Clinical Outcomes of Patients with Chronic Myeloid Leukemia and COVID-19 Infection-A Single Center Survey.

Background: Previous research has shown different effects of hematological malignancies on the outcome of patients with COVID-19 infection depending on the type of disease and the treatment received. This research was aimed at examining the clinical outcome of COVID-19 infection in positive patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. Methods: We collected retrospective information on chronic myeloid leukemia patients who were treated and monitored in our institution during the pandemic period. Within this cohort, we recorded COVID-19 positive symptomatic patients and analyzed their basic characteristics, symptoms, severity, and outcome. Results: In the study cohort when COVID-19 was diagnosed, 86.7% of patients were on first-generation tyrosine kinase inhibitors therapy-imatinib. At the time of infection, 70% of patients were in molecular remission, 23.4% in complete cytogenetic remission, and 3.3% in complete hematological response. Most patients had symptomatic disease. Within the analyzed group, 56.7% of patients had asymptomatic/mild COVID-19 infection, 23.3% of patients had moderate symptoms which did not require hospitalization, and 20% of patients had severe/critical symptoms that required admission to the intensive care unit. More than half of the patients interrupted treatment with tyrosine kinase inhibitors temporarily during COVID-19. There were no deaths due to COVID-19 infection. Conclusions: In compliance with other larger clinical studies, analysis of the clinical outcome of COVID-19 infection in patients with chronic myeloid leukemia on tyrosine kinase inhibitors therapy in this study showed that they do not have an increased risk for COVID-19 infection and that they have a mild course of the disease with recovery.

Marine toxin domoic acid induces in vitro genomic alterations in human peripheral blood cells.

Domoic acid (DA) is an excitatory marine neurotoxin produced by diatoms Pseudo-nitzschia spp. as a defence compound that accumulates in the food web and is associated with amnesic shellfish poisoning in humans. Although its toxicity has been well established in marine species, there is limited data on DA cytogenotoxicity in human non-target cells. Therefore, we aimed to investigate the cytogenotoxic potential of DA (0.01-10 µg/mL) in human peripheral blood cells (HPBCs) using a battery of bioassays in vitro. In addition, the influence of DA on oxidative stress parameters as a possible mechanism of action was assessed. Results revealed that DA induced dose- and time-dependent cytotoxic effects. DA significantly affected genomic instability by increasing the frequency of micronuclei and nuclear buds. Furthermore, a slight induction of primary DNA strand breaks was detected after 24 h of exposure accompanied by a significant increase in the number of abnormal size tailed nuclei. No induction of hOGG1 (human 8-oxoguanine DNA glycosylase) sensitive sites was determined upon exposure to DA. Additionally, DA induced oxidative stress by increased production of reactive oxygen species accompanied by changes in glutathione, superoxide dismutase, malondialdehyde and protein carbonyl levels. Overall, the obtained results showed adverse genotoxic effects of DA in non-target HPBCs.

Evaluation of oxidative stress responses in human circulating blood cells after imatinib mesylate treatment - Implications to its mechanism of action.

Imatinib mesylate (IM) is the first developed protein kinase inhibitor and recently it has topped consumption rates among targeted and total anticancer drugs. Although there are indications that IM possesses cyto/genotoxic activities against normal non-target cells as well, there is a lack of information regarding the underlying mechanism involved in those actions. Therefore, we aimed to evaluate the response of human circulating blood cells towards oxidative stress after IM treatment (0.0001-10 µg/mL) in vitro. Based on the results, IM had an influence on all of the oxidative stress parameters tested. Lower concentrations of IM induced an increase of glutathione level, following its decrease at higher IM concentrations indicating impairment in oxidative stress defences. Concomitant to a glutathione decrease, an increase of malondialdehyde and protein carbonyls level was observed indicating oxidative damage of lipids and proteins. The observed effects overlapped with the observed formation of oxidative base damage detected by formamidopyrimidine-DNA glycosylase modified-comet assay indicating that IM managed to induce oxidative DNA damage. Our results provide novelty in their mechanistic approach to IM-induced toxicity in non-target cells and suggest that IM can affect blood cells and induce oxidative stress.

Results of open tibial fracture treatment using external fixation.

Introduction: Open lower leg fractures are the most common open fractures of the locomotor system and their treatment is associated with a number of complications. Objective: The aim of the paper was to present the results of the treatment of 68 patients with open lower leg fractures, as well as the complications that accompany the treatment of these fractures. Methods: In the analyzed group, there were 45 (66.18%) men and 23 (33.82%) women. The majority of patients ­ 33 (48.53%) of them ­ were injured in motor vehicle accidents, whereas 24 (35.29%) patients sustained injuries due to falls from heights. In two (2.94%) patients the cause of open tibial fractures was gunshot injuries. In the analyzed group, there were 18 (26.47%) type I open fractures, 21 (30.88%) type II open fractures, 19 (27.94%) type IIIA open fractures, seven (10.29%) type IIIB open fractures, and three (4.41%) type IIIC open fractures. Results: The tibial shaft fracture healed without serious complications in 50 (73.53%) patients, whereas in 18 (26.47%) patients we observed some complications. Nonunion was found in 10 (14.71%) patients, osteitis in four (5.88), malunion in two (2.94%) patients. Milder complications such as soft tissue pin tract infection developed in 13 (19.12%) patients, infection of the open fracture wound soft tissue was observed in four (5.88%) patients. Conclusion: Basic principles in the treatment of open lower leg fractures in this study are thorough primary open fracture wound treatment followed by the delayed wound closure, stable fracture fixation using unilateral external skeletal device, proper antibiotic treatment and tetanus prophylaxis. The results correlate with similar studies.