Contraceptive methods in adolescence: a narrative review of guidelines.

PURPOSE: Adolescent pregnancy, while recently in decline, remains a matter in need of addressing. Education and counselling are deemed crucial and this review aims at comparing published contraceptive guidelines, thus resolving any surrounding misconceptions. MATERIALS AND METHODS: Recently published contraception guidelines regarding adolescent pregnancy were retrieved. In particular, guidelines and recommendations from ACOG, RCOG, SOCG, AAP, CPS, NICE, CDC, and WHO were compared and reviewed based on each guideline's method of reporting. RESULTS: Three categories of contraceptive methods are available for adolescents and recommendations on their initiation should be made based on their efficacy, according to all guidelines. Therefore, long acting reversible contraceptives (LARCs) should be highly recommended as the most effective method (typical use failure rate: 0.05%), followed by short-acting hormonal contraceptives (typical use failure rate: 3-9%). The third contraceptive option includes contraceptives used in the moment of intercourse and displays the lowest effectiveness (typical use failure rate: 12-25%), mostly due to its dependence on personal consistency, however offers protection against STI transmission. CONCLUSION: Adolescents should be encouraged to initiate contraception, with LARCs being the primary choice followed by short-acting hormonal contraception. However, regardless of the chosen effective contraceptive method, the use of condom is necessary for STI prevention.

Adolescent pregnancy, while recently in decline, remains a matter in need of addressing. The use of contraceptive methods such as LARCs and short-acting hormonal contraceptives should be encouraged and suggested based on effectiveness with the addition of condom for STI prevention.

The role of endoglin and its soluble form in pathogenesis of preeclampsia.

Preeclampsia remains till today a leading cause of maternal and fetal morbidity and mortality. Pathophysiology of the disease is not yet fully elucidated, though it is evident that it revolves around placenta. Cellular ischemia in the preeclamptic placenta creates an imbalance between angiogenic and anti-angiogenic factors in maternal circulation. Endoglin, a transmembrane co-receptor of transforming growth factor ß (TGF-ß) demonstrating angiogenic effects, is involved in a variety of angiogenesis-dependent diseases with endothelial dysfunction, including preeclampsia. Endoglin expression is up-regulated in preeclamptic placentas, through mechanisms mainly induced by hypoxia, oxidative stress and oxysterol-mediated activation of liver X receptors. Overexpression of endoglin results in an increase of its soluble form in maternal circulation. Soluble endoglin represents the extracellular domain of membrane endoglin, cleaved by the action of metalloproteinases, predominantly matrix metalloproteinase-14. Released in circulation, soluble endoglin interferes in TGF-ß1 and activin receptor-like kinase 1 signaling pathways and inhibits endothelial nitric oxide synthase activation, consequently deranging angiogenesis and promoting vasoconstriction. Due to these properties, soluble endoglin actively contributes to the impaired placentation observed in preeclampsia, as well as to the pathogenesis and manifestation of its clinical signs and symptoms, especially hypertension and proteinuria. The significant role of endoglin and soluble endoglin in pathophysiology of preeclampsia could have prognostic, diagnostic and therapeutic perspectives. Further research is essential to extensively explore the potential use of these molecules in the management of preeclampsia in clinical settings.

Circulating serum and plasma levels of micro-RNA in type-1 diabetes in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a complex metabolic disorder characterized by hyperglycaemia, with constantly increasing incidence in paediatric population. The discovery of new molecules, such as microRNAs, and their possible interactions with T1DM create novel aspects in the diagnosis of the disease. METHODS: This systematic review and meta-analysis adhered to PRISMA guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and Clinicaltrials.gov. were searched up to 20 April 2020. Inclusion criteria for individual studies were quantification of microRNAs in serum/plasma samples and study groups consisting of children and adolescents with T1DM and healthy controls. Primary outcome of the study was the qualitative expression of microRNAs between the two groups. Statistical analysis was performed with Comprehensive Meta-Analysis Software v3.0. Methodological quality of included studies was assessed using Newcastle-Ottawa scale. RESULTS: A total of 484 studies were retrieved from the initial search of the databases. These were subsequently limited to seven included studies. Seven microRNAs demonstrated contrasting expression between the two groups, with two of them showing significant overexpression in T1DM group (miR-181:95% CI: 0.429 to 1.341 P < .001, miR-210:95% CI: 0.381 to 0.852, P < .001) and one micro-RNA being significantly overexpressed in control group (miR-375:95% CI: 0.293 to 1.459, P = .003). CONCLUSION: A total of three micro-RNA molecules appeared to have a significantly different expression in T1DM patients, serving as a possible diagnostic panel of biomarkers. These findings may contribute as reference for future research to further support the use of microRNAs as a novel diagnostic tool in T1DM.

Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature.

Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs' biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to ß-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity.

Breast Carcinogenesis during Pregnancy: Molecular Mechanisms, Maternal and Fetal Adverse Outcomes.

Breast cancer is a common type of cancer diagnosed during pregnancy, with increasing incidence over the last years, as more women choose to delay childbearing. Compared to breast cancer in general population, pregnancy-associated breast cancer (PABC) is significantly different in its terms of epidemiology, diagnostic and therapeutic management, while it exhibits particularly aggressive behavior, deriving from its unique molecular and biological profile. Although not fully elucidated, the pathophysiological basis of PABC can be traced back to a combination of hormonal and immune changes during pregnancy, breast involution and altered gene expression. There is considerable controversy in the existing literature about the influence of PABC on pregnancy outcomes, regarding both short- and long-term effects on maternal and fetal/neonatal health. The majority of PABC patients have advanced-stage disease at initial diagnosis and face a significantly poorer prognosis, with decreased survival rates. The most commonly reported adverse obstetrical-fetal events are preterm delivery and prematurity-associated neonatal morbidity, while other neonatal treatment-associated complications might also occur, even when safe therapeutic options are applied during pregnancy. The objective of the present comprehensive review was to summarize current knowledge and up-to-date evidence about the pathophysiological, molecular and biological basis of PABC, as well as its association with adverse maternal, obstetrical, fetal and neonatal outcomes.

The Prognostic Significance of BRAF Gene Analysis in Children and Adolescents with Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type. Mutations energizing the mitogen-activated-protein kinase (MAPK) pathway are definitely related to PTC. Its most common genetic alteration is in proto-oncogene B-Raf (BRAF). Mutated BRAF is proposed as a prognostic tool in adult PTC. We conducted a systematic review and meta-analysis evaluating the association of mutated BRAF gene and prognostic clinicopathological characteristics of PTC in children/adolescents. Systematic search for relevant studies included PubMed, MEDLINE, Scopus, clinicaltrials.gov and Cochrane Library. Pooled estimates of odds ratios for categorical data and mean difference for continuous outcomes were calculated using random/fixed-effect meta-analytic models. BRAFV600E mutation presents a pooled pediatric/adolescent prevalence of 33.12%. Distant metastasis is significantly associated with mutated BRAF gene (OR = 0.32, 95% CI = 0.16-0.61, p = 0.001). Tumor size (MD = -0.24, 95% CI = -0.62-0.135, p = 0.21), multifocality (OR = 1.13, 95% CI = 0.65-2.34, p = 0.74), vascular invasion (OR = 1.17, 95% CI = 0.67-2.05, p = 0.57), lymph node metastasis (OR = 0.92, 95% CI = 0.63-1.33, p = 0.66), extra-thyroid extension (OR = 0.78, 95% CI = 0.53-1.13, p = 0.19) and tumor recurrence (OR = 1.66, 95% CI = 0.68-4.21, p = 0.376) presented no association or risk with BRAF mutation among pediatric/adolescent PTC. Mutated BRAF gene in children and adolescents is less common than in adults. Mutation in BRAF relates significantly to distant metastasis among children/adolescents with PTC.

Predictive Factors for Pediatric Craniopharyngioma Recurrence: An Extensive Narrative Review.

Despite being classified as benign tumors, craniopharyngiomas (CPs) are associated with significant morbidity and mortality due to their location, growth pattern, and tendency to recur. Two types can be identified depending on age distribution, morphology, and growth pattern, adamantinomatous and papillary. The adamantinomatous CP is one of the most frequently encountered central nervous system tumors in childhood. Our aim was to review the relevant literature to identify clinical, morphological, and immunohistochemical prognostic factors that have been implicated in childhood-onset CP recurrence. Lack of radical surgical removal of the primary tumor by an experienced neurosurgical team and radiotherapy after a subtotal excision has been proven to significantly increase the recurrence rate of CP. Other risk factors that have been consistently recognized in the literature include younger age at diagnosis (especially <5 years), larger tumor size at presentation, cystic appearance, difficult tumor location, and tight adherence to surrounding structures, as well as the histological presence of whorl-like arrays. In addition, several other risk factors have been studied, albeit with conflicting results, especially in the pediatric population. Identifying risk factors for CP recurrence is of utmost importance for the successful management of these patients in order to ultimately ensure the best prognosis.

Soluble endoglin concentration in maternal blood as a diagnostic biomarker of preeclampsia: A systematic review and meta-analysis.

OBJECTIVE: Preeclampsia is a main cause of maternal and fetal morbidity and mortality. Research about maternal circulating diagnostic biomarkers is continuously performed, often with conflicting results that necessitate quantitative synthesis. Objective of this meta-analysis is to examine the value of soluble endoglin as predictor of preeclampsia separately at each pregnancy trimester, therefore exploring its potential usage as diagnostic biomarker in preeclampsia. STUDY DESIGN: This systematic review and meta-analysis adhered to PRISMA and MOOSE guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and ClinicalTrials.gov were searched up to April 20, 2020. Included studies were those comparing soluble endoglin levels in maternal serum or plasma at any pregnancy trimester, between women who subsequently developed preeclampsia and normotensive pregnant women being low-risk for preeclampsia development. Primary outcome was development of preeclampsia, while soluble endoglin levels in 1 st, 2nd and 3rd trimester of pregnancy were examined as possible predictors of preeclampsia. Subgroup analysis was performed regarding time of preeclampsia onset (early, late). Methodological quality of included studies was assessed using Newcastle-Ottawa scale. Overall quality of evidence for primary and secondary outcomes was evaluated using GRADEpro GD tool. RESULTS: There were overall 20 studies included in meta-analysis, enrolling 1146 preeclamptic and 1675 normotensive pregnant women. Soluble endoglin concentration (ng/mL) was significantly higher in preeclamptic women during 2nd (8 studies, MD:5.554, 95 %CI:2.671-8.436, P < .001, I2 = 97 %) and 3rd trimester (12 studies, MD:31.006, 95 %CI:24.734-37.278, P < .001, I2 = 98 %). Levels were also higher during 1st trimester; however, the difference was marginally not significant (MD:1.105, 95 %CI: -0.071 to 2.282, P = .06, I2 = 64 %). Furthermore, levels were significantly higher both in early-onset and late-onset preeclamptic vs normotensive pregnancies, (4 studies, MD:51.611, 95 %CI:2.250-100.972, P = .04, I2 = 97 %), (5 studies, MD:12.426, 95 %CI:7.863-16.989, P < .001, I2 = 98 %) respectively. However, when comparing directly early and late-onset preeclamptic women, no significant difference was detected (3 studies, MD:20.725, 95 %CI: -11.601 to 53.052, P = .209, I2 = 93 %). CONCLUSIONS: Soluble endoglin levels were consistently higher in preeclamptic compared to normotensive pregnant women almost throughout pregnancy. Our results firmly indicate soluble endoglin's potential use as predictor of preeclampsia. Further studies are required to support the use of soluble endoglin as a diagnostic tool for preeclampsia in clinical settings.