Recurrent, metastatic disease represents the most frequent cause of death for patients with thyroid cancer, and radioactive iodine (RAI) remains a mainstay of therapy for these patients. Unfortunately, many thyroid cancer patients have tumors that no longer trap iodine, and hence are refractory to RAI, heralding a poor prognosis. RAI-refractory (RAI-R) cancer cells result from the loss of thyroid differentiation features, such as iodide uptake and organification. This loss of differentiation features correlates with the degree of mitogen-activated protein kinase (MAPK) activation, which is higher in tumors with BRAF (B-Raf proto-oncogene) mutations than in those with RTK (receptor tyrosine kinase) or RAS (rat sarcoma) mutations. Hence, inhibition of the mitogen-activated protein kinase kinase-1 and -2 (MEK-1 and -2) downstream of RAF (rapidly accelerated fibrosarcoma) could sensitize RAI refractivity in thyroid cancer. However, a significant hurdle is the development of secondary tumor resistance (escape mechanisms) to these drugs through upregulation of tyrosine kinase receptors or another alternative signaling pathway. The sodium iodide symporter (NIS) is a plasma membrane glycoprotein, a member of solute carrier family 5A (SLC5A5), located on the basolateral surfaces of the thyroid follicular epithelial cells, which mediates active iodide transport into thyroid follicular cells. The mechanisms responsible for NIS loss of function in RAI-R thyroid cancer remains unclear. In a study of patients with recurrent thyroid cancer, expression levels of specific ribosomal machinery—namely PIGU (phosphatidylinositol glycan anchor biosynthesis class U), a subunit of the GPI (glycosylphosphatidylinositol transamidase complex—correlated with RAI avidity in radioiodine scanning, NIS levels, and biochemical response to RAI treatment. Here, we review the proposed mechanisms for RAI refractivity and the management of RAI-refractive metastatic, recurrent thyroid cancer. We also describe novel targeted systemic agents that are in use or under investigation for RAI-refractory disease, their mechanisms of action, and their adverse events.

Objective This study aimed to assess the association between neonatal antibiotic exposure and the risk of childhood obesity. Study Design This retrospective cohort study enrolled neonates born between 2011 and 2015 and followed up until 5 years. The incidence of obesity at 5 years old, and other characteristics were compared between the antibiotic-exposed and unexposed groups. Chi-square test was conducted on categorical variables and Student's t-test for normally distributed continuous variable. Significant variables (p < 0.05) in bivariate analysis were modelled in a stepwise multivariate logistic regression analysis to ascertain independent predictors of obesity at 5 years. Results Of the 1,447 subjects, 749 (51.8%) received ampicillin and gentamicin, and 333 (23%) were obese. Neonates exposed to antibiotics were more likely to be obese compared with those unexposed (26 vs. 20%, p = 0.01). In the adjusted model, this association persisted (adjusted odds ratio: 1.37, p = 0.02). Conclusion Neonatal antibiotic exposure is associated with early childhood obesity and may play a significant role in the weight trajectories of these children. Hence, antibiotic stewardship in this period cannot be overemphasized. Key Points

Familial hypocalciuric hypercalcemia (FHH) is usually a benign condition divided into three types. FHH-3 occurs in about 20% of the cases and is caused due to missense mutations in AP2S1 (adaptor-related protein complex 2 subunit sigma 1) involving the codon Arg15 (p.R15). We report a case of FHH-3 with a heterozygous mutation in the AP2S1 gene on chr19_47349359 C>T, c.44G>A, p.Arg15His. There are a handful of reports describing the clinical features in patients diagnosed with FHH-3. Herein, we describe the laboratory and clinical features associated with a case of FHH-3 with mutation in the Arg15His codon of the AP2S1 gene.

Prominent coronary artery (CA) flow observed on a fetal echocardiogram has been associated with fetal growth restriction and myocardial dysfunction. We present two cases with this finding, in the presence of congenital heart ... | Find, read and cite all the research you need on Tech Science Press