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Background: Acute colonic pseudo-obstruction (ACPO) is characterized by severe colonic distension without mechanical obstruction. It has an uncertain pathogenesis and poses diagnostic challenges. This study aimed to explore risk factors and clinical outcomes of ACPO in polytrauma patients and contribute information to the limited literature on this condition., Methods: This retrospective study, conducted at a Level 1 trauma center, analyzed data from trauma patients with ACPO admitted between July 2009 and June 2018. A control cohort of major trauma patients was used. Data review encompassed patient demographics, abdominal imaging, injury characteristics, analgesic usage, interventions, complications, and mortality. Statistical analyses, including logistic regression and correlation coefficients, were employed to identify risk factors., Results: There were 57 cases of ACPO, with an incidence of 1.7 per 1,000 patients, rising to 4.86 in major trauma. Predominantly affecting those older than 50 years (75%) and males (75%), with motor vehicle accidents (50.8%) and falls from height (36.8%) being the commonest mechanisms. Noteworthy associated injuries included retroperitoneal bleeds (RPBs) (37%), spinal fractures (37%), and pelvic fractures (37%). Analysis revealed significant associations between ACPO and shock index >0.9, Injury Severity Score >18, opioid use, RPBs, and pelvic fractures. A cecal diameter of ≥12 cm had a significant association with cecal ischemia or perforation., Conclusion: This study underscores the significance of ACPO in polytrauma patients, demonstrating associations with risk factors and clinical outcomes. Clinicians should maintain a high index of suspicion, particularly in older patients with RPBs, pelvic fractures, and opioid use. Early supportive therapy, vigilant monitoring, and timely interventions are crucial for a favorable outcome. Further research and prospective trials are warranted to validate these findings and enhance understanding of ACPO in trauma patients., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Tibial plateau fractures, which are intra-articular injuries of the knee joint, are often difficult to treat and have a high complication rate, including early-onset osteoarthritis. The most common treatment for complex tibial plateau fractures is surgical fixation. Additionally, orthopaedic surgeons often use bone defect fillers to address bone defects caused by the injury. Currently, there is no consensus on the best method of fixation and on whether bone defect fillers are necessary., Objectives: To assess the benefits and harms of different surgical interventions and bone defect fillers for treating tibial plateau fractures., Search Methods: We searched CENTRAL, MEDLINE, Embase, and trial registries up to March 2023. We also searched conference proceedings and the grey literature., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs comparing surgical interventions for treating tibial plateau fractures and different types of filler for bone defects., Data Collection and Analysis: Two review authors independently screened search results, selected studies, extracted data, and assessed risk of bias. We calculated risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes, with 95% confidence intervals (CIs). Our primary outcomes (and the specific measures we considered most relevant) were generic quality of life (general health score in the 36-item Short-Form Health Survey (SF-36)), patient-reported lower limb function (Hospital for Special Surgery (HSS) score), and adverse events (frequency of unplanned reoperation). We used GRADE to assess the certainty of evidence., Main Results: We included 15 trials in the review, with a total of 948 adult participants. Nine trials compared different types of fixation, and six trials evaluated different types of bone graft substitutes. All 15 trials were small and at high risk of bias. We considered most available evidence to be of very low certainty, meaning we have very little confidence in the results. Only limited pooling was possible. One trial compared circular fixation combined with insertion of percutaneous screws (hybrid fixation) versus standard open reduction and internal fixation (ORIF) in 82 people with open or closed Schatzker types V or VI tibial plateau fractures. At 24 months' follow-up, hybrid fixation compared with ORIF may have little or no effect on SF-36 general health score (MD 6 points higher, 95% CI 7.7 points lower to 19.7 points higher; 66 participants), patient-reported lower limb function according to the HSS score (MD 7 points higher, 95% CI 2.4 points lower to 16.4 points higher; 66 participants), or frequency of unplanned reoperation (RR 0.78, 95% CI 0.45 to 1.32; 83 fractures (82 participants)). However, the evidence for all three outcomes is very uncertain. Three trials (with 242 participants) compared single-plating ORIF versus double-plating ORIF. There may be little to know difference in patient-reported lower limb function (HSS score) at 24 months' follow-up in people who undergo single-plating ORIF compared with those who undergo double-plating ORIF (MD 0.2 points higher, 95% CI 2.12 points lower to 2.52 points higher; 1 study, 84 participants), but the evidence is very uncertain. There were no data for quality of life or unplanned reoperation at 24 months' follow-up. Six trials (including 368 participants) compared bone substitute versus autologous bone graft (autograft) for managing bone defects. No trials reported SF-36 general health score, HSS score, or frequency of unplanned reoperation at 24 months' follow-up., Authors' Conclusions: There is insufficient evidence to ascertain the best method of fixation or the best method of addressing bone defects during surgery in people with tibial plateau fractures. Further well-designed RCTs with larger sample sizes are warranted., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Aims: Our primary aim was to establish the proportion of female orthopaedic consultants who perform arthroplasty via cases submitted to the National Joint Registry (NJR), which covers England, Wales, Northern Ireland, the Isle of Man, and Guernsey. Secondary aims included comparing time since specialist registration, private practice participation, and number of hospitals worked in between male and female surgeons., Methods: Publicly available data from the NJR was extracted on the types of arthroplasty performed by each surgeon, and the number of procedures of each type undertaken. Each surgeon was cross-referenced with the General Medical Council (GMC) website, using GMC number to extract surgeon demographic data. These included sex, region of practice, and dates of full and specialist registration., Results: Of 2,895 surgeons contributing to the NJR in 2023, 102 (4%) were female. The highest proportions of female surgeons were among those who performed elbow (n = 25; 5%), shoulder (n = 24; 4%), and ankle (n = 8; 4%) arthroplasty. Hip (n = 66; 3%) and knee arthroplasty (n = 39; 2%) had the lowest female representation. Female surgeons had been practising for a median of 10.4 years since specialist registration compared to 13.7 years for males (p < 0.001). Northern Ireland was the region with the highest proportion of female arthroplasty surgeons (8%). A greater proportion of male surgeons worked in private practice (63% vs 24%; p < 0.001) and in multiple hospitals (74% vs 40%; p < 0.001)., Conclusion: Only 4% of surgeons currently contributing cases to the NJR are female, with the highest proportion performing elbow arthroplasty (5%). Female orthopaedic surgeons in the NJR are earlier in their careers than male surgeons, and are less involved in private practice. There is a wide geographical variation in the proportion of female arthroplasty surgeons., Competing Interests: C. B. Hing reports that the editorial stipend for The Knee for Elsevier is unrelated to this work. C. E. H. Scott declares a department grant and payment for education delivery from Stryker; consulting fees from Stryker, Smith & Nephew, and Osstec; being on the data safety monitoring board for the PASHION trial; and being a board member of The Bone & Joint Journal, all of which are also unrelated to this paper., (© 2024 Abelleyra Lastoria et al.)

Introduction: Noise-Induced Hearing Loss (NIHL) is a condition caused by repeated exposure to loud noise, with operating theatre personnel potentially at risk. The aims of this study were to establish the typical noise levels in orthopaedic theatres and to compare these to The Control of Noise at Work Regulations 2005., Materials and Methods: We measured the average noise levels in 40 trauma and orthopaedic surgeries in a single centre. We used the Decibel X app to take measurements, then performed corrections to ascertain noise levels at the surgeon's ear (L eq ). The daily noise exposure level for theatre staff for each procedure (L EP, d ) and the L EP, d over an average 8-hour working day when performing different groups of procedures were calculated. Data were analysed using descriptive statistics, ANOVA, t-test and the Pearson coefficient of correlation., Results: The L EP, d lower action value (80 dBA) as set by the Health and Safety Executive (HSE) was met by performing a single revision total knee replacement or a right open ankle debridement. Assuming three procedures are conducted per list, lists consisting of joint replacements (82 dBA) or medium elective procedures (81 dBA) exceed this lower limit. Additionally, lists comprising large and medium bone fractures would be within 1 dB of the limit (79 dBA and 79 dBA, respectively). Soft tissue (74 dBA), arthroscopic (73 dBA), and small bone fracture (71 dBA) procedures had the lowest L EP, d . The greatest contributors to noise levels were surgical instruments. The number of people in the room made a significant difference to noise levels (p = 0.032)., Conclusions: We have established the baseline noise levels in various orthopaedic procedures. Measures should be taken to meet UK regulations. Further research should determine suitable measures for protection from hearing damage for theatre staff and evaluate the risks high noise levels pose to patients., (© 2024. The Author(s).)

Objective: To evaluate patient preference for short (gist) or detailed/extensive decision aids (DA) for genetic testing at ovarian cancer (OC) diagnosis., Design: Cohort study set within recruitment to the Systematic Genetic Testing for Personalised Ovarian Cancer Therapy (SIGNPOST) study (ISRCTN: 16988857)., Setting: North-East London Cancer Network (NELCN) population., Population/sample: Women with high-grade non-mucinous epithelial OC., Methods: A more detailed DA was developed using patient and stakeholder input following the principles/methodology of IPDAS (International Patients Decision Aids Standards). Unselected patients attending oncology clinics evaluated both a pre-existing short and a new long DA version and then underwent mainstreaming genetic testing by a cancer clinician. Appropriate inferential descriptive and regression analyses were undertaken., Main Outcome Measures: Satisfaction, readability, understanding, emotional well-being and preference for long/short DA., Results: The mean age of patients was 66 years (interquartile range 11), and 85% were White British ethnicity. Of the participants, 74% found DAs helpful/useful in decision-making. Women reported higher levels of satisfaction (86% versus 58%, p < 0.001), right amount of information provided (76.79% versus49.12%, p < 0.001) and improved understanding (p < 0.001) with the long DA compared with the short DA. There was no statistically significant difference in emotional outcomes (feeling worried/concerned/reassured/upset) between 'short' and 'long' DA; 74% of patients preferred the long DA and 24% the short DA. Patients undergoing treatment (correlation coefficient (coef) = 0.603; 95% CI 0.165-1.041, p = 0.007), those with recurrence (coef = 0.493; 95% CI 0.065-0.92, p = 0.024) and older women (coef = 0.042; 95% CI 0.017-0.066, p = 0.001) preferred the short DA. Ethnicity did not affect outcomes or overall preference for long/short DA., Conclusions: A longer DA in OC patients has higher satisfaction without increasing emotional distress. Older women and those undergoing treatment/recurrence prefer less extensive information, whereas those in remission preferred a longer DA., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone., Methods: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated., Results: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths., Conclusions: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

Background: In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction in deaths in the multimodal screening group compared with the no screening group. Therefore, we did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy., Methods: UKCTOCS was a 13-centre randomised controlled trial of screening postmenopausal women from the general population, aged 50-74 years, with intact ovaries. The trial management system randomly allocated (2:1:1) eligible participants (recruited from April 17, 2001, to Sept 29, 2005) in blocks of 32 using computer generated random numbers to no screening or annual screening (multimodal screening or ultrasound screening) until Dec 31, 2011. Follow-up was through national registries until June 30, 2020. An outcome review committee, masked to randomisation group, adjudicated on ovarian cancer diagnosis, histotype, stage, and cause of death. In this study, analyses were intention-to-screen comparisons of women with high-grade serous cancer at censorship (Dec 31, 2014) in multimodal screening versus no screening, using descriptive statistics for stage and treatment endpoints, and the Versatile test for survival from randomisation. This trial is registered with the ISRCTN Registry, 22488978, and ClinicalTrials.gov, NCT00058032., Findings: 202 562 eligible women were recruited (50 625 multimodal screening; 50 623 ultrasound screening; 101 314 no screening). 259 (0·5%) of 50 625 participants in the multimodal screening group and 520 (0·5%) of 101 314 in the no screening group were diagnosed with high-grade serous cancer. In the multimodal screening group compared with the no screening group, fewer were diagnosed with advanced stage disease (195 [75%] of 259 vs 446 [86%] of 520; p=0·0003), more had primary surgery (158 [61%] vs 219 [42%]; p<0·0001), more had zero residual disease following debulking surgery (119 [46%] vs 157 [30%]; p<0·0001), and more received treatment including both surgery and chemotherapy (192 [74%] vs 331 [64%]; p=0·0032). There was no difference in the first-line combination chemotherapy rate (142 [55%] vs 293 [56%]; p=0·69). Median follow-up from randomisation of 779 women with high-grade serous cancer in the multimodal and no screening groups was 9·51 years (IQR 6·04-13·00). At censorship (June 30, 2020), survival from randomisation was longer in women with high-grade serous cancer in the multimodal screening group than in the no screening group with absolute difference in survival of 6·9% (95% CI 0·4-13·0; p=0·042) at 18 years (21% [95% CI 15·6-26·2] vs 14% [95% CI 10·5-17·4])., Interpretation: To our knowledge, this is the first evidence that screening can detect high-grade serous cancer earlier and lead to improved short-term treatment outcomes compared with no screening. The potential survival benefit for women with high-grade serous cancer was small, most likely due to only modest gains in early detection and treatment improvement, and tumour biology. The cumulative results of the trial suggest that surrogate endpoints for disease-specific mortality should not currently be used in screening trials for ovarian cancer., Funding: National Institute for Health Research, Medical Research Council, Cancer Research UK, The Eve Appeal., Competing Interests: Declaration of interests UM had stock ownership, awarded by University College London (UCL) until October, 2021, in Abcodia, which holds the licence for risk of ovarian cancer algorithm (ROCA). UM and MKBP have received grants and AG-M, AR, SA, and MB have been funded by grants from the Medical Research Council (MRC), Cancer Research UK, the National Institute for Health Research (NIHR), and The Eve Appeal. UM has also received grants from the Australian National Health and Medical Research Council (NHMRC) and salary support from University College London Hospitals Biomedical Research Centre. UM, AG-M, and SA report research collaboration contracts with Cambridge University, QIMR Berghofer Medical Research Institute, Intelligent Lab on Fiber, RNA Guardian, Micronoma, MercyBio Analytics, Imperial College London, University of Innsbruck, and Dana Farber USA. UM holds patent number EP10178345.4 for Breast Cancer Diagnostics. UM received an honorarium for a lecture from the New York Obstetrical Society (USA), and was reimbursed for travel by New York Obstetrical Society, US National Cancer Policy Forum, and Robinson College, Cambridge, UK. UM is a member of Tina's Wish Scientific Advisory Board (USA) and Research Advisory Panel, Yorkshire Cancer Research (UK). She has been a member of International Alliance for Cancer Early Detection (ACED); data monitoring committee for the mixed COVID-19 vaccines study in India; Good Clinical Practice Professional Certification Scheme steering committee, CDSA, India; Clinical and Public Health Fellowship Selection Committee, Wellcome Trust DBT India Alliance; Prevention Expert Review Panel, Population Research Committee, Cancer Research UK; and chair of the data monitoring committee for GEM3. AG-M is a member of ACED Gynaecological Cancer Working Group and is ACED codirector Research Domain Trials. MKBP was an Associate Member of the EME funding committee while the project was active. SA reports funding to UCL from Abcodia between 2011 and 2020. SJS codeveloped ROCA in 1995, which was patented by Massachusetts General Hospital, MA, USA, and Queen Mary University of London, London, UK, and is owned by these universities (the patent has expired). Massachusetts General Hospital and Queen Mary University of London granted a licence for the ROCA to Abcodia in 2014. SJS reports stock options from SISCAPA Assay Technologies for participation on a board and from the US National Cancer Institute, NIHR, and Mercy Bioanalytics. SJS participated in the independent data monitoring committee for GRAIL, and served on the clinical advisory board for Guardant Health (for which he was paid consulting fees), and on the Scientific Advisory Board for LUNGevity. SJS also has a collaboration agreement with Freenome. IJJ reports grants from Eve Appeal Charity, MRC, Cancer Research UK, and NIHR during the conduct of the study. IJJ coinvented the ROCA in 1995. Massachusetts General Hospital and Queen Mary University of London granted a licence for the ROCA to Abcodia in 2014. IJJ is non-executive director, shareholder, and consultant to Abcodia and has rights to royalties from sales of the ROCA. IJJ founded (in 1985), was a trustee of (2012–14), and is now an Emeritus trustee (2015–present) of The Eve Appeal, one of the funding agencies for UKCTOCS. LF reports MRC funding for the psychosocial group of the UKCTOCS study 2001–13, paid to University of Sussex. NS received honoraria from AstraZeneca–MSD and GSK for participation in advisory boards. AJM was a member of NIHR Health Technology Assessment and Efficacy and Mechanism Evaluation editoral board (2012–22). RM reports funding from The Eve Appeal, Rosetrees Trust, Barts Charity, Yorkshire Cancer Research, Ovacure, British Gynaecological Cancer Society, AstraZeneca, and GSK. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Colon cancer resection can be technically difficult in the obese (OB) population. Robotic surgery is a promising technique but its benefits remain uncertain in OB patients. The aim of this study is to compare OB versus non-obese (NOB) patients undergoing robotic colon surgery, as well as OB patients undergoing robotic versus open or laparoscopic colonic surgery., Methods: A systematic review and meta-analysis was performed. Primary outcome measures included length of stay (LOS), surgical site infection (SSI) rate, complications, anastomotic leak and oncological outcomes., Results: A total of eight studies were included, with five comparing OB and NOB patients undergoing robotic colon surgery included in meta-analysis. A total of 263 OB patients and 400 NOB patients formed the sample for meta-analysis. There was no significant difference between the two groups in operative time, conversion to open, LOS, lymph node yield, anastomotic leak and postoperative ileus. There was a trend towards a significant increase in overall complications and SSI in the OB group (32.3% OB versus 26.8% NOB for complications, 14.2% OB versus 9.9% NOB for SSI). The three included studies comparing surgical techniques were too heterogeneous to undergo meta-analysis., Conclusion: Robotic colon surgery is safe in obese patients, but high-quality prospective evidence is lacking. Future studies should report on oncological safety and the cost-effectiveness of adopting the robotic technique in these challenging patients., (© 2022 Royal Australasian College of Surgeons.)

Introduction: Minimally invasive surgical techniques are being successfully used to treat locally advanced and recurrent pelvic malignancy of colorectal origin. This review aims to describe the application of minimally invasive approaches to pelvic exenteration and compare current reported surgical outcomes., Methods and Results: A literature search was performed of PubMed, Google Scholar and EMBASE for studies on pelvic exenteration with locally advanced or recurrent rectal cancer utilising minimally invasive techniques. A total of 22 studies were reviewed, including four case reports describing novel approaches., Discussion: Laparoscopic, robotic and trans-anal total mesenteric excision (TaTME) aided pelvic exenteration methods have recently demonstrated low post-operative morbidity and mortality trends. Minimally invasive methods also have improved rates of R0 resection in modest cohort studies. Hybrid methods have also been proposed to overcome observed technical difficulties such as the narrow male pelvis and obese habitus. There is still limited data beyond case report and small cohort studies on challenging patient groups such as those with recurrent rectal cancer or bony involvement, as a consequence of patient selection for these novel approaches., Conclusion: International, multicentre studies have provided the best opportunity to explore efficacy of these methods on a larger scale. Further research is required into patient selection, safety and long-term outcomes of these approaches within high volume centres practicing beyond the surgical learning curve., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

In the United Kingdom, endometrial biopsy reports traditionally consist of a morphologic description followed by a conclusion. Recently published consensus guidelines for reporting benign endometrial biopsies advocate the use of standardized terminology. In this project we aimed to assess the acceptability and benefits of this simplified "diagnosis only" format for reporting non-neoplastic endometrial biopsies. Two consultants reported consecutive endometrial biopsies using 1 of 3 possible formats: (i) diagnosis only, (ii) diagnosis plus an accompanying comment, and (iii) the traditional descriptive format. Service users were asked to provide feedback on this approach via an anonymized online survey. The reproducibility of this system was assessed on a set of 53 endometrial biopsies among consultants and senior histopathology trainees. Of 370 consecutive benign endometrial biopsies, 245 (66%) were reported as diagnosis only, 101 (27%) as diagnosis plus a brief comment, and 24 (7%) as diagnosis following a morphologic description. Of the 43 survey respondents (28 gynecologists, 11 pathologists, and 4 clinical nurse specialists), 40 (93%) preferred a diagnosis only, with 3 (7%) being against/uncertain about a diagnosis only report. Among 3 histopathology consultants and 4 senior trainees there was majority agreement on the reporting format in 53/53 (100%) and 52/53 (98%) biopsies. In summary, we found that reporting benign specimens within standardized, well-understood diagnostic categories is an acceptable alternative to traditional descriptive reporting, with the latter reserved for the minority of cases that do not fit into specific categories. This revised approach has the potential to improve reporting uniformity and reproducibility., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) ( p < 0.001). The median age was 54 (IQR = 51-62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51-71) in BRCA wild-type ( p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA -testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

Background: Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS., Methods: In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032., Findings: Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group., Interpretation: The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended., Funding: National Institute for Health Research, Cancer Research UK, and The Eve Appeal., Competing Interests: Declaration of interests UM has stock ownership awarded by University College London (UCL) in Abcodia, which holds the licence for ROCA. She has received grants from the Medical Research Council (MRC), Cancer Research UK, the National Institute for Health Research (NIHR), and The Eve Appeal. She holds patent number EP10178345.4 for Breast Cancer Diagnostics. MP has received grants and AG-M, MB, AR, CK, GC, and SKM have been funded by grants from MRC, Cancer Research UK, NIHR, and The Eve Appeal. RM has received grants from The Eve Appeal, Rosetrees Charity, and Barts Charity, and personal fees from AstraZeneca. SJS holds the (expired) patent for ROCA, patented and owned by Massachusetts General Hospital and Queen Mary University of London, licenced to Abcodia. He reports stock options from SISCAPA Assay Technologies, and personal fees from Abcodia, Guardant Health, and Freenome, outside the submitted work. IJJ reports grants from Eve Appeal Charity, Medical Research Council, Cancer Research UK, and NIHR during the conduct of the study. He co-invented the ROCA in 1995, it was patented by Massachusetts General Hospital and Queen Mary University of London and is owned by these universities. Massachusetts General Hospital and Queen Mary University of London granted a licence to ROCA to Abcodia in 2014. IJJ is non-executive director, shareholder, and consultant to Abcodia and has rights to royalties from sales of the ROCA. He founded (1985), was a trustee of (2012–14), and is now an Emeritus trustee (2015–present) of The Eve Appeal, one of the funding agencies for UKCTOCS. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Irish health services have been repurposed in response to the COVID-19 pandemic. Critical care services have been re-focused on the management of COVID-19 patients. This presents a major challenge for specialities such as cardiothoracic surgery that are reliant on intensive care unit (ICU) resources., Aim: The aim of this study was to evaluate the impact of the COVID-19 pandemic on activity at the cardiothoracic surgical care at the National Cardiothoracic Surgery and Transplant Centre., Methods: A comparison was performed of cardiac surgery and transplant caseload for the first 4 months of 2019 and 2020 using data collected prospectively on a customised digital database., Results: Cardiac surgery activity fell over the study period but was most impacted in March and April 2020. Operative activity fell to 49% of the previous years' activity for March and April 2020. Surgical acuity changed with 61% of all cases performed as inpatient transfers after cardiology admission in contrast with a 40% rate in 2019. Valve surgery continued at 89% of the expected rate; coronary artery bypass surgery was performed at 61% of the expected rate and major aortic surgery at 22%. Adult congenital heart cases were not performed in March or April 2020. One heart and one lung transplant were performed in this period., Conclusions: In March and April of 2020, the spread of COVID-19 and the resultant focus on its management resulted in a reduction in cardiothoracic surgery service delivery.

The current study examined the collateral effects of an antecedent intervention for decreasing speech volume on vocal stereotypy. After teaching the participant to use a conversational voice level by providing visual feedback from a decibel meter app, conversational voice levels were differentially reinforced in the presence of a green card. Differential effects in voice magnitude during a green-card condition and a no-card condition were demonstrated using an alternating-treatments design. Results showed a decrease in volume of speech during the green-card condition, an overall decrease in vocal stereotypy, and a decrease to zero levels in loud stereotypical vocalizations. The implications of these findings on the treatment of vocal stereotypy are discussed., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (© Association for Behavior Analysis International 2021.)

Subclassification of endometrial carcinoma (EC) based on morphologic features alone has been shown to have suboptimal reproducibility, both in regard to biopsy versus hysterectomy findings, as well as interobserver agreement. This restricts the role of morphologic classification of EC as a tool for risk prediction and therefore treatment planning. A diagnostic algorithm based on The Cancer Genome Atlas (TCGA) classification of EC holds promise for improving accuracy in risk prediction. This classifies EC into 4 groups: those harbouring mutations in the exonuclease domain of DNA polymerase epsilon, POLE (POLEmut), those showing a mismatch repair defect, those showing mutations in TP53 (p53abn) and a heterogenous group showing none of these 3 abnormalities (currently termed no specific molecular profile). These groups can be accurately and reproducibly diagnosed on biopsy samples using a limited panel of tests, namely immunohistochemistry for mismatch repair proteins and p53, and testing for POLE exonuclease domain pathogenic variants. In this article we briefly review the biology, testing and interpretation of POLE and mismatch repair defects in EC.

Female athletes are at a greater risk for anterior cruciate ligament (ACL) injuries than males. Current training programs for ACL injury reduction focus on muscle strengthening, appropriate movement patterns, and balance training. However, there is limited research on effective strategies to teach youth female soccer athletes how to properly perform desired movements associated with a decreased risk of ACL injuries. Behavioral skills training (BST) programs have been shown to be effective in teaching a wide variety of skills, but research on applications to sports is limited. This study evaluated a BST package for teaching a stepwise agility program to 3 youth female soccer athletes that consisted of verbal instructions, modeling, rehearsal, and feedback, which included video replay. Results showed a significant improvement in the number of steps the participants performed correctly relative to baseline, as well as maintenance of skills at follow-up. Implications for coaches and athletes, as well as limitations and directions for future research, are discussed., Competing Interests: Conflict of interestThe authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this article., (© Association for Behavior Analysis International 2020.)

The introduction of genomic studies has enabled assessment of the clonality of synchronous tumours involving the ovary and other sites in the female genital tract in a definitive way. This has led to the abandonment of conventional approaches to primary site assignment, and the recognition that most such synchronous neoplasms are clonally related single tumours with metastatic spread, rather than independent primary tumours. These discoveries have implications for diagnostic practice, analogous to the gradual change over the last few decades in our approach to mucinous neoplasms of the ovary metastatic from the gastrointestinal tract. In this review, we first examine the routes of metastasis to the ovary, and then discuss the diagnostic and clinical implications of concurrent ovarian carcinomas arising in combination with endometrial, endocervical and tubal carcinomas. It is proposed that cases of primary low-grade endometrioid endometrial carcinoma with a secondary unilateral ovarian tumour, both with indolent characteristics, may be classified as 'FIGO stage IIIA-simulating independent primary tumours', with a comment that conservative management would be appropriate. It should be recognised that human papillomavirus-associated endocervical adenocarcinomas may result in synchronous or metachronous ovarian metastases that appear to be unrelated to the primary tumour, and that these may be managed conservatively in the absence of other sites of disease. In cases of tubo-ovarian high-grade serous carcinoma, tubal intraepithelial or contralateral adnexal involvement should count as a pelvic disease site for staging purposes., (© 2019 John Wiley & Sons Ltd.)

High-grade serous (HGSC) stands apart from the other ovarian cancer histotypes in being the most frequent, in occurring as part of a genetic predisposition in a significant proportion of cases, and in having the poorest clinical outcomes. Although the pathologic diagnosis of HGSC is now made with high accuracy, there remain areas of disagreement regarding viewpoints on tissue site of origin and designation of primary site, with impact on staging in low-stage cases, as well as difficulties in reproducible and clinically relevant reporting of HGSC in specimens taken after neoadjuvant chemotherapy. These areas are discussed in the current article., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Aims: The treatment of patients with tubo-ovarian high-grade serous carcinoma (HGSC) is increasingly based on diagnosis on small biopsy samples, and the first surgical sample is often taken post-chemotherapy. p53 and WT1 are important diagnostic markers for HGSC. The effect of neoadjuvant chemotherapy on p53 and WT1 expression has not been widely studied. We aimed to compare p53 and WT1 expression in paired pre-chemotherapy and post-chemotherapy samples of HGSC., Methods and Results: Immunohistochemistry (IHC) was carried out for p53 and WT1 on paired omental HGSC samples pre-chemotherapy and post-chemotherapy. p53 IHC was recorded as normal (wild-type) or abnormal (mutation-type), and was further classified as overexpression, complete absence, or cytoplasmic. WT1 IHC was classified as positive or negative. A subset of cases were further assessed for the extent of nuclear immunoreactivity of WT1 by use of the H-score. Fifty-seven paired samples were stained with p53. Fifty-six of 57 (98%) cases showed mutation-type p53 staining. Pre-chemotherapy and post-chemotherapy IHC results were concordant in 55 of 57 (96%) cases. For WT1, pre-chemotherapy and post-chemotherapy IHC results were concordant in 56 of 58 (97%) cases. In 23 paired WT1 cases, the mean post-treatment H-score decreased from 227 [range 20-298, standard deviation (SD) 64] to 151 (range 0-288, SD 78) (P = 0.0008)., Conclusions: Immunohistochemical expression of p53 (abnormal/mutation-type pattern) and WT1 in HGSC is almost universal and is largely concordant before and after chemotherapy. This finding underscores the reliability of these diagnostic markers in small samples and in surgical samples following neoadjuvant chemotherapy, with very few exceptions. A novel finding was the significant diminution in intensity of WT1 staining following chemotherapy., (© 2017 John Wiley & Sons Ltd.)

Given the recent interest in the use of video self-modeling (VSM) to provide instruction within iPod apps and other pieces of handheld mobile assistive technologies, investigating appropriate prerequisite skills for effective use of this intervention is particularly timely and relevant. To provide additional information regarding the efficacy of VSM for students with autism and to provide insights into any possible prerequisite skills students may require for such efficacy, the authors investigated the use of VSM in increasing the instances of effective initiations of interpersonal greetings for three students with autism that exhibited different pre-intervention abilities. Results showed that only one of the three participants showed an increase in self-initiated greetings following the viewing of videos edited to show each participant self-modeling a greeting when entering his or her classroom. Due to the differences in initial skill sets between the three children, this finding supports anecdotally observed student prerequisite abilities mentioned in previous studies that may be required to effectively utilize video based teaching methods.

We investigated teacher versus student seat selection in the context of group and individual seating arrangements. Disruptive behavior during group seating occurred at twice the rate when students chose their seats than when the teacher chose. During individual seating, disruptive behavior occurred more than three times as often when the students chose their seats. The results are discussed in relation to choice and the matching law.

This study examined the effects of text messaging class arrival to an academic counselor on the attendance and punctuality of 4 college student athletes. Each participant had a history of class tardiness and was considered to be at risk for academic failure. Class attendance and punctuality improved for all participants.

The following paper serves primarily to discuss the nature and cause of the multiple, documented illnesses suffered by the 18th Century Spanish artist Francisco Goya y Lucientes. In doing so it explores the artist's defiance of contemporary social mores, religious doctrines and the rigid standards of artistic romanticism. Furthermore, it examines the impact of illness upon artistic expression and the apparent correlation between heightened artistic proficiency and clinical depression with particular reference to the aforementioned artist. In addition, it provides a brief insight into the complexion of medical practice in Spain during the period of the Inquisition contrasted with those standards of conduct encompassed within the newly emerging movement of Enlightenment.