RESUMEN
Non-bacterial thrombotic endocarditis (NBTE) is a very rare condition characterized by sterile thrombi formation on cardiac valves and is often associated with hypercoagulation states, such as malignancy and autoimmune disorders. We present the case of a 74-year-old patient admitted to the intensive care unit with acute respiratory failure, who had a history of COVID-19 infection five months prior to admission, despite having received certified vaccination. The patient developed NBTE involving the mitral valve, alongside acute respiratory distress syndrome (ARDS). In spite of the exclusion of cancer and systemic connective tissue disorders, the patient's condition rapidly deteriorated, leading to treatment-resistant multi-organ failure and demise, despite aggressive management, including anticoagulation therapy, mechanical ventilation, and renal replacement therapy. This case underscores the need for further research into the mechanisms underlying NBTE in the absence of traditional risk factors. Additionally, it highlights the importance of long-term anticoagulant therapy in NBTE management to mitigate the risk of embolic complications. Our case contributes to the growing body of literature identifying a subset of NBTE cancer-free patients with distinct characteristics, including those associated with current or past COVID-19 infection.
RESUMEN
Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.