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    Contemporary use of excimer laser in percutaneous coronary intervention with indications, procedural characteristics, complications and outcomes in a university teaching hospital.

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    BACKGROUND Excimer laser coronary atherectomy (ELCA) can be used as an adjunctive percutaneous coronary intervention treatment for challenging, heavily calcified lesions. Although previous studies have documented high rates of complication and restenosis, these predate the introduction of the smaller 0.9 mm laser catheter. As the coronary complexity has increased, there has been a renewed interest in the ELCA. This study investigates the indications, procedural characteristics, complications and outcomes of ELCA in a contemporary coronary interventional practice. METHODS This single-centre study retrospectively analysed 50 patients treated with ELCA between January 2013 and January 2019. RESULTS Patients had a mean age of 67.9±11.4 years with a male predominance (65.3%). 25 (50%) cases were performed in patients with stable angina. Failure to deliver the smallest available balloon/microcatheter was the most frequent indication in 32 (64%) cases for ELCA use. 30 (60%) of the procedures were performed via radial access. The 0.9 mm X-80 catheter was used in 41 (82%) of cases, delivering on average 9000±3929 pulses. ELCA-related complications included 2 coronary dissections and 1 perforation, all of which were covered with stents. No major complications could be directly attributed to the use of ELCA. There was one death and one case of stent thrombosis within 30 days of the procedure. CONCLUSION ELCA can be performed safely via the radial approach with a 0.9 mm catheter with a high success rate by suitably trained operators. The low procedure-related complications with contemporary techniques make this a very useful tool for complex coronary interventions, especially for difficult to dilate lesions and chronic total occlusion vessels

    Association of Metformin with Susceptibility to COVID-19 in People with Type 2 Diabetes.

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    OBJECTIVE Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes. RESEARCH DESIGN AND METHODS We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed. RESULTS There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding. CONCLUSION Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with

    Medium-term outcome of severe to critically ill patients with SARS-CoV-2 infection.

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    BACKGROUND The medium and long-term effects of severe SARS-CoV-2 infection on survivors are unknown. Here we studied the medium term effects of COVID-19 on survivors of severe disease. METHODS This is a retrospective, case series of 200 patients hospitalised across three large Birmingham hospitals with severe-to-critical COVID-19 infection 4-7 months from disease-onset. Patients underwent comprehensive clinical, laboratory, imaging, lung function test, quality of life and cognitive assessments. RESULTS At 4-7 months from disease-onset, 63.2% of patients experienced persistent breathlessness, 53.5% complained of significant fatigue, 37.5% reduced mobility and 36.8% pain. Serum markers of inflammation and organ injuries that persisted at hospital discharge had normalised on follow-up indicating no sustained immune response causing chronic maladaptive inflammation. Chest radiographs showed a complete resolution in 82.8%; and significantly improved or no change in 17.2%. Lung function test (LFT) revealed gas transfer abnormalities in 80.0% and spirometry in 37.6% patients. Patients with breathlessness had significantly high incidence of comorbidities, abnormal residual chest X-ray and LFT (p<0.01 to all). In all parameters assessed and persisting symptoms there was no statically significant difference between patients managed on hospital wards and on ITU groups. All patients reported a significantly reduced quality of life in all domains of the EQ-5D-5L quality of life measures. CONCLUSIONS AND RELEVANCE A significant proportion of COVID-19 with severe illness experience ongoing symptoms of breathlessness, fatigue, pain, reduced mobility, depression and reduced quality of life at 4-7 months from disease-onset. Symptomatic patients tend to have more residual CXR and LFT abnormalities

    Clinical prediction of genotypes in hypertrophic cardiomyopathy: A Systematic Review.

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    INTRODUCTION Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition and the most common cause of sudden cardiac death (SCD) in patients below the age of 35. Genetic testing is a vital part of HCM diagnostics, yet correlation with clinical phenotypes remains complex. Identifying clinical predictors of informative genetic testing may prevent unnecessary investigations and improve cost-effectiveness of services. This article reviews the current literature pertinent to identifying such predictors. METHODS Five literature databases were screened using a suitably designed search strategy. Studies investigating the correlation between having a positive genetic test for HCM and a range of clinical and radiological parameters were included in the systematic review. RESULTS 29 observational studies of a total of 9,486 patients were included. The main predictors of informative genetic testing were younger age, higher septal thickness, reverse septal curvature, family history of HCM and SCD, and the absence of hypertension. Two externally validated scoring systems have also been developed: the Mayo and Toronto scores. Novel imaging markers and complex algorithmic models are emerging predictors. CONCLUSION Using clinical predictors to decide whom to test is a feasible alternative to investigating all-comers. Nonetheless, currently there is not enough evidence to unequivocally recommend for or against this strategy. Further validation of current predictors and identification of new ones remain open research avenues

    Mineralocorticoid receptor antagonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease.

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    Diabetic kidney disease develops in about 40% of patients with diabetes and is the commonest cause of chronic kidney disease worldwide. Patients with chronic kidney disease, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular death. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with diabetic kidney disease dates back to studies that are now 20 or more years old. During the last few years sodium-glucose co-transporter-2 inhibitors have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with renin-angiotensin system blockers and sodium-glucose co-transporter-2 inhibitors, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of cardiovascular death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists reduce albuminuria and surrogate markers of cardiovascular disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In The FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease (FIDELIO-DKD) study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of diabetic kidney disease and the incidence of cardiovascular events with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of mineralocorticoid receptor antagonists, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic chronic kidney disease

    Mortality risk of surgically managing orthopaedic trauma during the COVID-19 pandemic.

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    AIMS It is imperative to understand the risks of operating on urgent cases during the COVID-19 (SARS-Cov-2 virus) pandemic for clinical decision-making and medical resource planning. The primary aim was to determine the mortality risk and associated variables when operating on urgent cases during the COVID-19 pandemic. The secondary objective was to assess differences in the outcome of patients treated between sites treating COVID-19 and a separate surgical site. METHODS The primary outcome measure was 30-day mortality. Secondary measures included complications of surgery, COVID-19 infection, and length of stay. Multiple variables were assessed for their contribution to the 30-day mortality. In total, 433 patients were included with a mean age of 65 years; 45% were male, and 90% were Caucasian. RESULTS Overall mortality was 7.6% for all patients and 15.9% for femoral neck fractures. The mortality rate increased from 7.5% to 44.2% in patients with fracture neck of femur and a COVID-19 infection. The COVID-19 rate in the 30-day postoperative period was 11%. COVID-19 infection, age, and Charlson Comorbidity Index were independent risk factor for mortality. CONCLUSION There was a significant risk of contracting COVID-19 due to being admitted to hospital. Using a site which was not treating COVID-19 respiratory patients for surgery did not identify a difference with respect to mortality, nosocomial COVID-19 infection, or length of stay. The COVID-19 pandemic significantly increases perioperative mortality risk in patients with fractured neck of femora but patients with other injuries were not at increased risk. Cite this article:  2021;2(5):330-336

    Zanubrutinib-induced liver injury: a case report and literature review.

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    BACKGROUND Zanubrutinib is a Bruton's tyrosine kinase inhibitor that has been recently licensed in refractory mantle cell lymphoma and under assessment in phase 3 clinical trials for other B cell malignancies. To date, there are no reported cases of hepatotoxicity secondary to zanubrutinib. We report the first case of severe liver injury due to zanubrutinib. CASE PRESENTATION A 56-year-old Caucasian male with a history of relapsed lymphoplasmacytic lymphoma was admitted to the hospital with new-onset jaundice, choluria, and pruritus for 10 days. He had been on zanubrutinib as part of a clinical trial for 30 months. His blood profile showed a severe hepatocellular injury with jaundice (alanine transaminase 2474 IU/L and total bilirubin 141 umol/L with mild coagulopathy). He had an extensive work-up including virology, autoimmune, and metabolic profiles in addition to abdominal ultrasound with no alternative explanation found for his liver injury. Zanubrutinib-induced liver injury was suspected, and causality assessment by the updated Roussel Uclaf Causality Assessment Method score showed a probable causal relationship with zanubrutinib. His liver histology was also consistent with drug-induced liver injury. His liver biochemistry improved following cessation of zanubrutinib and normalised after 8 weeks. CONCLUSION We report the first case of severe liver injury secondary to zanubrutinib after 30 months of treatment. This case raises clinical awareness regarding zanubrutinib-induced liver toxicity and the importance of drug withdrawal in the event of liver injury

    Outcomes measures in idiopathic intracranial hypertension.

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    IntroductionIdiopathic Intracranial Hypertension is condition characterised by raised intracranial pressure, papilledema, and normal neuroimaging (aside from radiological signs of raised intracranial pressure). Symptoms of idiopathic intracranial hypertension include chronic headaches and for some, visual loss. New treatments are an unmet clinical need.Areas coveredThe aim of this review is to present the evidence base and considered opinion on outcome measures to determine successful management of idiopathic intracranial hypertension.Expert opinionLess invasive measures of disease activity such as optical coherence tomography will continue to grow in this field, both as a measure of papilledema, and potentially as a surrogate for intracranial pressure and visual function. As a highly disabling aspect of the disease is headache, treatment outcomes for headache morbidity need to be appropriately chosen and standardized to allow comparison between trials

    Stromal cells in tertiary lymphoid structures: Architects of autoimmunity.

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    The molecular mediators present within the inflammatory microenvironment are able, in certain conditions, to favor the initiation of tertiary lymphoid structure (TLS) development. TLS is organized lymphocyte clusters able to support antigen-specific immune response in non-immune organs. Importantly, chronic inflammation does not always result in TLS formation; instead, TLS has been observed to develop specifically in permissive organs, suggesting the presence of tissue-specific cues that are able to imprint the immune responses and form TLS hubs. Fibroblasts are tissue-resident cells that define the anatomy and function of a specific tissue. Fibroblast plasticity and specialization in inflammatory conditions have recently been unraveled in both immune and non-immune organs revealing a critical role for these structural cells in human physiology. Here, we describe the role of fibroblasts in the context of TLS formation and its functional maintenance in the tissue, highlighting their potential role as therapeutic disease targets in TLS-associated diseases

    Heart failure in adults with congenital heart disease: a narrative review.

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    The number of adults with congenital heart disease (ACHD) has increased over the last decades due to advancements in medical care, including interventional and surgical therapies. We are therefore more frequently challenged by the long-term consequences of palliative or corrective surgery carried out during childhood. Although patients with ACHD may develop conditions related to general cardiovascular risk factors, such as coronary artery disease, the most common complications leading to morbidity and mortality are arrhythmias, heart failure and thromboembolic events. For the management of arrhythmias, current recommendations regarding ablation and device therapy must be considered, whilst also taking into account the anatomical limitations of their congenital heart defect or surgical pathways. Heart failure treatment in acute and chronic settings must also consider the particular anatomy present, including the nature of the systemic ventricle. Treatments strategies for ACHD are typically extrapolated from the respective guidelines in non-ACHD patients, despite a lack of evidence to support this strategy. Right heart failure can be especially challenging to manage in conditions where either a systemic right ventricle or shunt lesions resulting in volume and/or pressure loading of the right ventricle are present. All physicians and cardiologists in particular should be acquainted with the most common diseases in ACHD, their complications and management regime, especially with regards to heart failure as this is a common reason for acute presentation in the emergency department

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