Putative Complementary Compounds to Counteract Insulin-Resistance in PCOS Patients.

Polycystic ovary syndrome (PCOS) is the most frequent endocrine-metabolic disorder among women at reproductive age. The diagnosis is based on the presence of at least two out of three criteria of the Rotterdam criteria (2003). In the last decades, the dysmetabolic aspect of insulin resistance and compensatory hyperinsulinemia have been taken into account as the additional key features in the etiopathology of PCOS, and they have been widely studied. Since PCOS is a complex and multifactorial syndrome with different clinical manifestations, it is difficult to find the gold standard treatment. Therefore, a great variety of integrative treatments have been reported to counteract insulin resistance. PCOS patients need a tailored therapeutic strategy, according to the patient's BMI, the presence or absence of familiar predisposition to diabetes, and the patient's desire to achieve pregnancy or not. The present review analyzes and discloses the main clinical insight of such complementary substances.

Familial diabetes predisposes PCOS patients to insulin resistance (IR), reproductive impairment and hepatic dysfunction: effects of d-chiro inositol (DCI) and alpha lipoic acid (ALA) administration on hepatic insulin extraction (HIE) index.

ObjectivePCOS is a syndrome is characterized by 2 out of 3 of the criteria established during the Rotterdam Consensus Conference. Recently the issue of insulin resistance (IR) has caught attention.SubjectsA group of overweight/obese PCOS patients (n = 30) have been evaluated before and after 3 months of daily integrative administration of d-chiro inositol (DCI) (500 mg) and alpha lipoic acid (ALA) (300 mg).MethodsHormonal and metabolic profiles, oral glucose tolerance test (OGTT) for glucose, insulin and C-peptide response were performed in baseline conditions and after DCI plus ALA treatment. Hepatic Insulin Extraction (HIE) index was computed along the OGTT to evaluate the liver ability in degrading insulin.ResultsThe treatment decreased LH, Androstenedione (A), insulin plasma levels, BMI, HOMA index, AST and ALT. Considering patients for the presence (n = 17) or absence of familial diabetes (n = 13), the greatest improvements occurred in the former patients. Insulin response to OGTT was greatly reduced after the treatment interval in PCOS with familial diabetes. HIE computation disclosed that in presence of familial diabetes liver degradation of insulin is reduced thus leaving a higher amount of circulating insulin. DCI plus ALA administration decreased AST and ALT and restored hepatic insulin clearance since HIE profile was improved.ConclusionOur study demonstrates that in overweight/obese PCOS the predisposition to familial diabetes triggers IR not only through the endogenous impaired DCI and ALA synthesis but also through a reduced hepatic clearance of insulin. DCI plus ALA administration positively improved hormonal, metabolic profiles as well as liver function.

Seasonal onset of polymyalgia rheumatica: correlations with the pattern of clinical presentation, disease severity and outcome in 383 patients from a single centre.

OBJECTIVES: Polymyalgia rheumatica (PMR) is an inflammatory disorder, more common in the elderly, characterised by girdle pain and stiffness, constitutional symptoms and raised serological markers of inflammation. Studies on the seasonality of onset of PMR have shown conflicting results, possibly due to the different diagnostic criteria and onset recognition. In this study, the month of onset of PMR was evaluated in patients originating from one geographical area, visited by the same clinician. METHODS: In 383 PMR patients (245 women, median age 73 years, range 47-92 years) examined between 1990 and 2014, PMR was diagnosed according to Bird's criteria. The month of onset was recorded systematically during the patient's interview. Clinical features initially recorded included the location of joint involvement, the coexistence of temporal arteritis (TA) or peripheral arthritis, and the type of onset (acute if reported of 72h or less). Patient follow-up, PMR severity and outcome were also recorded throughout the study. RESULTS: We failed to identify any peak month (p=0.93) or season (p=0.45) for the onset of PMR. Timing of onset did not correlate with the clinical features, severity or outcome of PMR. Only when patients were also affected by concomitant TA, the onset of PMR was more often seen in autumn (p=0.02). Patients with PMR onset in autumn also has a greater risk of developing TA during their follow-up (p=0.03). By multiple regression, the only outcome predicted by autumn onset was the use of methotrexate (p=0.039). CONCLUSIONS: PMR showed no seasonality of onset, except for the subset associated with TA. A risk factor with seasonal variation is suggested for the pathogenesis of this form of PMR.

Advanced microvascular damage associated with occurence of sarcopenia in systemic sclerosis patients: results from a retrospective cohort study.

OBJECTIVES: Systemic sclerosis (SSc) is characterised by microvascular inflammatory damage, loss of capillaries and progressive systemic fibrosis. Capillary rarefaction may precede sarcopenia, we therefore evaluated the body composition and occurrence of sarcopenia in SSc patients, in relation to the peripheral microcirculatory status, assessed and scored by nailfold videocapillaroscopy (NVC) patterns, including capillary number count and microangiopathy evolution score (MES). METHODS: Body composition and bone mineral density were assessed by Dual X-ray absorptiometry and a dedicated software (GE Lunar, USA) in 43 SSc patients (age 64.1 ± 11.2 yrs, 83.7% women) affected by limited or diffuse cutaneous (74.4%) according to the 2013 EULAR/ACR criteria and 43 age-matched healthy subjects (HS). Sarcopenia was checked as relative skeletal muscle index (RSMI). Clinical, laboratory, body composition and bone parameters were analysed according to the different NVC patterns and MES. Means were compared by the Student's t test or by one way analysis of variance; medians were compared by the Kruskall Wallis test; and frequencies by the chi square test. RESULTS: Sarcopenia was found in 23.26% of SSc patients with a prevalence significantly higher than age matched HS (4.65%; p = 0.03). Interestingly, SSc patients with "late" NVC pattern showed a significantly higher prevalence of sarcopenia (43.75%) compared to "early" (9.1%) and "active" (12.5%) NVC patterns (p<0.0002). In addition, capillary density was found significantly lower in sarcopenic versus non sarcopenic patients (4.4±1.8 vs. 5.8±2.2, p<0.05). Finally, MES showed significantly most severe score in sarcopenic SSc patients (p<0.001): peripheral blood flow analised in a sample of sarcopenic SSc patients by Laser speckle contrast analysis (LASCA) showed lowest values (p<0.05). Total mass (TM), lean mass (LM), fat mass (FM) and bone mineral content (BMC) values were found significantly lower in sarcopenic SSc patients (p<0.0001, p<0.001, p=0.004, p=0.04, respectively). CONCLUSIONS: SSc patients with sarcopenia and altered body composition were found affected by the most severe NVC pattern ("late"), a significantly reduced/altered number of capillaries and microvascular array (MES), suggesting a strong link between severity of local microvascular failure and associated muscle sufferance.

Transvaginal high uterosacral ligament suspension: An alternative to McCall culdoplasty in the treatment of pelvic organ prolapse.

OBJECTIVES: Defects in female pelvic organ support are highly prevalent. Uterosacral ligament suspension at the time of primary prolapse repair (McCall culdoplasty) is a well-established surgical option to prevent prolapse recurrences. Recently Shull's high uterosacral ligament suspension technique has gained increasing popularity among Uro-Gynaecologists. A study carried out in 2017 by Spelzini et al. compared these two techniques, showing proper safety and efficacy in the treatment of prolapse, with no statistically significant differences as to operative time, complication rate, anatomical, functional and subjective outcomes [1]. Our study aims at comparing the effectiveness, complication rate, recurrence rate, quality of life and functional result of the two techniques. STUDY DESIGN: This is a retrospective study carried out on 224 patients who underwent vaginal cuff suspension for pelvic organ prolapse. Cases were extracted from hospital medical records of all women managed with surgical prolapse repair at our Gynaecology and Obstetrics department between January 2013 and February 2017. Shull suspension (group A) or McCall culdoplasty (group B) were performed according to surgeon's familiarity with the two suspension techniques. RESULTS: A total of 224 patients (69 in group A and 155 in group B) underwent surgical cuff suspension. Median operating time was 88 min for both techniques and ureteral injuries were very rare in both group A and B (1 and 0 respectively). In the evaluation of postoperative questionnaires, no statistically significant differences were found, except for "Urinary Impact Questionnaire" (UIQ), which showed significantly less urinary subjective symptoms in group A. Median follow up was 13 months in group A and 15 months in group B. Post-operative Pop-Q items analysis revealed only a higher Aa point in group A at 12 months follow up visit. Objective vaginal cuff recurrence was observed in 1 patient (1,4%) in group A and 4 patients in group B (2,6%) with no statistically significant difference between the two groups. CONCLUSIONS: Both uterosacral ligament suspension procedures are safe and highly effective. There were no statistically significant differences concerning surgical data, complication rates, and the majority of anatomical, functional and subjective outcomes between Shull suspension and McCall culdoplasty.

A circulating cell population showing both M1 and M2 monocyte/macrophage surface markers characterizes systemic sclerosis patients with lung involvement.

BACKGROUND: Systemic sclerosis (SSc) is a disorder characterized by immune system alterations, vasculopathy and fibrosis. SSc-related interstitial lung disease (ILD) represents a common and early complication, being the leading cause of mortality. Monocytes/macrophages seem to have a key role in SSc-related ILD. Interestingly, the classically (M1) and alternatively (M2) activated monocyte/macrophage phenotype categorization is currently under revision. Our aim was to evaluate if circulating monocyte/macrophage phenotype could be used as biomarker for lung involvement in SSc. To this purpose we developed a wide phenotype characterization of circulating monocyte/macrophage subsets in SSc patients and we evaluated possible relations with lung involvement parameter values. METHODS: A single centre cross-sectional study was performed in fifty-five consecutive SSc patients, during the year 2017. All clinical and instrumental tests requested for SSc follow up and in particular, lung computed tomography (CT) scan, pulmonary function tests (PFTs), Doppler echocardiography with systolic pulmonary artery pressure (sPAP) measurement, blood pro-hormone of brain natriuretic peptide (pro-BNP) evaluation, were performed in each patient in a maximum one-month period. Flow cytometry characterization of circulating cells belonging to the monocyte/macrophage lineage was performed using specific M1 (CD80, CD86, TLR2 and TLR4) and M2 surface markers (CD204, CD163 and CD206). Non-parametric tests were used for statistical analysis. RESULTS: A higher percentage of circulating CD204+CD163+CD206+TLR4+CD80+CD86+ and CD14+CD206+CD163+CD204+TLR4+CD80+CD86+ mixed M1/M2 monocyte/macrophage subsets, was identified to characterize patients affected by SSc-related ILD and higher systolic pulmonary artery pressure. Mixed M1/M2 monocyte/macrophage subset showed higher percentages in patients positive for anti-topoisomerase antibody, a known lung involvement predictor. CONCLUSIONS: The present study shows for the first time, through a wide flow cytometry surface marker analysis, that higher circulating mixed M1/M2 monocyte/macrophage cell percentages are associated with ILD, sPAP and anti-topoisomerase antibody positivity in SSc, opening the path for research on their possible role as pathogenic or biomarker elements for SSc lung involvement.