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Background Mitral annular disjunction (MAD) is a structural abnormality characterized by the distinct separation of the mitral valve annulus/left atrium wall and myocardium. Little is known about the significance of MAD in patients requiring mitral valve surgery. This evaluation evaluates the echocardiographic characteristics and patient outcomes for patients with and without MAD who require mitral valve surgery. Methods All patients who underwent mitral valve surgery and who had a pre-surgical transthoracic echocardiogram between 2013 and 2020 were included. Patient demographics and clinical outcomes were collected on review of patient electronic records. Results A total of 185 patients were included in the analysis of which 32.4% had MAD (average MAD length 8.4 mm). MAD was seen most commonly in patients with mitral valve prolapse and myxomatous mitral valves disease (90% and 60% respectively). In the patients with MAD prior to mitral valve surgery, only 3.9% had MAD post mitral valve surgery. There were no significant difference in the severity of post-operative mitral regurgitation, arrhythmic events or major adverse cardiovascular events in patients with and without MAD. Conclusions MAD is common in patients who undergo mitral valve surgery. Current surgical techniques are able to correct the MAD abnormality in the vast majority of patients. MAD is not associated with an increased risk of adverse clinical outcomes post mitral valve surgery.

ABSTRACT We present the case of a 28 year-old lady with a history of intravenous drug use who presented to our institution with symptomatic right heart failure secondary to tricuspid valve regurgitation. She presented with infective endocarditis leading to dyspnoea and peripheral oedema secondary to torrential tricuspid regurgitation. Transthoracic echocardiography confirmed right ventricular dysfunction and congestive hepatomegaly. Intra-operatively findings an infected and destroyed anterior leaflet of the tricuspid valve with posterior leaflet prolapse was found to cause severe tricuspid regurgitation. She had complex tricuspid valve reconstruction using anterior leaflet reconstruction using Admedus Cardiocel™ patch, posterior leaflet prolapse correction and commissural reduction with a McGoon imbrication and annuloplasty ring to stabilize the repair. This case demonstrates the importance of reconstructive tricuspid valve surgery in the setting of infective endocarditis. Furthermore, this case demonstrates the possibility of anterior leaflet excision and reconstruction with an excellent durable functional result.

Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations. We did a per-protocol pooled analysis of individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial (NCT00003636) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813). In the EORTC trial, eligible women had biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma. In the CHORUS trial, inclusion criteria were similar to those of the EORTC trial, and women with apparent FIGO stage IIIA and IIIB disease were also eligible. The main aim of the pooled analysis was to show non-inferiority in overall survival with neoadjuvant chemotherapy compared with upfront debulking surgery, using the reverse Kaplan-Meier method. Tests for heterogeneity were based on Cochran's Q heterogeneity statistic. Data for 1220 women were included in the pooled analysis, 670 from the EORTC trial and 550 from the CHORUS trial. 612 women were randomly allocated to receive upfront debulking surgery and 608 to receive neoadjuvant chemotherapy. Median follow-up was 7·6 years (IQR 6·0–9·6; EORTC, 9·2 years [IQR 7·3–10·4]; CHORUS, 5·9 years [IQR 4·3–7·4]). Median age was 63 years (IQR 56–71) and median size of the largest metastatic tumour at diagnosis was 8 cm (IQR 4·8–13·0). 55 (5%) women had FIGO stage II–IIIB disease, 831 (68%) had stage IIIC disease, and 230 (19%) had stage IV disease, with staging data missing for 104 (9%) women. In the entire population, no difference in median overall survival was noted between patients who underwent neoadjuvant chemotherapy and upfront debulking surgery (27·6 months [IQR 14·1–51·3] and 26·9 months [12·7–50·1], respectively; hazard ratio [HR] 0·97, 95% CI 0·86–1·09; p=0·586). Median overall survival for EORTC and CHORUS patients was significantly different at 30·2 months (IQR 15·7–53·7) and 23·6 months (10·5–46·9), respectively (HR 1·20, 95% CI 1·06–1·36; p=0·004), but was not heterogeneous (Cochran's Q, p=0·17). Women with stage IV disease had significantly better outcomes with neoadjuvant chemotherapy compared with upfront debulking surgery (median overall survival 24·3 months [IQR 14·1–47·6] and 21·2 months [10·0–36·4], respectively; HR 0·76, 95% CI 0·58–1·00; p=0·048; median progression-free survival 10·6 months [7·9–15·0] and 9·7 months [5·2–13·2], respectively; HR 0·77, 95% CI 0·59–1·00; p=0·049). Long-term follow-up data substantiate previous results showing that neoadjuvant chemotherapy and upfront debulking surgery result in similar overall survival in advanced tubo-ovarian cancer, with better survival in women with stage IV disease with neoadjuvant chemotherapy. This pooled analysis, with long-term follow-up, shows that neoadjuvant chemotherapy is a valuable treatment option for patients with stage IIIC–IV tubo-ovarian cancer, particularly in patients with a high tumour burden at presentation or poor performance status. National Cancer Institute and Vlaamse Liga tegen kanker (Flemish League against Cancer).

Major depressive disorder (MDD) and migraine are both more common among women than men. Women’s reproductive years are associated with increased susceptibility to recurrence of both conditions, suggesting a potential role of sex hormones in aetiology. We examined associations between comorbid migraine and clinical features of MDD in women, including relationships with lifetime reproductive events such as childbirth. Lifetime clinical characteristics and reproductive events in a well-characterised sample of 222 UK women with recurrent MDD, with (n = 98) and without (n = 124) migraine were compared. Women had all been recruited as part of a UK-based ongoing programme of research into the genetic and non-genetic determinants of mood disorders. Multivariate analysis showed a specific association between the lifetime presence of migraine and postpartum depression (PPD) within 6 weeks of delivery (OR = 2.555; 95% CI: 1.037–6.295, p = 0.041). This association did not extend to a broader definition of PPD with onset up to 6 months postpartum. All other factors included in the analysis were not significantly associated with the presence of migraine: family history of depression, younger age at depression onset, history of suicide attempt and severe premenstrual syndrome symptoms. The finding that women with MDD and comorbid migraine may be particularly sensitive to hormonal changes early in the postpartum period leads to aetiological hypotheses and suggests this group may be useful for future studies attempting to characterise PPD and MDD phenotypes. The refinement of such phenotypes has implications for individualising risk and treatment and for future biological and genetic studies.

Embolic events causing stroke and intracranial haemorrhage are among the most catastrophic complications of infective endocarditis (IE). A female patient presented with acute unilateral weakness following a 3-month history of fever, for which she had multiple remote consultations with her general practitioner. A brain MRI confirmed a left sided infarct with haemorrhagic transformation. Blood cultures grew Streptococcus mitis and her cardiac imaging showed an aortic valve vegetation with severe aortic regurgitation. Following 2 weeks of antibiotics she developed a new cerebral haemorrhage associated with a mycotic aneurysm which was treated with two coils. After discussions within the multidisciplinary meeting, she underwent aortic valve replacement 3 weeks later. She made a remarkable recovery and was discharged. Our case highlights the importance of face-to-face clinical review in the post-COVID era. It stresses that the management of patients with infective endocarditis and neurological complications is challenging and requires a multidisciplinary approach.

BackgroundOver recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs.ObjectiveTo explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC).MethodsBetween 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed.Results232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes.ConclusionsThe mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice.

The combination of patient illness and staff absence driven by seasonal viruses culminates in annual \"winter pressures\" on UK healthcare systems and has been exacerbated by COVID-19. In winter 2022/23 we introduce multiplex testing aiming to determine the incidence of SARS-CoV-2, influenza and respiratory syncytial virus (RSV) in our cohort of UK healthcare workers (HCWs). The pilot study was conducted from 28/11/2022-31/03/2023 within the SIREN prospective cohort study. Participants completed fortnightly questionnaires, capturing symptoms and sick leave, and multiplex PCR testing for SARS-CoV-2, influenza and RSV, regardless of symptoms. PCR-positivity rates by virus were calculated over time, and viruses were compared by symptoms and severity. Self-reported symptoms and associated sick leave were described. Sick leave rates were compared by vaccination status and demographics. 5,863 participants were included, 84.6% female, 70.3% ≥ 45-years, 91.4% of White ethnicity and 82.6% in a patient facing role. PCR-positivity peaked in early December for all three viruses (4.6 positives per 100 tests (95%CI 3.5, 5.7) SARS-CoV-2, 3.9 (95%CI 2.2, 5.6) influenza, 1.4 (95%CI 0.4, 2.4) RSV), declining to <0.3/100 tests after January for influenza/RSV, and around 2.5/100 tests for SARS-CoV-2. Over one-third of all infections were asymptomatic, and symptoms were similar for all viruses. 1,368 (23.3%) participants reported taking sick leave, median 4 days (range 1-59). Rates of sick leave were higher in participants with co-morbidities, working in clinical settings, and who had not been vaccinated (COVID-19 booster or seasonal influenza vaccine) versus those who had received neither vaccine (2.04 vs 1.41 sick days/100 days, adjusted Incidence Rate Ratio 1.47 (95%CI 1.38, 1.56). This pilot demonstrated the use of multiplex testing allowed better understanding of the impact of seasonal respiratory viruses and respective vaccines on the HCW workforce. This highlights the important information on asymptomatic infection and persisting levels of SARS-CoV-2 infection.

ObjectivesTo date the reported outcomes of surgical aortic valve replacement (SAVR) are mainly in the settings of trials comparing it with evolving transcatheter aortic valve implantation. We set out to examine characteristics and outcomes in people who underwent SAVR reflecting a national cohort and therefore ‘real-world’ practice.DesignRetrospective analysis of prospectively collected data of consecutive people who underwent SAVR with or without coronary artery bypass graft (CABG) surgery between April 2013 and March 2018 in the UK. This included elective, urgent and emergency operations. Participants’ demographics, preoperative risk factors, operative data, in-hospital mortality, postoperative complications and effect of the addition of CABG to SAVR were analysed.Setting27 (90%) tertiary cardiac surgical centres in the UK submitted their data for analysis.Participants31 277 people with AVR were identified. 19 670 (62.9%) had only SAVR and 11 607 (37.1%) had AVR+CABG.ResultsIn-hospital mortality for isolated SAVR was 1.9% (95% CI 1.6% to 2.1%) and was 2.4% for AVR+CABG. Mortality by age category for SAVR only were: <60 years=2.0%, 60–75 years=1.5%, >75 years=2.2%. For SAVR+CABG these were; 2.2%, 1.8% and 3.1%. For different categories of EuroSCORE, mortality for SAVR in low risk people was 1.3%, in intermediate risk 1% and for high risk 3.9%. 74.3% of the operations were elective, 24% urgent and 1.7% emergency/salvage. The incidences of resternotomy for bleeding and stroke were 3.9% and 1.1%, respectively. Multivariable analyses provided no evidence that concomitant CABG influenced outcome. However, urgency of the operation, poor ventricular function, higher EuroSCORE and longer cross clamp and cardiopulmonary bypass times adversely affected outcomes.ConclusionsSurgical SAVR±CABG has low mortality risk and a low level of complications in the UK in people of all ages and risk factors. These results should inform consideration of treatment options in people with aortic valve disease.

Cardiac fibrosis is mediated by the persistent activity of myofibroblasts, which differentiate from resident cardiac fibroblasts in response to tissue damage and stress signals. The signaling pathways and transcription factors regulating fibrotic transformation have been thoroughly studied. In contrast, the roles of chromatin factors in myofibroblast differentiation and their contribution to pathogenic cardiac fibrosis remain poorly understood. Here, we combined bulk and single-cell CRISPR screens to characterize the roles of chromatin factors in the fibrotic transformation of primary cardiac fibroblasts. We uncover strong regulators of fibrotic states including Srcap and Kat5 chromatin remodelers. We confirm that these factors are required for functional processes underlying fibrosis including collagen synthesis and cell contractility. Using chromatin profiling in perturbed cardiac fibroblasts, we demonstrate that pro-fibrotic chromatin complexes facilitate the activity of well-characterized pro-fibrotic transcription factors. Finally, we show that KAT5 inhibition alleviates fibrotic responses in patient-derived human fibroblasts.

A young woman presented with left sided chest pain. Chest radiography revealed a hyperexpanded left upper lobe and the rare diagnosis of congenital lobar emphysema was made. She was then found to be pregnant. Thoracotomy and left upper lobectomy were performed during the pregnancy without adverse effects to the mother or fetus. The implications of pregnancy on the surgical management of this rare condition are discussed.