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Objective: To assess whether the incidence and aggressiveness of molar pregnancy (MP) and postmolar gestational trophoblastic neoplasia (GTN) changed during the COVID‐19 pandemic. Design: Observational study with two separate designs: retrospective multicentre cohort of patients with MP/postmolar GTN and a cross‐sectional analysis, with application of a questionnaire. Setting: Six Brazilian Reference Centres on gestational trophoblastic disease. Population: 2662 patients with MP/postmolar GTN treated from March–December/2015–2020 were retrospectively evaluated and 528 of these patients answered a questionnaire. Methods: Longitudinal retrospective multicentre study of patients diagnosed with MP/ postmolar GTN at presentation and a cross‐sectional analysis, with application of a questionnaire, exclusive to patients treated during the period of study, to assess living and health conditions during the COVID‐19 pandemic compared with previous years. Main outcome measures: The incidence of MP/postmolar GTN. Results: Compared with the last 5 pre‐pandemic years, MP/postmolar GTN incidence remained stable during 2020 (COVID‐19 pandemic). Multivariable logistic regression, adjusted for the patient age, showed that during 2020, presentation with MP was more likely to be >10 weeks of gestation (adjusted odds ratio [aOR] 2.50, 95% confidence interval [CI] 1.90–3.29, P < 0.001), have a pre‐evacuation hCG level ≥100 000 iu/l (aOR 1.77, 95% CI 1.38–2.28, P < 0.001) and time to the initiation of chemotherapy ≥7 months (aOR 1.86, 95% CI 1.01–3.43, P = 0.047) when compared with 2015–2019. Conclusions: Although the incidence of MP/postmolar GTN remained stable during the COVID‐19 pandemic in Brazil, the pandemic was associated with greater gestational age at MP diagnosis and more protracted delays in initiation of chemotherapy for postmolar GTN. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs are small noncoding RNAs with important regulatory functions. Although well-studied in cancer, little is known about the role of microRNAs in premalignant disease. Complete hydatidiform moles are benign forms of gestational trophoblastic disease that progress to gestational trophoblastic neoplasia in up to 20% of cases; however, there is no well-established biomarker that can predict the development of gestational trophoblastic neoplasia.Objective: This study aimed to investigate possible differences in microRNA expression between complete moles progressing to gestational trophoblastic neoplasia and those regressing after surgical evacuation.Study Design: Total RNA was extracted from fresh frozen tissues from 39 complete moles collected at the time of uterine evacuation in Brazil. In the study, 39 cases achieved human chorionic gonadotropin normalization without further therapy, and 9 cases developed gestational trophoblastic neoplasia requiring chemotherapy. Total RNA was also extracted from 2 choriocarcinoma cell lines, JEG-3 and JAR, and an immortalized normal placenta cell line, 3A-subE. MicroRNA expression in all samples was quantified using microRNA sequencing. Hits from the sequencing data were validated using a quantitative probe-based assay. Significantly altered microRNAs were then subjected to target prediction and gene ontology analyses to search for alterations in key signaling pathways. Expression of potential microRNA targets was assessed by quantitative real-time polymerase chain reaction and western blot. Finally, potential prognostic protein biomarkers were validated in an independent set of formalin-fixed paraffin-embedded patient samples from the United States (15 complete moles progressing to gestational trophoblastic neoplasia and 12 that spontaneously regressed) using quantitative immunohistochemistry.Results: In total, 462 microRNAs were identified in all samples at a threshold of <1 tag per million. MicroRNA sequencing revealed a distinct set of microRNAs associated with gestational trophoblastic neoplasia. Gene ontology analysis of the most altered transcripts showed that the leading pathway was related to response to ischemia (P<.001). Here, 2 of the top 3 most significantly altered microRNAs were mir-181b-5p (1.65-fold; adjusted P=.014) and mir-181d-5p (1.85-fold; adjusted P=.014), both of which have been shown to regulate expression of BCL2. By quantitative real-time polymerase chain reaction, BCL2 messenger RNA expression was significantly lower in the complete moles progressing to gestational trophoblastic neoplasia than the regressing complete moles (-4.69-fold; P=.018). Reduced expression of BCL2 was confirmed in tissue samples by western blot. Immunohistochemistry in the independent patient samples revealed significantly lower cytoplasmic expression of BCL2 in the villous trophoblasts from cases destined for progression to gestational trophoblastic neoplasia compared with those that regressed, both with respect to staining intensity (optic density 0.110±0.102 vs 0.212±0.036; P<.001) and to the percentage of positive cells (16%±28% vs 49.4%±28.05%; P=.003).Conclusion: Complete moles progressing to gestational trophoblastic neoplasia are associated with a distinct microRNA profile. miR-181 family members and BCL2 may be prognostic biomarkers for predicting gestational trophoblastic neoplasia risk. [ABSTRACT FROM AUTHOR]

To investigate the efficacy and toxicity of etoposide, methotrexate, actinomycin D alternating with cyclophosphamide, and vincristine (EMACO) for treatment of gestational trophoblastic neoplasia, and for factors independently associated with EMACO resistance and disease-specific death in an international cohort. Medical records of GTN patients who received EMACO during 1986–2019 from gestational trophoblastic disease centers from four countries including the USA, Thailand, Hungary, and Brazil, were retrospectively reviewed. Among 335 GTN patients, 266 patients who received EMACO as primary chemotherapy were included in the primary treatment group, and 69 patients who received EMACO after relapse/resistance to single-agent chemotherapy were included in the prior treatment group. Three-quarters (76.1%) of all patients achieved remission, and the survival rate was 89%. The prior treatment group had better outcomes than the primary treatment group relative to remission rate (87.0% vs. 73.3%, p = 0.014) and number of EMACO cycles to achieve remission (3 vs. 6 cycles, p < 0.001). Sustained remission increased to 87.2% in EMACO-resistant patients treated with later-line chemotherapy. Number of metastatic organs ≥2 (adjusted odds ratio [aOR]: 2.33, p = 0.049) was the only independent predictor of EMACO resistance among overall patients. Interval from index pregnancy ≥7 months (aOR: 4.34, p = 0.001), and pretreatment hCG >100,000 IU/L (aOR: 2.85, p = 0.028) were independent predictors of EMACO resistance in the high-risk subgroup. The only factor independently associated with disease-specific death was EMACO resistance (aOR: 176.04, p < 0.001). EMACO is an effective treatment for GTN. Number of metastatic organs and EMACO resistance were the independent predictors of EMACO resistance and disease-specific death, respectively. • The response rate was 76.1% with 89% survival in GTN treated with EMACO as first line multiagent chemotherapy. • Number of metastatic organs ≥2 was an independent predictor of EMACO resistance. • EMACO resistance was an independent predictor of disease-specific death. • In high-risk GTN, interval pregnancy ≥7 months and hCG >105 IU/L were independent predictors of EMACO resistance. [ABSTRACT FROM AUTHOR]

Background: Patients with gestational trophoblastic neoplasia who have an International Federation of Gynaecology and Obstetrics (FIGO) risk score of 5 or 6 usually receive non-toxic single-agent chemotherapy as a first-line treatment. Previous studies suggest that only a third of patients have complete remission, with the remaining patients requiring toxic multiagent chemotherapy to attain remission. As stratification factors are unknown, some centres offer multiagent therapy upfront, resulting in overtreatment of many patients. We aimed to identify predictive factors for resistance to single-agent therapy to inform clinicians on which patients presenting with a FIGO score of 5 or 6 are likely to benefit from upfront multiagent chemotherapy.Methods: We did a multicentre, retrospective, cohort study of patients with gestational trophoblastic neoplasia presenting with a FIGO score of 5 or 6, who received treatment at three gestational trophoblastic neoplasia reference centres in the UK, Brazil, and the USA between Jan 1, 1964, and Dec 31, 2018. All patients who had been followed up for at least 12 months after remission were included. Patients were excluded if they had received a non-standard single-agent treatment (eg, etoposide); had been given a previously established first-line multiagent chemotherapy regimen; or had incomplete data for our analyses. Patient data were retrieved from medical records. The primary outcome was the incidence of chemoresistance after first-line or second-line single-agent chemotherapy. Variables associated with chemoresistance to single-agent therapies were identified by logistic regression analysis. In patient subgroups defined by choriocarcinoma histology and metastatic disease status, we did bootstrap modelling to define thresholds of pretreatment human chorionic gonadotropin concentrations and identify groups of patients with a greater than 80% risk (ie, a positive predictive value [PPV] of 0·8) of resistance to single-agent chemotherapy.Findings: Of 5025 patients with low-risk gestational trophoblastic neoplasia, we identified 431 patients with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6. All patients were followed up for a minimum of 2 years. 141 (40%) of 351 patients developed resistance to single-agent treatments and required multiagent chemotherapy to achieve remission. Univariable and multivariable logistic regression revealed metastatic disease status (multivariable logistic regression analysis, odds ratio [OR] 1·9 [95% CI 1·1-3·2], p=0·018), choriocarcinoma histology (3·7 [1·9-7·4], p=0·0002), and pretreatment human chorionic gonadotropin concentration (2·8 [1·9-4·1], p<0·0001) as significant predictors of resistance to single-agent therapies. In patients with no metastatic disease and without choriocarcinoma, a pretreatment human chorionic gonadotropin concentration of 411 000 IU/L or higher yielded a PPV of 0·8, whereas in patients with either metastases or choriocarcinoma, a pretreatment human chorionic gonadotropin concentration of 149 000 IU/L or higher yielded the same PPV for resistance to single-agent therapy.Interpretation: Approximately 60% of women with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6 achieve remission with single-agent therapy; almost all remaining patients have complete remission with subsequent multiagent chemotherapy. Primary multiagent chemotherapy should only be given to patients with metastatic disease and choriocarcinoma, regardless of pretreatment human chorionic gonadotropin concentration, or to those defined by our new predictors.Funding: None.Translation: For the Portuguese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

To investigate GTN lethality among Brazilian women comparing cases of death by GTN with those who survived, thereby identifying factors associated with GTN lethality. We retrospectively reviewed medical records of women with GTN treated at ten Brazilian GTN Reference Centers, from January 1960 to December 2017. We evaluated factors associated with death from GTN and used Cox proportional hazards regression models to identify independent variables with significant influence on the risk of death. From 2186 patients with GTN included in this study, 2092 (95.7%) survived and 89 (4%) died due to GTN. When analyzing the relative risk (RR), adjusted for WHO/FIGO score, patients with low risk disease had a significantly higher risk of death if they had choriocarcinoma (RR: 12.40), metastatic disease (RR: 12.57), chemoresistance (RR: 3.18) or initial treatment outside the Reference Center (RR: 12.22). In relation to patients with high-risk GTN, these factors were significantly associated with death due to GTN: the time between the end of antecedent pregnancy and the initiation of chemotherapy (RR: 4.10), metastatic disease (RR: 14.66), especially in brain (RR: 8.73) and liver (RR: 5.76); absence of chemotherapy or initial treatment with single agent chemotherapy (RR: 10.58 and RR: 1.81, respectively), chemoresistance (RR: 3.20) and the initial treatment outside the Reference Center (RR: 28.30). The risk of mortality from low and high-risk GTN can be reduced by referral of these patients to a Reference Center or, if not possible, to involve clinicians in a Reference Center with consultation regarding management. • Our study is the first to independently analyze risk factors for death among low and high-risk GTN, compared with survivors. • Choriocarcinoma, metastatic disease and initial treatment outside the Reference Center are risk factors for GTN lethality. • Concentrating treatment for GTN at Reference Centers is one strategy associated with reduced lethality from this disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether a human chorionic gonadotropin (hCG) level ≥20,000 IU/L four weeks after uterine evacuation for complete hydatidiform mole (CHM) is an appropriate indicator for initiating chemotherapy for the treatment of gestational trophoblastic neoplasia (GTN).Study Design: Historical database review of 1228 women with CHM who received treatment and follow-up between January 2000 and June 2013 at four Brazilian trophoblastic disease centers. The primary outcome measure was the progression from CHM to GTN. The secondary outcomes were the occurrence of uterine perforation, staging of GTN, WHO/FIGO risk score, and treatment (use of single- or multiagent chemotherapy).Results: An hCG level ≥20,000 IU/L four weeks after uterine evacuation for CHM, while occurring in only 6.1% of women, was the most important risk factor for the development of postmolar GTN (adjusted RR = 5.83; p < 0.01; CI: 3.47-9.79), with a sensitivity of 36.8%, a specificity of 98.6%, a positive predictive value of 80%, and a negative predictive value of 91.1%. On the other hand, there were no differences in postmolar GTN stage, prognostic score, or need for multiagent chemotherapy relative to hCG level ≥20,000 IU/L versus <20,000 IU/L.Conclusions: Although hCG level ≥20,000 IU/L four weeks after uterine evacuation for CHM was very predictive of development of post-molar GTN, delay in treatment until hCG plateau or increase did not affect outcomes, with no uterine perforations or treatment failures. [ABSTRACT FROM AUTHOR]

Objective: To relate the distance traveled from the patient's residence to the gestational trophoblastic neoplasia (GTN) reference center (RC) and the occurrence of unfavorable clinical outcomes, as well as to estimate the possible association between this distance and the risk of metastatic disease at presentation, the need for multiagent chemotherapy to achieve remission and loss to follow-up before remission., Study Design: Retrospective historical cohort study of patients with GTN followed at 8 Brazilian GTN-RC, from January 1st, 2000 - December 31st, 2017., Results: Evaluating 1055 cases of GTN, and using a receiver operating characteristic curve, we found a distance of 56 km (km) from the residence to the GTN-RC (sensitivity = 0.57, specificity = 0.61) best predicted the occurrence of at least one of the following outcomes: occurrence of metastatic disease, need for multiagent chemotherapy to achieve remission, or loss to follow-up during chemotherapy. Multivariate logistic regression adjusted by age, ethnicity, marital status and the reference center location showed that when the distance between residence and GTN-RC was ≥56 km, there was an increase in the occurrence of metastatic disease (relative risk - RR:3.27; 95%CI:2.20-4.85), need for multiagent chemotherapy (RR:1.36; 95%CI:1.05-1.76), loss to follow-up during chemotherapy (RR:4.52; 95CI:1.93-10.63), occurrence of chemoresistance (RR:4.61; 95%CI:3.07-6.93), relapse (RR:10.27; 95%CI:3.08-34.28) and death due to GTN (RR:3.62; 95%CI:1.51-8.67)., Conclusions: The distance between the patient's residence and the GTN-RC is a risk factor for unfavorable outcomes, including death from this disease. It is crucial to guarantee these patients get prompt access to the GTN-RC and receive follow-up support., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as to present the first 4 Brazilian cases of immunotherapy for GTN treatment., Methods: Three independent researchers searched five electronic databases (EMBASE, LILACS, Medline, CENTRAL and Web of Science), for relevant articles up to February/2023 (PROSPERO CRD42023401453). The quality assessment was performed using the Newcastle Ottawa scale for case series and case reports. The primary outcome of this study was the occurrence of complete remission. The presentation of the case reports was approved by the Institutional Review Board., Results: Of the 4 cases presented, the first was a low-risk GTN with methotrexate resistance unsuccessfully treated with avelumab, which achieved remission with sequential multiagent chemotherapy. The remaining 3 cases were high-risk multiagent-resistant GTN that were successfully treated with pembrolizumab, among which there were two subsequent gestations, one of them with normal pregnancy and healthy conceptus. Regarding the systematic review, 12 studies were included, only one of them on avelumab, showing a 46.7% complete remission rate. The remaining 11 studies were on pembrolizumab, showing an 86.7% complete remission rate, regardless of tumor histology. Both immunotherapies showed good tolerability, with two healthy pregnancies being recorded: one after avelumb and another after pembrolizumab., Conclusion: Immunotherapy showed effectiveness for GTN treatment and may be especially useful in cases of high-risk disease, where pembrolizumab achieves a high therapeutic response, regardless of the histological type, and despite prior chemoresistance to multiple lines of treatment., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To describe the natural history of hydatidiform mole (HM) after intracytoplasmic sperm injection (ICSI), emphasizing the clinical and oncological outcomes, as compared to patients who had HM after spontaneous conception (SC)., Study Design: Retrospective historical cohort study of patients with HM followed at the Rio de Janeiro Federal University, from January 1st 2000-December 31st 2020., Results: Comparing singleton HM after SC to those following ICSI there were differences in terms of maternal age (24 vs 34 years, p < 0.01), gestational age at diagnosis (10 vs 7 weeks, p < 0.01), preevacuation human chorionic gonadotropin levels (200,000 vs 99,000 IU/L, p < 0.01), occurrence of genital bleeding (60.5 vs 26.9%, p < 0.01) and hyperemesis (23 vs 3.9%, p = 0.02) at presentation, and time to remission (12 vs 5 weeks, p < 0.01), respectively. There were no differences observed in the cases of twin mole, regardless of the form of fertilization that gave rise to HM, except molar histology with greater occurrence of partial hydatidiform mole (10.7 vs 40.0%, p = 0.01) following ICSI. Univariate logistic regression for occurrence of postmolar GTN after ICSI identified no predictor variable for this outcome. However, after adjusting for maternal age and complete hydatidiform mole histology, multivariable logistic regression showed the risk of GTN with HM after ICSI had an adjusted odds ratio of 0.22 (95%CI:0.05-0.93, p = 0.04), suggesting a possible protective effect when compared to HM after SC., Conclusions: Singleton HM after ICSI are diagnosed earlier in gestation, present with fewer medical complications, and may be less likely to develop GTN when compared with HM after SC., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This work aimed to identify variables associated with increased risk of outcome severity as well as to describe clinical manifestations/symptoms and management of pesticide-related cases reported to a poison center in Brazil. An increased risk of more severe outcomes was observed when exposures occurred in rural areas, involved suicide attempts and moderately to extremely hazardous pesticides. Clinical manifestations with higher frequencies included vomiting, nausea, sialorrhea, headache, miosis and sweating. From the treatment initially applied to the patient, 51.91% encompassed gastric lavage, but this procedure was only recommended in 20.01% of cases by the CIATox. Identifying risk factors associated with poor outcome, describing clinical manifestations, and contrasting initial treatment measures adopted against those recommended by the Poison Center can help determine diagnosis, prognosis and ensure appropriate clinical interventions are used in cases of pesticide poisoning.

Objective: To relate preevacuation platelet count and leukogram findings, especially neutrophil/lymphocyte ratios (NLR) and platelet/lymphocyte ratios with the occurrence of gestational trophoblastic neoplasia (GTN) after complete hydatidiform mole (CHM) among Brazilian women., Methods: Retrospective cohort study of patients with CHM followed at Rio de Janeiro Federal University, from January/2015-December/2020. Before molar evacuation, all patients underwent a medical evaluation, complete blood count and hCG measurement, in addition to other routine preoperative tests. The primary outcome was the occurrence of postmolar GTN., Results: From 827 cases of CHM treated initially at the Reference Center, 696 (84.15%) had spontaneous remission and 131 (15.85%) developed postmolar GTN. Using optimal cut-offs from receiver operating characteristic curves and multivariable logistic regression adjusted for the possible confounding variables of age and preevacuation hCG level (already known to be associated with the development of GTN) we found that ≥2 medical complications at presentation (aOR: 1.96, CI 95%: 1.29-2.98, p<0.001) and preevacuation hCG ≥100,000 IU/L (aOR: 2.16, CI 95%: 1.32-3.52, p<0.001) were significantly associated with postmolar GTN after CHM. However, no blood count profile findings were able to predict progression from CHM to GTN., Conclusion: Although blood count is a widely available test, being a low-cost test and mandatory before molar evacuation, and prognostic for outcome in other neoplasms, its findings were not able to predict the occurrence of GTN after CHM. In contrast, the occurrence of medical complications at presentation and higher preevacuation hCG levels were significantly associated with postmolar GTN and may be useful to guide individualized clinical decisions in post-molar follow-up and treatment of these patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Braga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective:  There are few multinational studies on gestational trophoblastic neoplasia (GTN) treatment outcomes in South America. The purpose of this study was to assess the clinical presentation, treatment outcomes, and factors associated with chemoresistance in low-risk postmolar GTN treated with first-line single-agent chemotherapy in three South American centers., Methods:  Multicentric, historical cohort study including women with International Federation of Gynecology and Obstetrics (FIGO)-staged low-risk postmolar GTN attending centers in Argentina, Brazil, and Colombia between 1990 and 2014. Data were obtained on patient characteristics, disease presentation, and treatment response. Logistic regression was used to assess the relationship between clinical factors and resistance to first-line single-agent treatment. A multivariate analysis of the clinical factors significant in univariate analysis was performed., Results:  A total of 163 women with low-risk GTN were included in the analysis. The overall rate of complete response to first-line chemotherapy was 80% (130/163). The rates of complete response to methotrexate or actinomycin-D as first-line treatment, and actinomycin-D as second-line treatment postmethotrexate failure were 79% (125/157), 83% (⅚), and 70% (23/33), respectively. Switching to second-line treatment due to chemoresistance occurred in 20.2% of cases (33/163). The multivariate analysis demonstrated that patients with a 5 to 6 FIGO risk score were 4.2-fold more likely to develop resistance to first-line single-agent treatment ( p  = 0.019)., Conclusion:  1) At presentation, most women showed clinical characteristics favorable to a good outcome, 2) the overall rate of sustained complete remission after first-line single-agent treatment was comparable to that observed in developed countries, 3) a FIGO risk score of 5 or 6 is associated with development of resistance to first-line single-agent chemotherapy., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Study Objective: To present the first hysteroscopic findings of 2 cases of complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) within the context of the patients' clinical histories., Design: Presentation of 2 hysteroscopic videos with narration of the intrauterine findings of molar pregnancy (MP) from Rio de Janeiro Gestational Trophoblastic Disease Reference Center., Setting: MP is characterized by abnormal fertilization that generates 2 clinical syndromes: CHM and PHM [1]., Interventions: In the first case, the patient was aged 50 years, and hysteroscopy was indicated to assess abnormal uterine bleeding in the presence of normal serum human chorionic gonadotropin (hCG) and transvaginal ultrassonography showing an endometrial cavity with heterogeneous content. Hysteroscopy found translucent hydropic structures diagnosed as CHM. The negative hCG value was due to the hook effect (hCG after dilution: 2 240 000 IU/L). In the second case, an 18-year-old patient underwent hysteroscopy to assess the endometrial cavity with retained abortion at 7 weeks in which, during conservative management, the hCG level increased over 4 weeks from 25 000 IU/L to 58 000 IU/L. Hysteroscopy visualized the embryo with its umbilical cord and hydatidiform vesicles diagnosed as PHM., Conclusion: MP can be an incidental finding during hysteroscopy for abnormal uterine bleeding or retained abortion [2-4]. Knowing its morphology during hysteroscopy is helpful for the correct management of this uncommon clinical situation. Hysteroscopy as an adjunct diagnostic tool (not as first-line treatment for MP) can be of significant benefit in challenging clinical scenarios. Further studies should assess the possible risk of spreading molar cells into the peritoneal cavity owing to hysteroscopic fluid., (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

Pesticide poisoning is a significant public health problem responsible for an estimated three million poisoning cases per year and more than 250,000 deaths, most of which occur in underdeveloped countries. We evaluated pesticide exposure cases reported to a toxicological service center in Brazil, between 2012 and 2016. There were 3211 cases of pesticide exposure, with a high prevalence in adults aged 20-39 years (41.2%). Attempted suicide was the leading cause of pesticide cases (48%). Occupational exposure to pesticides of agricultural use was more frequently observed among men. Accidental exposure and attempted suicide were more frequently observed in urban areas while occupational exposure was more prevalent in rural areas. A higher exposure rate was observed among men in counties with higher agricultural activities. Establishing prevalence and cause of pesticide exposure is important to provide subsidy for evidence-based interventions in the field.

Objectives: This study aimed to evaluate the potential relationship between oxidative stress, dietary intake, and serum levels of antioxidants in patients with a complete hydatidiform mole (CHM) compared with controls., Methods: This was an observational cross-sectional study conducted in Rio de Janeiro, Brazil. A total of 140 women were enrolled in this study and divided into four groups: 43 patients with CHM, 33 women who had had an abortion, 32 healthy pregnant women, and 32 healthy non-pregnant women. All participants underwent blood sampling, assessment using a semiquantitative food frequency questionnaire, and anthropometric measurement. Blood samples were collected after overnight fasting (10-12 h). Vitamin levels (A, C, and E) were determined by ultra-performance liquid chromatography, and gamma-glutamyl transferase levels were assessed using an automated quantitative analysis system (Dimension®, Siemens)., Results: Although all groups showed sufficient serum vitamin A and E levels, the participants had inadequate dietary intake of these vitamins. Conversely, all groups had an insufficient serum level of vitamin C, despite adequate intake. The gamma-glutamyl transferase values did not differ significantly among the groups. However, elevated serum levels of this enzyme were observed in several patients., Conclusions: All groups exhibited high levels of oxidative stress, as evaluated by gamma-glutamyl transferase levels, and had inadequate intake of antioxidant vitamins. Therefore, the high exposure to oxidative stress found in our study, even in healthy pregnant and non-pregnant women, may increase the incidence of CHM in this region.

Objective: To evaluate the impact of periodic shortage of actinomycin-d (Act-d) in the treatment of Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN) after methotrexate and folinic acid rescue (MTX/FA) resistance, treated alternately with carboplatin or etoposide as a second-line regimen., Methods: Retrospective cohort that included patients with failure of first-line MTX/FA regimen for low-risk GTN treated at Rio de Janeiro Federal University, Universidade Federal de São Paulo and Irmandade da Santa Casa de Misericórdia de Porto Alegre, from January/2010- December/2017., Results: From 356 patients with low-risk GTN treated with MTX/FA, 75 (21.1%) developed resistance, of which 40 (53.3%) received Act-d, 23 (30.7%) carboplatin and 7 (9.3%) etoposide. Although patients treated with single-agent chemotherapy as a second-line regimen had comparable clinical and primary treatment characteristics, those treated with Act-d (80%, p = 0.033) or etoposide (71.4%, p = 0.025) had higher remission rates when compared with carboplatin (47.8%). Only 29% of patients treated with carboplatin received the chemotherapy cycles without delay compared to Act-d (98%, p < 0.001) or etoposide (85%, p = 0.009). Patients treated with carboplatin had significantly more hematological toxicity, notably anemia (30.4%, p = 0.008), lymphopenia (47.7%, p < 0.001) and thrombocytopenia (43.4%, p < 0.001), as well as a higher occurrence of febrile neutropenia (14.4%, p = 0.044) and vomiting (60%, p < 0.001) than those receiving Act-d (5%, none, 2.5%, none, 10%, respectively)., Conclusion: Carboplatin did not have a satisfactory clinical response rate, likely due to severe hematological toxicity, which postponed chemotherapy. Our results reinforce the preference for Act-d as a second-line agent in patients with low-risk GTN after MTX/FA resistance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The term gestational trophoblastic disease (GTD) includes both complete and partial moles, which are uncommon nonviable pregnancies with the potential to evolve into a malignancy known as gestational trophoblastic neoplasia. While highly curable, the potential for malignancy associated with molar pregnancies worries the patients, leading them to seek information on the internet. A Facebook page headed by Brazilian specialized physicians in GTD was created in 2013 to provide online support for GTD patients., Objective: The objective of our study was to describe the netnography of Brazilian patients with GTD on Facebook (FBGTD) and to evaluate whether their experiences differed depending on whether they received care in a Brazilian gestational trophoblastic disease reference center (BRC) or elsewhere., Methods: This was a cross-sectional study using G Suite Google Platform. The members of FBGTD were invited to participate in a survey from March 6 to October 5, 2017, and a netnographic analysis of interactions among the members was performed., Results: The survey was answered by 356 Brazilian GTD patients: 176 reference center patients (RCP) treated at a BRC and 180 nonreference center patients (NRCP) treated elsewhere. On comparing the groups, we found that RCP felt safer and more confident at the time of diagnosis of GTD (P=.001). RCP were more likely to utilize FBGTD subsequent to a referral by health assistants (P<.001), whereas NRCP more commonly discovered FBGTD through Web searches (P<.001). NRCP had higher educational levels (P=.009) and were more commonly on FBGTD for ≥ 6 months (P=.03). NRCP were more likely to report that doctors did not adequately explain GTD at diagnosis (P=.007), had more doubts about GTD treatment (P=.01), and were less likely to use hormonal contraception (P<.001). Overall, 89% (317/356) patients accessed the internet preferentially from home and using mobile phones, and 98% (349/354) patients declared that they felt safe reading the recommendations posted by FBGTD physicians., Conclusions: This netnographic analysis of GTD patients on FBGTD shows that an Web-based doctor-patient relationship can supplement the care for women with GTD. This resource is particularly valuable for women being cared for outside of established reference centers., (©Marisa Victoria Diniz, Sue Y Sun, Claudia Barsottini, Mauricio Viggiano, Roney C Signorini Filho, Bruna Sanches Ozane Pimenta, Kevin M Elias, Neil S Horowitz, Antonio Braga, Ross S Berkowitz. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.09.2018.)

Objective: To evaluate uterine evacuation of patients with molar pregnancy, comparing manual with electric vacuum aspiration., Methods: This is a retrospective cohort study of patients with molar pregnancy followed at the Rio de Janeiro Trophoblastic Disease Center from January 2007 to December 2016. The individual primary study outcomes were incomplete uterine evacuation, uterine perforation, development of uterine synechia, and development of postmolar gestational trophoblastic neoplasia. Secondary endpoints were other features of the perioperative outcomes (operative time, rate of transfusion, hemoglobin change, length of stay) and the clinical course of neoplasia (Prognostic Risk Score, presence of metastases, time to remission, and need for multiagent chemotherapy)., Results: Among 1,727 patients with molar pregnancy, 1,206 underwent electric vacuum aspiration and 521 underwent manual vacuum aspiration. After human chorionic gonadotropin normalization, patients with benign molar pregnancy were followed for 6 months and patients treated for gestational trophoblastic neoplasia were followed for 12 months. Baseline risk factors for gestational trophoblastic neoplasia and demographic features were similar between the treatment groups. Uterine synechia developed less frequently after manual vacuum aspiration than after electric vacuum aspiration, 6 of 521 vs 63 of 1,206 (adjusted odds ratio [OR] 0.21, 95% CI 0.09-0.49), despite no differences in the occurrence of incomplete uterine evacuation, 65 of 521 vs 161 of 1,206 (adjusted OR 0.93, 95% CI 0.69-1.27), development of postmolar gestational trophoblastic neoplasia, 90 of 521 vs 171 of 1,206 (adjusted OR 1.26, 95% CI 0.96-1.67), or the need for multiagent chemotherapy, 22 of 521 vs 41 of 1,206 (adjusted OR 0.81, 95% CI 0.73-1.28)., Conclusion: Manual vacuum aspiration appears to be similar to electric vacuum aspiration for treatment of molar pregnancy and may be associated with less development of uterine synechia.

To assess the quality of the primary health care network, the Ministry of Health created the Program for Improving Access and Quality in Primary Care (PMAQ), a national evaluation of family health teams. Thus, this study aims to present the geolocation of PMAQ 2012 quality indicators in the city of Rio de Janeiro. The PMAQ data show that, in the city of Rio de Janeiro, 65% of the teams achieved the performances "good" or "excellent," 34.7% "regular," and 0.3% "unsatisfactory." The results show a clear PMAQ polarization between teams units classified as optimal and regular in program areas 5 and 3, respectively.

Objective: To determine the clinical characteristics of multiple gestation with complete mole and coexisting fetus (CHMCF) in North and South America., Methods: Retrospective non-concurrent cohorts compromised of CHMCF from New England Trophoblastic Disease Center (NETDC) (1966-2015) and four Brazilian Trophoblastic Disease Centers (BTDC) (1990-2015)., Results: From a total of 12,455 cases of gestational trophoblastic disease seen, 72 CHMCF were identified. Clinical characteristics were similar between BTDC (n=46) and NETDC (n=13) from 1990 to 2015, apart from a much higher frequency of potentially life-threatening conditions in Brazil (p=0.046). There were no significant changes in the clinical presentation or outcomes over the past 5 decades in NETDC (13 cases in 1966-1989 vs 13 cases in 1990-2015). Ten pregnancies were electively terminated and 35 cases resulted in viable live births (60% of 60 continued pregnancies). The overall rate of gestational trophoblastic neoplasia (GTN) was 46%; the cases which progressed to GTN presented with higher chorionic gonadotropin levels (p=0.026) and higher frequency of termination of pregnancy due to medical complications (p=0.006) when compared to those with spontaneous remission., Conclusions: The main regional difference in CHMCF presentation is related to a higher rate of potentially life-threatening conditions in South America. Sixty percent of the expectantly managed CHMCF delivered a viable infant, and the overall rate of GTN in this study was 46%. Elective termination of pregnancy did not influence the risk for GTN; however the need for termination due to complications and higher hCG levels were associated with development of GTN in CHMCF., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To assess the influence of hydatidiform mole (HM) management setting (reference center versus other institutions) on gestational trophoblastic neoplasia (GTN) outcomes., Methods: This cohort study included 270 HM patients attending Botucatu Trophoblastic Diseases Center (BTDC, São Paulo State University, Brazil) between January 1990 and December 2009 (204 undergoing evacuation and entire postmolar follow-up at BTDC and 66 from other institutions [OIs]). GTN characteristics and outcomes were analyzed and compared according to HM management setting. The confounding variables assessed included age, gravidity, parity, number of abortions and HM type (complete or partial). Postmolar GTN outcomes were compared using Mann-Whitney's test, chi2 test or Fisher's exact test., Results: Postmolar GTN occurred in 34 (34/204 = 16.7%) BTDC patients and in 27 (27/66 = 40.9%) of those initially treated in other institutions. BTDC patients showed lower metastasis rate (5.8% vs. 48%, p = 0.003) and lower median FIGO (2002) score (2.00 [1.00, 3.00] vs. 4.00 [2.00, 7.00], p = 0.003]. Multiagent chemotherapy to treat postmolar GTN was required in 2 BTDC cases (5.9%) and in 8 OI cases (29.6%) (p = 0.017). Median time interval between molar evacuation and chemotherapy onset was shorter among BTDC patients (7.0 [6.0, 10.0] vs. 10.0 [7.0, 16.0], p = 0.040)., Conclusion: BTDC patients showed GTN characteristics indicative of better prognosis. This underscores the importance of GTD specialist centers.