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.

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.

Isolation and phenotypic characterization of tumor cells of patients with a diagnosis of ovarian cancer.

Ovarian cancer is the fifth leading cause of cancer-related deaths. It causes approximately 125,000 deaths per year worldwide; its diagnosis is made in advanced stages resulting in a high mortality rate. The objective of the study was optimizing the isolation of cells obtained from the solid tumor and ascitic fluid of patients with ovarian cancer and the phenotype with markers related to the epithelial-mesenchymal transition. For this, the solid tumor tissue was disaggregated and cultivated with different methodologies. As a result, cell growth was obtained and epi-immunofluorescence was performed using antibodies against E-cadherin, EpCAM, N-cadherin, vimentin, CD133, and CD44. The primary culture from the solid tumor was obtained using Dispase II and DMEM/F12. Finally, heterogeneity was detected in terms of the expression of mesenchymal and epithelial type markers in the two types of isolated cells. Additionally, CD133 and CD44 expression was detected, proteins associated with the tumor stem cells phenotype.

Same-Day Discharge in Minimally Invasive Surgery Performed by Gynecologic Oncologists: A Review of Patient Selection.

OBJECTIVE: To review the literature about same-day discharge (SDD) in minimally invasive surgery performed by gynecologic oncologists and identify factors associated with SDD and admission to provide selection criteria. DATA SOURCES: Systematic review of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and SCOPUS between May 2007 and May 2019. The search included the following medical subject heading terms and keywords: "same day discharge," "patient discharge," "minimally invasive surgical procedures," "hysterectomy," "gynecologic malignancy," "gynecologic neoplasm," "cervical cancer," "ovarian cancer," and "endometrial cancer." METHODS OF STUDY SELECTION: Articles published in English about women who underwent minimally invasive procedures for benign and malignant conditions of the reproductive tract performed by gynecologic oncologists (robotic or laparoscopic) and who received SDD or admission were included. The following were described: SDD and admission rate, readmission or unscheduled evaluation rates within 30 days after surgery, and associated factors for each one. TABULATION, INTEGRATION, AND RESULTS: Nine studies with a total of 16 423 patients were included. The complication rates in the studies were variable, with only 2 studies showing advantages in the SDD group with respect to intraoperative complications and wound complications. There were no statistically significant differences in postoperative complications in the first 30 days after the adoption of SDD. There were no higher readmission rates within the first 30 days in the group of patients who were discharged on the same day vs those admitted. The common factors associated with admission were as follows: age <70 years, surgery after 1 PM, duration of surgery more than 2 hours, and intraoperative complications. Other factors to consider were the presence of comorbidities that require follow-up within the hospital after surgery, adequate postoperative evaluation, and the patient accepting SDD. CONCLUSION: SDD seems to be safe and feasible in minimally invasive surgery performed by gynecologic oncologists. The proposed selection criteria includes the following: younger than 70 years, surgery before 1 PM, procedure less than 2 hours, and no intraoperative complications.

Smartphone-Based Platform for Affect Monitoring through Flexibly Managed Experience Sampling Methods.

The identification of daily life events that trigger significant changes on our affective state has become a fundamental task in emotional research. To achieve it, the affective states must be assessed in real-time, along with situational information that could contextualize the affective data acquired. However, the objective monitoring of the affective states and the context is still in an early stage. Mobile technologies can help to achieve this task providing immediate and objective data of the users' context and facilitating the assessment of their affective states. Previous works have developed mobile apps for monitoring affective states and context, but they use a fixed methodology which does not allow for making changes based on the progress of the study. This work presents a multimodal platform which leverages the potential of the smartphone sensors and the Experience Sampling Methods (ESM) to provide a continuous monitoring of the affective states and the context in an ubiquitous way. The platform integrates several elements aimed to expedite the real-time management of the ESM questionnaires. In order to show the potential of the platform, and evaluate its usability and its suitability for real-time assessment of affective states, a pilot study has been conducted. The results demonstrate an excellent usability level and a good acceptance from the users and the specialists that conducted the study, and lead to some suggestions for improving the data quality of mobile context-aware ESM-based systems.

Physical exercise increases overall brain oscillatory activity but does not influence inhibitory control in young adults.

Extant evidence suggests that acute exercise triggers a tonic power increase in the alpha frequency band at frontal locations, which has been linked to benefits in cognitive function. However, recent literature has questioned such a selective effect on a particular frequency band, indicating a rather overall power increase across the entire frequency spectrum. Moreover, the nature of task-evoked oscillatory brain activity associated to inhibitory control after exercising, and the duration of the exercise effect, are not yet clear. Here, we investigate for the first time steady state oscillatory brain activity during and following an acute bout of aerobic exercise at two different exercise intensities (moderate-to-high and light), by means of a data-driven cluster-based approach to describe the spatio-temporal distribution of exercise-induced effects on brain function without prior assumptions on any frequency range or site of interest. We also assess the transient oscillatory brain activity elicited by stimulus presentation, as well as behavioural performance, in two inhibitory control (flanker) tasks, one performed after a short delay following the physical exercise and another completed after a rest period of 15' post-exercise to explore the time course of exercise-induced changes on brain function and cognitive performance. The results show that oscillatory brain activity increases during exercise compared to the resting state, and that this increase is higher during the moderate-to-high intensity exercise with respect to the light intensity exercise. In addition, our results show that the global pattern of increased oscillatory brain activity is not specific to any concrete surface localization in slow frequencies, while in faster frequencies this effect is located in parieto-occipital sites. Notably, the exercise-induced increase in oscillatory brain activity disappears immediately after the end of the exercise bout. Neither transient (event-related) oscillatory activity, nor behavioural performance during the flanker tasks following exercise showed significant between-intensity differences. The present findings help elucidate the effect of physical exercise on oscillatory brain activity and challenge previous research suggesting improved inhibitory control following moderate-to-high acute exercise.

Radical parametrectomy after 'cut-through' hysterectomy in low-risk early-stage cervical cancer: Time to consider this procedure obsolete.

OBJECTIVE: The goal of this study is to identify predictive factors in patients with a diagnosis of early-stage cervical cancer after simple hysterectomy in order to avoid a radical parametrectomy. METHODS: A retrospective review was performed of all patients who underwent radical parametrectomy and bilateral pelvic lymphadenectomy at MD Anderson Cancer Center and at the Instituto de Cancerologia Las Americas in Medellin, Colombia from December 1999 to September 2017. We sought to determine the outcomes in patients diagnosed with low-risk factors (squamous, adenocarcinoma or adenosquamous lesions<2cm in size, and invading<10mm) undergoing radical parametrectomy and pelvic lymphadenectomy. RESULTS: A total of 30 patients were included in the study. The median age was 40.4years (range; 26-60) and median body mass index (BMI) was 26.4kg/m2 (range; 17.7-40.0). A total 22 patients had tumors<1cm and 8 had tumors between 1 and 2cm. A total of 6 (33%) of 18 patients had evidence of lymph-vascular invasion (LVSI). No radical parametrectomy specimen had residual tumor, involvement of the parametrium, vaginal margin positivity, or lymph node metastasis. None of the patients received adjuvant therapy. After a median follow-up of 99months (range; 6-160) only one patient recurred. CONCLUSION: Radical parametrectomy may be avoided in patients with low-risk early-stage cervical cancer detected after a simple hysterectomy. Rates of residual disease (parametrial or vaginal) and the need for adjuvant treatments or recurrences are very low.

Contextual factors multiplex to control multisensory processes.

This study analyzed high-density event-related potentials (ERPs) within an electrical neuroimaging framework to provide insights regarding the interaction between multisensory processes and stimulus probabilities. Specifically, we identified the spatiotemporal brain mechanisms by which the proportion of temporally congruent and task-irrelevant auditory information influences stimulus processing during a visual duration discrimination task. The spatial position (top/bottom) of the visual stimulus was indicative of how frequently the visual and auditory stimuli would be congruent in their duration (i.e., context of congruence). Stronger influences of irrelevant sound were observed when contexts associated with a high proportion of auditory-visual congruence repeated and also when contexts associated with a low proportion of congruence switched. Context of congruence and context transition resulted in weaker brain responses at 228 to 257 ms poststimulus to conditions giving rise to larger behavioral cross-modal interactions. Importantly, a control oddball task revealed that both congruent and incongruent audiovisual stimuli triggered equivalent non-linear multisensory interactions when congruence was not a relevant dimension. Collectively, these results are well explained by statistical learning, which links a particular context (here: a spatial location) with a certain level of top-down attentional control that further modulates cross-modal interactions based on whether a particular context repeated or changed. The current findings shed new light on the importance of context-based control over multisensory processing, whose influences multiplex across finer and broader time scales.

Attentional orienting to own and others' hands.

High-density electroencephalographic recordings were used to investigate the level of analysis at which attentional expectations modulate the processing of specific stimuli from the same perceptual category but differentiated in terms of a particular non-perceptual feature: body ownership. We used a task in which colour cues predicted whether a picture of a hand stimulus belonged to the participant or to somebody else. Participants were instructed to respond whether the target was a left or a right hand. Results revealed that the ERP pattern depended on stimulus ownership and attention orienting, which influenced the visual processing of own and someone else's hands differentially. Larger amplitude for others' than for own hands was shown at the N1 deflection (at the right hemisphere). Attentional effects were found at the P2 and P3 potentials. The P2 reflected an interaction between stimulus ownership and attentional orienting, due to a larger validity effect for others' hands. At the P3 level, the data showed a significant validity effect only for self-hand stimuli. In sum, our results suggest that (1) differences as a function of stimulus ownership can be detected at early levels of stimulus processing; (2) endogenous attention can be directed to exemplars within the same category, hand stimuli in this case; (3) the effects of attention are modulated by ownership.

Attention to individual identities modulates face processing.

The ability of attention to apply in a flexible manner to several types of information at various stages of processing has been studied extensively. However, the susceptibility of these effects to the nature of the idiosyncratic items being attended is less understood. In the current study, we used symbolic cues to orient the attention of participants to the subsequent appearance of the face of a famous person (the former king of Spain) or an unfamiliar face. These were matched in perceptual characteristics. Behavioral effects showed that face-specific attention optimized response speed in an orthogonal task when the target matched the cue (valid trials) compared to when it did not (invalid trials). According to topographical analyses of the electrophysiological data, the famous and unfamiliar faces engaged dissociable brain circuits in two different temporal windows, from 144 to 300 ms after target processing, and at a later 456-492 ms epoch. In addition, orienting attention to specific faces modulated the perceptual stages reflected in the P1 and N170 potentials but with a different laterality pattern that depended on the familiarity of the faces. Whereas only attention to the famous face enhanced the P1 potential at left posterior electrodes, with no corresponding effect for the unfamiliar face at this stage, the N170 was modulated at left posterior sites for the famous item and at right homologous electrodes for the unfamiliar face. Intermediate processing stages, previously linked to facial identity processing indexed by the P2 and N2 potentials, reflected item familiarity but were not affected by the cueing manipulation. At the P3 level, attention influenced again item processing but did so in an equivalent manner for the famous and unfamiliar face. Our results, showing that identity-specific attention modulates perceptual stages of facial processing at different locations depending on idiosyncratic stimulus familiarity, may inform comparison of studies employing items with different degrees of novelty.

Intense Physical Exercise Reduces Overt Attentional Capture.

The abrupt onset of a visual stimulus typically results in overt attentional capture, which can be quantified by saccadic eye movements. Here, we tested whether attentional capture following onset of task-irrelevant visual stimuli (new object) is reduced after a bout of intense physical exercise. A group of participants performed a visual search task in two different activity conditions: rest, without any prior effort, and effort, immediately after an acute bout of intense exercise. The results showed that participants exhibited (1) slower reaction time of the first saccade toward the target when a new object was simultaneously presented in the visual field, but only in the rest activity condition, and (2) more saccades to the new object in the rest activity condition than in the effort activity condition. We suggest that immediately after an acute bout of effort, participants improved their ability to inhibit irrelevant (distracting) stimuli.

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.

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.