Predicting disease recurrence in patients with endometriosis: an observational study.

BACKGROUND: Despite surgical and pharmacological interventions, endometriosis can recur. Reliable information regarding risk of recurrence following a first diagnosis is scant. The aim of this study was to examine clinical and survey data in the setting of disease recurrence to identify predictors of risk of endometriosis recurrence. METHODS: This observational study reviewed data from 794 patients having surgery for pelvic pain or endometriosis. Patients were stratified into two analytic groups based on self-reported or surgically confirmed recurrent endometriosis. Statistical analyses included univariate, followed by multivariate logistic regression to identify risk factors of recurrence, with least absolute shrinkage and selection operator (Lasso) regularisation. Risk-calibrated Supersparse Linear Integer Models (RiskSLIM) and survival analyses (with Lasso) were undertaken to identify predictive features of recurrence. RESULTS: Several significant features were repeatedly identified in association with recurrence, including adhesions, high rASRM score, deep disease, bowel lesions, adenomyosis, emergency room attendance for pelvic pain, younger age at menarche, higher gravidity, high blood pressure and older age. In the surgically confirmed group, with a score of 5, the RiskSLIM method was able to predict the risk of recurrence (compared to a single diagnosis) at 95.3% and included adenomyosis and adhesions in the model. Survival analysis further highlighted bowel lesions, adhesions and adenomyosis. CONCLUSIONS: Following an initial diagnosis of endometriosis, clinical decision-making regarding disease management should take into consideration the presence of bowel lesions, adhesions and adenomyosis, which increase the risk of endometriosis recurrence.

The use of the myometrial-cervical ratio in the ultrasound diagnosis of adenomyosis - A validation study.

BACKGROUND: Adenomyosis is a benign disorder defined by ectopic endometrial glands within the uterine myometrium. A study by Mooney et al reported the myometrial-cervical ratio (MCR), a novel ultrasound measurement that was found to improve the preoperative diagnosis of adenomyosis. AIMS: To validate the association between sonographic MCR and adenomyosis confirmed on histopathology in an independent patient group. MATERIALS AND METHODS: Single-centre retrospective cohort study including women who underwent hysterectomy between 1 January 2016 and 31 December 2018 for a benign, non-obstetric indication with an ultrasound at the study centre prior to surgery. Clinical details and histopathology were extracted. Ultrasound images were reviewed by a gynaecology ultrasound subspecialist blinded to histological findings. RESULTS: Eight hundred eighty-seven patients underwent hysterectomy in the study period for eligible indications; 317 had an ultrasound at the study centre and were included. There was no statistically significant association between the MCR and adenomyosis on histology when all patients were included; however, increased MCR was associated with adenomyosis when those with fibroids on ultrasound were excluded. The area under the receiver operating characteristic for this model was 0.614 (95% CI: 0.53 to 0.69). The optimal MCR cut-point in this subgroup was 1.79, which achieved 55.6% sensitivity and 62.8% specificity, with 58.5% correctly classified. There was no significant difference in MCR compared to traditional ultrasound markers of adenomyosis. CONCLUSIONS: In a population undergoing hysterectomy for benign and non-obstetric indications, the MCR applied to preoperative ultrasound was only weakly associated with a histological diagnosis of adenomyosis.

Participant understanding and recall of informed consent for induced pluripotent stem cell biobanking.

The ability to generate human induced pluripotent stem cells (iPSCs) has opened new avenues for human disease modelling and therapy. The aim of our study was to determine research participants' understanding of the information given when donating skin biopsies for the generation of patient-specific iPSCs. A customised 35-item questionnaire based on previous iPSC consent guidelines was sent to participants who had previously donated samples for iPSC research. The questionnaire asked pertinent demographic details, participants' motivation to take part in iPSC research and their attitudes towards related ethical issues. 234 participants were contacted with 141 (60.3 %) complete responses received. The median duration between recruitment and follow-up questioning was 313 days (range 10-573 days). The majority of participants (n = 129, 91.5 %) believed they understood what a stem cell was; however, only 22 (16.1 %) correctly answered questions related to basic stem cell properties. We found no statistically significant difference in responses from participants with different levels of education, or those with a health sciences background. The poor understanding amongst participants of iPSC research is unlikely to be unique to our study and may impact future research if not improved. As such, there is a need to develop an easily understood yet comprehensive consent process to ensure ongoing ethical progress of iPSC biobanking.

Risk of obstetric anal sphincter injuries (OASIS) and anal incontinence: A meta-analysis.

BACKGROUND: Obstetric anal sphincter injuries (OASIS) are the commonest cause of anal incontinence in women of reproductive age. We determined the risk of anal sphincter defects diagnosed by ultrasound, and the risk of anal incontinence in (i) all women who deliver vaginally, (ii) in women without clinical suspicion of OASIS, and (iii) after primary repair of sphincter injury, by systematic review. METHODS: We searched major databases until June 2018, without language restrictions. Random effects meta-analysis was used to obtain pooled estimates of ultrasound diagnosed OASIS and risk of anal incontinence symptoms at various time points after delivery, and of persistent sphincter defects after primary repair. We reported the association between ultrasound diagnosed OASIS and anal incontinence symptoms using relative risk (RR) with 95 % CI. RESULTS: We included 103 studies involving 16,110 women. Of all women who delivered vaginally, OASIS were diagnosed on ultrasound in 26 % (95 %CI, 21-30, I2 = 91 %), and 19 % experienced anal incontinence (95 %CI, 14-25, I2 = 92 %). In women without clinical suspicion of OASIS (n = 3688), sphincter defects were observed in 13 % (10-17, I2 = 89 %) and anal incontinence experienced by 14 % (95 % CI: 6-24, I2 = 95 %). Following primary repair of OASIS, 55 % (46-63, I2 = 98 %) of 7549 women had persistent sphincter defect with 38 % experiencing anal incontinence (33-43, I2 = 92 %). There was a significant association between ultrasound diagnosed OASIS and anal incontinence (RR 3.74, 2.17-6.45, I2 = 98 %). INTERPRETATION: Women and clinicians should be aware of the high risk for sphincter defects following vaginal delivery even when clinically unsuspected. This underlines the need of careful and systematic perineal assessment after birth to mitigate the risk of missing OASIS. We also noted a high rate of persistent defects and symptoms following primary repair of OASIS. This dictates the need for provision of robust training for clinicians to achieve proficiency and sustain competency in repairing OASIS.

A Need for Better Understanding Is the Major Determinant for Public Perceptions of Human Gene Editing.

The CRISPR/Cas system could provide an efficient and reliable means of editing the human genome and has the potential to revolutionize modern medicine; however, rapid developments are raising complex ethical issues. There has been significant scientific debate regarding the acceptability of some applications of CRISPR/Cas, with leaders in the field highlighting the need for the lay public's views to shape expert discussion. As such, we sought to determine the factors that influence public opinion on gene editing. We created a 17-item online survey translated into 11 languages and advertised worldwide. Topic modeling was used to analyze textual responses to determine what factors influenced respondents' opinions toward human somatic or embryonic gene editing, and how this varied among respondents with differing attitudes and demographic backgrounds. A total of 3,988 free-text responses were analyzed. Respondents had a mean age of 32 (range, 11-90) years, and 37% were female. The most prevalent topics cited were Future Generations, Research, Human Editing, Children, and Health. Respondents who disagreed with gene editing for health-related purposes were more likely to cite the topic Better Understanding than those who agreed to both somatic and embryonic gene editing. Respondents from Western backgrounds more frequently discussed Future Generations, compared with participants from Eastern countries. Religious respondents did not cite the topic Religious Beliefs more frequently than did nonreligious respondents, whereas Christian respondents were more likely to cite the topic Future Generations. Our results suggest that public resistance to human somatic or embryonic gene editing does not stem from an inherent mistrust of genome modification, but rather a desire for greater understanding. Furthermore, we demonstrate that factors influencing public opinion vary greatly amongst demographic groups. It is crucial that the determinants of public attitudes toward CRISPR/Cas be well understood so that the technology does not suffer the negative public sentiment seen with previous genetic biotechnologies.

Genome engineering in ophthalmology: Application of CRISPR/Cas to the treatment of eye disease.

The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) and CRISPR-associated protein (Cas) system has enabled an accurate and efficient means to edit the human genome. Rapid advances in this technology could results in imminent clinical application, and with favourable anatomical and immunological profiles, ophthalmic disease will be at the forefront of such work. There have been a number of breakthroughs improving the specificity and efficacy of CRISPR/Cas-mediated genome editing. Similarly, better methods to identify off-target cleavage sites have also been developed. With the impending clinical utility of CRISPR/Cas technology, complex ethical issues related to the regulation and management of the precise applications of human gene editing must be considered. This review discusses the current progress and recent breakthroughs in CRISPR/Cas-based gene engineering, and outlines some of the technical issues that must be addressed before gene correction, be it in vivo or in vitro, is integrated into ophthalmic care. We outline a clinical pipeline for CRISPR-based treatments of inherited eye diseases and provide an overview of the important ethical implications of gene editing and how these may influence the future of this technology.

A Global Social Media Survey of Attitudes to Human Genome Editing.

Ongoing breakthroughs with CRISPR/Cas-based editing could potentially revolutionize modern medicine, but there are many questions to resolve about the ethical implications for its therapeutic application. We conducted a worldwide online survey of over 12,000 people recruited via social media to gauge attitudes toward this technology and discuss our findings here.