Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the Nibrin (NBN) gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an “Eastern Slavic NBS hot spot.” The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; p=0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) (n=42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, p=0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy (n=7) and immunodeficiency (n=6). Overall, 9% of patients in this cohort reached adulthood. Adult survivors reported diminished quality of life with significant physical and cognitive impairments. Our study highlights the need to improve timely diagnosis and clinical management of NBS among Eastern Slavs. Genetic counseling and screening should be offered to individuals with a family history of NBS, especially in hot spot regions. © Copyright © 2021 Sharapova, Pashchenko, Bondarenko, Vakhlyarskaya, Prokofjeva, Fedorova, Savchak, Mareika, Valiev, Popa, Tuzankina, Vlasova, Sakovich, Polyakova, Rumiantseva, Naumchik, Kulyova, Aleshkevich, Golovataya, Minakovskaya, Belevtsev, Latysheva, Latysheva, Beznoshchenko, Akopyan, Makukh, Kozlova, Varabyou, Ballow, Ong, Walter, Kondratenko, Kostyuchenko and Aleinikova.We thank all doctors for clinical help for patients. We also appreciate the support of patient and their parents for agreeing to take part in this study. TP thanks Sergey?Nikulshin, Marika Grutupa, and Zanna Kovalova. We thank Joseph Dasso for editing this manuscript, primarily for proper English

Transfusion management of abdominal delivery in pregnant women at high risk of bleeding with hemostasis control

Objective of the study. Optimization of transfusion support of abdominal delivery in pregnant women at risk of obstetric haemorrhage using monitored management of haemostasis disorders.Study materials. The study group consisted of 24 women of 23-47 years old with abnormal placental invasion (API) and bleeding during caesarean section at a gestational age of 32-36 weeks. Group 1 consisted of 14 patients, who were injected with tranexamic acid as part of combined therapy; Group 2 consisted of 10 women, who were injected with aminomethylbenzoic acid as part of combined therapy.Results. All patients received instrumental autoerythrocyte reinfusion. Three patients of Group 1 (21.4%) with refractory bleeding received recombinant coagulation factor VIIa (Coagil, Russia) at a dose of 60 pg/kg body weight (average dose 6.6 ± 1.4 mg), adecrease in bleeding was observed, the operative treatment was completed in the form of metroplasty. In the early stages of bleeding, eight patients were injected with a prothrombin complex concentrate of 600-1,200 IU before administration of fresh-frozen plasma (FFP), which allowed to reduce the volume of donor FFP in these patients. The study of hemostasis showed a very high inverse relationship between extent of blood loss and fibrinogen level in the groups of patients.Conclusion. The use of factor VIIa in refractory major obstetric haemorrhage (MOH) in patients with API allows to reduce the blood loss, perform metroplasty, and preserve the woman’s fertility. Patient blood management (PCM) in pregnant women with API makes it possible to conduct organ-preserving treatment in 91.7% of women