic Leukemia.

Sweet's syndrome is characterized by the triad of fever, erythematous skin lesions and neutrophilia. The etiologic factors are quite variable, and granulocyte colony-stimulating factor (G-CSF) use is an extremely rare cause in children with Sweet's syndrome. We report a G-CSF induced Sweet's syndrome following autologous transplantation in a child with relapsed acute myeloblastic leukemia.

Life-threatening agranulocytosis, anemia, and plasmacytosis after dipyrone use for fever in a child.

Dipyrone or metamizole Na (Novalgin) is commonly used as an antipyretic, analgesic, and spasmolytic agent in some parts of the world; however, it is banned in developed countries because of severe side effects. Here we present a case of a 4-year-old boy who developed life-threatening agranulocytosis, anemia, and marked plasmacytosis in his bone marrow after dipyrone use for fever, which resolved with steroid therapy.

Diagnostic value of neopterin during neutropenic fever and determination of disease activity in childhood leukemias.

Neopterin, a pteridine group compound that is secreted from macrophages is shown to be increased in adult leukemia; however there are few studies in childhood leukemia. This study aimed to investigate neopterin levels during childhood leukemia treatment and neutropenic fever episodes for the possibility of using as a marker for disease activity and differentiation of infections. A total of 44 children with acute leukemia, 19 children with infection (control group 1) and 21 healthy children (control group 2) were studied. Median serum neopterin level before induction chemotherapy (day 0) in 25 children (patient group 1) was significantly higher (27.7 nmol/L) than those at the beginning of 30 febrile episodes in 19 children in bone marrow remission (2.2 nmol/L) (patient group 2) and in control group 2 (0.4 nmol/L) (p< 0.05). It was (27.7 nmol/L) also significantly higher in control group 1 than in patient group 2 and control group 2 (p< 0.05). Serum neopterin levels at day 15 (2.1 mmol/L) and day 33 (0.4 mmol/L) of induction were significantly lower than day 0 of ALL subgroup at patient group 1. There were no significant difference in neopterin levels between days 0, 3 and 5 of neutropenic fever as well as between patients with microbiologically and/or clinically documented infections and those with fever of unknown origin in patient group 2 (p> 0.05). Serum neopterin did not show significant correlation with absolute neutrophil count and absolute monocyte count (p> 0.05). In conclusion, elevated neopterin at diagnosis of leukemia with decrement during induction therapy suggest that it might be an indicator of leukemic process; however larger studies for its role in identifying infections are warranted.

Trends in hepatitis B and hepatitis C virus seropositivity among blood donors over 15 years screened in the blood bank of a university hospital.

Blood transfusion carries well defined risks including hepatitis B and hepatitis C virus transmission. In this study, records of blood donation candidates between the years 1996-2010 were retrospectively reviewed. A total of 220 841 apparently healthy adult donors were screened for hepatitis B surface antigen, anti-HCV with enzyme linked immunosorbent assay (ELISA) method. The overall prevalence of HbsAg and HCV were 1.07% and 0.39%, respectively. HBV seroprevelance decreased through years 1996-2010 but HCV seroprevelance showed a fluctuant course decreasing from 1996 to 2002. In order to decrease transfusion transmitted infections there should be centralized blood collection systems having qualified staff, equipment and non-remunerated voluntary blood donations must be strongly encouraged.

Platelet usage trends in a tertiary care hospital - Could it be less and less expensive?

Major bleeding is a life threatening complication of severe thrombocytopenia. The aim of this study was to find out the indications and the threshold for platelet transfusions in the pediatric patients of our hospital throughout 1 year. Records of the hospital's blood bank and the files of the patients were retrospectively reviewed. One hundred and four patients, between ages 0-18 years received 378 platelet units. Pretransfusion platelet counts were found to be significantly lower in hematology-oncology groups compared to other clinics (p<0.05). Single donor apheresis was found to be the major source of platelets in hematology (80.8%, n=147) and oncology (86.5%, n=45) clinics. There is a tendency for using apheresis products without proven superiority compared to platelet concentrates in terms of efficacy. This practice can be abandoned by continuous education.

Congenital cricopharyngeal achalasia: a rare cause of dysphagia in an infant.

Dysphagia secondary to congenital cricopharyngeal achalasia (CCA) is a rare condition in pediatric patients. We report a case of CCA in a 10-month-old boy presented with dysphagia, choking and nasal reflux. The diagnosis was made by barium studies. The patient was successfully treated by cricopharyngeal myotomy.