Andrea Tinelli

Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy.

CONTEXT Thyroid disease during pregnancy has been associated with multiple adverse outcomes. Whether all women should be screened for thyroid disease during pregnancy is controversial. OBJECTIVE The objective of the study was to determine whether treatment of thyroid disease during pregnancy decreases the incidence of adverse outcomes and compare the ability of universal screening vs. case finding in detecting thyroid dysfunction. DESIGN Women in the first trimester were randomly assigned to the universal screening group or case-finding group. Women in both groups were stratified as high risk or low risk based on risk factors for thyroid disease. All women in the universal screening group, and high-risk women in the case-finding group, were immediately tested for free T(4), TSH, and thyroid peroxidase antibody. Low-risk women in the case-finding group had their sera tested postpartum. SETTING The study was conducted at two ambulatory clinics of community hospitals in southern Italy. PATIENTS A total of 4562 women were randomly assigned to the universal screening or case-finding group. INTERVENTION Intervention included levothyroxine in women with a TSH above 2.5 mIU/liter in TPO antibody-positive women and antithyroid medication in women with a undetectable TSH and elevated free T(4). MAIN OUTCOME MEASURE Total number of adverse obstetrical and neonatal outcomes was measured. RESULTS No significant differences were seen in adverse outcomes between the case-finding and universal screening groups. Adverse outcomes were less likely to occur among low-risk women in the screening group than those in the case-finding group. CONCLUSIONS Universal screening compared with case finding did not result in a decrease in adverse outcomes. Treatment of hypothyroidism or hyperthyroidism identified by screening a low-risk group was associated with a lower rate of adverse outcomes.

Increased Pregnancy Loss Rate in Thyroid Antibody Negative Women with TSH Levels between 2.5 and 5.0 in the First Trimester of Pregnancy

CONTEXT The definition of what constitutes a normal TSH during pregnancy is in flux. Recent studies suggested that the first trimester upper limit of normal for TSH should be 2.5 mIU/liter. OBJECTIVE The objective of the study was to evaluate the pregnancy loss and preterm delivery rate in first-trimester thyroid peroxidase antibody-negative women with TSH values between 2.5 and 5.0 mIU/liter. DESIGN The present study is a component of a recently published large-scale prospective trial that evaluated the impact of levothyroxine treatment on maternal and neonatal complications in thyroid peroxidase-positive women with TSH levels above 2.5 mIU/liter. The present study evaluated 4123 thyroid peroxidase antibody-negative women with TSH levels at or below 5.0 mIU/liter. Women were divided into two groups based on their initial TSH: group A, TSH level below 2.5 mIU/liter, excluding hyperthyroid women defined as an undetectable TSH with an elevated free T(4), and group B, TSH level between 2.5 and 5.0 mIU/liter. SETTING The study was conducted at two ambulatory clinics of community hospitals in southern Italy. PATIENTS A total of 4123 women were evaluated. INTERVENTION There was no intervention. MAIN OUTCOME MEASURES The incidence of pregnancy loss and preterm delivery in group A as compared with group B was measured. RESULTS The rate of pregnancy loss was significantly higher in group B as compared with group A (6.1 vs. 3.6% respectively, P = 0.006). There was no difference in the rate of preterm delivery between the two groups. CONCLUSIONS The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter.

Diagnostic accuracy of transvaginal ultrasound for non‐invasive diagnosis of bowel endometriosis: systematic review and meta‐analysis

To critically analyze the diagnostic value of transvaginal sonography (TVS) for non‐invasive, presurgical detection of bowel endometriosis.

Thyroid Antibody Positivity in the First Trimester of Pregnancy Is Associated with Negative Pregnancy Outcomes

CONTEXT Thyroid antibody positivity during pregnancy has been associated with adverse outcomes including spontaneous miscarriage, recurrent miscarriage, and preterm delivery. OBJECTIVE The objective of the study was to determine whether thyroid antibody positivity in the first trimester of pregnancy in euthyroid women was associated with maternal and neonatal adverse outcomes. DESIGN The present trial is a component of a prospective trial published in 2010 that evaluated screening for thyroid disease during pregnancy and the impact of levothyroxine therapy in women who were thyroid peroxidase positive with a TSH above 2.5 mIU/liter. The present study compared 14 maternal and neonatal adverse outcomes in 245 women who were euthyroid (TSH < 2.5 mIU/liter) and thyroid peroxidase positive in the first trimester to 3348 women who were euthyroid and thyroid peroxidase negative in the first trimester. SETTING The study was conducted in southern Italy at the ambulatory clinics of two community hospitals. PATIENTS The study consisted of 3593 women. INTERVENTION There was no intervention. MAIN OUTCOME MEASURES The main outcome measures were 14 maternal and neonatal complications. RESULTS The main result was an increase in very preterm delivery (<34 wk gestation at delivery) [4.5 vs. 1.8%; χ(2)(df = 1) = 8.58; P = 0.003] and respiratory distress [3.3 vs. 1.2%; χ(2)(df = 1) = 7.80; P = 0.005] in women who were thyroid antibody positive. CONCLUSIONS The present study provides further evidence of an association between thyroid antibody positivity and very preterm delivery in euthyroid women. The association with respiratory distress should be considered preliminary and awaits further study.

Age-related pelvic floor modifications and prolapse risk factors in postmenopausal women

Objective: Genital prolapse is frequent in postmenopausal women; it describes the loss of support to the pelvic organs, resulting in a herniation of these into the vaginal channel. This problem affects 50% of parous women, and at least 50% of all women develop a mild form of genital prolapse after pregnancy. Methods: An extensive literature review from 1990 to 2008 was performed on prolapse etiology and its risk factors; analyzing the data, we reviewed the genetic and biological aspects, age-related prolapse, biological tissue modifications, surgical problems, pelvic musculature modifications, and neuropathy. Results: Data suggested that aging, pelvic trauma, and surgery evoke tissue denervation and devascularization, anatomic alterations, and increased degradation of collagen; all of these may lead to a decrease in mechanical strength and predispose an individual to prolapse. It has been demonstrated that there is a reduction in protein content and estrogens in uterosacral ligaments, in the vagina, and in the parametrium of women with prolapse. This is a possible explanation for why many surgical procedures to correct prolapse fail and recurrences after surgical correction are frequent. Conclusions: Even if the etiology of pelvic prolapse is poorly defined and multifactorial, aging risk factors, such as biomechanical abnormalities in connective tissue composition, hormonal deficiency, and irregular tissue metabolism, are nonmodifiable and therefore largely stated in clinical practice. Regardless of future developments, based on the reported findings, prolapse therapy will be more influenced by genetics, biological pelvic changes, changes in tissue homeostasis, and topical hormones, rather than general pelvic corrective surgical anatomy.

High rate of persistent hypothyroidism in a large-scale prospective study of postpartum thyroiditis in southern Italy.

CONTEXT The incidence of postpartum thyroiditis (PPT) varies widely in the literature. Limited data exist concerning the hormonal status of women with PPT at the end of the first postpartum year. OBJECTIVE Our aim was to conduct a large prospective study of the incidence and clinical course of PPT. DESIGN A total of 4394 women were screened for thyroid function and thyroid autoantibodies at 6 and 12 months postpartum. Women were classified as being at high or low risk of having thyroid disease before any thyroid testing. SETTING The study was conducted at two ambulatory clinics in southern Italy, an area of mild iodine deficiency. PATIENTS A total of 4394 pregnant women were studied. INTERVENTION There was no intervention. MAIN OUTCOME MEASURES We measured incidence, clinical presentation, and course of postpartum thyroiditis. RESULTS The incidence of postpartum thyroiditis was 3.9% (169 of 4384). Women classified as being at high risk for thyroid disease had a higher incidence of PPT than women classified as low risk (11.1 vs. 1.9%; odds ratio, 6.69; 95% confidence interval, 4.63, 9.68). Eighty-two percent of the 169 women with PPT had a hypothyroid phase during the first postpartum year. At the end of the first postpartum year, 54% of the 169 women had persistent hypothyroidism. CONCLUSIONS One of every 25 women in southern Italy developed PPT. Women at high risk for thyroid disease have an increased rate of PPT. The high rate of permanent hypothyroidism at 1 yr should result in a reevaluation of the widely held belief that most women with PPT are euthyroid at the end of the first postpartum year.

Uterine sliding sign: a simple sonographic predictor for presence of deep infiltrating endometriosis of the rectum

To evaluate whether the presence of uterorectal adhesions demonstrated by transvaginal sonography (TVS) could aid as a simple sonographic predictor for deep infiltrating endometriosis (DIE) of the rectum in patients with symptoms suggestive of endometriosis.

Resveratrol inhibits the epidermal growth factor-induced epithelial mesenchymal transition in MCF-7 cells

Carcinoma progression is associated with the loss of epithelial features, and the acquisition of a mesenchymal phenotype by tumour cells. Herein we show that exposure of MCF-7 cells to epidermal growth factor (EGF) resulted in morphological alterations characteristic of epithelial-to-mesenchymal transition (EMT). EGF treatment resulted in increased motility along with an up-regulation of transcription factors Slug, Zeb1, Zeb2, and mesenchymal markers Vimentin and N-cadherin. Treatment of MCF-7 cells with a combined stimulation of EGF and resveratrol, a naturally occurring stilbene with antitumor properties, failed to alter cell morphology, motility and overexpression of EMT markers induced by EGF. Using specific chemical inhibitors, we demonstrated that EGF-induced EMT is mediated by extracellular signal-regulated kinase 1/2 (ERK 1/2) signalling pathway and that resveratrol is able to repress EGF-induced ERK activation. In summary, these data provide new evidence of the inhibitory effect of resveratrol on EGF-induced EMT cell transformation.

Lapatinib/Paclitaxel polyelectrolyte nanocapsules for overcoming multidrug resistance in ovarian cancer.

The sonication-assisted layer-by-layer (SLBL) technology was developed to combine necessary factors for an efficient drug-delivery system: (i) control of nanocolloid size within 100 - 300 nm, (ii) high drug content (70% wt), (iii) shell biocompatibility and biodegradability, (iv) sustained controlled release, and (v) multidrug-loaded system. Stable nanocolloids of Paclitaxel (PTX) and lapatinib were prepared by the SLBL method. In a multidrug-resistant (MDR) ovarian cancer cell line, OVCAR-3, lapatinib/PTX nanocolloids mediated an enhanced cell growth inhibition in comparison with the PTX-only treatment. A series of in vitro cell assays were used to test the efficacy of these formulations. The small size and functional versatility of these nanoparticles, combined with their ability to incorporate various drugs, indicates that lapatinib/PTX nanocolloids may have in vivo therapeutic applications.

Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells

Phytochemicals constitute a heterogeneous group of substances with an evident role in human health. Their properties on cancer initiation, promotion and progression are well documented. Particular attention is now devoted to better understand the molecular basis of their anticancer action. In the present work, we studied the effect of resveratrol on the ovarian cancer cell line OVCAR-3 by a proteomic approach. Our findings demonstrate that resveratrol down-regulates the protein cyclin D1 and, in a concentration dependent manner, the phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β). The dephosphorylation of these kinases could be responsible for the decreased cyclin D1 levels observed after treatment. We also showed that resveratrol reduces phosphorylation levels of the extracellular signal-regulated kinase (ERK) 1/2. Chemical inhibitors of phosphatidylinositol 3-kinase (PI3K) and ERK both increased the in vitro therapeutic efficacy of resveratrol. Moreover, resveratrol had an inhibitory effect on the AKT phosphorylation in cultured cells derived from the ascites of ovarian cancer patients and in a panel of human cancer cell lines. Thus, resveratrol shows antitumor activity in human ovarian cancer cell lines targeting signalling pathway involved in cell proliferation and drug-resistance.