Expert consensus: Profiling and management of advanced or metastatic epithelial ovarian cancer / Consenso de expertos basado en la evidencia: perfilamiento y manejo del carcinoma epitelial de ovario de alto grado avanzado.

Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the "The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the "ESMO Standardized Operating Procedures Consensus Conference" were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/IV BRCA1/2 positive EOC who received platinumbased chemotherapy and obtained complete response/partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR. 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive "Arbeitsgemeinschaft Gynäkologische Onkologie ­ AGO" score or "I-model" positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. Combination chemotherapy (carboplatin/gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA 1/2 +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.

Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la "Conferencia de consenso de procedimientos operativos estandarizados de ESMO". Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral < 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales < 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (< 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.

Staying in control: Characterizing the mechanisms underlying cognitive control in high and low arousal states.

Throughout the day, humans show natural fluctuations in arousal that impact cognitive function. To study the behavioural dynamics of cognitive control during high and low arousal states, healthy participants performed an auditory conflict task during high-intensity physical exercise (N = 39) or drowsiness (N = 33). In line with the pre-registered hypotheses, conflict and conflict adaptation effects were preserved during both altered arousal states. Overall task performance was markedly poorer during low arousal, but not for high arousal. Modelling behavioural dynamics with drift diffusion analysis revealed evidence accumulation and non-decision time decelerated, and decisional boundaries became wider during low arousal, whereas high arousal was unexpectedly associated with a decrease in the interference of task-irrelevant information processing. These findings show how arousal differentially modulates cognitive control at both sides of normal alertness, and further validate drowsiness and physical exercise as key experimental models to disentangle the interaction between physiological fluctuations on cognitive dynamics.

Delving into the relationship between regular physical exercise and cardiac interoception in two cross-sectional studies.

Cardiac interoception, the ability to sense and process cardiac afferent signals, has been shown to improve after a single session of acute physical exercise. However, it remains unclear whether repetitive engagement in physical exercise over time leads to long-term changes in cardiac interoceptive accuracy. It is also unknown whether those changes affect the neural activity associated with the processing of afferent cardiac signals, assessed by the heart-evoked potential (HEP). In this study, we aimed to investigate this hypothesis through two cross-sectional studies, categorizing participants as active or inactive based on physical fitness (Study I; N = 45) or self-reported physical activity levels (Study II; N = 60). Interoception was assessed at rest using the HEP (Studies I and II), the Heartbeat Counting task (Study II), and the Rubber Hand Illusion (RHI) (Study II). Study I showed strong evidence of better cardiovascular fitness in the active group than in the inactive group as well as robust between-group differences in electrocardiogram (ECG) recordings. Study 2 replicated the clear differences in ECG as a function of regular physical activity. Those results were expected due to clear differences in physical activity habits. In contrast, our analysis revealed no robust differences between groups across cardiac interoception tasks and the RHI, although the direct relevance of these measures to interoception remains under investigation. In sum, our results do not provide convincing evidence to support a strong version of the notion that regular physical exercise is associated with an enhanced in cardiac interoception.

Individualized Mental Fatigue Does Not Impact Neuromuscular Function and Exercise Performance.

INTRODUCTION: Recent studies have questioned previous empirical evidence that mental fatigue negatively impacts physical performance. The purpose of this study was to investigate the critical role of individual differences in mental fatigue susceptibility by analyzing the neurophysiological and physical responses to an individualized mental fatigue task. METHODS: In a preregistered ( https://osf.io/xc8nr/ ), randomized, within-participant design experiment, 22 recreational athletes completed a time to failure test at 80% of their peak power output under mental fatigue (individual mental effort) or control (low mental effort). Before and after the cognitive tasks, subjective feeling of mental fatigue, neuromuscular function of the knee extensors, and corticospinal excitability were measured. Sequential Bayesian analysis until it reached strong evidence in favor of the alternative hypothesis (BF 10 > 6) or the null hypothesis (BF 10 < 1/6) were conducted. RESULTS: The individualized mental effort task resulted in a higher subjective feeling of mental fatigue in the mental fatigue condition (0.50 (95% confidence interval (CI), 0.39-0.62)) arbitrary units compared with control (0.19 (95% CI, 0.06-0.339)) arbitrary unit. However, exercise performance was similar in both conditions (control: 410 (95% CI, 357-463) s vs mental fatigue: 422 (95% CI, 367-477) s, BF 10 = 0.15). Likewise, mental fatigue did not impair knee extensor maximal force-generating capacity (BF 10 = 0.928) and did not change the extent of fatigability or its origin after the cycling exercise. CONCLUSIONS: There is no evidence that mental fatigue adversely affects neuromuscular function or physical exercise; even if mental fatigue is individualized, computerized tasks seem not to affect physical performance.

O esporte e o lazer no programa nacional de assistência estudantil: revisão sistemática da literatura / Sport and leisure in the national student assistance program: systematic literature review

Objetivou-se analisar as publicações sobre esporte e lazer no contexto da assistência estudantil nas bases de referências e averiguar a aderência do esporte e lazer como uma ação da política de assistência estudantil nas instituições federais de ensino superior. Trata-se de uma revisão sistemática da literatura estruturada em 8 passos: definição dos tópicos da pesquisa; escolha das bases; escolha das palavras-chave; pesquisa e armazenamento dos resultados encontrados; seleção dos materiais por resumo, considerando os critérios de inclusão/exclusão; extração de dados dos trabalhos selecionados; avaliação do material encontrado; e síntese e interpretação dos dados. O estudo é original por ser pioneiro em investigar, de maneira sistemática, a discussão do esporte e lazer no contexto da assistência estudantil. Ao agrupar as publicações e estruturar agenda de pesquisa, a partir do PNAES, garante ao estudo a originalidade e a relevância ao campo. Os principais resultados demonstram que a maioria dos estudos focam na verificação das ações prioritárias do PNAES desenvolvidas pelas IFES, seguida da avaliação da implementação do PNAES e o debate sobre o papel das IFES na formulação de políticas de esporte e lazer. O estudo amplia a discussão teórica do esporte como ação integrante no rol da assistência estudantil para além da figura de subsidiária das outras ações, além de estruturar indicações e sugestões de pesquisas futuras.

The objective was to analyze the publications on sport and leisure in the context of student assistance in the reference bases and to verify the adherence of sport and leisure as an action of the student assistance policy in federal institutions of higher education. This is a systematic review of the literature structured in 8 steps: definition of research topics; choice of bases; choice of keywords; search and storage of the results found; selection of materials by summary, considering the inclusion/exclusion criteria; data extraction from selected works; evaluation of the material found; and synthesis and interpretation of data. The study is original for being a pioneer in systematically investigating the discussion of sport and leisure in the context of student assistance. By grouping the publications and structuring the research agenda, based on the PNAES, it guarantees the study originality and relevance to the field. The main results show that most studies focus on verifying the priority actions of the PNAES developed by the IFES, followed by the evaluation of the implementation of the PNAES and the debate on the role of the IFES in the formulation of sports and leisure policies. The study extends the theoretical discussion of sport as an integral action in the role of student assistance beyond the subsidiary figure of other actions, in addition to structuring indications and suggestions for future research.

An umbrella review of randomized control trials on the effects of physical exercise on cognition.

Extensive research links regular physical exercise to an overall enhancement of cognitive function across the lifespan. Here we assess the causal evidence supporting this relationship in the healthy population, using an umbrella review of meta-analyses limited to randomized controlled trials (RCTs). Despite most of the 24 reviewed meta-analyses reporting a positive overall effect, our assessment reveals evidence of low statistical power in the primary RCTs, selective inclusion of studies, publication bias and large variation in combinations of pre-processing and analytic decisions. In addition, our meta-analysis of all the primary RCTs included in the revised meta-analyses shows small exercise-related benefits (d = 0.22, 95% confidence interval 0.16 to 0.28) that became substantially smaller after accounting for key moderators (that is, active control and baseline differences; d = 0.13, 95% confidence interval 0.07 to 0.20), and negligible after correcting for publication bias (d = 0.05, 95% confidence interval -0.09 to 0.14). These findings suggest caution in claims and recommendations linking regular physical exercise to cognitive benefits in the healthy human population until more reliable causal evidence accumulates.

Preoperative brachytherapy for early-stage cervical cancer: Systematic review and meta-analysis.

OBJECTIVE: To assess the rate of pathological response rate, and the oncological outcomes of preoperative brachytherapy (PBT) in early-stage cervical cancer. METHODS: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and meta-analyses (PRISMA) statement. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from inception until April 2022. Only English and French articles were included. Studies containing data about pathology response or oncological outcomes among patients who received PBT as compared to those who underwent up-front surgery in early-stage cervical cancer were included. This study was registered in PROSPERO (CRD42022319036). RESULTS: Thirteen studies met the inclusion criteria, 3 randomized controlled trials (RCT), and 10 non-randomized studies (NRS). The 5-year survival was significantly higher in the PBT group compared with the up-front surgery group (OR 1.78, 95% CI 1.11-2.84, I2 = 0%) in the NRS. Recurrence rate was significantly lower in the PBT group compared with in up-front surgery group in the analysis of the RCT but not in NRS, (OR 0.34, 95% CI 0.13-0.91, I2 not applicable) and (OR 0.72, 95% CI 0.26-1.95, I2 = 51%) respectively. PBT was associated with a statistically significant lower rate of positive margins (OR 0.28, 95% CI 0.09-0.89; I2 = 42%) in the RCT and with a significantly higher rate of complete pathology response (CPR) in the RCT analysis (OR 2.55, 95% CI 1.11-5.85, I2 = 0%) and in the NRS (OR 9.64, 95% CI 1.88-49.48, I2 = 76%) compared with the up-front surgery group. CONCLUSION: Preoperative brachytherapy in patients with early-stage cervical cancer could improve pathologic and oncologic outcomes, but it should be assessed in high-quality randomized controlled trials before its implementation in clinical practice.

The brain in flow: A systematic review on the neural basis of the flow state.

BACKGROUND: Flow state is a subjective experience that people report when task performance is experienced as automatic, intrinsically rewarding, optimal and effortless. While this intriguing phenomenon is the subject of a plethora of behavioural studies, only recently researchers have started to look at its neural correlates. Here, we aim to systematically and critically review the existing literature on the neural correlates of the flow state. METHODS: Three electronic databases (Web of Science, Scopus and PsycINFO) were searched to acquire information on eligible articles in July, 2021, and updated in March, 2022. Studies that measured or manipulated flow state (through questionnaires or employing experimental paradigms) and recorded associated brain activity with electroencephalography (EEG), functional magnetic resonance (fMRI) or functional near-infrared spectroscopy (fNIRS) or manipulated brain activity with transcranial direct current stimulation (tDCS) were selected. We used the Cochrane Collaboration Risk of Bias 2 (RoB 2) tool to assess the methodological quality of eligible records. RESULTS: In total, 25 studies were included, which involved 471 participants. In general, the studies that experimentally addressed flow state and its neural dynamics seem to converge on the key role of structures linked to attention, executive function and reward systems, giving to the anterior brain areas (e.g., the DLPC, MPFC, IFG) a crucial role in the experience of flow. However, the dynamics of these brain regions during flow state are inconsistent across studies. DISCUSSION: In light of the results, we conclude that the current available evidence is sparse and inconclusive, which limits any theoretical debate. We also outline major limitations of this literature (the small number of studies, the high heterogeneity across them and their important methodological constraints) and highlight several aspects regarding experimental design and flow measurements that may provide useful avenues for future studies on this topic.

Different underlying mechanisms for high and low arousal in probabilistic learning in humans.

Humans are uniquely capable of adapting to highly changing environments by updating relevant information and adjusting ongoing behaviour accordingly. Here we show how this ability -termed cognitive flexibility- is differentially modulated by high and low arousal fluctuations. We implemented a probabilistic reversal learning paradigm in healthy participants as they transitioned towards sleep or physical extenuation. The results revealed, in line with our pre-registered hypotheses, that low arousal leads to diminished behavioural performance through increased decision volatility, while performance decline under high arousal was attributed to increased perseverative behaviour. These findings provide evidence for distinct patterns of maladaptive decision-making on each side of the arousal inverted u-shaped curve, differentially affecting participants' ability to generate stable evidence-based strategies, and introduces wake-sleep and physical exercise transitions as complementary experimental models for investigating neural and cognitive dynamics.

Correction: Mental Fatigue Might be Not So Bad for Exercise Performance After All: A Systematic Review and Bias-Sensitive Meta-Analysis.

[This corrects the article DOI: 10.5334/joc.126.].

Neoadjuvant chemotherapy prior to fertility-sparing surgery in cervical tumors larger than 2 cm: a systematic review on fertility and oncologic outcomes.

BACKGROUND: Management of cervical cancer tumors >2 cm has been a subject of controversy, with management often considered as either up-front radical trachelectomy or neoadjuvant chemotherapy before fertility-sparing surgery. METHODS: A systematic literature review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO). We searched Medline through PubMed, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, and OVID between January 1985 and December 2020. Eligibility criteria for selecting studies were English language, randomized controlled trials, and observational studies including information on fertility and oncologic outcomes. All titles were managed in EndNote X7. Risk of bias was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist for observational studies. RESULTS: Twenty-three studies with 205 patients who received neoadjuvant chemotherapy were included. The majority of patients (92.2%, n=189) had stage IB FIGO 2009 cervical cancer. The preferred regimen used was cisplatin in combination with paclitaxel or ifosfamide (80%, n=164). One hundred and eighty patients (87.8%) underwent fertility-sparing surgery; radical vaginal trachelectomy, abdominal trachelectomy, conization, and simple trachelectomy were performed in 62 (34.4%), 49 (27.2%), 34 (18.9%), and 26 (14.4%) women, respectively. In nine patients (5%) the type of procedure was not specified. The follow-up time reported in all studies ranged between 6 and 69 months. In 112 women who sought a pregnancy after surgery, 84.8% (n=95) achieved a gestation.The global recurrence and death rates were 12.8% and 2.8%, respectively. CONCLUSION: Neoadjuvant chemotherapy followed by fertility-sparing surgery is a promising strategy that might allow fertility preservation in highly selected patients with cervical cancer with tumors >2 cm while providing acceptable oncologic outcomes. Results of prospective studies are required to validate its oncological safety. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020203789.

Novel evidence on the effect of tramadol on self-paced high-intensity cycling.

The use of tramadol is a controversial topic in cycling. In order to provide novel evidence on this issue, we tested 29 participants in a pre-loaded cycling time trial (TT; a 20-min TT preceded by 40-min of constant work-rate at 60% of the VO2max) after ingesting 100 mg of tramadol (vs placebo and paracetamol (1.5 g)). Participants performed the Psychomotor Vigilance Task (PVT) at rest and a Sustained Attention to Response Task (SART) during the 60 min of exercise. Oscillatory electroencephalography (EEG) activity was measured throughout the exercise. The results showed higher mean power output during the 20-min TT in the tramadol vs. paracetamol condition, but no reliable difference was reported between tramadol and placebo (nor paracetamol vs. placebo). Tramadol resulted in faster responses in the PVT and higher heart rate during exercise. The main effect of substance was reliable in the SART during the 40-min constant workload (no during the 20-min TT), with slower reaction time, but better accuracy for tramadol and paracetamol than for placebo. This study supports the increased behavioural and neural efficiency at rest for tramadol but not the proposed ergogenic or cognitive (harmful) effect of tramadol (vs. placebo) during self-paced high-intensity cycling.

Does mental fatigue impair physical performance? A replication study.

The aim of this study is to replicate the hypothesis that mental fatigue impairs physical performance in a pre-registered (https://osf.io/wqkap/) within-subjects experiment. 30 recreationally active adults completed a time-to-exhaustion test (TTE) at 80% VO2max in two separate sessions, after completing a mental fatigue task or watching a documentary for 90 min. We measured power output, heart rate, (session) rating of perceived exertion (RPE) and subjective mental fatigue. Bayes factor analyses revealed extreme evidence supporting the alternative hypothesis that the mental fatigue task was more mentally fatiguing than the control task, BF01 = 0.009. However, we found moderate-to-strong evidence for the null hypothesis (i.e., no evidence of reduced performance) for average time in TTE (BF01 = 9.762) and anecdotal evidence for the null hypothesis in (session) RPE (BF01 = 2.902) and heart rate (BF01 = 2.587). Our data seem to challenge the idea that mental fatigue has a negative influence on exercise performance. Although we did succeed at manipulating subjective mental fatigue, this did not impair physical performance. However, we cannot discard the possibility that mental fatigue may have a negative influence under conditions not explored here, e.g., individualizing mentally fatiguing tasks. In sum, further research is warranted to determine the role of mental fatigue on exercise and sport performance.

Salpingectomía oportunista: patrones de práctica en un grupo de ginecólogos colombianos / Opportunistic Salpingectomy: patterns of practice in a group of colombian gynecologists

INTRODUCCIÓN Y OBJETIVOS: El cáncer de ovario es la neoplasia de origen ginecológico más letal y el 90% de los casos son de origen epitelial. Se ha postulado el origen del cáncer epitelial de ovario (CEO) en las fimbrias de las trompas de Falopio, por lo cual, se ha sugerido la realización de la salpingectomía oportunista como método de prevención primaria. La presente investigación tiene como objetivo determinar la frecuencia con que los ginecólogos adscritos a la Federación Colombiana de Ginecología y Obstetricia (FECOLSOG) incluyeron salpingectomías oportunistas en su práctica clínica durante los años 2017-2018. MÉTODOS: Se realizó una encuesta a los ginecólogos adscritos a la FECOLSOG. Las variables analizadas incluyeron características demográficas, práctica profesional, método de prevención primaria de cáncer de ovario en pacientes de bajo riesgo y la realización o no de la salpingectomía oportunista y sus respectivas razones. Las variables cualitativas se analizaron con frecuencias absolutas y relativas, mientras que las cuantitativas con medidas de tendencia central y desviaciones estándar con el software STATA 13. RESULTADOS: De 1765 ginecólogos contactados, 353 contestaron la encuesta (tasa de respuesta del 20%). El 62.5% de estos realizan salpingectomía oportunista en su práctica ginecológica y de estos, el 75.2% lo hizo para prevenir cáncer de ovario. Entre las razones manifestadas por los especialistas para no realizar salpingectomía oportunista, el 12.5% no la consideraba un factor de protección frente al cáncer de ovario y un 14.4% consideraba que incrementaba el riesgo de falla ovárica temprana y morbilidad asociada. CONCLUSIÓN: Aunque existen controversias en su realización, la salpingectomía oportunista muestra ser una conducta adoptada por ginecólogos adscritos a FECOLSOG. Se requieren investigaciones futuras para determinar la efectividad de la salpingectomía e implementar estrategias de prevención del cáncer epitelial de ovario.

INTRODUCTION AND OBJECTIVES: Ovarian cancer is the most lethal gynecological malignancy and 90% of cases are of epithelial origin. Recently, different investigations attribute their origin to the fimbriae of the fallopian tubes, reason why it has been suggested to perform elective salpingectomy for the prevention of high-grade adenocarcinoma, its most frequent histological variant. This research aims to determine the frequency with which gynecologists from the Colombian Federation of Gynecology and Obstetrics (FECOLSOG) included this procedure in their clinical practice during the years 2017-2018. METHODS: A survey was sent electronically to the gynecologists assigned to FECOLSOG on three different occasions with an interval of 15 days between them. The variables analyzed included demographic characteristics, professional practice, primary prevention method of Ovarian Cancer in low-risk patients and the performance or not of elective salpingectomy with their respective reasons. Qualitative variables were analyzed with absolute and relative frequencies, while quantitative variables with measures of central tendency and standard deviations with STATA 13 software. RESULTS: From 1765 gynecologists contacted at least once via email, 353 answered the survey, indicating a response rate of 20%. 62.5% perform elective salpingectomy in their gynecological practice and of these, 75.2% do so to prevent ovarian cancer. Among the reasons for not practicing salpingectomy, 12.5% ​​do not consider it a protective factor for ovarian cancer, and 14.4% believe that it increases the risk of early ovarian failure and morbidity. CONCLUSION: Elective salpingectomy is a promising procedure as a preventive measure against epithelial ovarian cancer. Although there are controversies regarding its performance, salpingectomy seems to be a common practice amongst gynecologists from FECOLSOG, and seems to have higher recurrence within this field. Future research is required to determine the effectiveness of salpingectomy and thus, implement the best strategies for ovarian cancer prevention.

CoVidAffect, real-time monitoring of mood variations following the COVID-19 outbreak in Spain.

The COVID-19 outbreak and the ensuing confinement measures are expected to bear a significant psychological impact on the affected populations. To date, all available studies designed to investigate the psychological effects of this unprecedented global crisis are based on cross-sectional surveys that do not capture emotional variations over time. Here, we present the data from CoVidAffect, a nationwide citizen science project aimed to provide longitudinal data of mood changes following the COVID-19 outbreak in the spanish territory. Spain is among the most affected countries by the pandemic, with one of the most restrictive and prolonged lockdowns worldwide. The project also collected a baseline of demographic and socioeconomic data. These data can be further analyzed to quantify emotional responses to specific measures and policies, and to understand the effect of context variables on psychological resilience. Importantly, to our knowledge this is the first dataset that offers the opportunity to study the behavior of emotion dynamics in a prolonged lockdown situation.