Hydroxyurea (HU) or hydroxycarbamide is a cytotoxic antimetabolite widely used to treat Philadelphia chromosome-negative Myeloproliferative Neoplasms (Ph-MPN) like Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF). Patients with Ph-MPN are at an increased risk of Non-melanoma skin cancers (NMSC). The cause of this finding remains uncertain. In this systematic review, we would like to know if chronic use of HU in this population is responsible for the sudden onset of NMSC. The results obtained will help the patients and clinicians with early diagnosis of cutaneous lesions and in optimizing the current treatment options for MPN. We conducted a multi-database literature search, applied eligibility criteria and quality assessment tools to the studies extracted, with an intention to include only fair to high-quality articles. We analyzed six observational studies and four traditional reviews. Two out of 10 studies concluded that no relationship exists between the incidence of NMSC and HU. The remaining eight studies indicated the association. According to these studies, the possible risk factors include old age, excessive exposure to sunlight, higher doses, and prolonged HU therapy duration. Ultraviolet (UV) radiation and HU play a combined role in carcinogenesis. Periodic dermatologic screening is essential in these patients. Prompt biopsy and accurate diagnosis can prevent the progression of cancer and decrease the associated morbidity and mortality. True incidence and causation cannot be ascertained due to the scarcity of research on this topic. Multi-center prospective studies in large groups of Ph-MPN patients are recommended to determine the temporal relationship between NMSC and HU treatment.
Cystic fibrosis (CF) is an autosomal recessive disease primarily affecting the respiratory system and gastrointestinal system. The life expectancy of patients with CF has significantly improved due to medical advancement and the effective use of screening techniques. However, new challenges have emerged. Particularly those involving cardiovascular pathology. This study aims to provide a better understanding of the different mechanisms that cause cardiovascular complications in patients with CF, which would help find an efficient treatment that not only prolongs survival but also improves their quality of life. This study extensively reviews different theories such as right ventricular hypertrophy due to lung pathology, ventricular interdependence, the association of nutritional deficiencies and severe cystic fibrosis transmembrane conductance regulator (CFTR) genotypes with myocardial fibrosis, effects of hypoxia, recurrent infections, and systemic inflammation of the heart and blood vessels that explain the direct or indirect involvement of the cardiovascular system in CF. For this review, 258 articles were retrieved from PubMed and Google Scholar. Out of which, a total of 12 high-quality articles were selected using appropriate quality assessment tools and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The result of this study suggests that early detection of cardiovascular dysfunction can improve the survival rate of the patient. Furthermore, this study could aid future researchers in the exploration of various best screening modality techniques for the early detection of cardiovascular dysfunction.
Testosterone replacement therapy (TRT) has become increasingly popular over the years and there has been an increasing debate on whether testosterone replacement should be offered to older men due to its association with cardiovascular events. In this study, we evaluated the risk of myocardial infarction (MI) associated with TRT in hypogonadal men through a meta-analysis. We carried out the analysis by following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and conducted a literature search utilizing the following databases: Google Scholar, PubMed, Science Direct, Cochrane Library trials, and ClinicalTrials.gov. The search strategy resulted in a total of 782 articles, after applying our inclusion and exclusion criteria. Six observational studies and two randomized controlled trials (RCTs) were included for the analysis. A total of 55,806 hypogonadal men with baseline testosterone levels <300ng/mL were included in the analysis. The intervention group received testosterone in various routes including transdermal patches, gels, mouth patches, testosterone injections, and deposits. The incidence of MI was taken to be the primary measure outcomes. The pooled data from eight studies showed MI incidence in 249 out of 11,720 (2.1%) in the TRT group and 1420 out of 33,086 (4.3%) in the control group. The pooled OD showed no statistically significant association of TRT and MI compared to the control group (OR = 0.76, 95% CI 0.36-1.31; p=0.48). The model revealed high heterogeneity with I 2 =79%. With sensitivity analysis and, excluding two studies out of the eight, the pooled data was able to achieve low heterogeneity with I 2 = 0%. The newly pooled data from six studies showed MI incidence in 226 out of 10,137 (2.2%) in the TRT group and 969 out of 36,304 (2.7%) in the control group. The pooled OD shows no statistical significance in the association between TRT treatment and MI compared to the control group. (OR =0.87, 95% CI 0.75-1.01; P =0.08). It appears that TRT does not increase the risk of MI as compared to the non-intervention group. Further RCTs with greater population size are needed that could produce more solid results, allowing more definitive conclusions to be made on this topic.
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