The personal experience of female obstetricians and gynaecologists with contraceptive use influences the guidance and prescription of contraceptive methods: a web-survey.

OBJECTIVE: To evaluate the influence of the personal experience of female obstetricians and gynaecologists (Obst/Gyns) who utilise contraceptive methods on the provision of these methods. METHODS: An anonymous online web-based survey was carried out with female Obst/Gyns. The instrument contained questions about their current and previous contraceptive methods use, factors that influenced the choice and satisfaction with the ongoing method, as well as the occurrence of adverse events. They were also asked whether the experience of any adverse events influenced their decision in prescribing any particular contraceptive method. RESULTS: 476/9000 (5.3%) female Obst/Gyns answered the survey. The most common contraceptive in use was the 52-mg levonorgestrel-intrauterine device (52-mg LNG-IUD) (34%), followed by non-Long-Acting Reversible Contraception hormonal methods (21.2%). More than half of the respondents (57.6%) reported having some adverse effects and 18.7% reported that the personal experience of an adverse effect with the use of a contraceptive method influenced the prescription of that method. CONCLUSION: Half of female Obst/Gyns encountered adverse events linked to contraceptive usage. Additionally, almost one-fifth believe that their own encounter with adverse effects from a contraceptive method impacts their decision to prescribe the same method.

Almost one-fifth of the female obstetrics and gynaecologists that answered the online survey reported that the personal experience of an adverse effect with the use of a contraceptive method influenced the prescription of that method.

Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations.

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

The HOPE study: evaluating the impact of an online educational resource for heavy menstrual bleeding on the patient-physician dynamic.

The Heavy menstrual bleeding: Evidence-based Learning for best Practice (HELP) Group developed an educational website about heavy menstrual bleeding (HMB). The "HMB improving Outcomes with Patient counseling and Education" (HOPE) project examined the website's impact on women's knowledge, confidence, and consultations with healthcare providers (HCPs). HOPE was a quantitative online survey of gynecologists and women with HMB in Brazil. After an initial consultation, patients had unlimited access to the website and completed a survey. HCPs also completed a survey about the sconsultation. After a second consultation, HCPs and patients completed another survey. HCP surveys assessed their perception of patients' awareness, understanding, and willingness to discuss HMB. Patient surveys assessed their knowledge, experience, and confidence in discussing HMB. Forty HCPs recruited 400 women with HMB. Based on HCP perceptions at the first consultation, 18 percent of patients had "good knowledge" or "very good knowledge" of HMB, increasing to 69 percent after patients had visited the website. Before and after visiting the website, 34 percent and 69 percent of patients, respectively, regarded their HMB knowledge as "goo.d" Additionally, 17 percent of women reported their anxiety as "highest" during the first consultation; this decreased to 7 percent during the second consultation. After visiting the HELP website, patients' knowledge of HMB improved and they were less anxious.

Provision of contraceptives by Brazilian general gynaecologists: a nationwide online survey.

OBJECTIVE: To assess the provision of contraceptives by Brazilian obstetricians and gynaecologists (Obst/Gyns) during medical consultation and associated factors. METHODS: An anonymous online survey was conducted with Obst/Gyns regarding age, gender, training, method counselling about and provision of long-acting reversible contraception (LARC). RESULTS: Of 16,000 Obst/Gyns, 610 (3.8%) answered the survey. After multiple regression analysis, female Obst/Gyns (reference) (OR male was 0.53 [95%CI 0.28-0.98], p = 0.044) and Obst/Gyns aged between 20 and 39 were more likely to provide an IUD. For hormonal-IUDs, Obst/Gyns who had had theoretical training in hormonal-IUD insertion (reference no training) (OR = 2.13 [95%CI 1.14-3.99], p = 0.018), those who work in a private facility or public hospital, and those that allowed more time during consultations (reference) (OR short time = 0.33 [95%CI 0.17-0.63], p < 0.001) were more likely to provide them. Obst/Gyns who were hands-on trained were more likely to provide subdermal implant (OR = 2.04 [95%CI 1.45-2.87], p < 0.001). CONCLUSIONS: There is a gap between theoretical and practical training received by this cohort of Obst/Gyns regarding LARCs, mainly contraceptive implants and hormonal-IUDs. The identification of barriers to offering contraceptives is essential to providing client-centred contraceptive care.

There is a gap between the theoretical and practical training received by Brazil-based Obst/Gyns regarding LARC methods, mainly subdermal implants and hormonal-IUDs. The identification of barriers is essential to providing client-centred contraceptive care.

Extremely brief mindfulness interventions for women undergoing breast biopsies: a randomized controlled trial.

PURPOSE: Mindfulness-based programs can reduce stress and help practitioners to have positive attitudes in their daily lives. This randomized controlled trial evaluated the impact of brief Mindfulness interventions on quantitative and qualitative stress parameters in patients undergoing imaging-guided breast biopsies. METHODS: Eighty-two women undergoing percutaneous imaging-guided breast biopsy were randomized into two groups: MBI group or standard care group. One week before the biopsy procedure, on the waiting room and during the biopsy procedure, the MBI group was exposed to mindfulness techniques and the standard care group received supportive dialogue from the biopsy team. Participants completed questionnaires measuring depression, anxiety and stress, demographics, and medical history, besides evaluating their pain experience through a visual analogue scale for pain and had their systolic and diastolic blood pressure, initial and final temperate, heart rate, oxygen saturation, and salivary cortisol measured. RESULTS: Participation in the mindfulness intervention group was associated with reduced levels of perceived stress, blood pressure, heart rate, and oxygen saturation compared to participation in the standard care group (P values < 0.05). No difference was observed regarding salivary cortisol levels, peripheral temperature, and pain perception between the two studied groups. CONCLUSION: Results indicate that an extremely brief mindfulness intervention is a feasible intervention, suggesting that Mindfulness-based programs may be beneficial to reduce discomfort in acutely stressful settings.

Barriers and myths that limit the use of intrauterine contraception in nulliparous women: a survey of Brazilian gynaecologists.

OBJECTIVE: To understand the extent to which barriers and misperceptions about intrauterine contraception (IUC) remain among Brazilian gynaecologists, particularly for nulliparous women. METHODS: An online survey was developed to assess Brazilian gynaecologists' knowledge and attitudes towards IUC. Data collected included demographic and professional data, main barriers when considering IUC for women in general and/or nulliparous women, attitudes towards inclusion of IUC in contraceptive counselling, and opinions on what could increase IUC prescription for nulliparous women. A question regarding knowledge about WHO medical eligibility criteria (WHO MEC) was also included in the survey. RESULTS: 101 gynaecologists completed the survey. The insertion rate in nulliparous women was 79.2%. Brazilian gynaecologists were more likely to consider IUC in counselling or provide it on request for parous than for nulliparous women (p<0.05) and perceived more complications in nulliparous women. 74.2% of gynaecologists recognised a higher risk of pelvic inflammatory disease (PID)/infertility associated with IUC use in nulliparous women than in parous women. Difficult and painful insertion were also relevant for 83.2% and 77.3% of the gynaecologists, respectively. Respondents showed a high level of awareness of the WHO MEC classification. CONCLUSIONS: The three most commonly reported barriers to considering IUC as a contraceptive option for nulliparous woman were concerns about PID and difficult or painful insertion. The challenge is to ensure that gynaecologists understand the evidence and do not disregard IUC as a potential option for nulliparous women.

Non-hormonal and hormonal intrauterine contraception: survey of patients' perceptions in four Latin American countries.

OBJECTIVES: This study sought to understand women's perceived barriers to the use of hormonal and non-hormonal intrauterine contraception in Latin America. METHODS: We developed an online survey for women in Argentina, Brazil, Colombia and Mexico who were seeking contraception. The questions aimed at evaluating patient awareness of negative stories and statements, as well as perceived barriers to the copper intrauterine device (IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS). RESULTS: The survey was mailed to 2300 women. A total of 1953 responses were received from Argentina (n = 465), Brazil (n = 380), Colombia (n = 613) and Mexico (n = 495). More women reported having heard negative stories about the copper IUD than about the LNG-IUS. More women believed that the copper IUD, rather than the LNG-IUS, was suitable only for those who had already had children. More women believed that weight gain (14.3% vs. 38.2%; p < 0.001), mood swings (14.1% vs. 38.7%; p < 0.001) and infertility (16.3% vs. 19.9%; p = 0.016) were possible side effects of the LNG-IUS. By contrast, more women believed that abortion (36% vs. 22.7%; p < 0.001), pelvic infections (42.1% vs. 15.7%; p < 0.001) and ectopic pregnancy (43.5% vs 23.5%; p < 0.001) were side effects more associated with the copper IUD. More believed the copper IUD was associated with less pain during placement and removal compared with the LNG-IUS (42.8% vs. 31.2%; p < 0.001). The perception of increased risk of contracting a sexual transmitted disease did not differ between the methods (IUD vs. LNG-IUS, 21.7% vs. 20.3%; p = 0.388). CONCLUSIONS: Respondents to a web-based survey in four Latin American countries have misperceptions regarding the adverse effects and risks of intrauterine contraception, which may hamper the use of these safe and efficient contraceptive methods. Education about the true risks and benefits involved is fundamental to improving patient acceptance and compliance as well as reducing unplanned pregnancies and unsafe abortions.

Epigenetic and expression analysis of TRAIL-R2 and BCL2: on the TRAIL to knowledge of apoptosis in ovarian tumors.

OBJECTIVE: This study assesses TRAIL-R2 (TNF-related apoptosis-inducing ligand receptor 2) and BCL2 (B cell CLL/lymphoma 2) expression as well as CpG island methylation within the TRAIL-R2 promoter in ovarian serous tumors and primary and metastatic serous EOC (epithelial ovarian cancer). METHODS: RNA and DNA were obtained from women with normal ovarian tissues (n = 18), ovarian serous cystadenoma tumors (n = 11) and serous EOC (n = 16) using Trizol®. Quantitative PCR was performed to quantify the relative levels of TRAIL-R2 and BCL2. The methylation frequency of the TRAIL-R3 promoter was assessed using a methylation-specific PCR assay after DNA bisulfite conversion. Differences between the groups were evaluated using the χ (2), Mann-Whitney U or Kruskal-Wallis tests, as indicated. RESULTS: We identified TRAIL-R2 and BCL2 mRNA expressed in all ovarian tumor groups, and there were significant differences between the groups. Both genes had low expression levels in ovarian serous cystadenoma and primary EOC tumors when compared with metastatic EOC. Methylation of the TRAIL-R2 promoter was frequently observed in all groups; however, there were no statistically significant associations. CONCLUSIONS: Primary EOC is associated with lower TRAIL-R2 and BCL2 expression levels, while metastatic EOC is associated with higher expression of these genes. Promoter DNA methylation was not related to this finding, suggesting there are other mechanisms involved in transcriptional control.

Fertility preservation in female cancer patients in Brazil: perceptions and attitudes of infertility specialists.

Objective: Fertility preservation is a priority in oncology for female cancer patients. However, there is a lack of communication between infertility specialists and oncologists. This study aimed to evaluate infertility specialists' perceptions and experiences regarding fertility preservation. Methods: Conduct an online survey to profile infertility specialists. Participants were infertility affiliated with the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO). The specialists received an online survey, which response rate were 30.9%, most of whom were in southern and southeastern. The survey consisted on 14 questions about the infertility specialists' location, techniques in clinical practice, treatment successful rate, patients idea, etc. Results: The average experience in human reproduction were 15.5 ± 10.2 years (mean ± standard deviation, range 1-40). Among reproductive-aged female cancer patients recommended for fertility preservation, 60.3 ± 28.8% (range 10-100%) underwent preservation procedures. Main barriers were cost (41%), oncologists' knowledge or acceptance (35%) and accessibility (9%). Most infertility specialists (58%) considered 40 years the limit for fertility preservation. Leukemia, lymphoma, breast and ovarian cancers were prioritized for fertility preservation, while lung, thyroid, gastric, and brain cancers were less relevant. Conclusion: This is the first Brazilian study about infertility specialists' perceptions on oncology patients access to fertility preservation. These patients primarily receive treatment in the public health system, while infertility specialists mainly work in the private healthcare. This healthcare mode is currently fragmented, but integrating these experts is enhancing patient access to fertility preservation. Studies on this topic are still warranted.

Vacuum-assisted excision: a safe minimally invasive option for benign phyllodes tumor diagnosis and treatment-a systematic review and meta-analysis.

Synopsis: This is a systematic review and meta-analysis comparing surgical excision with percutaneous ultrasound-guided vacuum-assisted excision (US-VAE) for the treatment of benign phyllodes tumor (PT) using local recurrence (LR) as the endpoint. Objective: To determine the frequency of local recurrence (LR) of benign phyllodes tumor (PT) after ultrasound-guided vacuum-assisted excision (US-VAE) compared to the frequency of LR after surgical excision. Method: A systematic review and meta-analysis [following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard] was conducted by comparing LR in women older than 18 years treated for benign PT by US-VAE compared with local surgical excision with at least 12 months of follow-up. Studies were retrieved from PubMed, Scopus, Web of Science, and Embase. The pooled effect measure used was the odds ratio (OR) of recurrence. Results: Five comparative prospective or retrospective observational studies published between January 1, 1992, and January 10, 2022, comparing surgical excision with percutaneous US-VAE for LR of benign PT met the selection criteria. Four were retrospective observational cohorts, and one was a prospective observational cohort. A total of 778 women were followed up. Of them, 439 (56.4%) underwent local surgical excision, and 339 (43.6%) patients had US-VAE. The median age of patients in the five studies ranged from 33.7 to 39 years; the median size ranged from 1.5 cm to 3.0 cm, and the median follow-up ranged from 12 months to 46.6 months. The needle gauge ranged from 7G to 11G. LR rates were not statically significant between US-VAE and surgical excision (41 of 339 versus 34 of 439; OR 1.3; p = 0.29). Conclusion: This meta-analysis suggests that using US-VAE for the removal of benign PT does not increase local regional recurrence and is a safe minimally invasive therapeutic option. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022309782.

Strength of round and uterosacral ligaments: a biomechanical study.

PURPOSE: To investigate the tensile biomechanical properties of round and uterosacral ligaments. METHODS: Tissue samples were obtained from 15 female cadavers without pelvic organ prolapse. Uniaxial tensile tests were performed to obtain stiffness and maximum stress of round and uterosacral ligaments. Correlations were calculated using the Pearson correlation coefficient. Statistical differences between groups were tested using Student's paired and unpaired t test. RESULTS: There was a great variability in the measurements of stiffness and maximum stress in pelvic ligaments. The round ligaments demonstrated stiffness of 9.1 ± 1.6 MPa (mean ± SEM) (ranging from 2 to 25.6 MPa) and maximum stress of 4.3 ± 0.7 MPa (ranging from 1.2 to 11.5 MPa). The stiffness of the uterosacral ligaments was 14.1 ± 1.4 MPa (ranging from 5.7 to 26.1 MPa) with maximum stress of 6.3 ± 0.8 MPa (ranging from 2.2 to 11.9 MPa). There was a strong positive correlation between stiffness and maximum stress in female pelvic ligaments (ρ = 0.851; p < 0.001). The uterosacral ligaments demonstrated higher stiffness and maximum stress compared to the round ligaments (p = 0.006 and p = 0.034; respectively). Age, body mass index and menopausal status were not associated with the biomechanical proprieties of round and uterosacral ligaments. Nulliparous women had lower uterosacral stiffness (15.5 ± 1.3 vs. 10 ± 1.8 MPa; p = 0.033) and maximum stress (8.2 ± 0.9 vs. 4.2 ± 1.1 MPa; p = 0.028) compared to parous women. CONCLUSION: The uterosacral ligaments are significantly more resistant than round ligaments. Parturition seems to enhance the stiffness and maximum stress of the ligaments.

Eating habits, anthropometry, lifestyle, and hypertension of a group of non-village indigenous women in Amazon, Brazil.

OBJECTIVE: The aim of this study was to describe the anthropometric characteristics, eating habits, and lifestyle of non-village indigenous women living in Manaus, AM, and their association with hypertension. METHODS: This cross-sectional (descriptive-analytical) study was carried out from January 2020 to December 2021 using a questionnaire for clinical, sociodemographic, and behavioral data. Non-pregnant women who belonged to Parque das Tribos for more than a year, declared themselves indigenous, and were over 18 years of age were included in the study. RESULTS: In total, 21 ethnicities were identified, and 95 indigenous women were evaluated. The average age group was 36±12.1 years, the average height was 157 cm, and the body mass index was 28.8 kg/m2. The prevalence of systemic arterial hypertension was ±40%, and 68.5% had excess weight, with 29.1% having class I obesity. In all, 35.8% consumed a lot of salt, sugar, and industrialized foods, and 88.4% were sedentary. CONCLUSION: Much of the sample presented excess weight, and almost all were sedentary. More than one-third had unappropriated eating habits. Hypertension was present in more than one-third of these indigenous women. There was an association between higher body mass index and hypertension. Knowing the characteristics of this group of non-village indigenous women may help determine the best health approach. The data demonstrate the necessity of preventive measures.

Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer.

OBJECTIVE: The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. METHODS: Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. RESULTS: We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T, and BRCA2 c.2T> G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. CONCLUSION: This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.

OBJETIVO: O presente estudo avaliou o perfil de mutações germinativas presentes em pacientes submetidas a aconselhamento genético para avaliação de risco para câncer de mama (CM), câncer de ovário (OC) e câncer de endométrio (CE) com possível padrão hereditário. MéTODOS: Foram analisados os prontuários de 382 pacientes que realizaram aconselhamento genético após consentimento informado. Um total de 55,76% dos pacientes (213/382) eram sintomáticos (história pessoal de câncer), e 44,24% (169/382) eram assintomáticos (ausência da doença). As variáveis analisadas foram idade, sexo, naturalidade, história pessoal ou familiar de CM, OC, CE bem como outros tipos de câncer associados a síndromes hereditárias. As diretrizes de nomenclatura da Human Genome Variation Society (HGVS) foram usadas para nomear as variantes e seu significado biológico foi determinado pela comparação de 11 bancos de dados. RESULTADOS: Identificamos 53 mutações distintas: 29 variantes patogênicas, 13 variantes de significado indeterminado e 11 benignas. As mutações mais frequentes foram BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T e BRCA2 c.2T > G. Além disso, 21 variantes parecem ter sido descritas pela primeira vez no Brasil. Além das mutações BRCA1/2, foram encontradas variantes em outros genes relacionados a síndromes hereditárias que predispõem a cânceres ginecológicos. CONCLUSãO: Este estudo permitiu conhecer melhor as principais mutações identificadas nas famílias do estado de Minas Gerais e demonstra a necessidade de avaliar a história familiar de câncer não ginecológico para avaliação do risco de CM, OC e CE. Além disso, é um esforço que contribui com estudos populacionais para avaliar o perfil de mutações de risco para câncer no Brasil.

Quality of information regarding abnormal uterine bleeding available online.

INTRODUCTION: The Internet and electronic devices with Internet access allow for a greater fluidity of information and speed of communication, especially in the field of health. Abnormal uterine bleeding (AUB) affects approximately 3-30% of women and can negatively impact their health and quality of life. Information regarding AUB that is available on the Internet may not be clear or accurate, rendering it difficult to understand and likely to result in delayed medical evaluation, which subsequently leads to worsening of the AUB. OBJECTIVE: To evaluate the quality of the information regarding AUB currently available on the Internet, including information regarding treatments. METHODS: The Google Trends website was searched for the most widely used English terms related to AUB. The identified descriptors were searched individually on the Google, Yahoo!, and Bing search engines. The first 10 results of each search were pre-selected and evaluated for inclusion in this study. Selected websites were categorically divided into two groups (news/magazine and academic) and individually analyzed by three experts using the DISCERN quality criteria (reliability, general quality, and quality of information) and the presence or absence of the Health on the Net Foundation Code of Conduct (HONcode®) seal. RESULTS: Of the 168 websites included in this study, 60.1% were allocated to the news/magazine group and 39.9% were allocated to the academic group. Over half of the websites (54.2%) did not have the HONcode® quality seal. Websites in the academic group were more likely to include accurate information regarding AUB with greater reliability than websites in the news/magazine group. There were no statistical differences regarding the general quality of the websites. Most websites were rated as either moderate quality (70.8%) or low quality (28.6%). The HONcode® criterion was found to be a confounding factor of the analyses, as the grouping and quality results of websites without this seal were significantly associated. In addition, websites in the news/magazines group were 6.7 times more likely to provide low quality information than websites in the academic group (odds ratio: 6.7; 95% confidence interval: 2.1-21.4). CONCLUSION: The information regarding AUB that is available on the Internet is of low to moderate quality. Academic websites present more reliable information of greater quality. The presence of the HONcode® seal is considered important to determine the quality of the content of a website, especially for news/magazine websites, and may help Internet users identify websites that contain more reliable information. Algorithms and applications that categorize the quality of information and the reliability of health content may be useful tools that can help patients clarify their symptoms for several conditions including AUB.

Systemic Inflammatory Patterns in Ovarian Cancer Patients: Analysis of Cytokines, Chemokines, and Microparticles.

OBJECTIVE: To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. MATERIALS AND METHODS: We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. RESULTS: Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1ß), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. CONCLUSION: The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.

OBJETIVO: Comparar os padrões de resposta inflamatória sistêmica em mulheres com câncer epitelial de ovário (CEO) ou sem evidência de doença maligna, bem como avaliar o perfil de respostas inflamatórias sistêmicas em tumores dos tipos 1 e 2. Esta é uma forma não invasiva e indireta de avaliar tanto a atividade tumoral quanto o papel do padrão inflamatório durante as respostas pró- e antitumorais. MéTODOS: Ao todo, 56 pacientes foram avaliados prospectivamente: 30 mulheres sem evidência de doença maligna e 26 mulheres com CEO. A quantificação plasmática de citocinas, quimiocinas e micropartículas (MPs) foi realizada por citometria de fluxo. RESULTADOS: Os níveis plasmáticos das citocinas pró-inflamatórias interleucina-12 (IL12), interleucina-6 (IL-6), fator de necrose tumoral alfa (tumor necrosis factor alpha, TNF-α, em inglês), interleucina-1 beta (IL-1ß), e interleucina-10 (IL-10), e da quimiocina de motivo C-X-C 9 (CXCL-9) e da quimiocina de motivo C-X-C 10 (CXCL-10) foram significativamente maiores em pacientes com EOC do que nos controles. Os níveis plasmáticos da citocina interleucina-17A (IL17A) e MPs derivados de células endoteliais foram menores em pacientes com CEO do que no grupo de controle. A frequência de leucócitos e de MPs derivadas de células endoteliais foi maior nos tumores de tipo 2 do que naqueles sem malignidade. Observou-se um número expressivo de citocinas e quimiocinas inflamatórias/regulatórias nos casos de CEO, além de correlações negativas e positivas entre elas, o que leva a uma maior complexidade dessas redes. CONCLUSãO: Este estudo mostrou que, por meio da construção de redes compostas por citocinas, quimiocinas e MPs, há maior resposta inflamatória sistêmica em pacientes com CEO e correlação mais complexa desses biomarcadores em tumores de tipo 2.

A phase II randomized clinical trial to assess toxicity and quality of life of breast cancer patients with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation in the context of COVID-19 crisis.

Purpose: This study, conducted during the COVID-19 crisis, primarily aimed to compare the acute toxicity between conventional fractionated radiation therapy (CF-RT) with hypofractionated radiation therapy (HF-RT) among patients who underwent breast-conserving surgery or mastectomy in whom breast or chest wall and regional nodal irradiation (RNI) were indicated. The secondary endpoints were both acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. Methods: In this open and non-inferiority randomized trial, patients (n = 86) were randomly allocated 2:1 in the CF-RT arm (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus the HF-RT arm (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE) and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) scale. For the patient-reported quality of life (QoL), the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23) were used. Lymphedema was assessed by comparing volume differences between the affected and contralateral arms using the Casley-Smith formula. Results: Grade 2 and grade 3 dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, and 0% vs. 6%, respectively; p = 0.022). HF-RT had a lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005), compared to CF-RT. No other differences in overall rates of physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT and CF-RT were registered. There was no statistical difference between groups regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000), and functional and symptom scales, during both the irradiation period and after 6 months of the end of treatment. The results revealed that the subset of patients up to 65 years or older did not show a statistical difference between both arm fractionation schedules (p > 0.05) regarding skin rash, fibrosis, and lymphedema. Conclusion: HF-RT was non-inferior to CF-RT, and moderate hypofractionation showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. Clinical trial registration: ClinicalTrials.gov, identifier NCT40155531.

Human papillomavirus prevalence and frequency of sexually transmitted diseases in encarcered women by self-sampling approach.

OBJECTIVE: This study aimed to assess the sociodemographic and clinical profile of women deprived of their liberty and to identify the prevalence of sexually transmitted diseases and human papillomavirus through self-sampling samples. METHODS: This is an epidemiological, cross-sectional, observational, and descriptive study of the prevalence and correlation of the diagnosis of human papillomavirus infection in 268 encarcered women in Amazonas submitted to self-sampling from June 2019 to September 2020 using the genotyping analysis. Patients with positive and inconclusive results were evaluated by commercialized PCR to detect pathogens causing sexually transmitted diseases. The sample size used was based on a convenience sample. RESULTS: In 268 women, human papillomavirus DNA was detected in 87 (32.5%) of them. Sexually transmitted diseases were detected in 30 (34.48%) of the 87 women with a positive or inconclusive result for human papillomavirus. Women with more than three pregnancies had a higher risk of human papillomavirus detection (p=0.004). CONCLUSION: The prevalence of human papillomavirus and other sexually transmitted diseases in encarcered women in Amazonas is 32.5 and 34.48%, respectively. Most women were single (60.4%) and reported having had more than 15 partners (90.8%).

In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare, autosomal dominant tumor predisposition syndrome characterized by variable development of multiple skin and uterus leiomyomas and aggressive forms of renal cell carcinoma (RCC). Mutations in fumarate hydratase (FH), one of the proteins in homologous recombination repair, precede the development of HLRCC with high penetrance. Considering the risk of early metastasis of RCC, FH has been included in mutation screening panels. The identification of a pathogenic FH variant guides the screening for tumors in the carriers. However, variants of uncertain significance (VUS) are frequent findings, limiting the clinical value of the mutation screening. Here, we describe the associated phenotype and an in-depth, multi-step Bioinformatic evaluation of the germline FH c.199T > G (p.Tyr67 > Asp) variant segregated in an HLRCC family. Evidence for FH c.199T > G; (p.Tyr67Asp) pathogenicity includes the variant segregation with the disease in three affected family members, its absence in populational databases, and the deep evolutionary conservation of the Tyr67 residue. At the protein level, this residue substitution causes the loss of molecular bonds and ionic interactions, affecting molecular dynamics and protein stability. Considering ACMG/AMP criteria, we propose the reclassification of the FH c.199T > G; (p.Tyr67Asp) variant to "likely pathogenic". In addition, the in-depth, in silico approach used here allowed us to understand how and why FH c.199T > G; (p.Tyr67Asp) could cause HLRCC. This could help in clinical management decisions concerning the monitoring of unaffected family members having this variant.