In 1990, the Italian Study Group for Turner's Syndrome (ISGTS) undertook a nationwide survey, involving the retrospective collection of cross-sectional data and longitudinal growth profiles of 772 girls with Turner's syndrome born between 1950 and 1990. The study was carried out in 29 pediatric endocrinological centers. In this first report, the familial characteristics and neonatal data of Turner girls are described, compared to those of the general population, and related to postnatal somatic development. Furthermore, charts for birth weight and growth standards for height and weight from infancy to adulthood are presented (these are the first charts based on a large sample from the Mediterranean area). The main findings were: (1) incidence of Turner births increases with parental age or parity; (2) most of the neonates are small for dates; (3) girls with normal birth weight tend to be both taller and heavier than girls with low birth weight during the whole growth period; and (4) a 10-cm difference in midparental height leads to a 6.5-cm difference in adult stature.
Continuous glucose monitoring (CGM) systems are an emerging technology that allows frequent glucose measurements to monitor glucose trends in real time. Their use as a diagnostic tool is still developing and appears to be promising. Combining intermittent glucose self-monitoring (SGM) and CGM combines the benefits of both. Significant improvement in the treatment modalities that may prevent the progress of prediabetes to diabetes have been achieved recently and dictates screening of high risk patients for early diagnosis and management of glycemic abnormalities. The use of CGMS in the diagnosis of early dysglycemia (prediabetes) especially in high risk patients appears to be an attractive approach. In this review we searched the literature to investigate the value of using CGMS as a diagnostic tool compared to other known tools, namely oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin (HbA1C) in high risk groups. Those categories of patients include adolescents and adults with obesity especially those with family history of type 2 diabetes mellitus, polycystic ovary syndrome (PCO), gestational diabetes, cystic fibrosis, thalassemia major, acute coronary syndrome (ACS), and after renal transplantation. It appears that the ability of the CGMS for frequently monitoring (every 5 min) glucose changes during real-life settings for 3 to 5 days stretches the chance to detect more glycemic abnormalities during basal and postprandial conditions compared to other short-timed methods.
1688 Objective: The introduction of several classes of targeted therapeutics for the treatment of chronic myelogenous leukemia (CML) raises the question of whether male fertility is affected and the degree of this affection, if any, among the different generations of tyrosine kinase inhibitors. When two drugs are equally effective, the drug with less toxic effect on fertility is favorable. Our aims were to evaluate semen parameters and pituitary gonadal function before and 4 months after starting tyrosine kinase inhibitors (TKI) namely, Dasatinib, Nilotinib, and Imatinib in patients with CML. Design: Prospective study. Setting, Patients, Interventions: We studied the effect of TKIs' first generation (Imatinib) and second generation ( Dasatinib and nilotinib) on semen parameters, endocrine functions in 20 euogonadal male patients with CML, and capacity to ejaculate, aged from 35 to 51 years. They were receiving either Imatinib, Dasatinib or Nilotinib as upfront therapy. We studied gonadotrophins (LH and FSH) and testosterone (T) secretion and evaluated sperm parameters before and after four months of using these TKIs. Main Outcome Measures and Results: Four months after starting TKIs there were significant decreases in serum testosterone, LH, FSH concentrations. The total sperm count, total and rapid progressive sperm motility, and % sperms with normal morphology decreased significantly versus before treatment. (table 1). After 4 months of therapy, Dasatinib effects on sperm count (SC), volume(SV), all sperm motilities and % of sperms with normal morphology(%NM) were significantly less harmful compared to Imatinib and Nilotinib. (Table 2). Significant correlations were found between serum T concentrations and semen parameters before and after TKIs therapy including SC ( r = 0.658 and r = 0.73 respectively, p < 0.001), rapid progressive motility (r = 0.675 and r = 0.758 respectively p < 0.001), and the % NM(r = 0.752 and r = 0.834 respectively, p < 0.001). After TKIs therapy, LH were correlated significantly with T concentrations ( r = 0.434, p < 0.001) and SV and SC (r = 0.439 and r = 0.376 respectively, p: 0.01). Conclusion: Our study suggests that in patients with CML TKIs are associated with significant decrease of sperm parameters and decreased concentrations of serum T, LH, FSH. These potentially toxic effects on spermatogenesis are less prominent in patients treated with Dasatinib compared to Imatinib and Nilotinib. The mechanisms and pathways for these effects need further human and/or experimental studies. Disclosures: Yassin: Hamad medical corporation MRC: Employment, Research Funding. Soliman:Hamad medical corporation MRC: Employment, Research Funding. Elawa:Hamad medical corporation MRC: Employment, Research Funding.
Introduction: Chronic Myeloid leukemia (CML) is a chronic myeloproliferative neoplasm with an increased undifferentiated proliferation of granulocytic lineage of the white blood cells. It is an acquired disorder of the hematopoietic stem cells due to a cytogenetic aberration known as the Philadelphia chromosome. It occurs due to a phenomenon of a reciprocal translocation between chromosomes t(9,22) and results in BCR/ABL fusion gene. The product of this gene has tyrosine kinase property, which predominantly causes the disease. Tyrosine kinase inhibitors (TKI) are the mainstay of the treatment to achieve remission, while bone marrow transplant is the only proven cure. Tuberculosis (TB), both active and reactivation of latent TB, remains the most common infectious disease worldwide and leads to high mortality. Currently, one-fourth of the global population has been infected by Mycobacterium tuberculosis. The incidence of TB has been reportedly increasing in patients with cancer. It has been mostly found in association with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Recently, the incidence increased in patients with CML during treatment with Imatinib (IM) has also been reported in a retrospective cohort study in Taiwan by Lui C-J et. al. and few other published cases in literature. This might be due to impairment of the T lymphocytes signal transduction leading to increased host susceptibility to TB, hepatitis B, and varicella-zoster infection. TB treatment is mainly based on the susceptibility of the Mycobacterium Tuberculosis to the anti-TB medications. First-line therapy includes of four drugs, Isoniazid (INH), Rifampicin (RIF), Pyrazinamide (PZA), and Ethambutol (EMB). Anti TB drugs administration also needs close monitoring because of potential side effects. These include, but not limited to hepatoxicity, optic neuritis, impaired color vision, peripheral neuropathy, and gastrointestinal disturbances. Their occurrence necessitate discontinuation of the culprit drug from the regimen. Certain anti TB drugs are also known to disrupt bioavailability of other drugs metabolized in the liver when concomitantly administered by influencing the hepatic cytochrome P450 enzyme. This happens while using anti-TB medication to treat concomitant TB infection in CML patients on tyrosine kinase inhibitors therapy. Methods and critical analysis of the reviewed study articles: The authors reviewed the current literature focusing on all articles addressing TB infections and their diagnosis and management in patients with CML (PubMed and Google Scholar between 2000 and 2020). Our review aimed to provide the necessary data to improve clinical diagnosis and clarify the management strategy of this condition. Conclusion and treatment proposal: Throughout our review of multiple research articles, it has been realized that patients with CML and other hematological malignancies and solid tumors (e.g., non-Hodgkin lymphoma, chronic lymphocytic leukemia, metastatic gastric tumors), have a higher risk of having TB infection. TB infection (pulmonary and extra-pulmonary) occurs 2-9 times more than the general population in patients with hematological malignancies. In CML patients, treatment therapy with Imatinib posed a higher risk of development of TB due to defective cellular immunity. Co-administration of 1st line anti Tb medications mainly rifampicin with standard TKIs therapy Imatinib and Dasatinib has resulted in sub-therapeutic levels of these drugs due to induction of CYP4503A enzyme. Either by changing the TB treatment regimen to a non-rifampicin based therapy line with a combination of a fluoroquinolone, increasing the dose, or switching to a different TKI class may result in clinical improvement. To the best of our knowledge, there are no randomized control trials, or FDA approved guidelines to treat concomitant TB infection in CML patients. Therefore, a clear strategy to deal with such a clinical condition is lacking. The immediate treatment for the concomitant disease has been suggested based on clinical experience and clinical response of some patients published in few case reports, case series, and retrospective cohort studies. After careful literature review, we put forth our management proposals, However it need further research studies and clinical trials to bring recommendations and guidelines. Disclosures No relevant conflicts of interest to declare.
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