Multiple Thromboembolic Events in Young Patient with Homozygous T-786C Mutation in the Endothelial Nitric Oxide Synthase Gene (ENOS).

Thromboembolic events are a common cause of morbidity and mortality with significant socioeconomic impact especially when young patients are affected. They are a rare medical event in young people and their clinical presentation can be mild or asymptomatic. The manifestation of symptoms and thrombotic events depends on both: the genetic mutations and the external risk factors that will induce the process. We present a case of a 34-year old young female, with three consecutive cerebrovascular insults in a period of ten years, and an acute myocardial infarction. There is a combination of gene mutations and polymorphism, with a predisposition to thromboembolic events. We emphasized the role of e-NOS (Endothelial nitric oxide synthase 786 T>C mutation) and the connection with smoking. The dual effect of the prolonged smoking and dysfunctional nitric oxide synthase in our young patient led to several thrombotic events. We discussed the various diagnostic tests and possible therapeutic and prophylactic strategies.

Milestones in Hematology and Oncology: From Fatal to Curable Disease.

Background: The comprehensive management of patients with Hodgkin's lymphoma (HL) is a success story in contemporary oncology. Over the past decades, the survival rate of patients with HL has significantly improved. The objective of this analysis is to evaluate and document the progress in the management of Hodgkin's lymphoma in patients in our country, reflected in their vital statistics, over time periods defined by the respective standard of treatment. Material and methods: The present study is designed as a retrospective-prospective study. We analyzed different modalities of treatment and compared 5 and 10-year overall survival rates in a total of 588 Hodgkin's lymphoma patients treated at the University Clinic for Hematology in Skopje during two consecutive time periods, before 2000 and after 2000. The entire observation period is from 1980 to 2020. All patients are above the age of 14, with a documented histopathological diagnosis of Hodgkin's lymphoma and with evaluable medical documentation, including clinical and laboratory data on their initial condition, the administered therapy, as well as the clinical follow-up of the patients. Results: The basic clinical features of the analyzed population across the two periods correlate with those reported in the relevant medical literature, with only slight deviations. Ten-year overall survival rates improved by 31.7% through the two calendar periods. During the last two decades of the previous century (1980-2000) the initial treatment options were COPP and COPP-like regimens for the vast majority of patients (94.7%), leading to disease remission in 80% of them. After 2000, 95.8% of de novo diagnosed patients have been treated with ABVD chemotherapy as a frontline choice and the complete response rate is 88.4%. We confirmed the superiority of ABVD in terms of efficacy, improved tumor and disease control, as well as its long-term clinical outcome. While in the past we had very limited options for relapsed/refractory HL patients, the analysis of the results of HL patients treated with various therapeutic approaches in the latter period, defines BEACOPP as the preferred choice. High-dose chemotherapy, followed by autologous hematopoietic stem cell graft, as a strategy for our R/R patients in the timeframe after 2000, ensures a 5-year overall survival for 51% of them, whereas 45% of the patients survive more than 10 years. Conclusion: This analysis from our Hodgkin's lymphoma database illustrates that there has been tremendous improvement in the long-term survival rates since the turn of this century. At our institution we strive to implement positive trends in practice, as suggested by relevant guidelines, regarding the evolution and progress in the diagnostic workup, treatment, and the overall management of patients with Hodgkin's disease. The objective would be to secure favorable vital statistics for our patient population, now reaching 83.5% at 10 years, which closely correlates with the data of more developed countries and centers. In future clinical trials we will also evaluate the efficacy of brentuximab-vedotin and new PD-1 blocking antibodies.

Reproductive Issues in Long-Term Surviving Patients following Therapy for Hodgkin's Disease in the Republic of North Macedonia: Risks of Infertility According to First-Line Treatment Regimens.

Infertility as a consequence of therapy presents a high psychosocial burden for HL patients. In the cohort of our analyzed patients, within the post-ABVD surviving patients, alterations of the spermogram were documented in a total of 6.1% of the male patients and 5.4% of the female patients developed amenorrhea. On the other hand, within the subgroup of surviving patients following BEACOPP chemotherapy, 60% of the male patients manifested defects in their spermogram, and as high as 28.6% of the female survivors reported loss of their monthly cycle. It has been reported on several occasions that even prior to treatment, the sperm of HL patients manifests poorer quality characteristics when analyzed against control specimens from healthy male donors. The analyzed results in ABVD-treated male HL patients confirm ABVD to be a safe regimen for males of all age categories, as well as for female patients under the age of thirty. In women above the age of 30, the infertility risk rate is relatively low (14%), which leaves the decision of preserving fertility to themselves. For all BEACOPP-treated female, as well as male patients, a consult with a reproductive medicine specialist is warranted prior to therapy, due to the high infertility risk, and the final decision should be made on an individual basis.