association of a large vulvar tumor in a in a young premenopausal woman with recurrent pseudoangiomatous stromal hyperplasia of the breasts

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Preventing Persistence of HPV Infection with Natural Molecules

Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination is the primary preventive strategy for HPV infections, but vaccines do not cover all types of HPV strains. Scientific research has uncovered the beneficial role of some natural supplements in preventing persistent HPV infections or treating HPV-related lesions. We review the current insight into the roles of natural molecules in HPV infection with a special focus on epigallocatechin gallate (EGCG), folic acid, vitamin B12, and hyaluronic acid (HA). Specifically, EGCG from green tea extracts plays a critical role in suppressing HPV oncogenes and oncoproteins (E6/E7), which are responsible for HPV oncogenic activity and cancer development. Folic acid and vitamin B12 are essential vitamins for multiple functions in the body, and accumulating evidence suggests their importance in maintaining a high degree of methylation of the HPV genome, thus decreasing the likelihood of causing malignant lesions. HA, due to its re-epithelizing property, may prevent HPV virus entry in damaged mucosa and epithelia. Thereby, based on these premises, the combination of EGCG, folic acid, vitamin B12, and HA may be a very promising therapeutic approach to prevent HPV persistence

Hysteroscopic and ultrasound evaluation of a novel degradable polymer film for the prevention of intrauterine adhesion formation after hysteroscopic surgery

•Womed Leaf is a degradable polymer film barrier for the prevention of intrauterine adhesions.•We captured a set of images for the first time that illustrates the behavior of DPF after insertion.•None of our participants reported adverse events in relation to Womed Leaf use.•Six weeks post hysteroscopic surgery and Womed Leaf insertion no film or synechiae were present. To collect information on the application and behavior of a novel degradable polymeric film (DPF) developed to prevent intra-uterine adhesions (IUAs) after hysteroscopic surgery. A prospective observational study conducted in a university hospital in Naples, Italy. Women undergoing hysteroscopic myomectomy, metroplasty or adhesiolysis, were eligible for the study. Women had their uterine cavity assessed by transvaginal ultrasound scan before their hysteroscopic surgery, which was followed by the DPF insertion. Ultrasonographic and hysteroscopic assessments were undertaken immediately after insertion then at 2 h, 2–5 days, and 6 weeks postoperative. The main outcome of interest was to assess the behavior of the DPF, from insertion to degradation, by ultrasound and hysteroscopy. Other outcomes included ease of DPF insertion, any patient reported adverse events and the presence of IUAs at 6 weeks. A total of 15 patients were enrolled into the study. The DPF insertion was reported to be very easy in almost all the cases and was visualized immediately and 2 h after insertion in all patients. At the 2–5 day follow-up 5 and 2 of the 15 participants still had the entire or partially hydrolyzed film respectively. By 6 weeks there was no evidence of the DPF in all women. No adverse events were reported at the time of insertion or follow-up. None of the study participants had IUAs at the 6-week assessment. According to this pilot study, the solid degradable polymer film, Womed Leaf, is a promising, easy to apply and well tolerated novel option for the prevention of intrauterine adhesion formation after hysteroscopic surgery

Evaluation and treatment of the infertile women with Asherman syndrome: an updated review focusing on the role of hysteroscopy

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Evaluation and treatment of infertile women with Asherman syndrome: an updated review focusing on the role of hysteroscopy

Asherman syndrome is a rare acquired clinical condition resulting in the obliteration of the uterine cavity causedby the presence of partial or complete fibrous intrauterine adhesions involving at least two-thirds of the uterine cavity potentially obstructing the internal cervical orifice. Common reported symptoms of the disease are alterations of the menstrual pattern with decreased menstrual bleeding leading up to amenorrhoea and infertility. Hysteroscopy is currently considered the gold standard diagnostic and therapeutic approach for patients with intrauterine adhesions. An integrated approach, including preoperative, intraoperative and postoperative therapeutic measures, however, are warranted owing to the complexity of the syndrome. This review aims to summarize the most recent evidence on the recommended preoperative, intraoperative and postoperative procedures to restore the uterine cavity and a functional endometrium, as well as on the concomitant use of adjuvant therapies to achieve optimal fertility outcomes

Abnormal Uterine Bleeding in Perimenopausal Women: The Role of Hysteroscopy and Its Impact on Quality of Life and Sexuality

Abnormal uterine bleeding (AUB) is a frequent symptom in perimenopausal women. It is defined as uterine bleeding in which the duration, frequency, or amount of bleeding is considered excessive and negatively affects the woman’s quality of life (QoL) and psychological well-being. In cases of structural uterine pathology, hysterectomy (usually performed via a minimally invasive approach) offers definitive symptom relief and is associated with long-lasting improvement of QoL and sexuality. However, over the past 30 years, uterus-preserving treatments have been introduced as alternatives to hysterectomy. Hysteroscopic polypectomy, myomectomy, or endometrial resec-tion/endometrial ablation are minimally invasive techniques that can be used as an alternative to hysterectomy to treat AUB due to benign conditions. Although associated with high patient satisfaction and short-term improvement in their QoL, hysteroscopic treatments do not eliminate the risk of AUB recurrence or the need for further intervention. Therefore, considering the impact of different treatment options on QoL and sexuality during preoperative shared decision making could help identify the most appropriate and personalized treatment options for perimenopausal women suffering from AUB

Hysteroscopy in the management of endometrial hyperplasia and cancer in reproductive aged women: new developments and current perspectives

Over the last twenty years, the incidence of early endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) among women of reproductive age is increasing rapidly, likely due to a combination of factors including increased prevalence of obesity and delayed of childbirths. Regarding preoperative diagnosis of endometrial neoplasia, it is still debated which is the most accurate and reliable method to obtain endometrial histopathological samples with fractional dilatation and curettage (D&C) having been considered, for a long time, as the method of choice. Nowadays, the advent of in-office endometrial biopsy with or without hysteroscopy has radically changed the approach, giving the opportunity to perform the endometrial biopsy under direct visualization. However, the lack of agreement about its diagnostic accuracy is still relevant. Since a significant number of women with AEH and/or EC are of childbearing age, a fertility-sparing diagnostic and therapeutic approach should be considered in all cases. The feasibility, safety and efficacy of fertility-sparing strategies involving hysteroscopic focal resections in conjunction with hormonal therapies have been evaluated and beneficial effects have been confirmed in several studies and one meta-analysis. Both local and systemic administration of hormonal therapies are currently used. Oral progestin, including medroxyprogesterone acetate (MPA) and megestrol acetate, are the most commonly used therapies. Nowadays, new therapeutic approaches, such as levonorgestrel intrauterine systems (LNG-IUS), gonadotropin-releasing hormone (GnRH) agonists, combined megestrol acetate and metformin, and other combinations of therapies are also used as first line therapies or after the hysteroscopic resection of the lesion. However, it is still unclear which approach provides higher clinical response with lower relapse rate, in addition to preserving fertility in women desiring to conceive. The aim of this narrative review is to summarize the available evidence regarding the evaluation and management with fertility-sparing treatments options of women with AEC and EC

Endometrial Biopsy: Indications, Techniques and Recommendations. An Evidence-Based Guideline for Clinical Practice

This practice guideline provides updated evidence for the gynecologist who performs endometrial biopsy (EB) in gynecologic clinical practice. An international committee of gynecology experts developed the recommendations according to AGREE Reporting Guideline. An adequate tissue sampling is mandatory when performing an EB. Blind methods should not be first choice in patients with suspected endometrial malignancy. Hysteroscopy is the targeted-biopsy method with highest diagnostic accuracy and cost-effectiveness. Blind suction techniques are not reliable for the diagnosis of endometrial polyps. In low resources settings, and in absence of the capacity to perform office hysteroscopy, blind techniques could be used for EB. Hysteroscopic punch biopsy allows to collect only limited amount of endometrial tissue. grasp biopsy technique should be considered first choice in reproductive aged women, bipolar electrode chip biopsy should be preferred with hypotrophic or atrophic endometrium. EB is required for the final diagnosis of chronic endometritis. There is no consensus regarding which endometrial thickness cut-off should be used for recommending EB in asymptomatic postmenopausal women. EB should be offered to young women with abnormal uterine bleeding and risk factors for endometrial carcinoma. Endometrial pathology should be excluded with EB in nonobese women with unopposed hyperestrogenism. Hysteroscopy with EB is useful in patients with abnormal bleeding even without sonographic evidence of pathology. EB has high sensitivity for detecting intrauterine pathologies. In postmenopausal women with uterine bleeding, EB is recommended. Women with sonographic endometrial thickness > 4mm using tamoxifen should undergo hysteroscopic EB

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic