Does the risk of arterial hypertension increase in the course of triptorelin treatment?

Gonadotropin-releasing hormone agonists (GnRH-a) are common treatment options for central precocious puberty (CPP) in childhood. GnRH-a treatment is useful and has a good safety profile, with minimal adverse effects and no severe long-term consequences. The common side effects in children are menopause-like symptoms and local adverse events at the injection site

Central precocious puberty in a girl with LEGIUS syndrome: an accidental association?

BACKGROUND: Central precocious puberty is a condition characterized by precocious activation of the hypothalamic-pituitary-gonadal axis. It may be idiopathic or secondary to organic causes, including syndromes such as Neurofibromatosis type 1 (NF1).CASE PRESENTATION: We presented a girl of 6years and 10months with almost 11 cafe-au-lait skin macules, without other clinical or radiological signs typical of NF1, and with a central precocious puberty. Genetic analysis evidenced the new variant NM-152594.2:c.304delAp. (Thr102Argfs*19) in SPRED1 gene, which allowed to diagnose Legius syndrome.CONCLUSIONS: We report for the first time a case of central precocious puberty in a girl with Legius syndrome. The presence of central precocious puberty in a child with characteristic cafe-au-lait macules should suggest pediatricians to perform genetic analysis in order to reach a definitive diagnosis. Further studies on timing of puberty in patients with RASopathies are needed to better elucidate if this clinical association is casual or secondary to their clinical condition

Phenotypic Overlap in Children with Tall Stature: A Case of Weaver Syndrome

Introduction: Tall stature is defined as length or height more than two standard deviations above the mean for age of the refer- ence population. There are different causes of tall stature from a familial trait or a transient anticipation of growth with no major consequences to growth disorders, such as endocrine disorder and syndromic conditions like overgrowth syndromes. Case Presentation: In this study, we reported the case of a 7-year-old girl with tall stature from birth. The patient showed a general- ized overgrowth, associated with extremely advanced bone age, dysmorphic features such as a broad forehead and large extremities, and a slight neurodevelopmental delay. Laboratory tests were normal, and the main hormonal disorders were ruled out. The diag- nosis of overgrowth syndrome was suspected according to the clinical presentation, and the diagnosis of Weaver syndrome was confirmed by the finding of the pathogenic mutation c.2050C > T p.(Arg684Cys) in EZH2 gene through next generation sequencing (NGS). Conclusions: Our patient showed phenotypical features related to different overgrowth syndrome characteristics. We underlined the difficulties in reaching a clinical diagnosis in presence of tall stature. The role of molecular biology, particularly genetic analysis by NGS approach, should be considered in cases of tall stature with phenotypic overlap

Reduced cell viability and apoptosis induction in human thyroid carcinoma and mesothelioma cells exposed to cidofovir

partially_open6noBesides its well-recognized antiviral activity, Cidofovir (CDV) has been shown to exert anticancer properties both within in vitro and in vivo models. The aim of this study was to evaluate the effects of CDV on still unexplored cultured cancer cells from human mesothelioma as well as breast, colon, liver, lung, prostate, and thyroid carcinomas. Overall, a dose- and time-dependent inhibition of cell viability was observed after CDV exposure. To clarify the mechanisms underlying CDV action, apoptotic cell death was investigated in two infected cell lines [Ist-Mes1 and Ist-Mes2 mesothelioma cells (SV40+)] and in two uninfected cell lines (NCI-H2425 mesothelioma cells and FTC-133 thyroid cancer cells), which resulted the most sensitive to CDV treatment. Reduced expression of procaspase-3 and increased expression of PARP p85 fragment were observed in both infected and uninfected mesothelioma cells, indicating apoptosis induction by CDV in a virus-independent manner. Similarly, the increase of the pro-apoptotic proteins p53, cytochrome c and caspase-3, the decrease of the survival protein Bcl-x, and the increment of Bax/Bcl-2 ratio revealed the occurrence of apoptosis in CDV-treated FTC-133. The presence of nuclear DNA fragmentation confirmed apoptotic cell death by CDV. Overall, our findings warrant further investigations to explore the therapeutic potential of CDV for human mesothelioma and follicular thyroid carcinoma.openCatalani, Simona; Palma, Francesco; Battistelli, Serafina; Nuvoli, Barbara; Galati, Rossella; Benedetti, SerenaCatalani, Simona; Palma, Francesco; Battistelli, Serafina; Nuvoli, Barbara; Galati, Rossella; Benedetti, Seren

The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications

Non-alcoholic fatty liver disease (NAFLD) represents a predominant hepatopathy that is rapidly becoming the most common cause of hepatocellular carcinoma worldwide. The close association with metabolic syndrome's extrahepatic components has suggested the nature of the systemic metabolic-related disorder based on the interplay between genetic, nutritional, and environmental factors, creating a complex network of yet-unclarified pathogenetic mechanisms in which the role of insulin resistance (IR) could be crucial. This review detailed the clinical and pathogenetic evidence involved in the NAFLD-IR relationship, presenting both the classic and more innovative models. In particular, we focused on the reciprocal effects of IR, oxidative stress, and systemic inflammation on insulin-sensitivity disruption in critical regions such as the hepatic and the adipose tissue, while considering the impact of genetics/epigenetics on the regulation of IR mechanisms as well as nutrients on specific insulin-related gene expression (nutrigenetics and nutrigenomics). In addition, we discussed the emerging capability of the gut microbiota to interfere with physiological signaling of the hormonal pathways responsible for maintaining metabolic homeostasis and by inducing an abnormal activation of the immune system. The translation of these novel findings into clinical practice could promote the expansion of accurate diagnostic/prognostic stratification tools and tailored pharmacological approaches

Benefits of rescreening newborns of mothers affected by autoimmune hypothyroidism

Infants of mothers with autoimmune hypothyroidism (AH) are at risk of developing late-onset hypothyroidism, often escaping at newborn screening. This condition might be caused both by the action of maternal antibodies and/or by maternal treatment

Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis

Epidermal growth factor receptor (EGFR) is a known diagnostic and, although controversial, prognostic marker of human glioblastoma multiforme (GBM). However, its functional role and biological significance in GBM remain elusive. Here, we show that multiple GBM cell subpopulations could be purified from the specimens of patients with GBM and from cancer stem cell (CSC) lines based on the expression of EGFR and of other putative CSC markers. All these subpopulations are molecularly and functionally distinct, are tumorigenic, and need to express EGFR to promote experimental tumorigenesis. Among them, EGFR-expressing tumor-initiating cells (TIC) display the most malignant functional and molecular phenotype. Accordingly, modulation of EGFR expression by gain-of-function and loss-of-function strategies in GBM CSC lines enhances and reduces their tumorigenic ability, respectively, suggesting that EGFR plays a fundamental role in gliomagenesis. These findings open up the possibility of new therapeutically relevant scenarios, as the presence of functionally heterogeneous EGFR(pos) and EGFR(neg) TIC subpopulations within the same tumor might affect clinical response to treatment

Safety and efficacy of totally minimally invasive right colectomy in the obese patients: a multicenter propensity score-matched analysis

Despite the well-known benefits of the minimally invasive approach for the right colon cancer treatment, less is known about its feasibility and advantages in morbid obese patients. The aim of this study is to compare the postoperative outcomes after totally minimally invasive right colectomy between the obese and non-obese population. Data derived from a prospectively maintained multicenter colorectal database were analysed, dividing the enrolled patients into two groups: obese (BMI > 29.99) patient group and non-obese patient group. Data about gender, age, American Society of Anesthesiologists (ASA) Score, tumor characteristics, operative time, anastomosis time, extraction site, incision length, intraoperative complications, postoperative complications, postoperative recovery, specimen length and retrieved nodes were taken to assess the achievement of the oncologic standards. After a propensity score matching, a total of 184 patients was included, 92 in each group. No differences were found in terms of demographic data and tumor characteristics. Intraoperative data showed a significant difference in terms of anastomosis time in favour of non-obese group (p < 0.0001). No intraoperative complications were recorded and no conversion was needed in both groups. No differences were found in terms of postoperative complications. There were no differences in terms of first mobilization (p = 0.745), time to first flatus (p = 0.241) time to tolerance to liquid and solid diet (p = 0.241 and p = 0.06) and length of hospital stay (p = 0.817). The analysis of oncologic outcomes demonstrated adequate results in both groups. The results obtained by our study confirmed the feasibility and safety of the totally minimally invasive approach even in obese population