PIK3CA Mutations and Their Impact on Survival Outcomes of Patients with Cervical Cancer: A Systematic Review

2020 ◽  
Vol 64 (6) ◽  
pp. 547-555
Author(s):  
Vasilios Pergialiotis ◽  
Christina Nikolaou ◽  
Dimitrios Haidopoulos ◽  
Maximos Frountzas ◽  
Nikolaos Thomakos ◽  
...  

<b><i>Introduction:</i></b> Several studies have implicated the PIK3/AKT pathway in the pathophysiology of cancer progression as its activation seems to be aberrant in several forms of cancer. The purpose of the present systematic review is to evaluate the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer. <b><i>Methods:</i></b> We used the Medline (1966–2020), Scopus (2004–2020), ClinicalTrials.gov (2008–2020), EMBASE (1980–2020), Cochrane Central Register of Controlled Trials (CENTRAL) (1999–2020), and Google Scholar (2004–2020) databases in our primary search along with the reference lists of electronically retrieved full-text papers. Statistical meta-analysis was performed with the RevMan 5.3 software. <b><i>Results:</i></b> Overall, 12 articles were included in the present study that comprised 2,196 women with cervical cancer. Of those, 3 studies did not report significant differences in survival outcomes among patients with mutated versus wild-type PIK3CA tumors, 5 studies reported decreased survival outcomes, and 3 studies revealed increased survival rates. The meta-analysis revealed that patients with the mutated PIK3CA genotypes had worse overall survival compared to patients with wild-type PIK3CA (HR 2.31; 95% CI: 1.51, 3.55; 95% PI: 0.54, 9.96; data from 3 studies) and the same was observed in the case of DFS rates (HR 1.82; 95% CI: 1.47, 2.25; 95% PI: 1.29, 2.56; data from 4 studies). <b><i>Conclusion:</i></b> Current evidence concerning the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer is inconclusive, although the majority of included studies support a potential negative effect, primarily among those with squamous cell carcinoma tumors.

2021 ◽  
Vol 10 (19) ◽  
pp. 4462
Author(s):  
Konstantinos G. Kyriakoulis ◽  
Anastasios Kollias ◽  
Garyphallia Poulakou ◽  
Ioannis G. Kyriakoulis ◽  
Ioannis P. Trontzas ◽  
...  

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.


BMJ Open ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. e020183
Author(s):  
Adolf Kofi Awua ◽  
Edna Dzifa Doe

IntroductionFor a country that lacks a national cervical cancer screening/prevention programme, there is the need to assess the volume of country-specific information, and the status of research on HPV and cervical cancer, in order to provide evidence that will inform policy and further research. The aim of this protocol is to plan an intended systematic review, which is to identify research gaps, prevent unnecessary duplication of work and enable collaboration.Methods and analysisThis protocol, developed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement and registered by PROSPERO (CRD42017075583), will apply a 13-point eligibility criteria to screening and selecting peer-reviewed research articles and grey literature. These will be obtained from searches in databases, including, among others, those of the National Centre for Biotechnology Information, Cochrane Central Register of Controlled Trials, Google Scholar and the digital collections database of research publications of Universities in Ghana. Collected data will be aggregated and summarised according to emerging themes and simple descriptive statistics.Ethics and disseminationThe study will use publicly available data and will not identify authors of the publication by name. In light of these and as has been indicted, research ethics clearance is not required for evidence syntheses in such reviews. The review will be published in peer-reviewed scientific journals and presented at local and internal conferences as the opportunity becomes available.PROSPERO registration numberCRD42017075583.


BMJ Open ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. e020991 ◽  
Author(s):  
Wen Wang ◽  
Wenwen Chen ◽  
Yanmei Liu ◽  
Reed Alexander C Siemieniuk ◽  
Ling Li ◽  
...  

ObjectiveTo assess the impact of adjunctive antibiotic therapy on uncomplicated skin abscesses.DesignSystematic review and network meta-analysis.Data sourcesMedline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov.Study selectionA BMJ Rapid Recommendation panel provided input on design, important outcomes and the interpretation of the results. Eligible randomised controlled trials (RCTs) included a comparison of antibiotics against no antibiotics or a comparison of different antibiotics in patients with uncomplicated skin abscesses, and reported outcomes prespecified by the linked guideline panel.Review methodsReviewers independently screened abstracts and full texts for eligibility, assessed risk of bias and extracted data. We performed random-effects meta-analyses that compared antibiotics with no antibiotics, along with a limited number of prespecified subgroup hypotheses. We also performed network meta-analysis with a Bayesian framework to compare effects of different antibiotics. Quality of evidence was assessed with The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsFourteen RCTs including 4198 patients proved eligible. Compared with no antibiotics, antibiotics probably lower the risk of treatment failure (OR 0.58, 95% CI 0.37 to 0.90; low quality), recurrence within 1 month (OR 0.48, 95% CI 0.30 to 0.77; moderate quality), hospitalisation (OR 0.55, 95% CI 0.32 to 0.94; moderate quality) and late recurrence (OR 0.64, 95% CI 0.48 to 0.85; moderate quality). However, relative to no use, antibiotics probably increase the risk of gastrointestinal side effects (trimethoprim and sulfamethoxazole (TMP-SMX): OR 1.28, 95% CI 1.04 to 1.58; moderate quality; clindamycin: OR 2.29, 95% CI 1.35 to 3.88; high quality) and diarrhoea (clindamycin: OR 2.71, 95% CI 1.50 to 4.89; high quality). Cephalosporins did not reduce the risk of treatment failure compared with placebo (moderate quality).ConclusionsIn patients with uncomplicated skin abscesses, moderate-to-high quality evidence suggests TMP-SMX or clindamycin confer a modest benefit for several important outcomes, but this is offset by a similar risk of adverse effects. Clindamycin has a substantially higher risk of diarrhoea than TMP-SMX. Cephalosporins are probably not effective.


BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e041184
Author(s):  
Dan Wang ◽  
Jin Li ◽  
Feilong Zhu ◽  
Qianqin Hong ◽  
Ming Zhang ◽  
...  

IntroductionBoth physical and mental disorders may be exacerbated in patients with COVID-19 due to the experience of receiving intensive care; undergoing prolonged mechanical ventilation, sedation, proning and paralysis. Pulmonary rehabilitation is aimed to improve dyspnoea, relieve anxiety and depression, reduce the incidence of related complications, as well as prevent and improve dysfunction. However, the impact of respiratory rehabilitation on discharged patients with COVID-19 is currently unclear, especially on patients who have been mechanically ventilated over 24 hours. Therefore, we aim to investigate the efficacy of respiratory rehabilitation programmes, initiated after discharge from the intensive care unit, on the physical and mental health and health-related quality of life in critical patients with COVID-19.Methods and analysisWe have registered the protocol on PROSPERO and in the process of drafting it, we strictly followed the checklist of Preferred Reporting Items for Systematic Review and Meta-Analysis Potocols. We will search the PubMed, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, WanFang, VIP information databases and Chinese Biomedical Literature Database. Additionally, ongoing trials in the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov and ISRCTN registry will be searched as well. Studies in English or Chinese and from any country will be accepted regardless of study design. Two review authors will independently extract data and assess the quality of included studies. Continuous data are described as standard mean differences (SMDs) with 95% CIs. Dichotomous data from randomised controlled trials are described as risk ratio(RR) with 95% CIs; otherwise, it is described as odds ratio(OR) with 95% CIs. I2 and the Cochrane’s Q statistic will be used to conduct heterogeneity assessment. The quality of evidence of main outcomes will be evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation(GRADE) criteria. When included studies are sufficient, we will conduct subgroup analysis and sensitivity analysis; the publication bias will be statistically analysed using a funnel plot analysis and Egger’s test.Ethics and disseminationOur review, planning to include published studies, does not need the request to the ethical committee. The final results of this review will be published in a peer-reviewed journal after completion.Patient and public involvementNo patient involved.PROSPERO registration numberCRD42020186791.


2020 ◽  
Author(s):  
Ben Grodzinski ◽  
Rory Durham ◽  
Oliver Mowforth ◽  
Daniel Stubbs ◽  
Mark R N Kotter ◽  
...  

Abstract Objective Degenerative cervical myelopathy (DCM) is a disabling neurological condition. The underlying degenerative changes are known to be more common with age, but the impact of age on clinical aspects of DCM has never been synthesised. The objective of this study is to determine whether age is a significant predictor in three domains—clinical presentation, surgical management and post-operative outcomes of DCM. Methods a systematic review of the Medline and Embase databases (inception to 12 December 2019), registered with PROSPERO (CRD42019162077) and reported in accordance with preferred reporting items of systematic reviews and meta-analysis (PRISMA) guidelines, was conducted. The inclusion criteria were full text articles in English, evaluating the impact of age on clinical aspects of DCM. Results the initial search yielded 2,420 citations, of which 206 articles were eventually included. Age was found to be a significant predictor in a variety of measures. Within the presentation domain, older patients have a worse pre-operative functional status. Within the management domain, older patients are more likely to undergo posterior surgery, with more levels decompressed. Within the outcomes domain, older patients have a worse post-operative functional status, but a similar amount of improvement in functional status. Because of heterogenous data reporting, meta-analysis was not possible. Conclusion the current evidence demonstrates that age significantly influences the presentation, management and outcomes of DCM. Although older patients have worse health at all individual timepoints, they experience the same absolute benefit from surgery as younger patients. This finding is of particular relevance when considering the eligibility of older patients for surgery.


Author(s):  
Fernando Magro ◽  
Maria Manuela Estevinho ◽  
Cláudia Camila Dias ◽  
Luís Correia ◽  
Paula Lago ◽  
...  

Abstract Background and Aims Interest in histology for ulcerative colitis [UC] has increased recently. This systematic review and meta-analysis aims to assess, for the first time, whether histological outcomes are more informative than endoscopic and clinical outcomes in distinguishing the impact of intervention over placebo in induction trials. Methods MEDLINE, ScienceDirect and Cochrane Central Register of Controlled Trials were searched to identify randomized placebo-controlled trials [RCTs] enrolling moderate-to-severe UC patients. Studies were assessed using the Quality Assessment Tool for Studies with Diverse Designs. We analysed the pooled proportion of patients achieving clinical, endoscopic and histological remission and response after a pharmacological intervention and compared the results with those of placebo-treated patients by using a random-effects model. Results From 889 identified records, 13 RCTs were included. The odds ratio [OR] for remission was higher in patients receiving intervention than in those under placebo for clinical (OR 2.13, 95% confidence interval [CI] 1.33–3.43), endoscopic [OR 1.46, 95% CI 0.19–11.18] and histological remission [OR 1.85, 95% CI 1.20–2.84]. Significant differences were observed for all response outcomes [clinical: OR 2.27, 95% CI 1.84–2.85; endoscopic: OR 2.16, 95% CI 1.51–3.10; histological: OR 3.63, 95% CI, 1.41–9.36]. No significant heterogeneity existed; no subgroup effects were found for duration of the induction or histological scale [p &gt; 0.05]. Clinical and histological remission and endoscopic response were concordant in discriminating interventions from placebo. Conclusion Histological outcomes are informative in trials of moderate-to-severe UC. Further studies analysing histology at the end of induction are needed to confirm its relevance in distinguishing the efficacy of an intervention over placebo in comparison to clinical and endoscopic outcomes and to explore its prognostic value.


2020 ◽  
pp. 026921552095193
Author(s):  
Alberto Saavedra-García ◽  
Jose A Moral-Munoz ◽  
David Lucena-Anton

Objective: To evaluate the current evidence on the effectiveness of simultaneous combination of mirror therapy and electrical stimulation in the recovery of upper limb motor function after stroke, compared with conventional therapy, mirror therapy or electrical stimulation isolated. Data sources: Articles published in PubMed, Web of Science, Scopus, Physiotherapy Evidence Database (PEDro), Cochrane Central register of controlled trials and ScienceDirect up to July 2020. Review methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Methodological quality was assessed using the PEDro tool. The RevMan 5.4 statistical software was used to obtain the meta-analysis, through the standardized mean difference and 95% confidence intervals (CI), and to evaluate the risk of bias. The GRADE approach was employed to assess the certainty of evidence. Results: Eight articles were included in this systematic review, seven were included in the meta-analysis. A total of 314 participants were analyzed. The overall quality of the articles included in this review was good. There was no overall significant mean difference on upper limb motor function after stroke using the Upper-Extremity Fugl-Meyer Assessment by 1.56 (95% CI = –2.08, 5.20; P = 0.40; moderate-certainty evidence) and the Box and Block Test results by 1.39 (95% CI = –2.14, 4.92; P = 0.44; high-certainty evidence). There was overall significant difference in the Action Research Arm Test by 3.54 (95% CI = 0.18, 6.90; P = 0.04; high-certainty evidence). Conclusion: Direct scientific evidence about the effectiveness of the combined therapy of mirror therapy and electrical stimulation simultaneously for the improvement of the upper limb motor function after stroke is lacking. Further high-quality and well-designed research is needed.


BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040282
Author(s):  
Zhiyuan Jiang ◽  
Zhaolun Cai ◽  
Yuan Yin ◽  
Chaoyong Shen ◽  
Jinming Huang ◽  
...  

IntroductionGenerally, complete resection with cancer cell negative (R0) margin has been accepted as the most effective treatment of gastric cancer and positive resection (R1/R2) margin has been associated with decreased survival to varied degrees. However, the independent impact of microscopical positive (R1) margin on long-term survival may be confounded. No meta-analysis has worked at the association between R1 margin and outcomes of gastric cancer and the available evidence are scant. Therefore, we plan to conduct a systematic review and meta-analysis to quantitatively explore the role of R1 margin on gastric (including oesophagogastric junction) cancer survival after curative intent resection.Methods and analysisThe protocol was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guideline. A systematic search of PubMed, Embase and the Cochrane Central Register of Controlled Trials databases will be performed from their inceptions to 30 April 2020 to identify randomised controlled trials (RCTs), cohort studies and case–control studies focusing on the impact of R1 margin on survival of gastric cancer after curative intent resection. The primary outcome will be the overall survival (OS) and disease-free survival (DFS) and the secondary outcomes will be 5-year OS rate and 5-year DFS rate. The Cochrane tool for bias assessment in randomised trials and Risk Of Bias In Non-randomised Studies-I for the assessment of bias in non-randomised studies (NRS) will be used. Statistical heterogeneity will be assessed by visual inspection of forest plots and measured using the I2 statistics. A fixed-effect model will be used when heterogeneity is low, otherwise, a random-effect model will be chosen. Publication bias will be assessed by funnel plots, subgroup analysis and sensitivity analysis will be performed in the right context. For each outcome, we will perform data synthesis separately for RCTs and NRS using Rev Man V.5.3 software and compile ‘summary of findings’ tables separately for RCTs and NRS using GRADEpro software. Grading of Recommendations, Assessment, Development and Evaluations considerations will also be used to make an overall assessment of the quality of evidence.Ethics and disseminationThere is no requirement for ethics approval because no patient data will be collected at an individual level in this systematic review and meta-analysis.The results of this systematic review will be published in a peer-reviewed journal and presented at relevant conferences, any deviations from the protocol will be clearly documented and explained in its final report.PROSPERO registration numberCRD42020165110.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2070 ◽  
Author(s):  
Fatma Ilgaz ◽  
Alex Pinto ◽  
Hülya Gökmen-Özel ◽  
Julio César Rocha ◽  
Esther van Dam ◽  
...  

There is an ongoing debate regarding the impact of phenylketonuria (PKU) and its treatment on growth. To date, evidence from studies is inconsistent, and data on the whole developmental period is limited. The primary aim of this systematic review was to investigate the effects of a phenylalanine (Phe)-restricted diet on long-term growth in patients with PKU. Four electronic databases were searched for articles published until September 2018. A total of 887 results were found, but only 13 articles met eligibility criteria. Only three studies had an adequate methodology for meta-analysis. Although the results indicate normal growth at birth and during infancy, children with PKU were significantly shorter and had lower weight for age than reference populations during the first four years of life. Impaired linear growth was observed until the end of adolescence in PKU. In contrast, growth impairment was not reported in patients with mild hyperphenylalaninemia, not requiring dietary restriction. Current evidence indicates that even with advances in dietary treatments, “optimal” growth outcomes are not attained in PKU. The majority of studies include children born before 1990s, so further research is needed to show the effects of recent dietary practices on growth in PKU.


Neurosurgery ◽  
2017 ◽  
Vol 80 (5) ◽  
pp. 701-715 ◽  
Author(s):  
Daniel Yavin ◽  
Steven Casha ◽  
Samuel Wiebe ◽  
Thomas E Feasby ◽  
Callie Clark ◽  
...  

Abstract BACKGROUND: Due to uncertain evidence, lumbar fusion for degenerative indications is associated with the greatest measured practice variation of any surgical procedure. OBJECTIVE: To summarize the current evidence on the comparative safety and efficacy of lumbar fusion, decompression-alone, or nonoperative care for degenerative indications. METHODS: A systematic review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (up to June 30, 2016). Comparative studies reporting validated measures of safety or efficacy were included. Treatment effects were calculated through DerSimonian and Laird random effects models. RESULTS: The literature search yielded 65 studies (19 randomized controlled trials, 16 prospective cohort studies, 15 retrospective cohort studies, and 15 registries) enrolling a total of 302 620 patients. Disability, pain, and patient satisfaction following fusion, decompression-alone, or nonoperative care were dependent on surgical indications and study methodology. Relative to decompression-alone, the risk of reoperation following fusion was increased for spinal stenosis (relative risk [RR] 1.17, 95% confidence interval [CI] 1.06-1.28) and decreased for spondylolisthesis (RR 0.75, 95% CI 0.68-0.83). Among patients with spinal stenosis, complications were more frequent following fusion (RR 1.87, 95% CI 1.18-2.96). Mortality was not significantly associated with any treatment modality. CONCLUSION: Positive clinical change was greatest in patients undergoing fusion for spondylolisthesis while complications and the risk of reoperation limited the benefit of fusion for spinal stenosis. The relative safety and efficacy of fusion for chronic low back pain suggests careful patient selection is required (PROSPERO International Prospective Register of Systematic Reviews number, CRD42015020153).


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