ABSTRACT
Breast cancer (BC) is the prevailing malignancy and major cause of cancer-related death in females. Doxorubicin is a part of BC neoadjuvant and adjuvant chemotherapy regimens. The administration of anthracycline derivates, such as doxorubicin, may cause several side effects, including hematological disfunction, gastrointestinal toxicity, hepatotoxicity, nephrotoxicity, and cardiotoxicity. Cardiotoxicity is a major adverse reaction to anthracyclines, and it may vary depending on individual differences in doxorubicin pharmacokinetics. Determination of specific polymorphisms of genes that can alter doxorubicin metabolism was shown to reduce the risk of adverse reactions and improve the safety and efficacy of doxorubicin. Genes which encode cytochrome P450 enzymes (CYP3A4 and CYP2D6), p-glycoproteins (ATP-binding cassette (ABC) family members such as Multi-Drug Resistance 1 (MDR1) protein), and other detoxifying enzymes were shown to control the metabolism and pharmacokinetics of doxorubicin. The effectiveness of doxorubicin is defined by the polymorphism of cytochrome p450 and p-glycoprotein-encoding genes. This study critically discusses the latest data about the role of gene polymorphisms in the regulation of doxorubicin's anti-BC effects. The correlation of genetic differences with the efficacy and safety of doxorubicin may provide insights for the development of personalized medical treatment for BC patients.
ABSTRACT
Objective: The aim of the study was to assess the role of mid-regional proadrenomedullin (MR-proADM) in comparison with routine laboratory tests in patients with COVID-19. Materials and methods: 140 hospitalized patients aged 18 and older with COVID-19 pneumonia were included in prospective single-center study. Routine analyses were performed, and MR-proADM level was measured within the first and the third hospital days using Human MR pro-ADM (Mid-regional pro-adrenomedullin) ELISA Kit with a sensitivity of 0.469 pmol/L (immunofluorescence assay). National Early Warning Score (NEWS) was used for primary assessment of the disease severity. According to disease outcome the patients were divided into two groups: discharged patients (n = 110, 78.6%) and deceased patients (n = 30, 21.4%). Results: The groups had no statistically significant difference in sex, comorbidity, body temperature, oxygen saturation level, heart rate, respiratory rate, and C-reactive protein (CRP) level and procalcitonin (PCT). The deceased patients had statistically significant difference in age (median, 76 years; interquartile range, 73.2-78.2 vs. median, 66 years; interquartile range, 62-67; p < 0.0001), NEWS value (median, 5; interquartile range, 3-8 vs. median, 2; interquartile range, 0-6; p <0.05), hospitalization period (median, 17; interquartile range, 7-35 vs. median, 6; interquartile range, 3-14), quantitative CT extent of lung damage > 50% [n = 26 (86.7%) vs. n = 9 (8.2%) p < 0.0001], level of leukocytes (median, 11.4 ×109/L; interquartile range, 6.2-15.5 vs. median, 5.3 ×109/L; interquartile range, 4.7-6.4; p = 0.003), level of neutrophils (median, 80.9%; interquartile range, 73.6-88.6 vs. median, 72.6%; interquartile range, 68.7-76.9; p = 0.027), level of MR-proADM at the first hospital day (median, 828.6 pmol/L; interquartile range, 586.4-1,184.6 vs. median, 492.6 pmol/L; interquartile range, 352.9-712.2; p = 0.02), and level of MR-proADM at the third hospital day (median, 1,855.2 pmol/L; interquartile range, 1,078.4-2,596.5 vs. median, 270.7 pmol/L; interquartile range, 155.06-427.1). Conclusion: Mid-regional proadrenomedullin has a higher prognostic value in patients with COVID-19 in comparison with routine inflammatory markers (leukocyte and neutrophils levels, CRP, and PCT) and NEWS.
ABSTRACT
BACKGROUND: Nonsteroid anti-inflammatory drugs represent an important osteoarthritis (OA) therapy component, but also a leading cause of gastropathy: one of the most frequent and serious OA therapy complications. The aim of the present study was to study the influence of GI health in an OA population receiving either ginger or diclofenac. METHODS: Forty-three (43) patients with confirmed OA (knee and hip) were included in a randomized controlled study. A ginger group of 21 patients (17 women, 4 men) was given a specific ginger combination daily (340 mg EV.EXT 35 Zingiber officinalis extract) for 4 weeks. A diclofenac group (positive control) of 22 patients (18 women, 4 men) received 100 mg diclofenac daily for the same period. Both groups also received 1000 mg glucosamine daily. Gastrointestinal pain and dyspepsia were evaluated according to the severity of dyspepsia assessment (SODA) form. Patients also underwent esophagogastroduodenoscopy (EGDS) including biopsy before and after the treatment. Serum gastrin-17 levels, and stomach mucosa prostaglandins (PG) E1, E2, F2α, and 6-keto PGF1α (PGI2) levels were measured. Arthritic pain was evaluated using the visual analogue scale (VAS) on standing and moving. RESULTS: The ginger group showed a slight but significantly lowered SODA pain and no change of SODA dyspepsia. EGDS showed significantly increased levels of PGE1, PGE2, and PGF2α in the stomach mucosa. This rise in gastric mucosa PG levels correlated with an increase in serum gastrin-17. On the other hand, the diclofenac group showed increased SODA pain and dyspepsia values with a corresponding significant decrease of stomach mucosa prostaglandins and general negative stomach mucosa degeneration. Both groups showed a relevant and significantly lowered VAS pain both on standing and moving. CONCLUSIONS: The ginger combination is as effective as diclofenac but safer in treating OA, being without effect on the stomach mucosa. The increased mucosal PGs synthesis in the ginger group supports an increased mucosa-protective potential. VAS; visual analogue scale, 0-100 mm.
