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Contralateral risk-reducing mastectomy (CRRM) rates have tripled over the last 2 decades. Reasons for this are multi-factorial, with those harbouring a pathogenic variant in the BRCA1 / 2 gene having the greatest survival benefit. On May 14th, 2013, Angelina Jolie shared the news of her bilateral risk-reducing mastectomy (BRRM), on the basis of her BRCA1 pathogenic variant status. We evaluated the impact of this news on rates of CRRM in women with increased risk for developing breast cancer after being diagnosed with unilateral breast cancer. The prospective cohort study included all women with at least a moderate lifetime risk of developing breast cancer who attended our family history clinic (1987–2019) and were subsequently diagnosed with unilateral breast cancer. Rates of CRRM were then compared between patients diagnosed with breast cancer before and after Angelina Jolie’s announcement (pre- vs. post-AJ). Of 386 breast cancer patients, with a mean age at diagnosis of 48 ± 8 years, 268 (69.4%) were diagnosed in the pre-AJ period, and 118 (30.6%) in the post-AJ period. Of these, 123 (31.9%) underwent CRRM, a median 42 (interquartile range: 11–54) days after the index cancer surgery. Rates of CRRM doubled following AJ’s news, from 23.9% pre-AJ to 50.0% post AJ ( p  < 0.001). Rates of CRRM were found to decrease with increasing age at breast cancer ( p  < 0.001) and tumour TNM stage ( p  = 0.040), and to increase with the estimated lifetime risk of breast cancer ( p  < 0.001) and tumour grade ( p  = 0.015) on univariable analysis. After adjusting for these factors, the step-change increase in CRRM rates post-AJ remained significant (odds ratio: 9.61, p  < 0.001). The AJ effect appears to have been associated with higher rates of CRRM amongst breast cancer patients with increased cancer risk. CRRM rates were highest amongst younger women and those with the highest lifetime risk profile. Clinicians need to be aware of how media news can impact on the delivery of cancer related services. Communicating objective assessment of risk is important when counselling women on the merits of risk-reducing surgery.

Microbial keratitis (MK) is the most common non-surgical ophthalmic emergency, and can rapidly progress, causing irreversible sight-loss. This study explored whether the COVID-19 (C19) national lockdown impacted upon the clinical presentation and outcomes of MK at a UK tertiary-care centre. Medical records were retrospectively reviewed for all patients with presumed MK requiring corneal scrapes, presenting between 23rd March and 30th June in 2020 (Y2020), and the equivalent time windows in 2017, 2018 and 2019 (pre-C19). In total, 181 and 49 patients presented during the pre-C19 and Y2020 periods, respectively. In Y2020, concurrent ocular trauma (16.3% vs. 5.5%, p = 0.030) and immunosuppression use (12.2% vs 1.7%, p = 0.004) were more prevalent. Despite proportionately fewer ward admissions during the pandemic (8.2% vs 32.6%, p<0.001), no differences were observed in baseline demographics; presenting visual acuity (VA; median 0.6 vs 0.6 LogMAR, p = 0.785); ulcer area (4.0 vs 3.0mm2, p = 0.520); or final VA (0.30 vs 0.30 LogMAR, p = 0.990). Whilst the overall rates of culture positivity were similar in Y2020 and pre-C19 (49.0% vs. 54.7%, p = 0.520), there were differences in the cultures isolated, with a lower rate of poly-microbial cultures in Y2020 (8.3% vs. 31.3%, p = 0.022). Patient characteristics, MK severity and final visual outcomes did not appear to be affected in the first UK lockdown, despite fewer patients being admitted for care. Concurrent trauma and systemic immunosuppression use were greater than in previous years. The difference in spectra of isolated organisms may relate to behavioural changes, such as increased hand hygiene.

Background Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity. Methods Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fibrosis was quantified on histology using collagen volume fraction (CVF mean ) compared to autopsy controls without cardiac pathology. Results 120 consecutive patients (64 ± 13 years; 71% male) were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients (234 biopsy samples in total). MR patients had more fibrosis compared to 8 autopsy controls (median: 14.6% [interquartile range 7.4–20.3] vs. 3.3% [2.6–6.1], P < 0.001); this difference persisted in the asymptomatic patients (CVF mean 13.6% [6.3–18.8], P < 0.001), but severity of fibrosis was not significantly higher in NYHA II-III symptomatic MR (CVF mean 15.7% [9.9–23.1] (P = 0.083). Fibrosis was patchy across biopsy sites (intraclass correlation 0.23, 95% CI 0.08–0.39, P = 0.001). No significant relationships were identified between CVF mean and CMR tissue characterisation [native T1, extracellular volume (ECV) or late gadolinium enhancement] or measures of LV function [LV ejection fraction (LVEF), global longitudinal strain (GLS)]. Although the range of ECV was small (27.3 ± 3.2%), ECV correlated with multiple measures of LV function (LVEF: Rho = − 0.22, P = 0.029, GLS: Rho = 0.29, P = 0.003), as well as NTproBNP (Rho = 0.54, P < 0.001) and exercise capacity (%PredVO 2 max: R = − 0.22, P = 0.030). Conclusions Patients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418

Background The interplay between ethnicity and socioeconomic deprivation for living-donor kidney transplantation (LDKT) opportunities is unclear. Methods Data for 2040 consecutive kidney-alone transplant recipients receiving an allograft between 1st January 2007 and 30th June 2020 at a single center were retrospectively analyzed. The associations between the proportions of transplants that were LDKT (versus deceased donation) and both ethnicity and socioeconomic deprivation were assessed, with the latter quantified by the Index of Multiple Deprivation (IMD) quintile. Results The cohort comprised recipients of White (64.7%), South Asian (21.7%), Black (7.0%) and other (6.6%) ethnic groups. Recipients tended to be from socioeconomically deprived areas, with the most deprived quintile being the most frequently observed (quintile 1: 38.6% of patients); non-White recipients were significantly more likely to live in socioeconomically deprived areas ( p  < 0.001). Overall, 36.5% of transplants were LDKT, with this proportion declining progressively with socioeconomic deprivation, from 50.4 to 27.6% in the least versus most deprived IMD quintile ( p  < 0.001). A significant difference across recipient ethnicities was also observed, with the proportion of LDKTs ranging from 43.2% in White recipients to 17.8% in Black recipients ( p  < 0.001). Both socioeconomic deprivation ( p  < 0.001) and ethnicity ( p  = 0.005) remained significant predictors of LDKT on multivariable analysis, with a significant interaction between these factors also being observed ( p  < 0.001). Further assessment of this interaction effect found that, whilst there was a marked difference in the proportions of transplants that were LDKT between White versus non-White recipients in the most socioeconomically deprived groups (39.5% versus 19.3%), no such difference was seen in the least deprived recipients (48.5% versus 51.9%). Conclusions Whilst both socioeconomic deprivation and non-White ethnicity are independent predictors for lower proportions of LDKTs, the significant interaction between the two factors should be appreciated.

ObjectivesMost sexual violence (SV) remains undisclosed to healthcare professionals. The aims of this study were to identify where support would be sought after SV and whether routine enquiry about SV was acceptable in a sexual healthcare setting.DesignAn online population-based survey collected data on a history of SV and preferences on support after SV, in addition to sociodemographic data. Respondents’ views on being routinely asked about SV were sought.Setting and participantsThis online survey was based in England, UK. There were 2007 respondents.ResultsThe police were the most frequent first choice for support after experiencing SV (n=520; 25.9%); however, this was less common in individuals in younger age groups (p<0.001) and in those with a history of SV (17.2% vs 29.9%, p<0.001). For the 27.1% (532 of 1960) of respondents who reported a history of SV, the first choice of place for support was Rape Crisis or similar third-sector organisation. The majority of respondents supported routine enquiry about SV during Sexual and Reproductive Health Service (SRHS) consultations (84.4%), although acceptability was significantly lower in older age groups.Conclusions and study implicationsA greater awareness of the influence of sociodemographic factors, including ethnicity, age, gender, disability and a history of SV, when planning and delivering services for those who have experienced SV is needed. A history of SV is common in the general population, and a ‘one-size-fits-all’ approach to encourage disclosure and access to support is unlikely to be optimal. Routine enquiry about SV is highly acceptable in an SRHS setting and likely to improve disclosure when appropriately implemented.

Purpose To evaluate management and outcome in a large series of patients with spermatic cord sarcomas (SCS), a rare malignancy. Methods Eighty-two patients with localized SCS treated at two dedicated sarcoma units between 1992 and 2013 were included. Disease-specific survival (DSS) and crude cumulative incidence of local recurrence and distant metastases (DM) were estimated by Kaplan–Meier plots and log rank tests. Results Median follow-up was 33 months (interquartile range 13–72 months). Sixty-one patients presented with primary disease. Liposarcoma was the most common histotype, but surprisingly, 37 % of tumors were of high grade. Seventeen patients (21 %) received radiotherapy and 12 patients (15 %) chemotherapy. Five-year DSS for the whole series was 92 % [95 % confidence interval (CI) 83–97]. Five-year rates of local recurrence and DM were 26 % (95 % CI 15–42) and 24 % (95 % CI 15–38), respectively. Tumor grade was found to be a significant predictor of both DSS and DM (both p  < 0.001). Quality of surgical margins was proved to affect the local outcome ( p  = 0.025), while the rates of distant metastases were found to differ significantly by histology ( p  = 0.010). Exclusively in the liposarcoma subgroup, quality of surgical margins was also directly associated with DSS ( p  = 0.043). Conclusions Wide excision of the tumor is critical for cure, especially in the liposarcoma subgroup. The role of radiotherapy and chemotherapy is not established.

Noninvasive monitoring of disease activity in autoimmune hepatitis (AIH) has potential advantages for patients for whom liver biopsy is invasive and with risk. We sought to understand the association of multiparametric magnetic resonance imaging (mpMRI) with clinical course of patients with AIH. We prospectively recruited 62 patients (median age, 55 years; 82% women) with clinically confirmed AIH. At recruitment, patients underwent mpMRI with LiverMultiScan alongside clinical investigations, which were repeated after 12‐18 months. Associations between iron‐corrected T1 (cT1) and other markers of disease were investigated at baseline and at follow‐up. Discriminative performance of cT1, liver stiffness, and enhanced liver fibrosis (ELF) to identify those who failed to maintain remission over follow‐up was investigated using the areas under the receiver operating characteristic curves (AUCs). Baseline cT1 correlated with alanine aminotransferase (Spearman’s correlation coefficient [rS] = 0.28, P = 0.028), aspartate aminotransferase (rS = 0.26, P = 0.038), international normalized ratio (rS = 0.35 P = 0.005), Model for End‐Stage Liver Disease (rS = 0.32, P = 0.020), ELF (rS = 0.29, P = 0.022), and liver stiffness rS = 0.51, P < 0.001). After excluding those not in remission at baseline (n = 12), 32% of the remainder failed to maintain remission during follow‐up. Failure to maintain remission was associated with significant increases in cT1 over follow‐up (AUC, 0.71; 95% confidence interval [CI], 0.52‐0.90; P = 0.035) but not with changes in liver stiffness (AUC, 0.68; 95% CI, 0.49‐0.87; P = 0.067) or ELF (AUC, 0.57; 95% CI, 0.37‐0.78; P = 0.502). cT1 measured at baseline was a significant predictor of future loss of biochemical remission (AUC, 0.68; 95% CI, 0.53‐0.83; P = 0.042); neither liver stiffness (AUC, 0.53; 95% CI, 0.34‐0.71; P = 0.749) nor ELF (AUC, 0.52; 95% CI, 0.33‐0.70; P = 0.843) were significant predictors of loss of biochemical remission. Conclusion: Noninvasive mpMRI has potential to contribute to risk stratification in patients with AIH.

Background: Advanced endoscopic technologies led to significant progress in the definition of endoscopic remission of ulcerative colitis (UC) and correlate better with histological changes, compared with standard endoscopy. However, while studies have assessed the diagnostic accuracy of endoscope technologies individually, there are currently limited data comparing between technologies. As such, the aim of this systematic review was to pool data from the existing literature and compare the correlations between endoscopy and histologic disease activity scores across endoscope technologies. Methods: We searched PubMed and Embase until February 2021 for eligible studies reporting the correlation between endoscopy and histology activity scores in UC. Studies were grouped by endoscope technology as standard-definition white light (SD-WLE), high-definition white light (HD-WLE) or electronic virtual chromoendoscopy (VCE) and comparisons made between these groups. Results: A total of N = 27 studies were identified, of which N = 12 were included in a meta-analysis of correlations between endoscopic and histological activity scores. Combining these studies identified considerable heterogeneity (I2: 89–93%) and returned a pooled correlation coefficient (ρ) for the SD-WLE group of 0.74, which did not differ significantly from HD-WLE (ρ: 0.65, p = 0.521) or VCE (ρ: 0.70, p = 0.801). In addition, N = 4 studies reported the accuracy of endoscopic activity scores on WLE and VCE to diagnose histological remission. Pooling these found significantly higher accuracy for VCE, compared with WLE [risk ratio: 1.13, 95% confidence interval (CI): 1.07–1.19, p < 0.001]. Conclusion: Activity scores assessed using endoscopy are strongly correlated with activity on histology regardless of endoscopic technology. VCE seems to be more accurate in predicting histological remission than WLE. However, given the heterogeneity between the included studies, head-to-head trials are warranted to confirm these findings.

BackgroundThere is increasing evidence to suggest vitamin D plays a role in immune and vascular function; hence, it may be of biological and clinical relevance for patients undergoing major surgery. With a greater number of randomised studies being conducted evaluating the impact of vitamin D supplementation on surgical patients, it is an opportune time to conduct further analysis of the impact of vitamin D on surgical outcomes.MethodsMEDLINE, EMBASE and the Cochrane Trials Register were interrogated up to December 2023 to identify randomised controlled trials of vitamin D supplementation in surgery. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool. A narrative synthesis was conducted for all studies. The primary outcome assessed was overall postoperative survival.ResultsWe screened 4883 unique studies, assessed 236 full-text articles and included 14 articles in the qualitative synthesis, comprising 1982 patients. The included studies were highly heterogeneous with respect to patient conditions, ranging from open heart surgery to cancer operations to orthopaedic conditions, and also with respect to the timing and equivalent daily dose of vitamin D supplementation (range: 0.5–7500 mcg; 20–300 000 IU). No studies reported significant differences in overall survival or postoperative mortality with vitamin D supplementation. There was also no clear evidence of benefit with respect to overall or intensive care unit length of stay.DiscussionNumerous studies have reported the benefits of vitamin D supplementation in different surgical settings without any consistency. However, this systematic review found no clear evidence of benefit, which warrants the supposition that a single biological effect of vitamin D supplementation does not exist. The observed improvement in outcomes in low vitamin D groups has not been convincingly proven beyond chance findings.Trial registration numberCRD42021232067.

ObjectiveTo evaluate whether topical therapy is linked to scores related to anxiety, depression and quality of life (QoL) in inflammatory eye disease (IED).Methods and analysisPatients with ocular surface disease (OSD, N=100) and Uveitis (N=100) completed self-administered validated questions on ocular symptoms and well-being, with supplemental questions on eye drop frequency.ResultsForty (20%) patients had scores consistent with depression and 33 (17%) anxiety. Anxiety, depression, QoL and OSD index (OSDI) scores did not differ significantly between OSD and Uveitis groups. In those with anxiety or depression, QoL was significantly reduced in all WHO Quality Of Life-BREF domains (all p<0.001). Multivariable analysis considering demographic and disease-related factors found daily topical drop frequency to be independently associated with anxiety (p=0.009) but not depression (p=0.300).ConclusionA high proportion of patients with IED demonstrated scores indicative of anxiety and depression. Preliminary evidence suggests that the frequency of topical eye drops potentially plays a significant role in the psychological health status of patients with IED .