Attitudes towards COVID­19 vaccination in patients with cancer: A cross­sectional study of 12 oncology centers.

Patients with cancer are a high-priority population for COVID-19 vaccination, as per guideline recommendations. The present cross-sectional study was performed to assess the perception of patients with cancer from Romania regarding COVID-19 vaccines. The study included 932 patients with solid and hematologic malignancies. This was a multicenter study including 12 oncology centers located in Western and Northwestern Romania. Between December 2021 and January 2022, patients with cancer completed an individual paper questionnaire regarding acceptance of the SARS-CoV-2 vaccination, type of vaccine, side effects and source of information. During the first year of the vaccination campaign in Romania, 58.05% (541/932) of the investigated patients received COVID-19 vaccines. The vaccination rate was highest in the 61-70 year age group (61.22%). The most frequently used vaccine was Pfizer-BioNTech (72%). There was a statistically significant association between the rate of vaccination and the area of residence and level of education (P<0.001), with rural residence and a lower level of education being predictive factors for COVID-19 vaccination hesitancy. Patients living in rural areas used non-medical sources (e.g. mass media, social platforms) as their main source of information (53.40%, 204/382), whereas patients living in urban areas (64.90%, 357/550) used predominantly medical sources (e.g. recommendations from oncologists and general practitioners). The main source of information among non-vaccinated patients was mass media (e.g. television, radio); 72.38% vs. 29.67% among vaccinated patients. For the latter, the primary source of information was the recommendations made by oncologists (59.70%) and general practitioners (56.76%). The most commonly reported side effect was injection site pain (20-33% for the first dose and 5-27% for the second dose). In conclusion, the present study confirmed that patients with cancer may be reluctant to receive a COVID-19 vaccine, mainly due to the fear of its potential side effects. Although there is scientific evidence to support the efficacy and safety of vaccines, the primary source of information for patients may affect vaccine uptake, thus affecting the efforts to stop the pandemic. Furthermore, the present study revealed that non-vaccinated patients preferred mass media as their main source of information, whereas vaccinated patients relied on the recommendations made by oncologists or general practitioners.

Current therapeutic approaches in the management of hemophilia-a consensus view by the Romanian Society of Hematology.

Hemophilia A (HA) and hemophilia B (HB) are rare disorders, being caused by the total lack or under-expression of two factors from the coagulation cascade coded by genes of the X chromosome. Thus, in hemophilic patients, the blood does not clot properly. This results in spontaneous bleeding episodes after an injury or surgical intervention. A patient-centered regimen is considered optimal. Age, pharmacokinetics, bleeding phenotype, joint status, adherence, physical activity, personal goals are all factors that should be considered when individualizing therapy. In the past 10 years, many innovations in the diagnostic and treatment options were presented as being either approved or in development, thus helping clinicians to improve the standard-of-care for patients with hemophilia. Recombinant factors still remain the standard of care in hemophilia, however they pose a challenge to treatment adherence because they have short half-life, which where the extended half-life (EHL) factors come with the solution, increasing the half-life to 96 hours. Gene therapies have a promising future with proven beneficial effects in clinical trials. We present and critically analyze in the current manuscript the pros and cons of all the major discoveries in the diagnosis and treatment of HA and HB, as well as identify key areas of hemophilia research where improvements are needed.

Assessment and Management of Cardiotoxicity in Hematologic Malignancies.

With the increasing overall survival of cancer patients due to recent discoveries in oncology, the incidence of side effects is also rising, and along with secondary malignancies, cardiotoxicity is one of the most concerning side effects, affecting the quality of life of cancer survivors. There are two types of cardiotoxicity associated with chemotherapy; the first one is acute, life-threatening but, fortunately, in most of the cases, reversible; and the second one is with late onset and mostly irreversible. The most studied drugs associated with cardiotoxicity are anthracyclines, but many new agents have demonstrated unexpected cardiotoxic effect, including those currently used in multiple myeloma treatment (proteasome inhibitors and immunomodulatory agents), tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia and some forms of acute leukemia, and immune checkpoint inhibitors recently introduced in treatment of refractory lymphoma patients. To prevent irreversible myocardial damage, early recognition of cardiac toxicity is mandatory. Traditional methods like echocardiography and magnetic resonance imaging are capable of detecting structural and functional changings, but unable to detect early myocardial damage; therefore, more sensible biomarkers like troponins and natriuretic peptides have to be introduced into the current practice. Baseline assessment of patients allows the identification of those with high risk for cardiotoxicity, while monitoring during and after treatment is important for early detection of cardiotoxicity and prompt intervention.

MECOM, HBS1L-MYB, THRB-RARB, JAK2, and TERT polymorphisms defining the genetic predisposition to myeloproliferative neoplasms: A study on 939 patients.

Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical myeloproliferative neoplasms (MPN), characterized by specific somatic mutations in JAK2, CALR or MPL genes. JAK2 46/1 and TERT rs2736100 polymorphisms are known to significantly predispose to MPN. This study aimed to establish the additional contribution of the recently described MECOM rs2201862, HBS1L-MYB rs9376092 and THRB-RARB rs4858647 polymorphisms to the occurrence of MPN. These three polymorphisms, along with JAK2 46/1 and TERT rs2736100 were genotyped in 939 MPN patients (454 with ET, 337 with PV and 148 with PMF) and 483 controls. MECOM rs2201862 associated significantly with each MPN entity, except for ET, and with all major molecular sub-types, especially those CALR-mutated (OR = 1.4; 95% CI = 1.1-1.8; P-value = .005). HBS1L-MYB rs9376092 associated only with JAK2 V617F-mutated ET (OR = 1.4; 95% CI = 1.1-1.7; P-value = .003). THRB-RARB rs4858647 had a weak association with PMF only (OR = 1.5; 95% CI = 1-2.1; P-value = .04). Surprisingly, JAK2 46/1 haplotype was associated significantly not only with JAK2 V617F-mutated MPN, but also with CALR-mutated MPN (OR = 1.4; 95% CI = 1.1-1.8; P-value = .01). TERT rs2736100 was associated equally strong with all MPN, regardless of phenotype or molecular sub-type. In conclusion, JAK2 46/1, TERT rs2736100 and MECOM rs2201862 are the chief predisposing polymorphisms to MPN.

TERT rs2736100 A>C SNP and JAK2 46/1 haplotype significantly contribute to the occurrence of JAK2 V617F and CALR mutated myeloproliferative neoplasms - a multicentric study on 529 patients.

Polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) represent typical myeloproliferative neoplasms (MPN), usually characterized by specific somatic driver mutations (JAK2 V617F, CALR and MPL). JAK2 46/1 haplotype and telomerase reverse transcriptase gene (TERT) rs2736100 A>C single nucleotide polymorphism (SNP) could represent a large fraction of the genetic predisposition seen in MPN. The rs10974944 C>G SNP, tagging the JAK2 46/1 haplotype, and the TERT rs2736100 A>C SNP were genotyped in 529 MPN patients with known JAK2 V617F, CALR and MPL status, and 433 controls. JAK2 46/1 haplotype strongly correlated to JAK2 V617F-positive MPN and, to a lesser extent, CALR-positive MPN. The TERT rs2736100 A>C SNP strongly correlated to all MPN, regardless of the phenotype (PV, ET or PMF) and major molecular subtype (JAK2 V617F- or CALR-positive). While both variants have a significant contribution, they have nuanced consequences, with JAK2 46/1 predisposing essentially to JAK2 V617F-positive MPN, and TERT rs2736100 A>C having a more general, non-specific effect on all MPN, regardless of phenotype or major molecular subtype.

Non-variceal upper gastrointestinal bleeding: clinical, therapeutic and evolution aspects. Comparison between a tertiary medical center and a municipal hospital.

Upper gastrointestinal bleeding (UGIB) is one of the most common emergencies in gastroenterology practice. In recent years, the introduction of urgent upper gastrointestinal endoscopy (UGIE) and of the treatment with proton pump inhibitors (PPIs) in high doses has resulted in an improvement of the treatment outcome in patients with UGIB, but without a significant improvement in mortality rates. In our study we compared the epidemiological, clinical, therapeutic, and prognostic aspects in patients with non-variceal UGIB admitted over a period of one year in a tertiary center where urgent UGIE is a routine procedure and in a municipal hospital where UGIE with endoscopic hemostasis is not available. Patients admitted to the tertiary medical center had more clinical and endoscopic severity factors compared to those from the municipal hospital: they were older, with more frequent intake of NSAIDs, several comorbidities, some of them severe, and more severe posthemorrhagic anemia. The endoscopic examination revealed that active bleeding and stigmata of recent hemorrhage were more frequent in these patients. Urgent UGIE and, where necessary because of lesions, endoscopic hemostasis were performed in most of these patients. Patients admitted to the municipal hospital were treated more frequently with high-dose intravenous PPIs. Patients undergoing urgent UGIE and endoscopic therapy had a shorter duration of hospitalization. However, there were no differences regarding the need for surgery or mortality rates. The results of our study are consistent with the literature.

Primary non-Hodgkin lymphoma of the orbit presenting with massive bilateral periorbital tumors.

Extranodal onset can be seen in approximately 25-40% of the cases of non- Hodgkin lymphomas and diagnosis is often difficult due to nonspecific symptoms. Orbital lymphomas represent approximately 50% of the orbital malignancies. Common symptoms and signs at presentation are: palpable tumor, exophtalmia, dyplopia and decreased vision. Diagnosis can be made only by biopsy and early treatment is important in order to increase the chance of cure. We present the case of a patient whose diagnosis and treatment were delayed due to refusal of biopsy and, although complete remission of lymphoma was obtained, the vision loss was permanent because of prolonged compression on the optic nerves. A particularity of this case is the presence of massive periorbital tumors on admission to the hospital, incorporating the eye globes completely and causing impressive facial deformity.