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Acute myeloid leukemia (AML) is caused by a defective precursor leading to malignant clonal expansion, often with FMS-like tyrosine kinase-3 receptor (FLT3) mutations, particularly internal tandem duplication (ITD), which has a poor prognosis. Quizartinib, a second-generation FLT3 inhibitor, has FDA approval for relapsed/refractory AML with FLT3/ITD mutation. It has shown promise in clinical studies since 2013 due to its excellent oral absorption and potent activity on FLT3. This review explores Quizartinib's mechanism of action, efficacy in monotherapy or combination with chemotherapy, drug interactions, adverse events, resistance mechanisms and future research directions.
Discover Quizartinib's journey in AML treatment: from its targeted FLT3 inhibition mechanism to overcoming resistance. Clinical trials show promise, but the battle against side effects continues. #Quizartinib #AML #FLT3resistance #ClinicalTrials.
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Background: Hereditary transthyretin (ATTRv) amyloidosis, a multifaceted disorder affecting multiple systems, substantially diminishes patients' physical capabilities and overall quality of life. Patisiran and Vutrisiran, two Ribonucleic acid (RNA) interference therapies, target reducing both pathogenic and wild-type transthyretin (TTR) protein levels. This systematic review assesses the effectiveness and safety of these treatments in managing ATTRv. Methods: A comprehensive, thorough literature search across databases including Embase, PubMed, Web of Science, Cochrane Central, and Google Scholar yielded 858 studies. Following removing duplicate and irrelevant articles, 676 distinct studies underwent review. These studies, conducted on a global scale, encompassed a range of methodologies, including clinical trials and indirect treatment comparisons. Results: Ten studies, spanning a total population of 756 patients, were selected for in-depth analysis. Patisiran and Vutrisiran consistently demonstrated significant improvements in primary and secondary endpoints related to neuropathy, quality of life, and cardiac function. Both medications were well-tolerated, with primarily mild to moderate adverse events. Indirect treatment comparison studies indicated Vutrisiran's superiority over Tafamidis in treating ATTRv amyloidosis. Conclusion: This systematic review recommends using Patisiran and Vutrisiran to treat ATTRv amyloidosis. The findings suggest that these RNA interference therapies improve neuropathy, quality of life, and cardiac symptoms. The results indicate sustained benefits over prolonged treatment, with satisfactory safety profiles. However, potential biases, conflicts of interest in the studies, and limited follow-up periods in some trials necessitate cautious interpretation. Future research should address these limitations and provide more robust evidence for the long-term efficacy and safety of Patisiran and Vutrisiran in ATTRv treatment.
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Background: We aim to present incidence rates and geographical distribution of most common early-onset gastrointestinal cancers (EOGICs), including early-onset esophageal cancer (EOEC), gastric cancer (EOGC) and colorectal cancer (EOCRC) in Iran, 2014-2018. Methods: Data on new cases of EOEC, EOGC and EOCRC were obtained from publicly available annual reports of the Iranian National Population-based Cancer Registry (INPCR). Incidence rates were calculated using the population data available from the Statistical center of Iran. We considered the World standard population for calculation of age-standardized incidence rates (ASR). We also calculated 95% confidence intervals (CIs) for ASR. All rates are presented per 100000 person-years. Results: Overall, 19,679 new cases of EOGIC were registered by the INPCR between 2014 and 2018. The ASRs (95% CI) of EOEC, EOGC and EOCRC were 0.49 (95% CI: 0.47-0.51), 1.67 (1.63-1.71), and 3.07 (3.01-3.13) per 100,000 person-years, respectively. Our findings indicate decreasing and constant trends in the ASR of EOEC and EOGC during the study period, 2014-2018. There was an increasing trend in the ASR of EOCRC. We also found geographical disparities in the incidence rates of EOGICs across provinces of Iran, suggesting the highest ASRs of EOEC in Golestan (1.3), EOGC in Ilam (2.99) and EOCRC in Ilam (4.49). Conclusion: Our findings suggested that the incidence rate of EOCRC is consistently increasing. We also found variations in the incidence of EOGICs among different provinces. Further investigations are recommended to clarify the time trends and risk factors of EOGICs in Iran.
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BACKGROUND: Lipoprotein a (LP(a)), an LDL-like lipoprotein, known as a risk factor for cardiovascular diseases, has a controversial association with diabetic retinopathy in patients with type 2 diabetes-the current systematic review aimed to critically assess the association between LP(a) and diabetic retinopathy. METHODS: A systematic review of relevant studies was conducted after a thorough search in PubMed, Scopus, and Google Scholar electronic databases. We used English observational, case-control, and prospective cohort studies published up to August 2022, including type 2 diabetic patients as the population, diabetic retinopathy as the outcome, and LP(a) as the intervention. RESULT: 17 relevant studies, including 4688 patients with diabetes, were included in this systematic review. While in 13 studies, Lipoprotein(a) was recognized as a risk factor for diabetic retinopathy, only three studies reported no evidence of a relationship between the two. Also, another study showed a mixed outcome of the relationship between LP(a) and diabetic retinopathy. CONCLUSION: High serum lipoprotein(a) in patients with type 2 diabetes is considered a risk factor for diabetic retinopathy. However, further large-scaled cohort studies are still required to validate this finding.