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PURPOSE To create a nomogram including the translational speed of the microkeratome blade, microkeratome head size and precut tissue thickness to predict the postcut thickness for Descemet stripping automated endothelial keratoplasty to obtain the thinnest possible graft. METHODS This prospective study incorporated 48 grafts for DSAEK from March 2017 to June 2020. Corneal tissue for DSAEK was prepared by 3 experienced physicians using the Moria Evolution 3E (Moria Inc, Antony, France) microkeratome with 400, 450 and 500 μm head sizes. Precut central corneal thickness was measured with a DGH 550 handheld pachymeter (Pachette 2), taking an average of 3 readings. The microkeratome head was selected according to precut tissue thickness. The selected microkeratome head size was 150 μm less than the donor cornea thickness. Two translational speeds were used for the microkeratome cuts. One month after surgery, the central lenticular thickness was measured with a Visante® Optical Coherence Tomography caliper (Carl Zeiss Meditec Inc, Germany). A descriptive analysis was performed. RESULTS Forty-eight donor grafts were prepared. Mean graft thickness was 97.58 ± 29.84 μm (range 39-176 μm). Of the 48 samples, central graft thickness was

Introduction: Vulvovaginal atrophy (VVA) is a chronic condition caused by estrogen deficiency. It affects around 50% of postmenopausal women, reducing their general and sexual quality of life as well as the quality of their personal relationships. Aim: The aim of this clinical guide is to set out an individualized approach to the management of VVA with topical estrogens and non-hormonal preparations. Materials and methods: Literature review and consensus of expert opinion. Summary recommendations: An individualized approach is required for the management of VVA. Topical low-dose estrogens are effective and also alleviate urinary incontinence and prevent recurrent urinary tract infections. Women should not be denied long-term use of topical estrogens as long as they feel that this treatment is of benefit to them, because the safety data are reassuring. Non-hormonal preparations (lubricants and moisturizers) should be the first-line treatment for VVA in women taking adjuvant endocrine therapies for cancers considered to be hormone-dependent. They can be used over the long term. Sistema de Investigacion y Desarrollo (SINDE) ; Vice-Rectorado de Investigacion & Postgrado (VRIP) of the Universidad Catolica de Santiago de Guayaquil, Guayaquil, Ecuador

The objective of this project is to create eligibility criteria for the use of menopausal hormone therapy (MHT) similar to those established for contraceptive methods. A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by patients with medical conditions based on the best available evidence. The project protocol, which was registered in the Open Science Framework platform (DOI 10.17605/OSF.IO/ J6WBC), will be conducted in two phases. As a first step we will conduct a series of systematic reviews on the safety of MHT, addressing eight clinical questions. The findings of these systematic reviews will help to inform a structured process in which a panel of experts will define the eligibility criteria according to a specific framework, which will facilitate the discussion and development process. For the first time, a set of eligibility criteria, based on clinical evidence and developed according to the most rigorous methodological tools, will be defined. This will provide health professionals with a powerful decisionmaking tool that can be used in the management of menopausal symptoms.

In this case-report we describe the first reported case of early-onset fungal interface keratitis (IK) after Descemet Membrane Endothelial Keratoplasty (DMEK) successfully treated with penetrating keratoplasty (PK) during the active stage of infection. A patient with graft failure after Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) was operated on with DMEK. Donor rim culture and broth were positive for Candida albicans. Several interface infiltrates were confirmed and localized using anterior segment optical coherence tomography. Three days after diagnosis, observing clear signs of intraocular infection, the graft was removed with simultaneous washed-up of anterior chamber with fluconazole 1% followed by a PK and intrastromal corneal injections of fluconazole. A best-corrected visual acuity of 20/20 was achieved. This case highlights the importance of analysing every donor rim and broth, despite the patient doesn't show any symptoms or signs during the post-operative period. PK is a viable treatment option in early-onset interface keratitis.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital., SCOPUS: re.j, info:eu-repo/semantics/published

Diet is a crucial variable for a healthy life. A rapidly growing number of studies in recent years support the hypothesis that the Mediterranean diet (MedDiet) has a beneficial effect on certain body systems, but the highly varied objectives and quality of these publications warrants an updated assessment. In the present review we performed a comprehensive evaluation of current evidence on the impact of the MedDiet on human health, assessing its effect on the incidence or progression of the main non-communicable diseases and their intermediate outcomes and risk factors. We scrutinised the clinical evidence from observational studies and randomised controlled trials. Cardiovascular disease was the condition with most information. The MedDiet showed a general preventive effect, which was reproduced to varying degrees for certain intermediate cardiovascular outcomes such as blood pressure, lipids, obesity, metabolic syndrome and diabetes. Benefits were also found for several types of cancer, brain function (including cognition, mood and to a lesser extent Parkinson's disease) and mortality. The quality of the published evidence was, however, generally moderate or low. In conclusion, the MedDiet shows a favourable impact on health. General adoption of a MedDiet is concordant with current policies promoting healthy and sustainable nutrition worldwide. Nonetheless, more high-quality research is needed to improve the consistency of the findings.

Objectives To ascertain whether women with a history of biochemical pregnancies (BPs) in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycles have decreased chances of live birth (LB); and (2) to build a predictive model for LB in this particular population of infertile women. Methods In order to achieve the first objective, data from 1536 women that had a LB using autologous fresh or frozen embryos, or dropped out of further IVF/ICSI treatments after completing one to three unsuccessful treatment cycles were retrospectively analyzed. A subpopulation of 90 women that experienced one or more BPs in our assisted reproduction unit were selected to build a predictive logistic regression model for LB. Results LB percentages significantly decreased from a value of 55.3 % in women with no history of previous BPs to 30.9 % and 11.1 % in women that displayed a history of one or more than one BP, respectively. Three out of 35 selected potential predictors were finally included into the model: “number of the last embryo transfer cycle resulting in a BP”, “women’s age”, and “oligo-, astheno-, and/or teratozoospermia”. The value of the c-statistic was 0.819 (asymptotic 95 % CI: 0.724-0.913). The model adequately fitted the data with no significant over or underestimation of predictor effects. Conclusion (1) A history of BPs is negatively associated with later chance of LB in women undergoing a series of IVF/ICSI treatment cycles; and (2) LB probability of women with a history of BPs can be predicted using a model with excellent discriminatory capacity.

To introduce a prognostic model for women’s assisted fecundity before starting the first IVF/ICSI treatment cycle. In contrast to previous predictive models, we analyze two groups of women at the extremes of prognosis. Specifically, 708 infertile women that had either a live birth (LB) event in the first autologous IVF/ICSI cycle (“high-assisted-fecundity women”, n = 458) or did not succeed in having a LB event after completing three autologous IVF/ICSI cycles (“low-assisted-fecundity women”, n = 250). The initial sample of 708 women was split into two sets in order to develop (n = 531) and internally validate (n = 177) a predictive logistic regression model using a forward-stepwise variable selection. Seven out of 32 initially selected potential predictors were included into the model: women’s age, presence of multiple female infertility factors, number of antral follicles, women’s tobacco smoking, occurrence of irregular menstrual cycles, and basal levels of prolactin and LH. The value of the c-statistic was 0.718 (asymptotic 95% CI 0.672–0.763) in the development set and 0.649 (asymptotic 95% CI: 0.560–0.738) in the validation set. The model adequately fitted the data with no significant over or underestimation of predictor effects. Women’s assisted fecundity may be predicted using a relatively small number of predictors. This approach may complement the traditional procedure of estimating cumulative and cycle-specific probabilities of LB across multiple complete IVF/ICSI cycles. In addition, it provides an easy-to-apply methodology for fertility clinics to develop and actualize their own predictive models.

The rising incidence of bone pathologies such as osteoporosis and osteoarthritis is negatively affecting the functional status of millions of patients worldwide. The genetic component of these multifactorial pathologies is far from being fully understood, but in recent years several epigenetic mechanisms involved in the pathophysiology of these bone diseases have been identified. The aim of the present study was to compare the serum expression of four miRNAs in women with hip fragility fracture (OF group), osteoarthritis requiring hip replacement (OA group) and control women (Ctrl group). Serum expression of miR-497-5p, miR-155-5p, miR-423-5p and miR-365-3p was determined in a sample of 23 OA women, 25 OF women and 52 Ctrl women. Data shown that women with bone pathologies have higher expression of miR-497 and miR-423 and lower expression of miR-155 and miR-365 than control subjects. Most importantly, miR-497 was identified as an excellent discriminator between OA group and control group (AUC: 0.89, p p = 0.002). Our data suggest that circulating miR-497 may represent a significant biomarker of OA, a promising finding that could contribute towards future early-stage diagnosis of this disease. Further studies are required to establish the role of miR-155, miR-423 and miR-365 in bone pathologies.

PURPOSE: The present study aims to ascertain whether there is a causal relationship between women’s disease conditions present at the starting time of the first intended oocyte retrieval cycle and IVF/ICSI outcomes, primarily odds of live birth in the first IVF/ICSI treatment. METHODS: This is a retrospective study of infertile healthy and diseased women that had a live birth and/or exhibited a complete first oocyte retrieval cycle. Generalized Estimating Equations (GEE) models were applied to adjust standard errors for the potential correlation among women exhibiting the same infertility etiology. Confounders to be controlled for in these GEE models were previously selected following a strict stepwise methodology. RESULTS: Compared to healthy women, diseased women exhibited lower odds of live birth (OR (95% CI) 0.704 (0.576–0.860)). Further screening analyses indicated that subclinical iodine-deficiency hypothyroidism together with autoimmune thyroiditis contributed significantly to decrease odds of live birth (OR (95% CI) 0.720 (0.608–0.853)). Another important contribution arose from practically all the remaining morbid conditions analyzed. These diseases were individually associated with lower odds of live birth, although differences were non-significant. Notwithstanding, differences became significant after merging these diseases in a single group (OR (95% CI) 0.605 (0.394–0.930)). CONCLUSION: There is a significant causal association between most diseases present at the starting time of the first intended oocyte retrieval cycle and lower odds of live birth in the first IVF/ICSI treatment.

Background Erenumab was approved in Europe for migraine prevention in patients with ≥4 monthly migraine days (MMD). In Spain, Novartis started a personalized managed access program which allowed free access to erenumab before official reimbursement. The Headache Study Group of the Spanish Neurological Society started a registry to monitor real-world safety and efficacy, and all Spanish headache experts were invited to participate. Methods Patients fulfilled ICHD3 criteria for migraine and had ≥ 4MMD. Sociodemographic and clinical data were registered as well as MMD, headache frequency (MHD), prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and PROs: HIT6, MIDAS, and PGIC. A >50% reduction of MMD after 3 months was considered as response. Results We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 hospitals from February 2019 – to – June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Average of prior preventive treatment failure was >7 (BoNT/A had been used by 95.2%). Most patients (67,6%) started with erenumab 70mg. 61% of patients were also taking oral preventive drugs or getting simultaneous BoNT/A (27.6%). Responder rate was 37.1% and the mean reduction of MMD was -6.28 and MHD: -8.6. Regarding PROs: MIDAS: -35 p., HIT6: -11.6 p., PIGC: 4.7 p. Predictors of good response were: HIT6 score ( p =0.01), prior preventive treatment failures ( p =0.026), absence of MOH ( p =0.039), and simultaneous BoNT/A treatment ( p

Purpose: To analyze the target induced astigmatism (TIA), surgically induced astigmatism (SIA), difference vector (DV), and correction index (CI) in the correction of astigmatism with phakic lenses, and its influence on visual acuity, and to analyze the safety and efficacy indexes of the correction of high and low power astigmatism with toric phakic lenses. Design: Retrospective comparative study. Methods: The medical records of patients that were operated on at the research center during the period were analyzed. Results were divided into Low Astigmatism Group – LAG (33 eyes) and High Astigmatism Group – HAG (93 eyes) according to the implanted toric ICL lens power. Preoperative refraction and resultant postoperative refraction were analyzed by vector analysis. Visual acuity pre and postop, with and without optical correction, were compared. Results: A total of 126 eyes were studied. The average preop refraction was −5.02 D sphere with −2.61 D cylinder. The average ICL lens power implanted was −8.31 D sphere +2.77 D cylinder. Refractive remaining was −0.01 ± 0.11 D sphere −0.15 ± 0.28 D cylinder. The arithmetic average angle of error in the astigmatism correction was 1.08°. The resultant cylinder was −0.03 ± 0.12 D and −0.19 ± 0.30 D in the low and high astigmatism groups, respectively, with a mean UDVA −0.01 ± 0.10 and 0.01 ± 0.16 and CDVA −0.03 ± 0.08 and −0.01 ± 0.17 for each group. The safety and efficacy indexes for the low astigmatism group were 1.09 ± 0.16 and 1.05 ± 0.17, respectively, with 1.11 ± 0.17 and 1.06 ± 0.16 for the high astigmatism group. Conclusions: The correction of astigmatism by the implantation of toric phakic lenses of the posterior chamber is safe and effective, independently of the amount of cylinder corrected.

Background Cancer is the second leading cause of mortality worldwide. Integrating different levels of care by implementing screening programmes, extending diagnostic tools and applying therapeutic advances may increase survival. We implemented a cancer fast-track programme (CFP) to shorten the time between suspected cancer symptoms, diagnosis and therapy initiation. Patients and methods Descriptive data were collected from the 10 years since the CFP was implemented (2009-2019) at the Clinico-Malvarrosa Health Department in Valencia, Spain. General practitioners (GPs), an oncology coordinator and 11 specialists designed guidelines for GP patient referral to the CFP, including criteria for breast, digestive, gynaecological, lung, urological, dermatological, head and neck, and soft tissue cancers. Patients with enlarged lymph nodes and constitutional symptoms were also considered. On identifying patients with suspected cancer, GPs sent a case proposal to the oncology coordinator. If criteria were met, an appointment was quickly made with the patient. We analysed the timeline of each stage of the process. Results A total of 4493 suspected cancer cases were submitted to the CFP, of whom 4019 were seen by the corresponding specialist. Cancer was confirmed in 1098 (27.3%) patients: breast cancer in 33%, urological cancers in 22%, gastrointestinal cancer in 19% and lung cancer in 15%. The median time from submission to cancer testing was 11 days, and diagnosis was reached in a median of 19 days. Treatment was started at a median of 34 days from diagnosis. Conclusions The findings of this study show that the interval from GP patient referral to specialist testing, cancer diagnosis and start of therapy can be reduced. Implementation of the CFP enabled most patients to begin curative intended treatment, and required only minimal resources in our setting., Highlights • Our CFP easily connects GPs and hospital specialists. • Our CFP shortens assessment time in patients with suspected cancer, adding to quality care. • Our CFP decreases emotional stress in patients without cancer.

Background There is debate on the role of estrogens in modulating the risk for atherosclerosis in women. Our purpose was to investigate whether the size of the estrogenic impact was independently associated with variation of carotid intima-media thickness (IMT) in healthy late postmenopausal women. The levels of circulating estrogens have been used in previous studies but the influence of SNPs of the estrogen receptors (ER) α and β has not been investigated.Methods We performed a crossed-sectional study of 91 women in a university hospital. We used a double approach in which, in addition to the measurement of estradiol levels by ultrasensitive methods, genetic variants (SNPs) associated with differing expression of the ER α and β genes were assessed. Multivariable analysis was used to examine the association of candidate factors with the value of IMT and plaque detection at both the carotid wall and the sinus.Results The levels of glucose were directly associated with IMT at both the carotid wall (pERβ was directly associated with IMT at both the carotid wall (p=0.001) and the sinus (p=0.002).Conclusions Poorer estrogenic impact, as concordant with a SNP variant imposing reduced expression of the ERβ, was directly associated with IMT at both the carotid wall and the sinus. Glucose level, vitamin D only for the carotid wall, and age only for the sinus, also emerged as independent factors in the IMT variance.

INTRODUCTION: The prevalence of urinary incontinence and of other lower urinary tract symptoms increases after the menopause and affects between 38 % and 55 % of women aged over 60 years. While urinary incontinence has a profound impact on quality of life, few affected women seek care. AIM: The aim of this clinical guide is to provide an evidence-based approach to the management of urinary incontinence in postmenopausal women. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Healthcare professionals should consider urinary incontinence a clinical priority and develop appropriate diagnostic skills. They should be able to identify and manage any relevant modifiable factors that could alleviate the condition. A wide range of treatment options is available. First-line management includes lifestyle and behavioral modification, pelvic floor exercises and bladder training. Estrogens and other pharmacological interventions are helpful in the treatment of urgency incontinence that does not respond to conservative measures. Third-line therapies (e.g. sacral neuromodulation, intravesical onabotulinum toxin-A injections and posterior tibial nerve stimulation) are useful in selected patients with refractory urge incontinence. Surgery should be considered in postmenopausal women with stress incontinence. Midurethral slings, including retropubic and transobturator approaches, are safe and effective and should be offered.

Proteïna TDP-43; Esclerosi lateral amiotròfica; Demència frontotemporal Proteína TDP-43; Esclerosis lateral amiotrófica; Demencia frontotemporal TDP-43 protein; Amyotrophic lateral sclerosis; Frontotemporal dementia Cognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP-43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concomitant pathologies on cognitive impairment in ALS patients. We analyzed a postmortem series of 104 ALS patients and retrospectively reviewed clinical and neuropathological data. We assessed the burden and extent of concomitant pathologies, the role of APOE ε4 and mutations, and correlated these findings with cognitive status. We performed a logistic regression model to identify which pathologies are related to cognitive impairment. Cognitive decline was recorded in 38.5% of the subjects. Neuropathological features of frontotemporal lobar degeneration (FTLD) were found in 32.7%, explaining most, but not all, cases with cognitive impairment. Extent of TDP-43 pathology and the presence of hippocampal sclerosis were associated with cognitive impairment. Mutation carriers presented a higher burden of TDP-43 pathology and FTLD more frequently than sporadic cases. Most cases (89.4%) presented some degree of concomitant pathologies. The presence of concomitant pathologies was associated with older age at death. FTLD, but also Alzheimer’s disease, were the predominant underlying pathologies explaining the cognitive impairment in ALS patients. In sum, FTLD explained the presence of cognitive decline in most but not all ALS cases, while other non-FTLD related findings can influence the cognitive status, particularly in older age groups. SBE is a recipient of the Rio-Hortega post-residency grant from the Instituto de Salud Carlos III, Spain. This study was partially funded by Fundació Marató de TV3 (grant no. 20141610 to EG and no. 20143710 to RRG) and Fondo Europeo de Desarrollo Regional (FEDER) (PI15/01618 to RRG). AA is funded by Departament de Salut de la Generalitat de Catalunya, Pla estratègic de recerca i innovació en salut (PERIS) 2016–2020 (SLT002/16/00329). JG is recipient of the Instituto de Salud Carlos III-FEDER grants (PI16/01673 and PI19/00593)

Objective Experimental studies suggest that lipids affect bone metabolism. We aimed to elucidate whether lipid levels are associated with bone mineral density (BMD) in a cohort of postmenopausal women. Design A cross-sectional study of participants in the Chronic Ailment Reduction after MENopause (CARMEN) cohort. Women underwent assessment of clinical and analytical parameters, including fasting lipid levels. BMD was assessed at both lumbar spine and hip. Homogeneity in the cohort was optimized by filtering out a series of confounding variables with a known impact on bone. Main outcome measures Association of BMD at lumbar spine and femoral neck with lipid levels. Results A total of 667 of the 1304 screened women were analyzed. A strong correlation was revealed between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in univariate analysis. Multivariate analysis detected a significant positive association of HDL-C with BMD at both spine (p = 0.007) and femoral neck (p = 0.013). Other independent predictors of spine BMD were years since menopause (ysm, negatively associated), and body mass index (BMI) and estradiol, both positively associated with BMD. The other independent variables in the femoral neck were ysm and glucose (negatively associated) and BMI, estradiol, and phosphate, all positively associated with BMD. Conclusion Levels of HDL-C, but not TC, LDL-C or triglycerides, were positively associated with BMD at both the lumbar spine and femoral neck in a homogeneous cohort of postmenopausal women.

Introduction Dyslipidemias are common and increase the risk of cardiovascular disease. The menopause transition is associated with an atherogenic lipid profile, with an increase in the concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein B (apoB) and potentially lipoprotein (a) [Lp(a)], and a decrease in the concentration of high-density lipoprotein cholesterol (HDL-C). Aim The aim of this clinical guide is to provide an evidence-based approach to management of menopausal symptoms and dyslipidemia in postmenopausal women. The guide evaluates the effects on the lipid profile both of menopausal hormone therapy and of non-estrogen-based treatments for menopausal symptoms. Materials and methods Literature review and consensus of expert opinion. Summary recommendations Initial management depends on whether the dyslipidemia is primary or secondary. An assessment of the 10-year risk of fatal cardiovascular disease, based on the Systematic Coronary Risk Estimation (SCORE) system, should be used to set the optimal LDL-C target. Dietary changes and pharmacological management of dyslipidemias should be tailored to the type of dyslipidemia, with statins constituting the mainstay of treatment. With regard to menopausal hormone therapy, systemic estrogens induce a dose-dependent reduction in TC, LDL-C and Lp(a), as well as an increase in HDL-C concentrations; these effects are more prominent with oral administration. Transdermal rather than oral estrogens should be used in women with hypertriglyceridemia. Micronized progesterone or dydrogesterone are the preferred progestogens due to their neutral effect on the lipid profile. Tibolone may decrease TC, LDL-C, TG and Lp(a), but also HDL-C concentrations. Low-dose vaginal estrogen and ospemifene exert a favorable effect on the lipid profile, but data are scant regarding dehydroepiandrosterone (DHEA). Non-estrogen-based therapies, such as fluoxetine and citalopram, exert a more favorable effect on the lipid profile than do sertraline, paroxetine and venlafaxine. Non-oral testosterone, used for the treatment of hypoactive sexual desire disorder/dysfunction, has little or no effect on the lipid profile.

We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (

Evidence from different sources sustains a pro-oncogenic role of hormones, estrogens and progestogens, on the breast. The issue is of interest for young women, who are exposed to the hormonal changes imposed by the ovarian cycle and, often, take hormones with contraceptive purposes. Experimental and clinical studies show that both estrogens and progesterone are involved in mammary development during puberty and lactation, the changes being observed across mammalian species, including humans. Estrogen receptors, and more particularly the alpha isoform, participate in molecular processes of stem cells differentiation and epithelial proliferation through paracrine actions implicating growth factors. Progesterone also contributes through paracrine mechanisms involving one member of the tumor necrosis factor (TNF) family, the receptor activator of nuclear factor κB ligand (RANKL) and its receptor (RANK). Epidemiological studies have found that the length of the exposure to endogenous hormones, as determined by an early menarche or a late menopause, is a risk factor for breast cancer. Additional evidence has derived from studies with compounds modulating the estrogen or the progesterone receptors. Selective estrogen receptor modulators (SERM), like tamoxifen, have been shown to decrease the risk of breast cancer in both pre- and post-menopausal women. Aromatase inhibitors, which drastically reduce the levels of circulating estrogens, have reproduced the findings. The selective progesterone receptor modulators (SPRM) have been less investigated and issues concerning safety have arisen. These observations have interest for young women. High-risk women may consider the use of SERMs, for example, to reduce their risk. Much more common is the case of women who take hormones for contraception. The goal of the present article is twofold: i) to summarize the actual knowledge of the mechanisms implicating estrogens and progestogens on the risk for breast cancer and ii) to provide rationality for the debate about potential cancer risk of hormonal contraceptives, frequently used by premenopausal women.

OBJECTIVES: To compare progestin ovarian stimulation protocols with gonadotropin-releasing hormone analogue (agonists and antagonists) protocols on newborn outcomes. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and BioMed Central databases were searched for studies comparing progestin prime ovarian stimulation (PPOS) protocols with gonadotropin-releasing hormone analogues. Data were pooled by meta-analysis using a random effects model. MAIN OUTCOME MEASURES: Primary endpoint was the risk of newborn congenital malformations. RESULTS: A total of 4 studies involving 9274 live-born infants were included. No important harm was observed with PPOS in terms of congenital malformations (OR 0.92; 95% CI 0.63–1.34; p = 0.65) (very low quality of evidence (QOE)) and low birth weight (OR 1.06; 95% CI 0.95–1.18; p = 0.29) (very low QOE) as compared with GnRH-a short protocols. In addition, a trend to a lower risk of preterm birth (OR 0.90; 95% CI 0.80–1.02; p = 0.10) (very low QOE) was found among patients treated with a PPOS protocol. CONCLUSIONS: PPOS protocols, compared with GnRH-a protocols, are associated with a similar congenital malformation risk profile. Therefore, PPOS might represent a safe and appealing treatment option for infertile patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-020-01755-0) contains supplementary material, which is available to authorized users.

AIM We aimed to measure the effectiveness and quality of life (QoL) 10 years after transobturator suburethral tape surgery. METHODS We carried out a prospective observational study of 42 women assessed 10 years after surgical intervention with the transobturator technique. The main outcome measures were subjective and objective cure or improvement, complications, and changes in QoL. RESULTS The median abdominal leak point pressure had been 92 (82-113) mL H2 O prior to surgery. Thirty-six women (85.7%) remained cured (negative cough test) and 13 (31%) reported urine leakage during physical activity, percentages which were similar to those at a previous assessment at the 5th year. Urgency urinary incontinence was reported by 18 women (42.9%), 16 of whom required the use of anticholinergic drugs. Nineteen women had undergone some form of surgical pelvic reconstruction concomitantly with the TOT procedure, four of whom presented with relapse. The QoL tests indicated that cure and improvement persisted in 85.7% (n = 36, Urogenital Distress Inventory-6) and 92.9% (n = 39, Incontinence Impact Questionnaire-7) of the 42 evaluable women, respectively. CONCLUSION Rates of objective and subjective effectiveness remained stable after 10 years of surgery and QoL did not deteriorate significantly during that interval. The increase in urgency incontinence needs to be further investigated.

Introduction Postmenopausal osteoporosis is a highly prevalent disease. Prevention through lifestyle measures includes an adequate calcium intake. Despite the guidance provided by scientific societies and governmental bodies worldwide, many issues remain unresolved. Aims To provide evidence regarding the impact of calcium intake on the prevention of postmenopausal osteoporosis and critically appraise current guidelines. Materials and methods Literature review and consensus of expert opinion. Results and conclusion The recommended daily intake of calcium varies between 700 and 1200 mg of elemental calcium, depending on the endorsing source. Although calcium can be derived either from the diet or supplements, the former source is preferred. Intake below the recommended amount may increase fragility fracture risk; however, there is no consistent evidence that calcium supplementation at, or above, recommended levels reduces risk. The addition of vitamin D may minimally reduce fractures, mainly among institutionalised people. Excessive intake of calcium, defined as higher than 2000 mg/day, can be potentially harmful. Some studies demonstrated harm even at lower dosages. An increased risk for cardiovascular events, urolithiasis and even fractures has been found in association with excessive calcium intake, but this issue remains unresolved. In conclusion, an adequate intake of calcium is recommended for general bone health. Excessive calcium intake seems of no benefit, and could possibly be harmful.

Background: The COVID-19 pandemic has disrupted many aspects of clinical practice in oncology, particularly in making timely cancer diagnosis. Our public health system has been concerned about potential delays leading to a higher proportion of patients with advanced stages. Our cancer diagnosis fast-track program (CFP) in the Clinic-Malvarrosa Health department in Valencia (Spain) is connecting primary care (PC) with different specialists to speed cancer diagnosis and treatment upon well founded suspicion. A 10-year evaluation of our CFP has recently been published. The aim of this analysis was to investigate the impact of the COVID-19 pandemic on the CFP. Methods: We analysed the programme flow during the state of emergency starting on March 16, 2020 for one year. Results: During that year, 975 suspected cancer cases were submitted to the CFP. The submissions only decreased during the times of highest COVID-19 incidence and stricter lockdown (March, April and October 2020). However, referrals were slightly higher than in the two previous years (average 877). Of those 975 patients, 817 were seen by the corresponding specialist. A cancer diagnosis was confirmed in 197 (24.1%) with 33% urological, 23% breast, 16% gastrointestinal and 9% lung cancer. Median time from referral to the specialist visit was 13 (interquartile range, 8 to 22 days) days and a diagnosis was reached in a median of 18 days (interquartile range, 10 to 30 days). In cancer patients, treatment was started in around 30 days (interquartile range, 13.5 to 51 days) from the time of diagnosis. Sixty-one percent of cancers were found in an early stage, 20% in a locally advanced stage, and 19% in an advanced stage. These intervals and proportions were similar to the previous years. Conclusions: Our programme has proven to be a reliable tool to help PC physicians referring patients with cancer suspicion cancer, maintaining its normal flow and efficacy despite the current pandemic. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

European healthcare systems are increasingly being challenged to respond to female genital mutilation (FGM). This study explores the FGM experiences of migrant women coming from FGM-practicing countries residing in a European host country. A qualitative phenomenological study was carried out and 23 participants were included. Data were collected through 18 face-to-face open-ended interviews and a focus group and were analysed using Giorgi’s four-step phenomenological approach. Three main themes were derived: “FGM consequences”, “healthcare received” and “tackling FGM”. Participants highlighted obstetric, gynaecological and genitourinary consequences such as haemorrhages, perineal tears, caesarean delivery, risk of infection, dysmenorrhea, urinary tract infections and dysuria, consequences for sexuality, mainly, dyspareunia, loss of sexual interest and decreased quality of sexual intercourse, and psychological consequences such as loss of self-esteem, feelings of humiliation and fear of social and familial rejection. Women perceived a profound lack of knowledge about FGM from health providers and a lack of sensitive and empathetic care. Some women perceived threatening and disproportionate attitudes and reported negative experiences. Participants highlighted the importance of educating, raising awareness and improving prevention and detection strategies. The findings disclose the need to improve training and institutional plans to address structural and attitudinal barriers to health equity across migrant families in their host countries.

Endometriosis is a chronic inflammatory disease that has been associated with an increased risk of ovarian cancer, especially epithelial tumors. Transvaginal ultrasound is a first-line diagnostic method for the assessment of endometriosis, and of endometriomas, the ovarian cystic form of endometriosis. Endometriomas usually have typical ultrasound features that allow them to be easily diagnosed. When atypical images are observed, such as solid areas with vascular flow, their malignancy should be ruled out, especially in peri-menopausal women. Early diagnosis of these tumors is essential because immediate surgical treatment is crucial for prognosis. Malignant neoplasms associated with endometriomas are, in the vast majority of cases, clear cell and endometrioid adenocarcinomas. In some cases seromucinous tumors have been described, but mainly in their borderline stage. A case is presented in which a patient developed an invasive seromucinous ovarian neoplasm on an endometrioma.

Key Clinical Message In young patients with T1D, neurological manifestations of cerebral hypertension should suggest the possibility of a cerebral venous sinus thrombosis (CVST). In these patients an inherited prothrombotic risk factor, including factor V Leiden G1691A gene mutation, should be considered during an event of thrombosis. Improving the glycemic control is the first factor that should be controlled in a patient who carries a genetic prothrombotic risk factor. Anticoagulant treatment should be started as son as CVST has been diagnosed. Long‐term antithrombotic treatment with tinzaparin 175 IU/kg/day, a low‐molecular weight heparin (LMWH), could be reliable and well tolerated, although an indefinite special follow‐up, including neurological controls, is advisable even in asymptomatic patients.

This study represented a translational study that first compared gene expression of B cells of BM from ovariectomized and control mice, and then analyzed some of the differentially expressed genes in women. Results showed novel genetic associations with bone phenotypes and points to the CD80 gene as relevant in postmenopausal bone loss. Osteoporosis is a multifactorial disease with a strong genetic component. However, to date, research into osteoporosis has only been able to explain a small part of its heritability. Moreover, several components of the immune system are involved in the regulation of bone metabolism. Among them, B cells occupy a prominent place. The study consisted of two stages. In the first, gene expression in bone marrow B cells is compared between ovariectomized and SHAM control mice using microarrays. In the second, we studied the association of polymorphisms in some differentially expressed genes (DEG) in a cohort of postmenopausal women. The present study has found 2791 DEG (false discovery rate (FDR)

Background In natalizumab-treated relapsing-remitting MS (RRMS) patients, various extended interval dosing strategies are under evaluation to minimize severe treatment-associated side effects, mainly progressive multifocal leukoencephalopathy development. Up to now, it has not been presented any approach, even in form of assay design, to determine the optimal percentage of CD49d receptor occupancy (RO) associated with a favorable clinical, radiological, and immunological response. Methods A multiparametric quantitative flow cytometry method was settled to measure CD49d RO on peripheral blood lymphocytes. The analytical protocol was tested in a 6-month follow-up from 19 RRMS patients treated with the natalizumab standard dosing of every 4 weeks or an extended-interval dosing of every 6 weeks. Results Extended natalizumab dose schedule promoted an increase of CD49d molecules per cell surface and a reduction of CD49d RO levels. The reduction observed on CD49d RO was not only depending on dose schedule but also on individual parameters such as body mass. Interestingly, individual clinical outcome was apparently the same between the different dose schedules or even better with the extended interval dosing. Conclusions Following up CD49d RO levels with a well-regulated monitoring work scheme is crucial to further identify over-/under-treated patients and to define a safe, personalized natalizumab regimen. © 2017 International Clinical Cytometry Society

Introduction: Globally, the total number of people with depression exceeds 300 million, and the incidence rate is 70 % greater in women. The perimenopause is considered to be a time of increased risk for the development of depressive symptoms and major depressive episodes. Aim: The aim of this position statement is to provide a comprehensive model of care for the management of depressive symptoms in perimenopausal and early menopausal women, including diagnosis, treatment and follow-up. The model integrates the care provided by all those involved in the management of mild or moderate depression in midlife women. Materials and methods: Literature review and consensus of expert opinion. Summary recommendations: Awareness of depressive symptoms, early detection, standardized diagnostic procedures, personalized treatment and a suitable follow-up schedule need to be integrated into healthcare systems worldwide. Recommended treatment comprises antidepressants, psychosocial therapies and lifestyle changes. Alternative and complementary therapies, although widely used, may help with depression, but a stronger evidence base is needed. Although not approved for this indication, menopausal hormone therapy may improve depressive symptoms in peri- but not in postmenopausal women, especially in those with vasomotor symptoms. Sistema de Investigation y Desarrollo (SINDE) Vice-Rectorado de Investigacion & Postgrado (VRIP) of the Universidad Catolica de Santiago de Guayaquil

The Mediterranean diet (MedDiet) represents the crystallisation of the centuries-old cooking legacies of different civilisations. The association of the MedDiet with longevity and low cardiovascular risk prompted the Seven Countries Study, which provided epidemiological evidence on the health effects of diet. This led to further studies, both epidemiological and interventional. Scales to measure adherence as well as studies of food components have consolidated a body of knowledge that is of great interest to institutions and governmental agencies. The recognition of its benefits for health has made the widespread introduction of the MedDiet an urgent challenge. Parallel efforts are being made to extend research through experimental and clinical studies. The purpose of this review is to present the historical background of the MedDiet, the main steps leading to the recognition of its health benefits, and the current strategy to facilitate its global implementation.

PURPOSE: To call attention to the fact that cumulative live birth (LB) proportions exhibit an inverted pattern to that displayed by each individual oocyte retrieval cycle (ORC-specific LB proportions) as well as when grouping together all the ORCs undergone by a woman (TNORC-specific LB proportions). METHODS: A retrospective study of 1433 infertile women that had a LB using autologous fresh or frozen embryos and/or dropped out of IVF/ICSI treatment after completing a maximum number of three treatment cycles. Generalized Estimating Equations (GEE) and standard and landmark Kaplan-Meier survival analyses were applied. RESULTS: A standard Kaplan-Meier analysis indicated that cumulative LB proportions rose as number of ORCs increased (0.320, 0.484, and 0.550 at ORC 1, 2, and 3, respectively). In contrast, landmark ORC-specific LB proportions showed an inverted pattern (0.320, 0.242, and 0.127 at ORC 1, 2, and 3, respectively). GEE models revealed that women’s clinical outcomes decreased as TNORCs increased. In particular, compared to women that experienced just one ORC, women that underwent two and three ORCs displayed higher incidences of cycle cancellations before either oocyte retrieval or embryo transfer, and clinical pregnancy losses, and lower odds of LB. CONCLUSION: Infertile women should be informed that cumulative LB probabilities exhibit an inverted pattern to that displayed by each individual ORC as well as when grouping together all the ORCs undergone by a woman.

Simoncini, Tommaso/0000-0002-2971-0079; Chung, Hsin-Fang/0000-0003-3261-5942; Mishra, Gita/0000-0001-9610-5904 WOS:000468709100014 PubMed ID: 31027683 Introduction: While the associations of genetic, reproductive and environmental factors with the timing of natural menopause have been extensively investigated, few epidemiological studies have specifically examined their association with premature (< 40 years) or early natural menopause (40-45 years). Aim: The aim of this position statement is to provide evidence on the predictors of premature and early natural menopause, as well as recommendations for the management of premature and early menopause and future research. Materials and methods: Literature review and consensus of expert opinion. Results and conclusions: Strong genetic predictors of premature and early menopause include a family history of premature or early menopause, being a child of a multiple pregnancy and some specific genetic variants. Women with early menarche and nulliparity or low parity are also at a higher risk of experiencing premature or early menopause. Cigarette smoking (with a strong dose-response effect) and being underweight have been consistently associated with premature and early menopause. Current guidelines for the management of premature and early menopause mainly focus on early initiation of hormone therapy (HT) and continued treatment until the woman reaches the average age at menopause (50-52 years). We suggest that clinicians and health professionals consider the age at menopause of the relevant region or ethnic group as part of the assessment for the timing of HT cessation. In addition, there should be early monitoring of women with a family history of early menopause, who are a child of a multiple pregnancy, or who have had early menarche (especially those who have had no children). As part of preventive health strategies, women should be encouraged to quit smoking (preferably before the age of 30 years) and maintain optimal weight in order to reduce their risk of premature or early menopause.

Here, we describe a protocol for the implementation of a heterologous mouse model in which progression of endometriosis can be assessed in real time through noninvasive monitoring of fluorescence emitted by implanted ectopic human endometrial tissue. For this purpose, biopsies of human endometrium are obtained from donor women ongoing oocyte donation. Human endometrial fragments are cultured in the presence of adenoviruses engineered to express cDNA for the reporter fluorescent protein mCherry. Upon visualization, labeled tissues with an optimal rate of fluorescence after infection are subsequently chosen for the implantation in recipient mice. One week prior to the implantation surgery, recipient mice are oophorectomized, and estradiol pellets are placed subcutaneously to sustain the survival and growth of lesions. On the day of surgery mice are anesthetized, and peritoneal cavity accessed through a small (1.5 cm) incision by the linea-alba. Fluorescently labeled implants are tweezed, briefly soaked in glue and attached to the peritoneal layer. Incisions are sutured, and animals left to recover for a couple of days. Fluorescence emitted by endometriotic implants is usually non-invasively monitored every 3 days for 4 weeks with an in vivo imaging system. Variations in the size of endometriotic implants can be estimated in real time by quantification of the mCherry signal and normalization against the initial time-point showing maximal fluorescence intensity. Traditional preclinical rodents of models of endometriosis do not allow non-invasive monitoring of lesion in real time but rather allow evaluation of the effects of drugs assayed at the end point. This protocol allows one to track lesions in real time and is more useful to explore the therapeutic potential of drugs in preclinical models of endometriosis. The main limitation of the model thus generated is that non-invasive monitoring is not possible over long periods of time due to the episomal expression of Ad-virus.

The drastic reduction in the circulating levels of estrogens along the menopausal transition triggers a list of symptoms, where hot flashes (HF) constitute a frequently reported episode. Women describe hot flashes as a sudden feeling of heat affecting the upper body, trunk, head, and neck and spreading upwards or, less frequently, downwards. The whole phenomenon is described as a heat wave, which is accompanied by sweating and reddening of the skin, and that persists for short intervals, of minutes or even seconds. HF present during day and night and, when intense enough, affect the quality of sleep and provoke frequent waking-up episodes.

Osteoporosis is a noncommunicable disease with increasing incidence at a global level. The burden of the disease particularly concerns women. A drastic and rapid decline in the circulating levels of estrogens, a key regulator of bone metabolism, is responsible for the increase in bone loss after menopause. Cells with a role in bone metabolism, osteoblasts, osteoclasts and osteocytes, have estrogen receptors. The fall in estrogens increases the differentiation of osteoclasts from progenitors in the bone marrow. A significant expansion in the resorption process follows.

Peripheral blood biomarkers able to predict disease activity in multiple sclerosis (MS) patients have not been identified yet. Here, we analyzed the immune phenotype of T lymphocyte subpopulations in peripheral blood samples from 66 RRMS patients under DMF (n=22) or fingolimod (n=44) treatment, by flow cytometry. A correlation study between the percentage and absolute cell number of each lymphocyte subpopulation with the presence of relapses or new MRI lesions during 12-month follow-up was performed. Patients who had undergone relapses showed at baseline higher percentage of Th1CM cells (relapsed: 11.60±4.17%vs. nonrelapsed: 9.25±3.17%, p<0.05) and Th1Th17CM cells (relapsed: 15.65±6.15%vs. nonrelapsed: 10.14±4.05%, p<0.01) before initiating DMF or fingolimod treatment. Kaplan-Meier analysis revealed that patients with Th1Th17CM (CD4+CCR7+CD45RA-CCR6+CXCR3+) cells>11.48% had a 50% relapse-free survival compared to patients with Th1Th17CMcells<11.48% whose relapse-free survival was 88% (p=0.013, log-rank test). Additionally, a high percentage of Th1Th17CM cells was also found in patients with MRI activity (MRI activity: 14.02±5.87%vs. no MRI activity: 9.82±4.06%, p<0.01). Our results suggest that the percentage of Th1Th17CM lymphocytes at baseline is a predictive biomarker of activity during the first 12 months of treatment, regardless of the treatment.

Physical inactivity not only places women's health at risk during menopause, but also increases menopausal problems. Abundant evidence links habitual physical exercise (PE) to a better status on numerous health indicators and better quality of life and to the prevention and treatment of the ailments that typically occur from mid-life onwards. We can infer that PE is something more than a lifestyle: it constitutes a form of therapy in itself. A panel of experts from various Spanish scientific societies related to PE and menopause (Spanish Menopause Society, Spanish Cardiology Society, Spanish Federation of Sports Medicine) met to reach a consensus on these issues and to decide the optimal timing of and methods of exercise, based on the best evidence available.

In addition to governing key functions in bone metabolism and the immune system, the RANK/RANKL/OPG system plays a role in the vascular system, particularly in vascular calcification and atherosclerosis. Given that these 2 phenotypes are considered a major cause of high blood pressure (BP), in this study we analyzed the association of SNPs in RANK and OPG genes with blood pressure. An observational study was conducted of 2 SNPs in the RANK gene (rs884205 and rs78326403) and 1 in the OPG gene (rs4876869) with systolic (SBP) and diastolic blood pressure (DBP) in a cohort of 695 women. Data analysis revealed a statistically significant association between the SNP rs884205 and BP pressure (SBP and DBP). Analyzing this relationship by the dominant inheritance model for this SNP (allele risk: A), women of the AA/AC genotype showed higher BP than women of the CC genotype, both for SBP (P = .001) and for DBP (P = .003), and these associations both surpassed the Bonferroni threshold for multiple comparisons. Multivariate regression analysis including known predictors of BP as independent variables was performed to evaluate the strength of this association, which in the case of the SNP rs884205 of the RANK gene remained statistically significant after adjustment for both SBP (P = .0006) and DBP (P = .005), demonstrating the key role of this SNP in BP. We report a robust association between the SNP rs884205 in RANK gene and BP in women, and this SNP is validated as a candidate in cardiovascular risk studies.

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b(mid) regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-alpha was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2 - and TMPRSS2 - which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

Background The practice of Female Genital Mutilation (FGM) is a deeply-rooted tradition in 30 Sub-Saharan and Middle-East countries which affects approximately 200 million women and girls worldwide. The practice leads to devastating consequences on the health and quality of life of women and girls in both the short and long term. Globalizing processes and migration flows have recorded cases of this practice worldwide representing for healthcare professionals an emerging challenge on how to approach their healthcare in a transcultural, ethical and respectful way. No survey to assess knowledge, attitudes and practices on FGM among primary healthcare professionals has been conducted in the Valencian region of Spain to date. Methods The main purpose of this study is to assess the perceptions, knowledge, practices and attitudes of the primary healthcare professionals in relation to FGM in the Clínic-Malvarrosa healthcare area of Valencia. A cross-sectional descriptive study was conducted based on a self-administered questionnaire to general practitioners, paediatricians, nurses, midwives, gynaecologists, social workers and others. Results A total of 321 professionals answered the questionnaire. Less than 5% of professionals answered that they had ever found a case of FGM during their professional practice and 21.8% answered that they had ever worked with population at risk of FGM. Almost 15% of professionals answered that they had received training on FGM but of those who had received training, only 22.7% correctly identified the typology of FGM and less than 5% correctly identified the geographical area. Only 6.9% of the respondents admitted to know some protocol of action, being midwives, paediatricians and social workers the most aware professionals of such protocols. Conclusion This study demonstrates that FGM is a problem present in the population attending primary healthcare services in Valencia. However, the professionals showed a profound lack of knowledge around concept, typology, countries of prevalence of FGM and existent protocols of action. It is healthcare professional duty to recognize this situation and to follow the right protocols of action, refer these women and their families to the most appropriate services and professionals that fit their needs, ensuring a multidisciplinary, positive and transcultural care for these families. Electronic supplementary material The online version of this article (10.1186/s12913-018-3396-z) contains supplementary material, which is available to authorized users.

Management of pelvic organ prolapse (POP) is a common and challenging task. Nowadays older women are more active than they were in the past, and the development of POP disrupts quality of life and impairs social and personal activities. The menopausal transition is a time of vulnerability, during which many women start experiencing symptoms and signs of POP. The role of hormonal changes or of hormonal therapies in influencing the development or progression of POP has been explored extensively. The management of POP requires considerable clinical skills. Correct diagnosis and characterization of the prolapse and an identification of the individual woman's most bothersome symptoms are the hallmark of appropriate initial management. Therapy is multimodal and often multidisciplinary, and requires a competence in pelvic medicine and surgery. The integration of hormonal, non-hormonal and surgical strategies is important and needs to be adjusted to changing circumstances on an individualized basis. When surgery is required, optimal management requires clinicians who are familiar with the advantages and disadvantages of all the available strategies and who are able to use these strategies in a tailored manner. Complex cases should be sent to specialist referral centers. Management of POP should be integrated into the practice of healthcare professionals dealing in menopause.

Introduction Whether menopause increases the risk of type 2 diabetes mellitus (T2DM) independently of ageing has been a matter of debate. Controversy also exists about the benefits and risks of menopausal hormone therapy (MHT) in women with T2DM. Aims To summarise the evidence on 1) the effect of menopause on metabolic parameters and the risk of T2DM, 2) the effect of T2DM on age at menopause, 3) the effect of MHT on the risk of T2DM, and 4) the management of postmenopausal women with T2DM. Materials and methods Literature review and consensus of experts’ opinions. Results and conclusion Metabolic changes during the menopausal transition include an increase in and the central redistribution of adipose tissue, as well as a decrease in energy expenditure. In addition, there is impairment of insulin secretion and insulin sensitivity and an increase in the risk of T2DM. MHT has a favourable effect on glucose metabolism, both in women with and in women without T2DM, while it may delay the onset of T2DM. MHT in women with T2DM should be administered according to their risk of cardiovascular disease (CVD). In women with T2DM and low CVD risk, oral oestrogens may be preferred, while transdermal 17β-oestradiol is preferred for women with T2DM and coexistent CVD risk factors, such as obesity. In any case, a progestogen with neutral effects on glucose metabolism should be used, such as progesterone, dydrogesterone or transdermal norethisterone. Postmenopausal women with T2DM should be managed primarily with lifestyle intervention, including diet and exercise. Most of them will eventually require pharmacological therapy. The selection of antidiabetic medications should be based on the patient’s specific characteristics and comorbidities, as well on the metabolic, cardiovascular and bone effects of the medications.

Aims Fingolimod, an orally active immunomodulatory drug for relapsing-remitting multiple sclerosis (RRMS), sequesters T cells in lymph nodes through functional antagonism of the sphingosine-1-phosphate receptor, reducing the number of potential autoreactive cells that migrate to the central nervous system. However, not all RRMS patients respond to this therapy. Our aim was to test the hypothesis that by immune-monitoring RRMS patient's leukocyte subpopulations it is possible to find biomarkers associated with clinical response to fingolimod. Methods Results Prospective study. Analysis of peripheral blood mononuclear cell subpopulations by multiparametric flow cytometry, at baseline and +1, +3, +6, +12 months of follow-up in 40 RRMS patients starting fingolimod therapy. Fingolimod treatment induced a severe lymphopenia affecting mainly T and B cells. A relative increase in T-reg (memory T-reg: 3.8 +/- 1.0% baseline vs 8.8 +/- 4.4% month +1; activated T-reg: 1.5 +/- 0.7% baseline vs 3.7 +/- 2.1% month +1, P < 0.001) as well as transitional B cells (10.5 +/- 12.3% baseline vs 18.7 +/- 14.6% month +1, P < 0.001) was observed. Interestingly, lymphocyte subpopulations were already at baseline significantly different in responder patients. The percentage of recent thymic emigrants (RTE) used to stratify fingolimod responder, and no responder patients was the best biomarker (4.0 +/- 1.4% vs 7.4 +/- 1.9%, respectively [P < 0.001]). Conclusion The results support that immune-monitoring of lymphocyte subpopulations in peripheral blood is a promising tool to select RRMS candidate for fingolimod treatment.