Statins Effects on Blood Clotting: A Review.

Statins are powerful lipid-lowering drugs that inhibit cholesterol biosynthesis via downregulation of hydroxymethylglutaryl coenzyme-A reductase, which are largely used in patients with or at risk of cardiovascular disease. Available data on thromboembolic disease include primary and secondary prevention as well as bleeding and mortality rates in statin users during anticoagulation for VTE. Experimental studies indicate that statins alter blood clotting at various levels. Statins produce anticoagulant effects via downregulation of tissue factor expression and enhanced endothelial thrombomodulin expression resulting in reduced thrombin generation. Statins impair fibrinogen cleavage and reduce thrombin generation. A reduction of factor V and factor XIII activation has been observed in patients treated with statins. It is postulated that the mechanisms involved are downregulation of factor V and activated factor V, modulation of the protein C pathway and alteration of the tissue factor pathway inhibitor. Clinical and experimental studies have shown that statins exert antiplatelet effects through early and delayed inhibition of platelet activation, adhesion and aggregation. It has been postulated that statin-induced anticoagulant effects can explain, at least partially, a reduction in primary and secondary VTE and death. Evidence supporting the use of statins for prevention of arterial thrombosis-related cardiovascular events is robust, but their role in VTE remains to be further elucidated. In this review, we present biological evidence and experimental data supporting the ability of statins to directly interfere with the clotting system.

Effects of Non-Ablative Solid-State Vaginal Laser (SSVL) for the Treatment of Vulvovaginal Atrophy in Breast Cancer Survivors after Adjuvant Aromatase Inhibitor Therapy: Preliminary Results.

BACKGROUND: One of the side effects of anti-estrogen treatments in breast cancer survivors (BCSs), especially with aromatase inhibitor (AI) treatment, is the frequent appearance of vulvo-vaginal atrophy (VVA). We aim to evaluate the efficacy, safety and feasibility of a new type of non-ablative Solid-State Vaginal Laser (SSVL) treatment in BCSs with VVA. METHODS: A total of 30 BCSs with a history of AI use and symptoms of VVA were treated with a non-ablative SSVL (LASEmaR 1500™-EUFOTON)in this non-randomized pilot study. The effects of the laser have been evaluated at baseline, 10 wk and 24 wk using a visual analogue scale (VAS), the Vaginal Health Index (VHI), the Vulvar Health Index (VuHI), the Female Sexual Function Index (FSFI), the EORTC QLQ-BR23, the Vaginal Maturation Index (VMI) and vaginal pH. RESULTS: At 10-week follow-up vs. baseline there were no statistically significant differences in FSFI, lubrication and EORTC QLQ-BR23. In all the subjective (dyspareunia, VHI, VuHI, FSFI, QLQ) and objective parameters (VMI and pH) there was a statistically significant improvement at the 6-month follow-up. Satisfaction was very high (4.7 out of 5), with 95.7% of patients being satisfied, more than or very satisfied. CONCLUSIONS: Preliminary results of SSVL treatment of VVA and dyspareunia in BCSs after AI treatment suggest clinical improvement, without relevant side effects and with a high degree of satisfaction.

Genitourinary Syndrome of Menopause in Breast Cancer Survivors: Current Perspectives on the Role of Laser Therapy.

Genitourinary syndrome of menopause (GSM) is a frequent consequence of iatrogenic menopause or anti-estrogenic adjuvant therapies in breast cancer survivors (BCSs). GSM may profoundly affect sexual health and quality of life, and a multidimensional unique model of care is needed to address the burden of this chronic heterogeneous condition. Severe symptoms may be insufficiently managed with non-hormonal traditional treatments, such as moisturizers and lubricants, recommended as the first-line approach by current guidelines, because concerns exist around the use of vaginal estrogens, particularly in women on aromatase inhibitors (AIs). Vaginal laser therapy has emerged as a promising alternative in women with GSM who are not suitable or do not respond to hormonal management, or are not willing to use pharmacological strategies. We aim to systematically review current evidence about vaginal laser efficacy and safety in BCSs and to highlight gaps in the literature. We analyzed results from 20 studies, including over 700 BCSs treated with either CO2 or erbium laser, with quite heterogeneous primary outcomes and duration of follow up (4 weeks-24 months). Although evidence for laser efficacy in BCSs comes mostly from single-arm prospective studies, with only one randomized double-blind sham-controlled trial for CO2 laser and one randomized comparative trial of erbium laser and hyaluronic acid, available data are reassuring in the short term and indicate effectiveness of both CO2 and erbium lasers on the most common GSM symptoms. However, further studies are mandatory to establish long-term efficacy and safety in menopausal women, including BCSs.

Altered profile of glycosylated proteins in serum samples obtained from patients with Hashimoto's thyroiditis following depletion of highly abundant proteins.

Objectives: Hashimoto's thyroiditis (HT) is one of the most common autoimmune disorders; however, its underlying pathological mechanisms remain unclear. Although aberrant glycosylation has been implicated in the N-glycome of immunoglobulin G (IgG), changes in serum proteins have not been comprehensively characterized. This study aimed to investigate glycosylation profiles in serum samples depleted of highly abundant proteins from patients with HT and propose the potential functions of glycoproteins for further studies on the pathological mechanisms of HT. Methods: A lectin microarray containing 70 lectins was used to detect and analyze glycosylation of serum proteins using serum samples (N=27 HT; N=26 healthy control [HC]) depleted of abundant proteins. Significant differences in glycosylation status between HT patients and the HC group were verified using lectin blot analysis. A lectin-based pull-down assay combined with mass spectrometry was used to investigate potential glycoproteins combined with differentially present lectins, and an enzyme-linked immunosorbent assay (ELISA) was used to identify the expression of targeted glycoproteins in 131 patients with papillary thyroid carcinoma (PTC), 131 patients with benign thyroid nodules (BTN) patients, 130 patients with HT, and 128 HCs. Results: Compared with the HC group, the majority of the lectin binding signals in HT group were weakened, while the Vicia villosa agglutinin (VVA) binding signal was increased. The difference in VVA binding signals verified by lectin blotting was consistent with the results of the lectin microarray. A total of 113 potential VVA-binding glycoproteins were identified by mass spectrometry and classified by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses. Using ELISA, we confirmed that lactoferrin (LTF) and mannan-binding lectin-associated serine protease 1 (MASP-1) levels were elevated in the serum of patients with HT and PTC. Conclusion: Following depletion of abundant proteins, remaining serum proteins in HT patients exhibited lower glycosylation levels than those observed in HCs. An increased level of potential VVA-binding glycoproteins may play an important role in HT development. LTF and MASP-1 expression was significantly higher in the serum of HT and PTC patients, providing novel insight into HT and PTC.

Therapeutic Choices for Genitourinary Syndrome of Menopause (GSM) in Breast Cancer Survivors: A Systematic Review and Update.

(1) Background: Genitourinary syndrome of menopause (GSM) is a medical condition that can affect breast cancer survivors (BCS). This is a complication that often can occur as a result of breast cancer treatment, causing symptoms such as vaginal dryness, itching, burning, dyspareunia, dysuria, pain, discomfort, and impairment of sexual function. BCS who experience these symptoms negatively impact multiple aspects of their quality of life to the point that some of them fail to complete adjuvant hormonal treatment; (2) Methods: In this systematic review of the literature, we have analyzed possible pharmacological and non-pharmacological treatments for GSM in BCS. We reviewed systemic hormone therapy, local hormone treatment with estrogens and androgens, the use of vaginal moisturizers and lubricants, ospemifene, and physical therapies such as radiofrequency, electroporation, and vaginal laser; (3) Results: The data available to date demonstrate that the aforementioned treatments are effective for the therapy of GSM and, in particular, vulvovaginal atrophy in BCS. Where possible, combination therapy often appears more useful than using a single line of treatment; (4) Conclusions: We analyzed the efficacy and safety data of each of these options for the treatment of GSM in BCS, emphasizing how often larger clinical trials with longer follow-ups are needed.

Spatiotemporal changes of tissue glycans depending on localization in cardiac aging.

Heart failure is caused by various factors, making the underlying pathogenic mechanisms difficult to identify. Since cardiovascular disease tends to worsen over time, early diagnosis is key for treatment. In addition, understanding the qualitative changes in the heart associated with aging, where information on the direct influences of aging on cardiovascular disease is limited, would also be useful for treatment and diagnosis. To fill these research gaps, the focus of our study was to detect the structural and functional molecular changes associated with the heart over time, with a focus on glycans, which reflect the type and state of cells. METHODS: We investigated glycan localization in the cardiac tissue of normal mice and their alterations during aging, using evanescent-field fluorescence-assisted lectin microarray, a technique based on lectin-glycan interaction, and lectin staining. RESULTS: The glycan profiles in the left ventricle showed differences between the luminal side (medial) and wall side (lateral) regions. The medial region was characterized by the presence of sialic acid residues. Moreover, age-related changes in glycan profiles were observed at a younger age in the medial region. The difference in the age-related decrease in the level of α-galactose stained with Griffonia simplicifolia lectin-IB4 in different regions of the left ventricle suggests spatiotemporal changes in the number of microvessels. CONCLUSIONS: The glycan profile, which retains diverse glycan structures, is supported by many cell populations, and maintains cardiac function. With further research, glycan localization and changes have the potential to be developed as a marker of the signs of heart failure.

Pharmacotherapy for female sexual dysfunctions (FSDs): what is on the market and where is this field heading?

INTRODUCTION: Female sexual dysfunctions (FSDs) are common in women of any age and have a huge impact on quality of life and relationships. They have a multifaceted etiology limiting the development of pharmacotherapies with a high rate of effectiveness. Safety issues are also a concern. AREAS COVERED: The authors report the most recent advances in pharmacotherapy for premenopausal and postmenopausal women with a main focus on hypoactive sexual desire disorders (HSDD) and associated sexual symptoms. Good levels of evidence have emerged for psychoactive agents, such as flibanserin and bremelanotide, as well as hormonal compounds (transdermal testosterone). The authors also report briefly on intravaginal DHEA (prasterone), local estrogen therapy (LET), and ospemifene to manage effectively vulvovaginal atrophy/genitourinary syndrome of menopause (VVA/GSM). In addition, they discuss promising therapeutic options highlighting the main reasons that hamper the availability of new labeled products. Finally, they include the importance of the multimodal approach to address FSDs. EXPERT OPINION: Approved pharmacotherapies for FSD are limited. Validated multidimensional instruments and adequate objective measures of physical and mental responses to sexual external and internal incentives are mandatory to identify women suitable to chronic or on-demand treatments and to assess their pattern of response in research and practice.

Pore-Forming Cardiotoxin VVA2 (Volvatoxin A2) Variant I82E/L86K Is an Atypical Duplex-Specific Nuclease.

VVA2 (volvatoxin A chain 2) is a cardiotoxic protein purified from Volvariella volvacea. Its biological activities include hemolysis, writhing reaction, neurotoxicity, and ventricular systolic arresting activity. The cytotoxicity of VVA2 was mainly considered due to its pore-forming activity. Here we report a novel biological activity of its variants VVA2 I82E/K86K as a duplex-specific nuclease. Recombinant VVA2 variant I82E/L86K (Re-VVA2 I82E/L86K), deprived of the oligomerization property, shows increased nuclease activity compared to VVA2. Re-VVA2 I82E/L86K converts supercoiled DNA (Replicative form I, RF I) into nicked form (RF II) and linear form (RF III) in the presence of Mg2+ or Mn2+. Besides plasmid DNA, it also exhibits nuclease activity on E. coli genomic DNA rather than ssDNA or RNA. Re-VVA2 I82E/L86K preferentially cleaves dG-dC-rich dsDNA regions and shows the best performance at pH 6-9 and 55 °C. Our structure-function study has revealed amino acid E111 may take an active part in nuclease activity through interacting with metal ions. Based on the sequences of its cleavage sites, a "double-hit" mechanism was thereby proposed. Given that Re-VVA2 I82E/L86K did not exhibit the conserved nuclease structure and sequence, it is considered an atypical duplex-specific nuclease.

Vasoactive Inotropic Score as a Prognostic Factor during (Cardio-) Respiratory ECMO.

The vasoactive inotropic score (VIS) is calculated as a weighted sum of all administered vasopressor and inotropic medications and quantifies the amount of pharmacological cardiovascular support in patients with the most severe combined cardiopulmonary failure supported with extracorporeal membrane oxygenation (ECMO). This study evaluated (1) whether VIS prior to the initiation of ECMO is an independent predictor of survival in these patients and (2) whether VIS might guide the selection of the appropriate extracorporeal cannulation modality (Veno-Venous 'V-V' or Veno-VenoArterial 'V-VA'). In this study, 39 V-VA and 182 V-V ECMO runs were retrospectively analyzed. VIS immediately prior to ECMO initiation (pre-ECMO) was 40 (10/113) in all patients, 30 (10/80) in patients with V-V ECMO and 207 (60/328) in patients with V-VA ECMO. Pre-ECMO VIS was an independent predictor of survival in univariate (AUC = 0.68, p = 0.001) and multi-variable analyses (p = 0.02). Pre-ECMO VIS was clearly associated with mortality (p = 0.001) in V-V ECMO group; however, V-VA ECMO disrupted this association (p = 0.18). Therefore, in conjunction with echocardiography, VIS might assist in selecting the appropriate ECMO cannulation strategy as patients with a pre-ECMO VIS ≥ 61.4 had significantly lower odds of survival compared to those with lower VIS.

Generation of an anticoagulant aptamer that targets factor V/Va and disrupts the FVa-membrane interaction in normal and COVID-19 patient samples.

Coagulation cofactors profoundly regulate hemostasis and are appealing targets for anticoagulants. However, targeting such proteins has been challenging because they lack an active site. To address this, we isolate an RNA aptamer termed T18.3 that binds to both factor V (FV) and FVa with nanomolar affinity and demonstrates clinically relevant anticoagulant activity in both plasma and whole blood. The aptamer also shows synergy with low molecular weight heparin and delivers potent anticoagulation in plasma collected from patients with coronavirus disease 2019 (COVID-19). Moreover, the aptamer's anticoagulant activity can be rapidly and efficiently reversed using protamine sulfate, which potentially allows fine-tuning of aptamer's activity post-administration. We further show that the aptamer achieves its anticoagulant activity by abrogating FV/FVa interactions with phospholipid membranes. Our success in generating an anticoagulant aptamer targeting FV/Va demonstrates the feasibility of using cofactor-binding aptamers as therapeutic protein inhibitors and reveals an unconventional working mechanism of an aptamer by interrupting protein-membrane interactions.

CO2-Laser therapy and Genitourinary Syndrome of Menopause: A Systematic Review and Meta-Analysis.

BACKGROUND: Genitourinary syndrome of menopause (GSM) is a widespread condition with a great impact on quality of life and self-image. AIM: We aimed to systematically review the current literature on CO2-Laser therapy efficacy for the treatment of GSM. METHODS: MEDLINE and Embase databases were systematically queried in December 2020 Studies included women with a diagnosis of Vulvo-Vaginal Atrophy (VVA) or GSM without an history of gynaecological and/or breast cancer, pelvic organ prolapse staged higher than 2, pelvic radiotherapy or Sjogren's Syndrome. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42021238121. OUTCOMES: Effects of CO2-Laser therapy on GSM symptoms assessed through subjective or objective efficacy measurement methods. RESULTS: A total of 803 articles were identified. Of these, 25 studies were included in this review for a total of 1,152 patients. All studies showed a significant reduction in VVA and/or GSM symptoms (dryness, dyspareunia, itching, burning, dysuria). The pooled mean differences for the symptoms were: dryness -5.15 (95% CI:-5.72,-4.58; P < .001; I2:62%; n = 296), dyspareunia -5.27 (95% CI:-5.93,-4.62; P < .001; I2:68%; n = 296), itching -2.75 (95% CI:-4.0,-1.51; P < .001; I2:93%; n = 281), burning -2.66 (95% CI:-3.75, -1.57; P < .001; I2:86%; n = 296) and dysuria -2.14 (95% CI:-3.41,-0.87; P < .001; I2:95%; n = 281). FSFI, WHIS and VMV scores also improved significantly. The pooled mean differences for these scores were: FSFI 10.8 (95% CI:8.41,13.37; P < .001; I2:84%; n = 273), WHIS 8.29 (95% CI:6.16,10.42; P < .001; I2:95%; n = 262) and VMV 30.4 (95% CI:22.38,38.55; P < .001; I2:24%; n = 68). CO2-Laser application showed a beneficial safety profile and no major adverse events were reported. CLINICAL IMPLICATIONS: Vaginal laser treatment resulted in both a statistically and clinically significant improvement in GSM symptoms. FSFI improved significantly in all 8 included studies but it reached a clinically relevant level only in 2 of them. STRENGTHS & LIMITATIONS: The strength of the current meta-analysis is the comprehensive literature search. We reported data from a high number of patients (1,152) and high number of laser applications (more than 3,800). The main limitations are related to the high heterogeneity of the included studies investigating laser effects. Moreover, most of them are single center and nonrandomized studies. CONCLUSION: The data suggest that CO2-Laser is a safe energy-based therapeutic option for the management of VVA and/or GSM symptoms in postmenopausal women; however, the quality of the body of evidence is "very low" or "low". Filippini M, Porcari I, Ruffolo AF, et al., CO2-Laser therapy and Genitourinary Syndrome of Menopause: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:452-470.

Sexuality, pelvic floor/vaginal health and contraception at menopause.

A multitude of biopsychosocial factors influences sexual health at midlife, a common concern in daily practice along with vaginal and pelvic health. Health-care providers (HCPs) need to be proactive in dealing with possible symptoms because in most cases early management prevents distress and improves quality of life. Female sexual dysfunctions (FSDs) may have a complex etiology but sexual history is not difficult implementing basic knowledge of risk factors and some skills helping women to cope with hormonal and age-related changes. This work summarizes key points to approach sexual symptoms in midlife women, providing principles to diagnose and manage hypoactive sexual desire disorder (HSDD) and genitourinary syndrome of menopause (GSM)/vulvovaginal atrophy (VVA), as well as manage contraceptive needs.

The role of hormone therapy in urogenital health after menopause.

Menopause represents an endocrine challenge to urogenital health, as oestrogens deprivation and androgens decline significantly contributes to age-related involution of vulvovaginal tissues and lower urinary tract. Genitourinary syndrome of menopause (GSM) is a clinical entity including the chronic and progressive condition of vulvovaginal atrophy (VVA) and encompassing both anatomical and functional consequences of menopause. The term GSM describes genital, sexual and urinary symptoms with a detrimental impact on quality of life (QOL). Several treatment options are available, but many barriers are still present to adequately diagnose and treat GSM. This review aims to present current evidences about epidemiology, aetiology, diagnosis and treatment of GSM, with a focus on prescription medications [low-dose local oestrogen therapy (LET), prasterone (DHEA) and the SERM ospemifene] for urogenital symptoms in healthy postmenopausal women and in special populations, including women with premature ovarian insufficiency (POI) and breast cancer survivors (BCS).

Treatment of Vulvovaginal Atrophy with Fractional CO2 Laser: Evaluating Real-World Data.

Objective: We aimed to evaluate real-world data for the use of fractional CO2 laser therapy for treating symptoms of vulvovaginal atrophy (VVA). Background: VVA is widespread and can reduce the patients' quality of life. There is a lack of data regarding its therapy with laser, especially for daily practice (i.e., real-world data). Methods: Thirty-six patients were treated in a single medical center. They consisted of pre- and postmenopausal women and received three fractional CO2 laser therapy treatments with 3-6 weeks between each treatment. Each patient financed the treatment privately. The symptoms pain, pruritus, dyspareunia, burning, dryness, and dysuria were recorded with a visual analog scale (1-10) before the first, second, and third laser treatment. The data were examined retrospectively. Results: Pain was reduced from a mean of 2.5 points (minimum 0, maximum 9 points) to 1.1 (minimum 0, maximum 8 points) before the third laser treatment. Pruritus showed a mean score of 3.8 (minimum 0, maximum 10 points). This decreased to 1.4 (minimum 0, maximum 8 points). Dyspareunia scored a mean of 6.8 (minimum 0, maximum 10 points). After two laser therapies, the score was 3.3 (minimum 0, maximum 8 points). Burning showed 4.2 points (minimum 0, maximum 10 points). Having experienced two laser therapy sessions, the patients scored 1.5 (minimum 0, maximum 9 points) points. The severity of dryness dropped from 6.5 (minimum 0, maximum 10 points) to 3.3 (minimum 0, maximum 9 points). Dysuria was stated with 1.8 points (minimum 0, maximum 10 points) before the first and 0.5 points (minimum 0, maximum 6 points) before the third laser therapy. All changes showed statistical significance (p < 0.002). Conclusions: This real-world data propose fractional CO2 laser to reduce VVA-associated genital discomfort, thus being a valuable therapy option for pre- and postmenopausal women.

Vascular access in ECMO.

In critically ill patients, deserving extracorporeal membrane oxygenation (ECMO), choosing the right pattern of cannulation such as veno-venous (VV), veno-arterial (VA), veno-veno-arterial (VVA), and central; selecting the appropriate size cannulae; and good cannulation techniques are all pre-requisites for the successful outcome of ECMO. We are describing the selection criteria for choosing appropriate size cannulae, cannulation configurations, available cannulae, and possible complications. A brief note on anticoagulation was added.

The therapeutic effect of dehydroepiandrosterone (DHEA) on vulvovaginal atrophy.

Vulvovaginal atrophy (VVA) is a chronic disease that mostly occurs in postmenopausal women. After menopause, insufficient sex hormones affect the anatomy of the vagina and cause drastic physiological changes. The main histopathological studies of VVA show that postmenopausal estrogen deficiency can lead to the increase of intermediate/parabasal cells, resulting in the loss of lactobacillus, elasticity and lubricity, vaginal epithelial atrophy, pain, dryness. Although the role of estrogen hormones in the treatment of VVA has always been in the past, it is now widely accepted that it also depends on androgens. Estrogen drugs have many side effects. So, Dehydroepiandrosterone（DHEA）is promising for the treatment of VVA, especially when women with contraindications to estrogen have symptoms. This review is expected to understand the latest developments in VVA and the efficacy of DHEA.

Pathological, molecular and phylogenic study of fowlpox virus in domesticated chickens of Tikrit City, Iraq / Estudo patológico, molecular e filogenético do vírus da varíola aviária em frangos de corte domesticados da cidade de Tikrit, Iraque

Fowlpox virus (FPV) is one of the viruses affecting chickens worldwide, causing pathological and economic losses in the poultry industry. Viral lesions are easily recognizable by the eye and usually appear in the featherless areas, especially the head. Moreover, the virus could lead to blindness and mortality in some cases. This study diagnosed the suspected fowlpox cases, identified and classified the causative agent. We also analyzed the differences and similarities of closely related viruses at the neighboring and regional countries. Fifty samples were collected from three locations of Tikrit city from the domesticated chickens, which showed cutaneous lesions. Virus DNA was extracted directly from tissue samples before the nested PCR technique was performed. The virion core protein (P4b) gene is partially sequenced and analyzed with routine histological sectioning. Results showed that the virus causes pock lesions of dermal hyperplasia and hyperkeratosis. Hyperplasia and congestion of the chorioallantoic membrane were also recorded. The study also showed that the DNA of FPV could be extracted directly from animal tissue without further purification. The sequence analysis showed that the FPV was confirmed in all samples clustered in clade A identical with Iranian and Egyptian isolates. In conclusion, this study approved that the virus belongs to the classical dermal type of poxviruses and the short genetic distances between viruses related to closely neighboring countries. We also concluded that the conservative P4b gene included mutation sites that make this gene practical for diagnosing the virus and phylogenetic analysis.(AU)

O vírus da varíola aviária (VVA) é um dos vírus que acometem os frangos de corte em todo o mundo, causando perdas patológicas e econômicas na indústria aviária. As lesões causadas pelo vírus são facilmente reconhecidas pela observação visual e usualmente aparecem nas áreas do corpo das aves livres de penas, especialmente na cabeça. Além disso, em alguns casos a doença pode provocar a cegueira e a mortalidade de animais acometidos. O presente trabalho foi delineado para diagnosticar casos suspeitos de varíola aviária, identificar o agente causal e classificá-lo. Adicionalmente foram analisadas diferenças e similaridades com outros vírus estreitamente relacionados em localidades vizinhas e regionais. Cinquenta amostras foram colhidas em três localidades da cidade de Tikrit de frangos de corte, domesticados, que apresentavam lesões cutâneas. O DNA do vírus foi extraído diretamente das amostras de tecidos antes que a técnica de PCR fosse realizada. As proteínas do core do vírus, gene (P4b), foram parcialmente sequenciadas de analisadas em secções da rotina histológica. Os resultados obtidos revelaram que o vírus causa lesões variólicas com hiperplasia dermal e hiperqueratose. A hiperplasia e a congestão da membrana corioalantóica também foram registradas. O estudo também revelou que o DNA do VVA pode ser extraído diretamente de tecidos animais sem a realização de uma pré-purificação. A análise sequencial revelou que o VVA foi confirmado em todas as amostras agrupando-se em uma classe A, idêntica com isolados iranianos e egípcios. A conclusão obtida foi que o presente trabalho confirmou que o vírus pertence ao tipo dérmico clássico dos poxvirus e que as curtas distâncias genéticas entre os vírus relacionados são encontrados em países vizinhos. Também foi concluído que o gene conservador P4b inclui pontos de mutação que o tornam um gene prático para diagnosticar o vírus em análises filogenéticas.(AU)

No increase in incidence or risk of recurrence of breast cancer in ospemifene-treated patients with vulvovaginal atrophy (VVA).

OBJECTIVE: To estimate the incidence and recurrence of breast cancer (BC) in patients with vulvovaginal atrophy (VVA) treated with ospemifene and matched untreated VVA patients using real-world data. STUDY DESIGN: Retrospective matched cohort study. MAIN OUTCOME MEASURES: VVA patients were identified from the 2011-2018 US MarketScan® insurance claims database. For incidence, ospemifene-treated VVA patients without evidence of BC prior to index treatment were matched to two untreated VVA controls similarly without history of BC on age, index VVA year, geographic region, Charlson Comorbidity categories, and follow-up time. BC after the index treatment was identified by BC diagnosis codes, mastectomy, chemotherapy, or radiation procedure. Incidence rate, rate ratio (RR) and their 95 % confidence intervals (CI) were calculated. The process was repeated to estimate BC recurrence in patients with a history of BC in 1:1, 1:2 and 1:3 matches. RESULTS: 1728 ospemifene users and 3456 untreated patients met the inclusion and matching criteria for assessing incidence. The average number of days for which ospemifene was supplied was 314 (standard deviation [SD] = 340). Average follow-up time from index treatment was 937 days (SD = 392) for treated patients and 915 days (SD = 396) for controls. BC incidence rates per 1000 person-years was 2.03 (95 % CI: 1.06-3.91) for treated patients and 3.53 (95 % CI: 2.49-4.99) for controls (RR = 0.58, 95 % CI: 0.28-1.21). No difference in recurrence was observed between ospemifene-treated and matched untreated patients. Ten (32.3 %) treated vs. 25 (40.3 %) controls in the 1:2 matched analysis had a recurrence. CONCLUSION: No differences were observed in the BC incidence and recurrence rates in ospemifene users compared with matched controls.

Effect of Vitamin D Supplement on Vulvovaginal Atrophy of the Menopause.

The effects of oral vitamin D supplements on vaginal health in postmenopausal women with vulvovaginal atrophy (VVA) was evaluated. A double-blinded, randomized placebo-controlled trial was conducted for 12 weeks to investigate changes on vaginal maturation index (VMI), vaginal pH, and the visual analog scale (VAS) of VVA symptoms. The vitamin D group received oral ergocalciferol, at 40,000 IU per week, while the placebo group received an identical placebo capsule. Eighty postmenopausal women were enrolled. There were no significant differences in baseline characteristics between both groups. In an intention-to-treat analysis, VMI, vaginal pH, and VAS of VVA symptoms showed no significant differences between both groups at the six and 12 weeks. However, the mean difference of VMI in the vitamin D group between baseline and at six weeks showed significant improvement (5.5 + 16.27, p <0.05). Moreover, the mean vaginal pH and VAS of VVA patients in the vitamin D group were significantly improved at both six and 12 weeks compared to baseline. The oral vitamin D supplementation for 12 weeks potentially improves vaginal health outcomes in postmenopausal women with VVA symptoms, demonstrated by the improved mean VMI, vaginal pH, and VAS at six and 12 weeks between baseline, however, no significant differences were observed from the placebo treatment.

Carbon dioxide laser treatment for vulvovaginal atrophy in women treated for breast cancer: Preliminary results of the feasibility EPIONE trial.

BACKGROUND AND OBJECTIVE: Quality of life preservation after anti-cancer therapy is a major challenge for breast cancer survivors. Approximately 42-70% of patients who receive systemic therapy for breast cancer, including endocrine therapy, will develop vulvovaginal atrophy (VVA). For these patients, the commonly proposed gel-based treatments for topical applications are restrictive. Recently, innovative, non-hormonal therapeutic approaches, such as laser therapy, have emerged. The purpose of this feasibility study is to investigate the safety and efficacy of CO2 laser therapy in women with a history of breast cancer. MATERIAL AND METHODS: This prospective monocentric study included 20 patients with vulvovaginal atrophy who were treated at Henri Mondor University Hospital between 2017 and 2018. We included patients with a vaginal health index (VHI) score<15 and a contraindication for hormone administration due to a history of breast cancer. Two carbon dioxide laser sessions were used. The treatment was delivered using the following settings: vaginal tightening, FinePulse (pulse width 0.9ms), and energy density of 11.5J/cm2 that allows coverage of 70% of the targeted vaginal area to be treated. All patients had their follow-up visit at one (M1), three (M3), and six (M6) months after the first treatment to evaluate efficacy of the treatment on vulvovaginal atrophy. Vaginal health index score and female sexual distress (FSD) score were used to assess treatment efficacy and its impact on sexual quality of life. A score≥11 was associated with sexual dysfunction. The vaginal health index and female sexual distress scores were evaluated at baseline, M1, M3, and M6 of follow-up. RESULTS: The mean age of the patients was 56.1±8.8 years (range, 27-69 years). Seventeen of the 20 patients had experienced menopause (mean menopausal age, 51.25±1.5 years). At inclusion, the mean vaginal health index and the female sexual distress scores were 10.58±1.71 and 21.36±15.10, respectively. Fourteen out of 20 patients (70%) had FSD scores≥11 at the baseline. At M1, the mean vaginal health index score increased significantly to 13.42±2.3 (P=0.03), which represented an improvement of 21% from the baseline. A persistent and significant improvement in the vaginal health index score was observed at M6, with the score increasing to 16.75±4.23 post-treatment (P<0.0001), representing a 34% improvement from the mean baseline score. The mean female sexual distress at M1 was 19.83±13.57, representing a 7% decrease compared to the baseline scores (P<0.01). At M3, the female sexual distress significantly decreased to 13.88±15.58, representing an improvement of 35% (P=0.006). It increased to 10.35±14.7 at M6, representing an improvement of 52% (P=0.001). At M3, 35% of the patients had a female sexual distress score>11, and at M6, only 15% had a female sexual distress score>11. No side effects were reported during follow-up. CONCLUSION: This pilot feasibility study showed that carbon dioxide laser treatment appears to be an effective and safe method to improve the trophicity and decrease vaginal mucosal dryness in women with vulvovaginal atrophy that developed after systemic breast cancer therapy.