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In mammalian cells, the level of the iron-storage protein ferritin (Ft) is tightly controlled by the iron-regulatory protein-1 (IRP-1) at the posttranscriptional level. This regulation prevents iron acting as a catalyst in reactions between reactive oxygen species and biomolecules. The ultraviolet A (UVA) radiation component of sunlight (320-400 nm) has been shown to be a source of oxidative stress to skin via generation of reactive oxygen species. We report here that the exposure of human primary skin fibroblasts, FEK4, to UVA radiation causes an immediate release of \"free\" iron in the cells via proteolysis of Ft. Within minutes of exposure to a range of doses of UVA at natural exposure levels, the binding activity of IRP-1, as well as Ft levels, decreases in a dose-dependent manner. This decrease coincides with a significant leakage of the lysosomal components into the cytosol. Stabilization of Ft molecules occurs only when cells are pretreated with lysosomal protease inhibitors after UVA treatment. We propose that the oxidative damage to lysosomes that leads to Ft degradation and the consequent rapid release of potentially harmful \"free\" iron to the cytosol might be a major factor in UVA-induced damage to the skin.

Sinus of Valsalva aneurysms (SVAs) are uncommon but important entities. They are most often congenital in origin, resulting from incomplete fusion of the aortic media to the aortic valve annulus. Less frequently, they may be acquired, usually secondary to infective endocarditis. Unruptured aneurysms may be clinically silent and diagnosed incidentally, but can also produce symptoms as a consequence of mass effect on related structures. Rupture may present with sudden hemodynamic collapse but can have a more insidious onset depending upon the site and size of the perforation. Early diagnosis is imperative and can usually be made reliably by transthoracic echocardiography. However, transesophageal echocardiography may sometimes be required for confirmation. Cardiovascular magnetic resonance imaging (CMRI) and multi-detector computed tomography are being increasingly utilized for evaluation of SVAs and can offer valuable complimentary information. CMRI in particular enables a comprehensive assessment of anatomy, function and flow in a single sitting. Surgical repair forms the mainstay of treatment for both ruptured and unruptured aneurysms and has low complication rates. This article provides an overview of the pathological and clinical aspects of SVAs and discusses in detail the role of advanced imaging modalities in their evaluation.

An electrocardiogram-gated MRI study was performed on a 1.5-T scanner (Ingenia; Philips Healthcare), comprising cine bright-blood prepared steady-state free precession (SSFP) in standard cardiac planes (2-chamber, 4-chamber, LV outflow tract, and LV short axis stack), static black-blood prepared fast spin echo sequences with T1 and T2 weighting and post contrast images following gadolinium administration using an inversion recovery technique. [...]cardiovascular MRI is the modality of choice for differentiation and characterization of a cardiac mass having numerous advantages over echocardiography including an unrestricted field of view and superior soft tissue resolution.

IntroductionCardiac syncope occurs when the heart fails to maintain cardiac output to match cerebral need and can occur due to either mechanical/structural defect of the heart or secondary to an arrhythmia. It has a raised 1-year mortality with some figures estimating this as high as 30%. Implantable loop recorders (ILR) are a useful diagnostic tool in patients presenting with syncope or pre-syncope to ascertain a cardiac cause. A higher number of patients are presenting with advancing age and undergoing ILR implantation. Subsequently, they end up requiring a cardiac implantable electronic device (CIED) implantation, adding to additional costs, exposure to procedural complications and frequent hospitalisations. The aim of this study was to investigate the number of patients undergoing CIED implantation following implantation of ILRs for syncope and identify predictors of CIED implantation in patients presenting with syncope.MethodsA retrospective analysis of 736 patients who underwent ILR implantation at our teaching hospital trust between November 2012 to October 2020. Data on demographics, clinical characteristics, pathology results, ECGs, holter findings and CIED implanted was collected using the local electronic patient record system. The data was analysed using SPSS software. Univariable and multivariable regression analysis and ROC curve analysis was carried out to determine prediction model for CIED implantation.ResultsThe mean age of patients who underwent an ILR implantation was 65 +/- 19 years. 22% of patients required CIED implantation, 68% of patients did not require a cardiac device and were safely discharged and 10% of patients died during follow up. Age (p < 0.001), male sex (p = 0.006), impaired left ventricular function (p = 0.04) and presence of hypertension (p = 0.04) were found to be independent predictors of CIED implantation on univariable and multivariable regression analysis (see table 1).Abstract 97 Table 1Linear regression analysis of predictors of CIED implantation Variable Beta (95% confidence interval) p value Univariate Age 0.007 (0.005 – 0.008) <0.001 Sex -0.104 (-0.165 – -0.044) 0.001 Presence of CAD 0.102 (0.025 – 0.179) 0.01 LV Function -0.151 (-0.237 – -0.064) 0.001 Presence of hypertension 0.166 (0.106 – 0.227) <0.001 Presence of valvular heart disease 0.103 (0.028 – 0.178) 0.007 History of previous stroke/TIA 0.063 (-0.032 – 0.159) 0.20 Presence of CKD 0.148 (0.055 – 0.241) 0.002 Multivariate Age 0.006 (0.004 – 0.007) <0.001 Sex -0.081 (-0.139 – -0.023) 0.006 LV Function -0.089 (-0.173 – -0.006) 0.04 Presence of hypertension 0.068 (0.004 – 0.132) 0.04 ConclusionOld age, presence of coronary artery disease, impaired left ventricular function and presence of hypertension are inter-linked and in our study were found to be key predictors of poor prognosis and thus requiring CIED implantation. We propose a scoring system based on age >75, male sex, presence of ischaemic heart disease, heart failure and hypertension as key markers of conduction abnormalities requiring CIED implantation (see figure 1).Conflict of InterestNone

Abstract Background Amlodipine is the most commonly prescribed calcium channel blocker (CCB), used in the treatment of a variety of cardiovascular conditions. Calcium channel blockers remain a well-established cause of cardiovascular drug overdose. We present the case of an intentional overdose with 250 mg of amlodipine resulting in acute left ventricular dysfunction and myocarditis. Case summary A 46-year-old man with no significant past medical history presented to the emergency department 8 h after intentionally ingesting 250 mg of amlodipine. Although initially asymptomatic with unremarkable physical examination, the patient developed progressively worsening dyspnoea over the next 2 days. Subsequent findings from chest X-ray, electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging (MRI) were consistent with a diffuse myocarditis process with severe left ventricular systolic dysfunction. The patient was managed with diuretics and discharged once stable. Discussion Our case highlights myocarditis as a potential complication of CCB overdose. Amlodipine is the most commonly prescribed CCB and is associated with cardiac toxicity at high doses. The long duration of action and high volume of distribution of amlodipine further increase the risk of morbidity and mortality from overdose. Known cardiac complications of amlodipine overdose include bradycardia, myocardial depression, and pulmonary oedema secondary to heart failure; however, diffuse myocarditis is a complication that has not previously been described in the literature. The mechanism of development of this complication remains unclear.

False-negative 16S ribosomal RNA gene PCR reactions can occur in the presence of inhibitors of the DNA polymerase within clinical samples or as a result of the vagaries of sampling (ie, processing a piece of tissue that does not contain any bacteria). Delivery of OPAT requires appropriate funding, support and infrastructure, coupled with the ability to rapidly access inpatient services and obtain urgent expert advice if needed.\\n Daptomycin, a recently licensed lipopeptide, is also recommended as an alternative agent for patients who are intolerant to vancomycin or have infection caused by vancomycin-resistant isolates.

IntroductionThere appears to be growing evidence that increasing consultant-led multidisciplinary team (MDT)-delivered care is associated with better patient outcomes, quicker decision making and more efficient uses of resources. There is still inconsistency across different hospitals, on how consultant led care can be best delivered when treating inpatients. Our hypothesis was that compared to a five single on call day service by separate Cardiologists, a consultant-led oncall week which consists of a twice daily inpatient ward round by the same consultant would improve patient outcomes in terms of discharge rates (DRs), length of stay (LoS), inpatient mortality rates (MRs) and readmission rates (RRs).SettingsGood Hope Hospital is a 521 bed district general hospital with 6 consultant cardiologists, and has an inpatient capacity of 6 CCU and 22 cardiology beds. Traditionally, all patients on CCU as well as new patients on the ward were reviewed by the on call consultant who was on call on a set day of the week. After the initial post take ward round, these patients were seen on a twice weekly basis by their admitting consultants and were looked after by junior doctors In the interim.MethodsThis was a retrospective observational study of inpatient average length of stay and discharge rates between April 2012 to March 2015 and included the data of 3289 patients. The intervention was implemented on 1st November 2013. All data were collected by the hospital IT department on a daily basis and reported on a monthly basis. We compared the inpatient MRs and RRs to assess any adverse effects on the quality of patient care. Statistical analysis was performed using student T-test. The p value <0.005 was considered significant. Results are expressed as means ± SD.ResultsThe data of 2058 patients prior to the consultants of the week method were compared to 1771 after the change. The monthly means ± SD of discharge rates, length of stay, readmission rate and mortality rate are shown in table 1. There is a significant increase in discharges and reduction in length of stay following the intervention. Despite a 15% increase in patient discharge rate, the readmission rate and inpatient mortality rate did not change significantly.ConclusionsFocused daily consultant input has a significant impact on reducing inpatient length of stay, ensuring timely discharges, and saving the NHS resources in bed days and creating more beds available for new admissions.Abstract 96 Table 1Comparison of monthly patient discharges, length of stay, readmission rate and inpatient mortality prior to and after the interventionVariableMonthly mean (April 2012 to November 2013)Monthly mean (December 2013 to February 2015)P value Discharged patients (n)103 ± 12118 ± 17P = 0.008Length of stay (days)7.9 ± 1.06.4 ± 1.0P = 0.0001Readmission rate (%)21.7 ± 7.9%23.4 ± 6.6%P = 0.56Inpatient Mortality (%)4.3 ± 1.6%4.2 ± 1.5%P = 0.96

Infective endocarditis (IE) remains a difficult condition to diagnose and treat and is an infection of high consequence for patients, causing long hospital stays, life-changing complications and high mortality. A new multidisciplinary, multiprofessional, British Society for Antimicrobial Chemotherapy (BSAC)-ledWorking Party was convened to undertake a focused systematical review of the literature and to update the previous BSAC guidelines relating delivery of services for patients with IE. A scoping exercise identified new questions concerning optimal delivery of care, and the systematic review identified 16 231 papers of which 20 met the inclusion criteria. Recommendations relating to endocarditis teams, infrastructure and support, endocarditis referral processes, patient follow-up and patient information, and governance are made as well as research recommendations. This is a report of a joint Working Party of the BSAC, British Cardiovascular Society, British Heart Valve Society, British Society of Echocardiography, Society of Cardiothoracic Surgeons of Great Britain and Ireland, British Congenital Cardiac Association and British Infection Association.

IntroductionDifferentiating chest pain that is caused by coronary artery disease (CAD) versus non-cardiac causes of chest pain is challenging. NICE guidelines recommend diagnosis should be made clinically with, if needed, functional cardiac imaging and invasive coronary angiography (CA). However, international studies reveal a surprising variation in the number of patients with 'normal' coronary arteries on elective CA (18.8-59%), potentially due to an overreliance on invasive investigations, inadequate pre-procedural clinical risk assessment and underuse of non-invasive imaging.AimWhat proportion of elective CA at Good Hope Hospital (GHH) were 'normal' and were they referred appropriately according to the current NICE guidelines?MethodsWe reviewed 738 coronary angiographies performed between September 2012-September 2013 at GHH. Of these, 377 patients had elective CA for chest pain.Angiogram findings were divided into 3 categories; interventional management.>50% stenosis of any vessel managed medically.'Normal' coronary arteries (<50% stenosis in any artery and not for increased medical management).We risk stratified patients with 'normal' coronary arteries on CA according to the NICE guidelines in order to assess the proportion of inappropriate referrals.ResultsOf the 377 elective CA for chest pain, 48% (182) had 'normal' coronary arteries. Of these, 44% were referred inappropriately according to NICE guidelines. Further analysis of those patients who had normal coronary arteries and were referred inappropriately, revealed that patients had often not received the recommended non-invasive imaging or they were over investigated but under-treated.ConclusionGHH lies within the international parameters for the proportion of 'normal' elective CA. Nevertheless, according to NICE guidelines, too many patients have invasive CA unnecessarily at GHH. This in part can be explained by an overreliance on CA and the underuse of functional imaging to diagnose CAD. Furthermore, one could argue that inadequate pre-procedural clinical risk assessment is exposing patients to avoidable risks and wastes NHS resources. However, our findings can also be explained in part by some genuine concerns that cardiologists have with the NICE guidelines on stable chest pain. In particular, the evidence base and practicalities of functional cardiac imaging as well as concern with the idea of managing patients without proven coronary artery disease with lifelong medication.In any case, standardising and improving the referral system in order to adjust the threshold required to proceed for a CA may improve the procedural specificity by reducing the number of 'normal' angiograms.