The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis.

BACKGROUND: Glucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus. METHODS: Three databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects. RESULTS: Five studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low. CONCLUSIONS: Within this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable. TRIAL REGISTRATION: PROSPERO identifier: CRD42023393020.

Translation and validation into Brazilian Portuguese of the English version of the International Consultation on Incontinence Modular Questionnaire for Male Lower Urinary Tract Symptoms (ICIQ-MLUTS).

OBJECTIVES: To translate and cross-culturally adapt the English version of the International Consultation on Incontinence Modular Questionnaire for Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) into Brazilian Portuguese and evaluate its psychometric properties. INTRODUCTION: Male lower urinary tract symptoms (LUTS) are frequent and commonly assessed with questionnaires. The ICIQ-MLUTS is a robust instrument that investigates the main aspects of LUTS in men and their impact on quality of life. Although highly recommended, Grade A is not as popular as the International Prostate Symptom Score (IPSS) and remained untranslated and unvalidated for Brazilian Portuguese. METHODS: After authorization by the Advisory Board of the International Consultation on Incontinence (ICIQ) the translation process was conducted according to the standard guidelines and the ICIQ validation protocol. Internal consistency was assessed using Cronbach's ⍺ coefficient and values > 0.7 were considered satisfactory. To assess test-retest reliability and reproducibility, Spearman's correlation coefficient and intraclass correlation coefficient were used. For group data, a Spearman correlation coefficient or an intraclass correlation coefficient of at least 0.70 demonstrates good test-retest reliability. A p < 0.05 was considered significant. RESULTS: One hundred and eighty-six, aged 61.41 ± 11.01 years, suffering from LUTS participated in the study between January 2021 and October 2022. Cronbach's ⍺, 0.875, demonstrated the internal consistency of the Portuguese version of ICIQ-MLUTS. The intraclass correlation coefficient of 0.912 (0.882; 0.935 - 95% CI) for the test-retest evidenced the stability and validity of the instrument. Likewise, Spearman's correlation coefficient highlighted the agreement between IPSS and ICIQ-MLUTS, 0.906, <0.001. DISCUSSION: The Portuguese version of the ICIQ-MLUTS demonstrated internal consistency, stability, and validity, in addition to agreement with the IPSS. CONCLUSION: The ICIQ-MLUTS, translated and validated into Brazilian Portuguese, is a robust and reliable instrument to assess LUTS in Brazilian men and can be used in the evaluation of treatment and research.

Ten-eleven-translocation 2 (TET2) is downregulated in myelodysplastic syndromes.

TET2, a member of the ten-eleven-translocation (TET) family genes that modify DNA by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), is located in chromosome 4q24 and is frequently mutated in myeloid malignancies. The impact of TET2 mutation on survival outcomes is still controversial; however, functional studies have proved that it is a loss-of-function mutation that impairs myeloid cell differentiation and contributes to the phenotype of myeloid neoplasia. We, herein, aimed to investigate TET2 expression in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). A significantly decreased TET2 expression was observed in bone marrow cells from AML (n = 53) and patients with MDS (n = 64), compared to normal donors (n = 22). In MDS, TET2 expression was significantly reduced in RAEB-1/RAEB-2 compared to other WHO 2008 classifications, and a lower TET2 expression was observed at the time of MDS disease progression in four of five patients. In multivariate analysis, low TET2 expression (P = 0.03), male gender (P = 0.02), and WHO 2008 classification (P < 0.0001) were independent predictors of poorer overall survival. These results suggest that defective TET2 expression plays a role in the MDS pathophysiology and predicts survival outcomes in this disease.

Thyroid uptake and scintigraphy using 99mTc pertechnetate: standardization in normal individuals.

CONTEXT: Thyroid uptake and scintigraphy using 99mTc-pertechnetate has proven to be more advantageous than with 131I-iodide, since the images have better quality, the procedure is faster and the patient is submitted to a lower radiation dose. OBJECTIVE: The purpose of this study was to standardize a simple and fast methodology for performing thyroid uptake and scintigraphy and to determine the normal values for 99mTc- pertechnetate uptake. TYPE OF STUDY: Prospective, non-randomized. SETTING: Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, Campinas State University. PARTICIPANTS: The study consisted of 47 normal individuals, 30 women and 17 men, with ages ranging from 19 to 61 years (mean of 33 years). PROCEDURES: The laboratory assessment of thyroid function consisted of serum dosages of ultra-sensitive thyroxin and thyrotrophin. Twenty minutes after an intravenous injection of 10 mCi (370 MBq) of 99mTc-pertechnetate, the images were obtained on a computerized scintillation camera equipped with a low-energy high-resolution parallel hole collimator. RESULTS: All the individuals were euthyroid both on clinical and laboratory evaluation. The baseline thyroid 99mTc-pertechnetate uptake ranged from 0.4 to 1.7%. The uptake values obtained in these normal individuals showed that 95% presented a thyroid uptake that ranged from 0.4 to 1.5% of the injected dose. CONCLUSION: The assessment of thyroid structure and function using 99mTc-pertechnetate is a simple, fast and efficient method, which could easily become a part of the routine studies in nuclear medicine laboratories.

Thyroid uptake and scintigraphy using 99mTc pertechnetate: standardization in normal individuals

CONTEXT: Thyroid uptake and scintigraphy using 99mTc-pertechnetate has proven to be more advantageous than with 131I-iodide, since the images have better quality, the procedure is faster and the patient is submitted to a lower radiation dose. OBJECTIVE: The purpose of this study was to standardize a simple and fast methodology for performing thyroid uptake and scintigraphy and to determine the normal values for 99mTc- pertechnetate uptake. TYPE OF STUDY: Prospective, non-randomized. SETTING: Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, Campinas State University. PARTICIPANTS: The study consisted of 47 normal individuals, 30 women and 17 men, with ages ranging from 19 to 61 years (mean of 33 years). PROCEDURES: The laboratory assessment of thyroid function consisted of serum dosages of ultra-sensitive thyroxin and thyrotrophin. Twenty minutes after an intravenous injection of 10 mCi (370 MBq) of 99mTc-pertechnetate, the images were obtained on a computerized scintillation camera equipped with a low-energy high-resolution parallel hole collimator. RESULTS: All the individuals were euthyroid both on clinical and laboratory evaluation. The baseline thyroid 99mTc-pertechnetate uptake ranged from 0.4 to 1.7 percent. The uptake values obtained in these normal individuals showed that 95 percent presented a thyroid uptake that ranged from 0.4 to 1.5 percent of the injected dose. CONCLUSION: The assessment of thyroid structure and function using 99mTc-pertechnetate is a simple, fast and efficient method, which could easily become a part of the routine studies in nuclear medicine laboratories