Konstantinos A. Toulis

Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis.

Hypoadiponectinemia might represent a risk factor for nonalcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to evaluate the serum total adiponectin levels in patients with simple nonalcoholic fatty liver (NAFL), those with nonalcoholic steatohepatitis (NASH), and controls. Data were extracted from PubMed, EMBASE, and Cochrane Central Register of Controlled Trials electronic databases (up to December 2009). The main outcome was the weighted mean differences (WMDs) in adiponectin between comparison groups. Twenty-eight studies were included in the systematic review. A meta-analysis of 27 studies that reported data on 2243 subjects (698 controls and 1545 patients with NAFLD) was performed. Controls had higher serum adiponectin compared with NAFL patients (12 studies, random-effects WMD [95% confidence interval {CI}] = 3.00 [1.57-4.43], I² = 80.4%) or NASH patients (19 studies, random-effects WMD [95% CI] = 4.75 [3.71-5.78], I² = 84.1%). The NASH patients demonstrated lower adiponectin compared with NAFL patients (19 studies, random-effects WMD [95% CI] = 1.81 [1.09-2.53], I² = 71.7%). By performing a meta-regression analysis, body mass index, age, sex, and type 2 diabetes mellitus failed to account for heterogeneity. However, the performance of liver biopsy on controls had significant effect on the outcome and accounted for 76.7%, 85.5%, and 22.8% of the between-study variance for comparisons between controls vs NAFLD, NAFL, and NASH patients, respectively. Based on liver histology, serum adiponectin levels are similar in NAFL patients and controls, but hypoadiponectinemia may play an important pathophysiological role in the progression from NAFL to NASH.

Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome

BACKGROUND The relation between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD) remains unclear. In an attempt to provide high-quality evidence on the relation between PCOS and CVD, relevant literature for CVD risk markers [C-reactive protein (CRP), homocysteine (Hcy), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), lipoprotein (a) [Lp(a)], advanced glycation end-products (AGEs), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1) and fibrinogen] in women with PCOS was reviewed and analyzed. METHODS A systematic search was conducted electronically using specific eligibility criteria. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated and combined appropriately. To ensure synthesis of the best available evidence, sensitivity analyses were performed. RESULTS A total of 130 data sets were included in 11 different outcomes, involving 7174 and 5076 CVD markers in women with PCOS and controls, respectively. Women with PCOS demonstrated significantly elevated CRP [WMD (95% CI) 0.99 (0.77-1.21)], Hcy [2.25 (1.46-3.03)], PAI-1 antigen [16.96 (7.25-26.28)], PAI-1 activity [0.71 (0.18-1.23)], VEGF [1.72 (0.96-2.48)], ADMA [0.19 (0.08-0.3)], AGEs [3.91 (2.36-5.45)] and Lp(a) [0.81 (0.58-1.04)] concentrations compared with controls, yet with significant between-study heterogeneity. Borderline significance (not robust in the sensitivity analyses) was detected for TNF-α [0.75 (0.07-1.44)], ET-1 [1.06 (0.52-1.59)] and fibrinogen [0.20 (0.01-0.39)], whereas no difference was detected for IL-6 [0.71 (-0.16 to 1.59)]. CONCLUSIONS Women with PCOS have increased serum concentrations of CVD risk markers compared with controls. Whether this apparent risk is translated into increased incidence of CVD in later life remains to be elucidated.

Risk of spontaneous miscarriage in euthyroid women with thyroid autoimmunity undergoing IVF: a meta-analysis.

OBJECTIVE To investigate whether thyroid autoimmunity (TAI) is associated with increased risk for spontaneous miscarriage in subfertile, euthyroid women undergoing IVF. DESIGN Meta-analysis of observational studies. PATIENT(S) Four prospective studies that reported data on 1098 subfertile women undergoing IVF (141 with TAI and 957 controls) were included in the meta-analysis. MAIN OUTCOME MEASURE Miscarriage risk ratio (RR). SECONDARY OUTCOME MEASURES Clinical pregnancy rate and delivery rate. RESULT(S) Euthyroid, subfertile women with TAI undergoing IVF demonstrated significantly higher risk for miscarriage compared with controls (four studies-fixed effects RR: 1.99, 95% confidence interval: 1.42- 2.79, P<0.001). No significant difference in clinical pregnancy and delivery rates was detected between groups. CONCLUSION Based on the currently available evidence, it appears that the presence of TAI is associated with an increased risk for spontaneous miscarriage in subfertile women achieving a pregnancy through an IVF procedure.

The use of androgens or androgen-modulating agents in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis

BACKGROUND The aim of this meta-analysis was to evaluate the role of androgens or androgen-modulating agents on the probability of pregnancy achievement in poor responders undergoing IVF. METHODS Medline, EMBASE, CENTRAL, Scopus and Web of Science databases were searched for the identification of randomized controlled trials evaluating the administration of testosterone, dehydroepiandrosterone (DHEA), aromatase inhibitors, recombinant luteinizing hormone (rLH) and recombinant human chorionic gonadotrophin (rhCG) before or during ovarian stimulation of poor responders. RESULTS In two trials involving 163 patients, pretreatment with transdermal testosterone was associated with an increase in clinical pregnancy [risk difference (RD): +15%, 95% confidence interval (CI): +3 to +26%] and live birth rates (RD: +11%, 95% CI: +0.3 to +22%) in poor responders undergoing ovarian stimulation for IVF. No significant differences in clinical pregnancy and live birth rates were observed between patients who received DHEA and those who did not. Similarly, (i) the use of aromatase inhibitors, (ii) addition of rLH and (iii) addition of rhCG in poor responders stimulated with rFSH for IVF were not associated with increased clinical pregnancy rates. In the only eligible study that provided data, live birth rate was increased in patients who received rLH when compared with those who did not (RD: +19%, 95% CI:+1 to +36%). CONCLUSIONS Based on the limited available evidence, transdermal testosterone pretreatment seems to increase clinical pregnancy and live birth rates in poor responders undergoing ovarian stimulation for IVF. There is insufficient data to support a beneficial role of rLH, hCG, DHEA or letrozole administration in the probability of pregnancy in poor responders undergoing ovarian stimulation for IVF.

Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis

What is known and Objectives:  Fibromyalgia (FBM) is a common chronic pain disorder affecting up to 2% of the general population. Current treatment options are mostly symptom‐based and limited both in efficacy and number. Two promising alternatives are gabapentin (GP) and pregabalin (PB). We aimed to estimate the efficacy and safety/tolerability of the two compounds in FBM through a systematic review and a meta‐analysis of relevant randomized double‐blind placebo‐controlled (RCT) were performed.

Risk of gestational diabetes mellitus in women with polycystic ovary syndrome: a systematic review and a meta-analysis

OBJECTIVE To evaluate the risk of gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS). DESIGN Systematic review and meta-analysis of observational studies. SETTING Tertiary Department of Reproductive Endocrinology. PATIENT(S) Five thousand two hundred ninety-three pregnant women (721 with PCOS and 4,572 controls without PCOS). INTERVENTION(S) Literature search in the electronic databases MEDLINE, EMBASE, and CENTRAL, study of the references of all relevant trials or reviews, and manual search of the abstracts from the major meetings in the field of human reproduction. MAIN OUTCOME MEASURE(S) Gestational diabetes mellitus odds ratio. RESULT(S) Women with PCOS demonstrated a significantly higher risk for the development of GDM as compared with women without PCOS (odds ratio 2.89, 95% confidence interval [CI] 1.68-4.98), yet with significant statistical heterogeneity (I(2) = 59.3%), durable to sensitivity analysis. In the subgroup of cohort studies, this finding remained robust (7.11, 95% CI 2.95-17.12), whereas in the subgroup of case-control studies, it did not (0.89, 95% CI 0.38-2.06). Metaregression modeling revealed a linear dependence of the outcome on study type and baseline risk (post hoc). CONCLUSION(S) Significant heterogeneity among studies and dependence of the outcome on study type make the higher risk of GDM in women with PCOS a questionable finding. The conduction of properly designed studies should precede any recommendation to pregnant women with PCOS in regard to the risk of GDM.

Efficacy and safety of denosumab in postmenopausal women with osteopenia or osteoporosis: a systematic review and a meta-analysis.

Receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine essential for osteoclast differentiation, activation, and survival. Denosumab, a human monoclonal antibody against RANKL, constitutes a promising antiresorptive agent for osteoporosis. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and other trial registries through January 2009. We selected randomized controlled trials (RCTs) of denosumab in women with low bone mass that described the changes on bone markers and bone mineral density (BMD) as well as the adverse events including fracture risk. We analyzed data from nine RCTs involving 10 329 participants. Although denosumab universally decreased bone markers and increased lumbar and hip BMD, the efficacy evaluation based on percentage (%) mean change from the baseline was not possible due to missing data. Denosumab was not associated with a significant reduction in fracture risk [OR (95% CI) 0.74 (0.33 to 1.64), p=0.45]. Increased risk of serious adverse events [OR (95% CI) 1.83 (1.10 to 3.04), p=0.02] and serious infections [OR (95% CI) 4.45 (1.15 to 17.14), p=0.03] were evident. In conclusion, although effective as an antiresorptive agent, denosumab has not yet proved its efficacy on fracture risk reduction while increased infection risk questions its safety.

The effect of teriparatide on serum Dickkopf-1 levels in postmenopausal women with established osteoporosis.

Objective  Parathyroid hormone increases the differentiation of osteoblast precursors through canonical wingless (Wnt) signalling, resulting in an osteoanabolic effect. We aimed to evaluate serum levels of the Wnt‐inhibitor Dickkopf‐1 (Dkk‐1) in postmenopausal women with established osteoporosis and their changes with teriparatide (TPTD – human recombinant PTH 1–34).

Inhibin B and anti-Müllerian hormone as markers of persistent spermatogenesis in men with non-obstructive azoospermia: a meta-analysis of diagnostic accuracy studies

INTRODUCTION A non-invasive test, which could predict the presence of sperm during a testicular sperm extraction (TESE) procedure in men with non-obstructive azoospermia (NOA), would be of profound clinical importance. Inhibin B (Inh-B) and anti-Müllerian hormone (AMH) have been proposed as direct markers of Sertoli cell function and indirect markers of spermatogenesis. METHODS A search was conducted in the electronic databases MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through June 2009. Thirty-six different studies reported data on the predictive value of one or more index markers (serum Inh-B: 32 studies, seminal Inh-B: 5 studies, serum AMH: 2 studies, seminal AMH: 4 studies) and were included in the systematic review. Nine studies, which had serum Inh-B as index marker, met the predefined criteria and were included in the meta-analysis. RESULTS Serum Inh-B demonstrated a sensitivity of 0.65 (95% confidence interval [CI]: 0.56-0.74) and a specificity of 0.83 (CI: 0.64-0.93) for the prediction of the presence of sperm in TESE. When the pre-test probability of 41% was incorporated in a Fagans nomogram, resulted in a positive post-test probability of 73% and a negative post-test probability of 23% for the presence of sperm in TESE. CONCLUSIONS Serum Inh-B cannot serve as a stand-alone marker of persistent spermatogenesis in men with NOA. Although limited, evidence on serum AMH and serum/seminal AMH do not support their diagnostic value in men with NOA.

Eating habits, health attitudes and obesity indices among medical students in northern Greece.

Medical students represent not only the final but also the most crucial opportunity for education in the field of healthy lifestyles and nutritional habits. Eating habits and obesity indices among medical students in southern Greece were described almost a decade ago. However, there is a lack of current, relevant data concerning students living in northern Greece. The purpose of the present study was to evaluate the body mass index distribution and nutritional and health-related behavior among medical students in northern Greece. The participants, 187 males (21.5 ± 1.9 years) and 203 females (21.3 ± 2.2 years), filled out a self-report questionnaire. Height and weight measurements were obtained. Dietary practices of fast food consumption (more frequent for males) and regular consumption of fruits and vegetables (more frequent for females) were reported. Females seemed to adopt different practices than males when trying to lose weight and were significantly better informed about the nutrient value of the food consumed. Although the prevalence of overweight (males: 32.1%, females: 8.4%) and obesity (males: 5.9%, females: 1.5%) in the present sample is lower compared to previous data, it remains high according to what would be health promoting. The above findings suggest a need for further improvement in strategies promoting healthier nutrition habits.