Use of hormones and risk of venous thromboembolism.

•The risk of venous thromboembolism (VTE) is not increased in women using long-acting reversible contraceptive methods (LARCs) with progestogens. •Oral contraceptives with levonorgestrel or norgestimate confer half the risk of VTE compared to oral contraceptives containing desogestrel, gestodene or drospirenone. •Progestogen-only pills do not confer an increased risk of VTE. •Women using transdermal contraceptive patches and combined oral contraceptives (COCs) are at an approximately eight times greater risk of VTE than non-users of hormonal contraceptives (HCs), corresponding to 9.7 events per 10,000 women/years. •Vaginal rings increase the risk of VTE by 6.5 times compared to not using HC, corresponding to 7.8 events per 10,000 women/years. •Several studies have demonstrated an increased risk of VTE in transgender individuals receiving hormone therapy (HT). •Hormone therapy during menopause increases the risk of VTE by approximately two times, and this risk is increased by obesity, thrombophilia, age over 60 years, surgery and immobilization. •The route of estrogen administration, the dosage and type of progestogen associated with estrogen may affect the risk of VTE in the climacteric. •Combined estrogen-progesterone therapy increases the risk of VTE compared to estrogen monotherapy. •Postmenopausal HT increases the risk of thrombosis at atypical sites.

Validation of Serological Methods for COVID-19 and Retrospective Screening of Health Employees and Visitors to the São Paulo University Hospital, Brazil.

Reliable serological tests for the detection of SARS-CoV-2 antibodies among infected or vaccinated individuals are important for epidemiological and clinical studies. Low-cost approaches easily adaptable to high throughput screenings, such as Enzyme-Linked Immunosorbent Assays (ELISA) or electrochemiluminescence immunoassay (ECLIA), can be readily validated using different SARS-CoV-2 antigens. A total of 1,119 serum samples collected between March and July of 2020 from health employees and visitors to the University Hospital at the University of São Paulo were screened with the Elecsys® Anti-SARS-CoV-2 immunoassay (Elecsys) (Roche Diagnostics) and three in-house ELISAs that are based on different antigens: the Nucleoprotein (N-ELISA), the Receptor Binding Domain (RBD-ELISA), and a portion of the S1 protein (ΔS1-ELISA). Virus neutralization test (CPE-VNT) was used as the gold standard to validate the serological assays. We observed high sensitivity and specificity values with the Elecsys (96.92% and 98.78%, respectively) and N-ELISA (93.94% and 94.40%, respectively), compared with RBD-ELISA (90.91% sensitivity and 88.80% specificity) and the ΔS1-ELISA (77.27% sensitivity and 76% specificity). The Elecsys® proved to be a reliable SARS-CoV-2 serological test. Similarly, the recombinant SARS-CoV-2 N protein displayed good performance in the ELISA tests. The availability of reliable diagnostic tests is critical for the precise determination of infection rates, particularly in countries with high SARS-CoV-2 infection rates, such as Brazil. Collectively, our results indicate that the development and validation of new serological tests based on recombinant proteins may provide new alternatives for the SARS-CoV-2 diagnostic market.

Relation between CANDIDA species isolated from vaginal mucosa and lesions caused by high-risk human papillomavirus hpv for cervical cancer

This study characterized and related yeasts of the genus Candida isolated from vaginal mucous membranes of women with lesions caused by high-risk HPV for cervical cancer. Forty-two women treated at the Lower Genital Tract Pathology Clinic of the University of São Paulo Medical School Hospital of Clinics were examined, with 30 high-grade (G1) uterine lesions with a mean age of 36.5 years ± 11. 1 and 12 with low grade (G2) uterine lesions with a mean age of 34.7 years ± 15.5. Clinical conditions and laboratory data on HPV were collected from patients' medical records; the socio-demographic data obtained from an appropriate questionnaire. For the study of association between the variables, Odds Ratio analysis was used from the STATA 13.1 program. Patients G1 had a higher prevalence for diabetes and the results indicated 27% prevalence of Candida spp. in vaginal mucosa, in G2 this was 33% in vaginal mucosa. Among the species found in vaginal mucosa of patients, Candida albicans was the most isolated with 88%, followed by C. tropicalis (8%) and C. glabrata (4%). The strains of C. albicans isolated from mucosa presented sensitivity to all antifungal agents tested, unlike the C. tropicalis strain isolated in G2 in vaginal mucosa, which presented a resistance profile to fluconazole. Thus, monitoring and supervision through clinical and laboratory testing of HPV patients is important, reinforcing the need for care, treatment and prevention of HPV-related infections and Candida spp.

Lactate secreted by cervical cancer cells modulates macrophage phenotype.

Cervical cancer continues to be a public health problem in developing countries. Previous studies have shown that cervical cancer cells display markers of aerobic glycolysis, indicating that these tumors are likely to secrete lactate. Mostly, lactate is recognized as a molecule capable of suppressing immune responses, through inhibition of T cells, Mϕs, and dendritic cells. We and others have previously shown that Mϕs are frequent cells infiltrating cervical cancers with the ability to inhibit antitumor immune responses and promote tumor growth through angiogenesis. Here, we have tested the hypothesis that lactate, secreted by cervical cancer cells, can modulate Mϕ phenotype. First, we showed higher lactate plasma concentrations in patients with increasing cervical lesion grades, with maximum concentration in the plasma of cancer patients, which supported our hypothesis. We then inhibited lactate production in tumor cell spheroids established from cervical cancer derived cell lines, using the lactate dehydrogenase inhibitor, oxamate, prior to co-culture with monocytes. Lactate mediated part of the crosstalk between tumor cells and Mϕs, promoting secretion of IL-1ß, IL-10, IL-6, and up-regulation of hypoxia induced factor-1α expression, and down-regulation of p65-NFκB phosphorylation in Mϕs. We also showed that Mϕs from co-cultures treated with oxamate were better inducers of T cell activation. Of note, experiments performed with inhibition of the monocarboxylate transporters rendered similar results. Our data confirms the hypothesis that lactate, secreted by cervical tumor cells, influences the phenotype of tumor Mϕs, promoting a suppressive phenotype.

B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses.

Immune evasion by tumors includes several different mechanisms, including the inefficiency of antigen presenting cells (APCs) to trigger anti-tumor T cell responses. B lymphocytes may display a pro-tumoral role but can also be modulated to function as antigen presenting cells to T lymphocytes, capable of triggering anti-cancer immune responses. While dendritic cells, DCs, are the best APC population to activate naive T cells, DCs or their precursors, monocytes, are frequently modulated by tumors, displaying a tolerogenic phenotype in cancer patients. In patients with cervical cancer, we observed that monocyte derived DCs are tolerogenic, inhibiting allogeneic T cell activation compared to the same population obtained from patients with precursor lesions or cervicitis. In this work, we show that B lymphocytes from cervical cancer patients respond to treatment with sCD40L and IL-4 by increasing the CD80+CD86+ population, therefore potentially increasing their ability to activate T cells. To test if B lymphocytes could actually trigger anti-tumor T cell responses, we designed an experimental model where we harvested T and B lymphocytes, or dendritic cells, from tumor bearing donors, and after APC stimulation, transplanted them, together with T cells into RAG1-/- recipients, previously injected with tumor cells. We were able to show that anti-CD40 activated B lymphocytes could trigger secondary T cell responses, dependent on MHC-II expression. Moreover, we showed that dendritic cells were resistant to the anti-CD40 treatment and unable to stimulate anti-tumor responses. In summary, our results suggest that B lymphocytes may be used as a tool for immunotherapy against cancer.

Referral gynecological ambulatory clinic: principal diagnosis and distribution in health services.

BACKGROUND: The association between gynecological diagnoses and their distribution in the health sectors provides benefits in the field of women's health promotion and in medical and interdisciplinary education, along with rationalization according to level of care complexity. Thus, the objective is analyze the clinical-demographic characteristics, main diagnoses in gynecological ambulatory care, and their distribution in health services. METHOD: This is a research project of retrospective audit study design with a chart review of data from 428 women treated at University Ambulatory Clinic of Women's Health, the facility in gynecology and training for Family and Community Medical Residents, São Paulo, Brazil, from 2012 to 2014. Clinical and demographic information, gynecological diagnoses (International Classification of Diseases), and distribution of health services (primary, secondary, and tertiary) were described. RESULTS: The female patients present non-inflammatory disorders of the female genital tract (81.07%, n = 347) and diseases of the urinary system (22.66%, n = 97) among the gynecological diagnoses. The chances of having benign breast disease and non-inflammatory disorders of the female genital tract during the reproductive period corresponds to being 3.61 (CI 1.00-16.29) and 2.56 times (CI 1.58-4.16) higher, respectively, than during the non-reproductive period. The non-inflammatory disorders of the female genital tract (93.33%, n = 28) are most related to the tertiary sector. The distribution in health services was the following: 71.30% (n = 305) in the primary sector, 21.70% (n = 93) in the secondary sector and 7% (n = 30) in the tertiary sector. CONCLUSION: The studied women presented non-inflammatory disorders of the female genital tract and diseases of the urinary system as determined by gynecological diagnoses. Low-assistance complexity followed in most cases.

Microperforated hymen: a case of delayed diagnosis.

Although the incidence of microperforated hymen (MH) is unclear, this hymenal subocclusive anomaly is considered a rare entity. Differently from imperforated hymen, MH may be asymptomatic until puberty when the women's quality of life is jeopardized. Depending on the size of the microperforation, MH's clinical features me be very similar to those found in imperforated hymen cases. However, MH may present infectious complications since the accumulated secretion retained in the vaginal canal has contact with the external environment and therefore represents a source of entry for infectious agents. The authors report a case of a 28-year-old woman who sought the gynecologist complaining of inability to have vaginal intercourse. She referred normal menses, but in fact, although regular, bleeding was filiform and was exteriorized only through the right side of the vagina. Physical examination and imaging disclosed a microperforation of the hymenal membrane at 10 o'clock position. Hymenotomy under general anesthesia was undertaken. Outcome was favorable and the patient could thenceforth have a normal life. We conclude that this anomaly may be overlooked, interfering on its incidence determination. The delayed onset of symptoms and psychological embarrassing aspects, which postpone gynecological consultation, may contribute for misdiagnoses. We call attention to a mandatory detailed anamnesis and thorough physical examination to diagnose this anomaly before the puberty, when complications are less frequent and treatment is advisable.

Ovarian adenosarcoma simulating a simple cyst in a young patient.

Müllerian adenosarcoma is a rare, mixed tumor that can occur throughout the female genital tract, but is most commonly found in the uterus. Ovarian adenosarcoma is rarer and has a poorer prognosis than uterine adenosarcoma. Data on the clinicopathological features of ovarian adenosarcoma are limited, and, due to its rarity, the management is controversial. The authors report a case of a 25-year-old patient who presented with recurrent abdominal pain. Sonography and laparotomy showed an ovarian cyst, and pathologic examination confirmed the diagnosis of cystic low-grade adenosarcoma. The patient remains free of recurrence 6 months after diagnosis. The authors call attention to the differential diagnosis of ovarian masses, especially in young patients, and to the lack of evidence on the management of this neoplasm in the literature.

Estudo da ação do estrogênio transdérmico, nos parâmetros tromboelastográficos de mulheres com antecedente de tromboembolismo venoso / Study of transdermic estrogen action in the thromboelastrographic parameter of women with venous thromboembolism antecedent

Foi oferecido estrogênio transdérmico a 29 mulheres entre 40 e 65 anos de idade e com antecedente de tromboembolismo venoso (grupo caso = 9 e grupo controle = 20) Foram realizados a contagem plaquetária, determinação do TP, TT e TTPA, níveis de fibrinogênio e a tromboelastografia no início e após 3 e 6 meses. Mulheres com antecedente de tromboembolismo venoso apresentaram hipercoagulabilidade em relação a indivíduos normais, conforme medido pela tromboelastografia O parâmetro G mostrou redução na amostra de PPP no grupo caso ao longo do tempo (p<0,05). Não se observou variação significante ao longo do tempo para as outras variáveis. Os níveis de fibrinogênio reduziram-se durante o estudo no grupo caso (p<0,05). Este estudo sugere que o estrogênio transdérmico não levou ao aumento da coagulabilidade sangüínea em mulheres com antecedente de tromboembolismo venoso / Twenty nine women aged 40 to 65 years with past history of venous thromboembolism were offered transdermal estrogen (case group = 9 and control group = 20 women). Platelet count, TP, TT, aTTP, fibrinogen levels and thromboelastography were performed at the beginning and after 3 and 6 months. Women with venous thromboembolism antecedents showed hypercoagulable state coTmpared to the Normal group, as measured by thromboelastography. There was a decrease in G parameter for PPP sample in Case group during the study period (p<0,05). No significant variation was observed along the time for the other variables. Fibrinogen levels decreased during the study period in case group (p<0,05). This study suggests that transdermic estrogen did not increase the blood coagulability in women with venous thromboembolism antecedents...

Climaterio: infeccao genitais e reposicao hormonal / Climateric: genital infections and hormonal replacement

O objetivo desta revisao, foi avaliar as informacoes da literatura, junto as observacoes dos autores, para analisar os aspectos relevantes que envolvem o periodo do climaterio, em relacao...

Aspectos etiopatogenicos e preventivos da doenca tromboembolica em ginecologia / Etiopatogenic and preventive aspects of thromboembolic disease in gynecology

Os autores fazem uma revisao sobre a doenca tromboembolica considerando os aspectos epidemiologico, etiopatogenico e profilatico relacionados ao cotidiano da pratica clinica do ginecologista. E dada maior enfase sobre os grupos de risco para esta doenca bem como os metodos de profilaxia relacionados a estes grupos

Tratamento do prolapso uterino pela histerectomia vaginal / Uterine prolapse treatment by vaginal histerectomy

Revisaram-se 278 prontuarios de pacientes com diagnostico de prolapso uterino, submetidos a histerectomia vaginal no periodo de janeiro de 1988 a dezembro de 1993, com o objetivo de avaliar as principais caracteristicas dessas pacientes, assim como a eficacia da terapeutica cirurgica empregada. Os resultados confirmaram que esta doenca atinge principalmente mulheres brancas, multiparas e com idade superior a cinquenta anos. A principal queixa era a presenca de "bola" na vagina, frequentemente associada a incontinencia urinaria de esforco. Em relacao ao procedimento cirurgico empregado, a histerectomia vaginal revelou-se excelente opcao disso, observou-se indice minimo de complicacoes relacionadas a essa cirurgia.