Pembrolizumab plus GX-188E therapeutic DNA vaccine in patients with HPV-16-positive or HPV-18-positive advanced cervical cancer: interim results of a single-arm, phase 2 trial.

BACKGROUND: Survival outcomes for patients with recurrent or advanced cervical cancer are poor. Pembrolizumab has been approved for the treatment of recurrent or metastatic cervical cancer, with an overall response rate of 14·3%. GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6-specific and E7-specific T-cell responses and cervical lesion regression in patients with cervical precancer. We aimed to investigate whether a combination of GX-188E therapeutic DNA vaccine plus pembrolizumab showed antitumour activity against recurrent or advanced cervical cancer. METHODS: In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced, inoperable cervical cancer, who were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically confirmed recurrent or advanced HPV-positive (HPV-16 or HPV-18) cervical cancer, and who had progressed after available standard-of-care therapy were recruited from seven hospitals in South Korea. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, and 19, with one optional dose at week 46 that was at the investigator's discretion, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the overall response rate within 24 weeks assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 in patients who received at least 45 days of treatment 45 days of treatment with at least one post-baseline tumour assessment, and this is the report of a planned interim analysis. This trial is registered with ClinicalTrials.gov, NCT03444376. FINDINGS: Between June 19, 2018, and March 20, 2020, 36 patients were enrolled and received at least one dose of the study treatment. 26 patients were evaluable for interim activity assessment, with at least one post-baseline tumour assessment at week 10. At the data cutoff date on March 30, 2020, median follow-up duration was 6·2 months (IQR 3·5-8·1). At 24 weeks, 11 (42%; 95% CI 23-63) of 26 patients achieved an overall response; four (15%) had a complete response and seven (27%) had a partial response. 16 (44%) of 36 patients had treatment-related adverse events of any grade and four (11%) had grade 3-4 treatment-related adverse events. Grade 3 increased aspartate aminotransferase, syncope, pericardial effusion, and hyperkalaemia, and grade 4 increased alanine aminotransferase were reported in one patient each. No treatment-related deaths were reported. INTERPRETATION: Treatment with GX-188E therapeutic vaccine plus pembrolizumab for patients with recurrent or advanced cervical cancer was safe and treatment-related adverse events were manageable. This combination therapy showed preliminary antitumour activity in this interim analysis, which could represent a new potential treatment option for this patient population. This trial is ongoing. FUNDING: National OncoVenture.

Sport-based physical activity intervention on body weight in children and adolescents: a meta-analysis.

Controversial results reported in past research pertaining to the effectiveness of sport-based physical activity interventions on weight loss. The purpose of this study was to assess the impact of sport-based physical activity intervention on body weight in children and adolescents using a meta-analysis. Academic Search Complete, Education Source, ERIC, Medline, ProQuest, PsycINFO and SportDiscus databases were searched from January 2000 to April 2015. Eighteen studies met following inclusion criteria: sport-based intervention studies; subjects aged 6-18 years; reported body weight; published in peer-reviewed journals written in English. The mean intervention duration was 17.72 weeks. The overall effect size (ES) was 0.52 (Cohen's d (ES) = 0.52, 95% CI = 0.08, 0.95, P = 0.021), using a random effects model. Moderator analyses results showed that the Q statistic for the sport type (individual sport or team sport, Qbetween (Qb) = 14.52, df = 1, P = 0.001) and diet control (Qbetween (Qb) = 8.85, df = 1, P = 0.001), explained the heterogeneity of ESs. Our study showed that there was a moderate overall effect of sport-based physical activity intervention on body weight reduction. The team sport type (ES = 1.05, 95% CI = 0.44, 1.66) and diet control group (ES = 0.84, 95% CI = 0.26, 1.41) appeared to be more effective in reducing body weight.

Effects of Training with Blood Flow Restriction on Muscular Strength: A Systematic Review and Meta-Analysis.

The purpose of this study was to analyze how blood flow restriction (BFR) training influences muscular strength through a systematic review and meta-analysis. The review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. The following databases were used to conduct the research: Academic Search Complete, Medline, Web of Science, SPORT-Discus, HealthSource: Consumer, and HealthSource: Nursing. The following search limitations were included in this study: full-text articles investigating the effects of BFR training on muscular strength, published in a peer-reviewed academic journal, and published in the English language. Out of 327 articles, 25 were eligible to be included in this study. Comprehensive meta-analysis v.3 software was used to run statistics of the collected data from each study. The results showed that BFR training positively affects muscular strength. However, no group difference was found by gender, duration, workload, and cuff type/pressure in current data. This study provides additional information that can be used in future studies to obtain optimum strength results during BFR training.

The Effectiveness of Physical Activity Interventions for Low-Income and Ethnic Minority Children and Youths: A Meta-Analysis.

BACKGROUND: Children and youths from low-income families and certain ethnic minority groups show high levels of risk and vulnerability to physical inactivity. The aim of this review was to examine the effectiveness of interventions to increase physical activity (PA) in children and youths from low-income and ethnic minority (LIEM) families. METHODS: Eight databases were systematically searched for PA interventions for LIEM children and youths. Twenty-six studies were included in the analyses. Effect sizes (ESs) were calculated using a random-effects model. The ESs were computed using Hedges g with 95% confidence interval. RESULTS: There were small to medium effects of interventions on PA in LIEM children and youth (Q = 1499.193, df = 30, P < .05; I2 = 97.999). Analyses on the moderator variables showed that ES for participants aged 9-12 years (ES = 0.542, P = .01); intervention length less than 13 weeks (ES = 0.561, P = .01); specialists as the intervention agent (ES = 0.680, P < .05); interventions without technology (ES = 0.363, P = .02); and interventions with a behavioral modification component (ES = 0.336, P = .03) were significantly different from zero. CONCLUSION: PA intervention can be an effective strategy to increase PA for LIEM children and youths.

Effects of exercise intervention on visceral fat in obese children and adolescents.

INTRODUCTION: This meta-analysis study was aimed to assess the effects of exercise intervention on visceral fat in obese children and adolescents. EVIDENCE ACQUISITION: Electronic database searches were performed in Academic Search Complete, CINAHL, Healthsource, MEDLINE, and SportDiscus, and from the earliest record to November 2017. Keywords included "exercise or training," "visceral fat," and "child or adolescent or youth." The inclusion criteria for eligible studies were as follows: 1) subjects were obese at baseline; 2) aged 6-19 years; 3) visceral fat was reported at baseline and after an intervention; and 4) studies were published in peer-reviewed journals written in English. EVIDENCE SYNTHESIS: A total of 207 studies were observed at the initial search and 73 effect sizes (ESs) were derived from the 34 selected studies. The overall exercise intervention effect was large (Cohen's d [ES]=-1.003, 95% CI=-1.114, -0.892). Moderator analyses results showed that gender (Qb=8.23, df=2, P=0.016), exercise type (Qb=10.68, df=2, P=0.005), and intervention length (Qb=24.71, df=2, P<0.001) influenced the overall ES. CONCLUSIONS: The group of both boys and girls (ES=-0.95) who participated combined exercise program (Aerobic + Resistance training; ES=-1.17) for 12 months (ES=-1.24) appeared to be the most effective exercise strategy for reducing visceral fat in obese youth.

Effect of Exercise Intervention on Flow-Mediated Dilation in Overweight and Obese Adults: Meta-Analysis.

The objective of this meta-analysis is to summarize the effect of exercise intervention on flow-mediated dilatation (FMD) in overweight and obese adults. We searched four electronic databases (PubMed/Medline, Scopus, and CINAHL) through June 2016 for relevant studies pertaining to the effectiveness of exercise intervention on FMD. Seventeen of the 91 studies identified met the inclusion criteria. Comprehensive Meta-Analysis software (version 3) was used to compute the standardized mean difference effect size (ES) and 95% CI using a random effects model. We calculated 34 ESs. We found that exercise intervention had medium and positive effects on FMD, with an overall ES of 0.522 (95% CI = 0.257, 0.786). Heterogeneity of ESs was observed (Qb = 239, p ≤ 0.001, I2 = 86.19), and the effect was moderated by comorbidity (Qb = 6.39, df = 1, p = 0.011). A large ES for the combination exercise, low intensity exercise, and comorbidity subgroups (ES = 0.82~1.24) was found. We conclude that while exercise intervention significantly improves FMD in overweight and obese adults, the effect may depend on the different characteristics of exercise intervention and on participants' demographics.

Stimulated penetrating keratoplasty using real-time virtual intraoperative surgical optical coherence tomography.

An intraoperative surgical microscope is an essential tool in a neuro- or ophthalmological surgical environment. Yet, it has an inherent limitation to classify subsurface information because it only provides the surface images. To compensate for and assist in this problem, combining the surgical microscope with optical coherence tomography (OCT) has been adapted. We developed a real-time virtual intraoperative surgical OCT (VISOCT) system by adapting a spectral-domain OCT scanner with a commercial surgical microscope. Thanks to our custom-made beam splitting and image display subsystems, the OCT images and microscopic images are simultaneously visualized through an ocular lens or the eyepiece of the microscope. This improvement helps surgeons to focus on the operation without distraction to view OCT images on another separate display. Moreover, displaying the OCT live images on the eyepiece helps surgeon's depth perception during the surgeries. Finally, we successfully processed stimulated penetrating keratoplasty in live rabbits. We believe that these technical achievements are crucial to enhance the usability of the VISOCT system in a real surgical operating condition.