The efficacy of topical imiquimod in high-grade cervical intraepithelial neoplasia:A systematic review and meta-analysis

Objective: A major side effect of cervical excision for high-grade cervical intraepithelial neoplasia (CIN) is premature birth. A non-invasive treatment for reproductive age women is warranted. The aim of the present study was to determine the efficacy of topical imiquimod in the treatment of high-grade CIN, defined as a regression to ≤CIN 1, and to determine the clearance rate of high-risk human papillomavirus (hr-HPV), compared with surgical treatment and placebo. Methods: Databases were searched for articles from their inception to February 2023.The study protocol number was INPLASY2022110046. Original studies reporting the efficacy of topical imiquimod in CIN 2, CIN 3 or persistent hr-HPV infections were included. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist. Results: Five studies were included (n = 463). Histological regression to ≤CIN 1 was 55% in imiquimod versus 29% in placebo, and 93% in surgical treatment. Imiquimod-treated women had a greater odds of histological regression to ≤CIN 1 than placebo (odds ratio [OR] 4.17, 95% confidence interval [CI] 2.03–8.54). In comparison to imiquimod, surgical treatment had an OR of 14.81(95% CI 6.59–33.27) for histological regression to ≤CIN 1. The hr-HPV clearance rate was 53.4% after imiquimod and 66% after surgical treatment (95% CI 0.62–23.77). Conclusions: The histological regression rate is highest for surgical treatment followed by imiquimod treatment and placebo.</p

Topical Imiquimod Treatment of High-grade Cervical Intraepithelial Neoplasia (TOPIC-3):A Nonrandomized Multicenter Study

Topical imiquimod could be an alternative, noninvasive, treatment modality for high-grade cervical intraepithelial neoplasia (CIN). However, evidence is limited, and there are no studies that compared treatment effectiveness and side effects of topical imiquimod cream to standard large loop excision of the transformation zone (LLETZ) treatment. A multi-center, nonrandomized controlled trial was performed among women with a histologic diagnosis of CIN 2/3. Women were treated with either vaginal imiquimod (6.25 mg 3 times weekly for 8 to 16 wk) or LLETZ according to their own preference. Successful treatment was defined as the absence of high-grade dysplasia at the first follow-up interval after treatment (at 20 wk for the imiquimod group and at 26 wk for the LLETZ group). Secondary outcome measures were high-risk human papillomavirus (hrHPV) clearance, side effects, and predictive factors for successful imiquimod treatment. Imiquimod treatment was successful in 60% of women who completed imiquimod treatment and 95% of women treated with LLETZ. hrHPV clearance occurred in 69% and 67% in the imiquimod group and LLETZ group, respectively. This study provides further evidence on topical imiquimod cream as a feasible and safe treatment modality for high-grade CIN. Although the effectiveness is considerably lower than LLETZ treatment, imiquimod treatment could prevent initial surgical treatment in over 40% of women and should be offered to a selected population of women who wish to avoid (repeated) surgical treatment of high-grade CIN

Evaluation of effectiveness of the PlasmaJet surgical device in the treatment of advanced stage ovarian cancer (PlaComOv-study): study protocol of a randomized controlled trial in the Netherlands

Background: The most important goal for survival benefit of advanced stage ovarian cancer is to surgically remove all visible tumour, because complete cytoreductive surgery (CCS) has been shown to be associated with prolonged survival. In a remarkable number of women, CCS is very challenging. Especially in women with many small metastases on the peritoneum and intestinal surface, conventional CCS with electrosurgery is not able to be “complete” in removing safely all visible tumour. In this randomized controlled trail (RCT) we investigate whether the use of the PlasmaJet Surgical Device increases the rate of CCS, and whether this indeed leads to a longer progression free and overall survival. The main research question is: does the use of the PlasmaJet Surgical Device in surgery for advanced stage ovarian cancer result in an increased number of complete cytoreductive surgeries when compared with conventional surgical techniques. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Methods: The study design is a multicentre single-blinded superiority RCT in two university and nine non-university hospitals in The Netherlands. Three hundred and thirty women undergoing cytoreductive surgery for advanced stage ovarian carcinoma (FIGO Stage IIIB-IV) will be randomized into two arms: use of the PlasmaJet (intervention group) versus the use of standard surgical instruments combined with electrocoagulation (control group). The primary outcome is the rate of complete cytoreductive surgery in both groups. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Quality of life will be evaluated using validated questionnaires at baseline, at 1 and 6 months after surgery and at 1, 2, 3 and 4 years after surgery Discussion: We hypothesize the additional value of the use of the PlasmaJet in CCS for advanced stage epithelial ovarian cancer. More knowledge about efficacy, side effects, recurrence rates, cost effectiveness and pathology findings after using the PlasmaJet Device is advocated. This RCT may aid in this void

Mechanisms of hypoxic up-regulation of versican gene expression in macrophages

Hypoxia is a hallmark of many pathological tissues. Macrophages accumulate in hypoxic sites and up-regulate a range of hypoxia-inducible genes. The matrix proteoglycan versican has been identified as one such gene, but the mechanisms responsible for hypoxic induction are not fully characterised. Here we investigate the up-regulation of versican by hypoxia in primary human monocyte-derived macrophages (HMDM), and, intriguingly, show that versican mRNA is up-regulated much more highly (&gt;600 fold) by long term hypoxia (5 days) than by 1 day of hypoxia (48 fold). We report that versican mRNA decay rates are not affected by hypoxia, demonstrating that hypoxic induction of versican mRNA is mediated by increased transcription. Deletion analysis of the promoter identified two regions required for high level promoter activity of luciferase reporter constructs in human macrophages. The hypoxia-inducible transcription factor HIF-1 has previously been implicated as a key potential regulator of versican expression in hypoxia, however our data suggest that HIF-1 up-regulation is unlikely to be principally responsible for the high levels of induction observed in HMDM. Treatment of HMDM with two distinct specific inhibitors of Phosphoinositide 3-kinase (PI3K), LY290042 and wortmannin, significantly reduced induction of versican mRNA by hypoxia and provides evidence of a role for PI3K in hypoxic up-regulation of versican expression

Three Design Principles of Language: The Search for Parsimony in Redundancy

In this paper we present three design principles of language – experience, heterogeneity and redundancy – and present recent developments in a family of models incorporating them, namely Data-Oriented Parsing/Unsupervised Data-Oriented Parsing. Although the idea of some form of redundant storage has become part and parcel of parsing technologies and usage-based linguistic approaches alike, the question how much of it is cognitively realistic and/or computationally optimally efficient is an open one. We argue that a segmentation-based approach (Bayesian Model Merging) combined with an all-subtrees approach reduces the number of rules needed to achieve an optimal performance, thus making the parser more efficient. At the same time, starting from unsegmented wholes comes closer to the acquisitional situation of a language learner, and thus adds to the cognitive plausibility of the model

Article Metrics Related Articles Toggle citation dialog Cite Toggle share dialog Share Toggle permissions dialog Request Permissions Explore More Download PDF Implications for Physical Activity in the Population With Low Back Pain

Low back pain is considered the most prevalent pain complaint affecting the general population, with a reported lifetime prevalence of up to 75%. It is a recognized societal problem from both a disablement and economic perspective, with costs exceeding that of coronary artery disease, respiratory infections, and diabetes. The traditional concept of low back pain having a favorable natural history paints an overly optimistic prognosis when considering recent epidemiological data. From a prognostic perspective, more than three quarters of individuals will have a recurrence of their symptoms within a year from the initial onset, and up to 40% report a permanent reduction in activity participation. Fear of movement and avoidance of physical activity participation have been associated with a less than desirable prognosis, often times leading to chronicity. Although numerous interventions with often contradictory findings have been described for the population with low back pain, a consensus of research has implicated the resumption and pursuit of appropriate physical activity as an efficacious intervention. This article reviews the current evidence pertaining to physical activity participation in the population with low back pain and provides recommendations for identifying individuals who may be at risk for chronicity resulting from fear and avoidance of activity

Serous endometrial intraepithelial carcinoma (SEIC): Current clinical practice in The Netherlands

Introduction: Serous endometrial intraepithelial carcinoma (SEIC) is a rare diagnosis, defined as an intraepithelial lesion with cells identical to serous type endometrial carcinoma. SEIC is considered to be potentially metastatic, however clear and robust data on prognosis are lacking, potentially leading to variability in clinical management. Objective: The aim is to establish the opinion of gynecologists on the optimal management of patients with SEIC. Methods: An online questionnaire with 15 multiple choice questions was sent to all gynecologists with expertise in gynecological oncology in 19 expert centers in The Netherlands. Results: A total of 24 gynecologists participated. The majority of respondents (n = 18/24, 75%) do not consult a guideline regarding the treatment of SEIC. In current practice, 14 of the 24 respondents perform surgical staging in women with SEIC (58.3%) while seven choose hysterectomy with bilateral salpingo-oophorectomy (29.2%), and three (12.5%) have no firm preference. Eleven of the 14 respondents who perform a surgical staging procedure believe that this is certainly the optimal treatment. The majority of respondents have no firm opinion on whether lymph node sampling or lymph node dissection is preferable during surgical staging (n = 15/23, 65.2%). Most respondents do not give adjuvant therapy (n = 15/24, 62.5%), 25.0% recommend brachytherapy (n = 6/24). Follow-up is for 5 years in almost all cases (n = 23/24). Conclusion: There is no consensus on the optimal surgical treatment and the use of adjuvant therapy for patients with SEIC. Our research team is therefore conducting a nationwide cohort study in which treatment modality, morbidity and survival will be evaluated