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Perimenopause represents a transition period of a woman's life during which physiological, affective, psychological, and social changes mark progression from a woman's fertile life to menopause, with wide sexual hormones fluctuations until the onset of hypergonadotropic hypogonadic amenorrhea. Contraception during menopause should not only avoid unwanted pregnancies, but also improve quality of life and prevent wide range of condition affecting this population. Hormonal contraceptives confer many noncontraceptive benefits for women approaching menopause: treatment of abnormal uterine bleeding, relief from vasomotor symptoms, endometrial protection in women using estrogen therapy, musculoskeletal protection, and mood disorders protection. The main point remains selecting the most adequate contraceptive option for each woman, considering her risk factor, comorbidities, and keeping in mind the possibility of continuing contraception until reaching menopause and even further, creating a bridge between perimenopause and menopause hormonal therapy. Correct perimenopause management should rely on individualized medical therapy and multidisciplinary approach considering lifestyle and food habits as part of general good health of a woman.

Highlights • PCOS women could be more exposed to SARS-CoV-2 infection: hyperandrogenism and insulin resistance could play a determining role in the pathophysiogenesis of the infection., The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with acute respiratory distress syndrome and infected patients have a relatively high risk of death. Emerging risk factors for poor outcome in this disease include age, male gender, cardiovascular co-morbidities including hypertension, prior cardiovascular disease, diabetes and more recently obesity. To date there are no data relating to SARS-CoV-2 in PCOS women. The present Clinical Opinion represents a summary of the epidemiological evidence and possible pathophysiological mechanisms regarding PCOS and COVID-19. PCOS women could be more susceptible to infections compared to non-PCOS women. Insulin resistance and the associated hyperinsulinaemia are drivers for enhanced steroidogenesis in women with PCOS. Weight-gain and obesity, through their worsening effects on insulin resistance, thereby drive enhanced steroidogenesis and hyperandrogenism. All these features represent key points to provide an explanation for the possible association between PCOS and SARS-CoV-2. Indeed, androgens may drive clinical results in COVID-19, through the expression of TMPRSS2, a cellular co-receptor necessary for SARS-CoV-2 infection and through androgen-mediated immune modulation. In women with PCOS the endocrine-immune axis leads to immune dysfunction with a state of chronic inflammation, and hyperandrogenism and IR with compensatory hyperglycaemia could play a determining role in the pathophysiogenesis of the infection. However, it is possible that only specific PCOS phenotypes may be more susceptible. In addition, vitamin D deficiency and gut dysbiosis are another important factor potentially involved in the increased risk of developing severe forms of COVID-19 in PCOS women. Further scientific investigations are needed with the aim of understanding which women are most at risk of becoming infected or developing complications, what are the causal mechanisms on which it is possible to intervene with prophylactic and therapeutic measures and what the long-term consequences will be on the health of these patients.

Objectives: The aim of the study was to update the results of a previous study published 10 years ago and compare the effect on hyperandrogenism of a newer progestin, dienogest (DNG), in a combined...

Massive fetomaternal hemorrhage (FMH) can cause devastating pregnancy outcomes. Perinatal prognosis may be improved by intrauterine transfusion, but the appropriate management for these pregnancies remains unclear. To determine the recurrence risk of FMH after intrauterine transfusion, we performed a systematic review of all case reports/series of patients with proven FMH treated with intrauterine transfusion and who had subsequent follow-up of at least 72 h until delivery. This revealed 13 cases, with 1 additional case from our institution. Ten patients (71.4%) had a second episode of FMH requiring a second intrauterine transfusion. Five patients (35.7%) required at least 3 intrauterine transfusions. The time interval between intrauterine transfusions was progressively reduced. The gestational age at the onset of signs/symptoms was 26.6 ± 2.1 weeks, and gestational age at delivery was 34.2 ± 4.2 weeks. Two cases of fetal demise (14.3%) and no neonatal deaths were recorded. Limited postnatal follow-up on 8 neonates was normal. The mean neonatal hemoglobin and transfusion rates were 13.2 ± 5.7 g/dL and 33.3%, respectively. Close fetal monitoring, likely daily, is necessary to recognize FMH recurrence. Several transfusions may be necessary once FMH is diagnosed if pregnancy is allowed to continue > 72 h.

Background The presence of submucous fibroids strongly impacts on IVF results, therefore, these patients should be considered for surgical or medical treatment. The aim of this study was to assess the role of Ulipristal acetate (UPA), a selective progesterone receptor modulator, in restoring uterine cavity deformation due to submucous fibroids, in infertile patients attempting an IVF treatment. The secondary study outcome was to evaluate the impact of preconception UPA treatment on rate of biochemical pregnancy, ongoing pregnancy, and live birth compared to a control group without fibroids. Methods Infertile patients with submucosal fibroid (Type 1 and Type 2 according to FIGO classification) were enrolled in the study as fibroids group and received 1 to 3 treatment cycles of UPA, according to their response, as reflected by fibroid volume reduction and restoration of normal uterine cavity. Patients in control group were randomly selected from a general IVF cohort by a ratio of 2:1 with fibroids group, matched by age, BMI, type and cause of infertility and antral follicle count. The impact of UPA on fibroids volume reduction was evaluated. IVF outcome was compared between groups. Results Twenty-six patients underwent UPA treatment revealed a mean volume reduction of their fibroids of 41%. A total of 15 (57.6%) biochemical pregnancy were obtained, resulting in 13 (50%) ongoing pregnancy and 9 (34.6%) healthy babies were already delivered. Similar results were obtained in control group. Conclusion Restoration of normal uterine cavity by UPA treatment prior to IVF treatment avoids surgery and establishes a pregnancy rate comparable to a control group without fibroids.

BackgroundThe aim of the study was to evaluate the clinical efficacy of long-term vaginal danazol treatment in fertile age women with adenomyosis on pain symptoms and abnormal uterine bleeding (AUB).MethodsA retrospective study on 66 young women with dysmenorrhea and/or dyspareunia, AUB and 2D-ultrasound diagnosis of adenomyosis was conducted at University Hospital of Siena (Italy). Women included were treated with a daily low-dose vaginal danazol (200 mg) for 6 months, followed by 2 different schedules: group A) continuous treatment for further 18 months (n = 30); group B) cyclic intermittent treatment with 3 months’ therapy followed by 3 months’ interval for further 18 months (n = 36). A visual analog scale (VAS) for pain symptoms, a pictorial blood-loss assessment chart (PBAC) for uterine bleeding, 2D-ultrasound signs of adenomyosis and quality-of-life measures were assessed at baseline and after both vaginal progestin regimens.ResultsThe pain symptoms, PBAC score and uterine volume were significantly reduced (pConclusionsA long-term treatment with vaginal danazol is effective to control pain and AUB in women with adenomyosis. The 6 months’ treatment followed by a cyclic 3 months’ treatment for further 18 months has the best compliance in symptomatic patients with adenomyosis.

Adenomyosis is a benign gynecological disorder associated with abnormal uterine bleeding, dysmenorrhea, dyspareunia and infertility, requiring a life-long management plan through medical or surgical treatment. The choice depends on woman's age, reproductive status and clinical symptoms. However, until now no drug labelled for adenomyosis is available; thus, the present review will focus on medical treatments currently used for adenomyosis and those in development.Adenomyosis may be considered a sex steroid hormone-related disorder associated with an intense inflammatory process. The use of gonadotropin-releasing hormone agonists (GnRH-a) for treating adenomyosis is described blocking the hypothalamic-pituitary-gonadal axis; however, it has long been associated with frequent and intolerable hypoestrogenic side effects. An antiproliferative effect of progestins suggests their use for treating adenomyosis, reducing bleeding and pain. Continuous oral norethisterone acetate or medroxyprogesterone acetate may help to inducing regression of adenomyosis, relief pain and reduce bleeding. The use of vaginal danazol has therapeutic effect on adenomyosis combining progestogenic and anti-inflammatory activity. The intrauterine device releasing levonorgestrel (Lng-IUD) is widely assessed in menorrhagia, and has been shown to be extremely effective in resolving pain and bleeding symptoms associated with adenomyosis. Recent data show a therapeutic effect of dienogest on adenomyosis symptoms.New drugs are under development for the treatment of adenomyosis, such as aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs), that produce a hypoestrogenic environment reducing pain, but are correlated with some adverse effects and a recurrence of symptoms after discontinuation of treatment. Selective progesterone receptor modulators (SPRMs) may reduce adenomyosis-associated pelvic pain, by inhibiting endometrial proliferation and suppressing adenomyotic lesion growth, as shown in animal models; however, the long-term effect with SPRMs needs further determination.

Background Urine neutrophil gelatinase‐associated lipocalin (NGAL) is a promising biomarker of acute kidney injury (AKI) in dogs. Objectives To evaluate the utility of urinary NGAL for characterizing AKI according to volume responsiveness, presence of inflammation and sepsis, and prognosis. Animals Dogs with AKI (n = 76) and healthy controls (n = 10). Methods Prospective study. Clinical and clinicopathologic data including absolute urine NGAL concentration (uNGAL) and NGAL normalized to urine creatinine concentration (uNGALC) were measured upon admission. Dogs were graded according to International Renal Interest Society (IRIS) AKI guidelines and compared based on AKI features: volume‐responsive (VR‐) AKI vs. intrinsic (I‐) AKI based on IRIS criteria; VR‐AKI and I‐AKI based on urine chemistry; inflammatory versus noninflammatory; septic versus nonseptic; and survivors versus nonsurvivors. Nonparametric statistics were calculated, and significance set at P

Objectives The current study was designed to evaluate the prevalence and prognostic significance of multiorgan dysfunction syndrome (MODS) in cats with sepsis. Methods Cats hospitalised in the intensive care unit of a veterinary university hospital with a diagnosis of sepsis were prospectively enrolled and divided according to disease severity and outcome (survivors; non-survivors). The feline acute patient physiological and laboratory evaluation (APPLE) scores were calculated upon admission, as previously described. Specific criteria to identify selected organ dysfunction (hepatic, renal, respiratory, cardiocirculatory, haemostatic) were adapted from the available human and veterinary literature, and evaluated at baseline and at the end of hospital stay. MODS was defined as the presence of at least two dysfunctional organs simultaneously. Non-parametric statistics were used for comparisons. Univariate and multivariate regression analyses to evaluate significant risk factors for death were carried out. Correlations between variables were assessed by the Spearman’s rank correlation coefficient. Significance was set at P Results A total of 43 cats with heterogeneous sources of sepsis were included. MODS was identified in 25/43 cats upon admission and in 32/43 cats at the end of hospital stay. Regression analyses showed a significantly elevated odds ratio for mortality for the presence of MODS, renal and cardiovascular dysfunction upon admission, as well as for the number of dysfunctional organs. The latter was the only variable retained by the model from the multivariate binary logistic regression analysis. Significant correlations were documented between the number of dysfunctional organs and the APPLE scores. Conclusions and relevance MODS is a frequent complication of feline sepsis, and is associated with worse outcomes. In particular, renal and cardiovascular dysfunction significantly increase the odds for death. Hence, systematic screening for organ dysfunction is advocated in cats with sepsis.

none 5 no The use of a low-dose infusion of intravenous lipid emulsion (ILE) in five young cats presented with acute neurotoxicity is reported. Suspected toxic compounds were permethrin (three, dermal), fipronil/eprinomectin/praziquantel (one, oral) and milbemycin (one, oral). Cats presented with acute onset of generalised tremors of variable severity. Initial treatment included toxin decontamination whenever possible, and control of neurological signs by administration of benzodiazepine and eventually a continuous rate infusion of propofol. Due to persisting clinical signs, a low-dose ILE therapy was additionally given. Discontinuation of treatment, once a resolution of neurological signs was achieved, ranged between two and nine hours from hospital admission. All the cats fully recovered and were discharged within 18–92 hours. No side effects were noticed and follow-up was normal. The authors report the use of a low-dose infusion of ILE as an adjunctive and safe treatment for the management of lipophilic intoxications in cats. mixed Marco Pelizzola, Clara Mattavelli, Roberta Troìa, Elsa Murgia, Massimo Giunti Marco Pelizzola, Clara Mattavelli, Roberta Troìa, Elsa Murgia, Massimo Giunti

The early diagnosis of acute leptospirosis is still a major challenge in dogs. The aim of this prospective study was to evaluate the suitability of two in-clinic tests detecting anti-leptospiral IgM and IgG antibodies in diagnosing canine leptospirosis. The performances of the two rapid tests were compared to the microscopic agglutination test (MAT) carried out on acute sera and to diagnostic criteria adopted in this study to confirm leptospirosis infection (MAT upon admission, convalescent MAT and quantitative real-time PCR on blood and/or urine). The dogs were enrolled on the basis of reported exposure to known risk factors and clinical presentation (acute kidney injury and/or systemic inflammatory response syndrome with multi-organ damage). Eighty-nine dogs included in the study were sub-grouped on the basis of the results of the diagnostic criteria adopted: (1) confirmed leptospirosis cases (42/89 dogs); (2) negative leptospirosis cases (36/89 dogs); and (3) unconfirmed leptospirosis cases (11/89 dogs). The results supported the usefulness of the two rapid diagnostic tests as a first in-clinic screening tool for suspected leptospirosis; positive results in the in-clinic tests in dogs with suggestive clinical and laboratory signs strongly indicated acute leptospirosis, while negative results required additional diagnostic investigation to exclude the infection. Confirmatory tests recommended for canine leptospirosis are still necessary in addition to the use of rapid in-clinic tests.

BACKGROUND The value of fractional excretion (FE) of electrolytes to characterize and prognosticate acute kidney injury (AKI) is poorly documented in dogs. OBJECTIVES To evaluate the diagnostic and prognostic roles of FE of electrolytes in dogs with AKI. ANIMALS Dogs (n = 135) with AKI treated with standard care (February 2014-December 2016). METHODS Prospective study. Clinical and laboratory variables including FE of electrolytes, were measured upon admission. Dogs were graded according to the AKI-IRIS guidelines and grouped according to AKI features (volume-responsive, VR-AKI; intrinsic, I-AKI) and outcome (survivors/non-survivors). Group comparison and regression analyses with hazard ratios (HR) evaluation for I-AKI and mortality were performed. P

Immature granulocytes (IG) are a marker of severe inflammatory states in human beings and animals, and have been linked to a diagnosis of sepsis and poor prognosis. The delta neutrophil index (DNI), automatically calculated by a haematological analyser, provides an estimate of circulating IG. In particular, an increased DNI value has been associated with the severity of sepsis, and mortality, in critically ill human beings. The aims of this study were to determine the DNI reference interval (RI) in healthy dogs, and to evaluate its diagnostic and prognostic significance in dogs with sepsis. A total of 118 dogs with sepsis undergoing a complete blood cell count (CBC) at the time of hospital admission were included retrospectively. Dogs with sepsis were compared to 20 dogs with primary immune-mediated haemolytic anaemia (IMHA) and 99 healthy controls. The DNI RI was set from 0 to 9.2%. The DNI was significantly higher in dogs with sepsis compared to dogs with IMHA and healthy dogs (P < 0.001), and significantly higher in dogs with septic shock compared to septic dogs without circulatory failure (P < 0.03). No differences were detected between survivors (78/118) and non-survivors (40/118). Septic dogs with a DNI above the RI had significantly higher frequencies of IG and toxic neutrophil changes on manual blood smear evaluation (P = 0.03 and P < 0.001, respectively). The DNI had a fair performance in identifying dogs with sepsis in this population and predicted septic shock. Larger prospective studies are needed to validate DNI measurement in dogs and to test its clinical utility.

The small, annual grass Brachypodium distachyon (L.) Beauv., a close relative of wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.), is a powerful model system for cereals and bioenergy grasses. Genome-wide association studies (GWAS) of natural variation can elucidate the genetic basis of complex traits but have been so far limited in B. distachyon by the lack of large numbers of well-characterized and sufficiently diverse accessions. Here, we report on genotyping-by-sequencing (GBS) of 84 B. distachyon, seven B. hybridum, and three B. stacei accessions with diverse geographic origins including Albania, Armenia, Georgia, Italy, Spain, and Turkey. Over 90,000 high-quality single-nucleotide polymorphisms (SNPs) distributed across the Bd21 reference genome were identified. Our results confirm the hybrid nature of the B. hybridum genome, which appears as a mosaic of B. distachyon-like and B. stacei-like sequences. Analysis of more than 50,000 SNPs for the B. distachyon accessions revealed three distinct, genetically defined populations. Surprisingly, these genomic profiles are associated with differences in flowering time rather than with broad geographic origin. High levels of differentiation in loci associated with floral development support the differences in flowering phenology between B. distachyon populations. Genome-wide association studies combining genotypic and phenotypic data also suggest the presence of one or more photoperiodism, circadian clock, and vernalization genes in loci associated with flowering time variation within B. distachyon populations. Our characterization elucidates genes underlying population differences, expands the germplasm resources available for Brachypodium, and illustrates the feasibility and limitations of GWAS in this model grass.