University Hospital South Manchester Research Articles

Comparison of Blood and Blood Product Transfusion in COVID-19 and Non-COVID-19 Patients Requiring Extracorporeal Membrane Oxygenation for Severe Respiratory Failure.

COVID-19 has resulted in an exponential increase in patients with severe respiratory failure requiring extracorporeal membrane oxygenation (ECMO). Patients on ECMO regularly require high volumes of blood and blood products but, so far, there has been no comparison of transfusion requirements between COVID-19 and non-COVID-19. Using electronic patient records at two major UK ECMO centres, Royal Papworth Hospital and University Hospital South Manchester, we reviewed the transfusion requirements of patients requiring ECMO between January 2019 to December 2021. A total of 271 patients, including 168 COVID-19 patients were available for analysis. Since COVID-19 patients spent almost twice as long on ECMO (27.1 vs. 14.16 days, p ≤ 0.0001) we indexed transfusion in both groups to days on ECMO to allow comparison. COVID-19 patients required less red blood cells (RBC) per day (0.408 vs. 0.996, p = 0.0005) but more cryoprecipitate transfusions (0.117 vs. 0.106, p = 0.022) compared to non-COVID-19 patients. COVID-19 patients had more than double the mortality of non-COVID-19 patients (47% vs. 20.4%, p = 0.0001) and those who died during the study period had higher platelet transfusion requirements (p = 0.007) than their non-COVID-19 counterparts. Transfusion requirements and coagulopathy differ between COVID-19 and non-COVID-19 patients. The distinctly different transfusion patterns between the two groups remain difficult to interpret, but further investigations may help explain the haematological aspects of severe COVID-19 infection.

Editorial introductions

Editorial introductions

Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness

IntroductionAdrenal incidentalomas are lesions that are incidentally identified while scanning for other conditions. While most are benign and hormonally non-functional, around 20% are malignant and/or hormonally active, requiring prompt intervention....

Impact of social deprivation, demographics and centre on HbA1c outcomes with continuous subcutaneous insulin infusion.

To assess the impact of social deprivation, demographics and centre on HbA1c outcomes with continuous subcutaneous insulin infusion (CSII) in adults with Type 1 diabetes. Demographic data, postcode-derived English Index of Multiple Deprivation data and 12-month average HbA1c (mmol/mol) pre- and post-CSII were collated from three diabetes centres in the north west of England, University Hospital of South Manchester (UHSM), Salford Royal Foundation Hospital (SRFT) and Manchester Royal Infirmary (MRI). Univariable and multivariable regression models explored relationships between demographics, Index of Multiple Deprivation, centre and HbA1c outcomes. Data were available for 693 (78%) individuals (UHSM, n=90; SRFT, n=112; and MRI, n=491) of whom 59% were women. Median age at CSII start was 39 (IQR 29.5-49.0)years and median diabetes duration was 20 (11-29) years. Median Index of Multiple Deprivation was 15193 (6313-25727). Overall median HbA1c improved from 69 to 64mmol/mol (8.5% to 8.0%) within the first year of CSII. In multivariable analysis, higher pre-CSII HbA1c was significantly associated with higher deprivation (P=0.036), being female (P<0.001), and centre (MRI; P=0.005). Following pre-CSII HbA1c adjustment, post-CSII HbA1c or HbA1c change were not related to demographic factors and deprivation, but remained significantly related to the centre; UHSM and SRFT had larger reductions in HbA1c with CSII compared with MRI [median -7.0 (-0.6%) vs. -6.0 (-0.55%) vs. -4.5 (-0.45%)mmol/mol; P=0.005]. Higher pre-CSII HbA1c levels were associated with higher deprivation and being female. CSII improves HbA1c irrespective of social deprivation and demographics. Significant differences in HbA1c improvements were observed between centres. Further work is warranted to explain these differences and minimize variation in clinical outcomes with CSII.

The Use of Porcine Acellular Dermal Matrix in Single-stage, Implant-based Immediate Breast Reconstruction: A 2-center Retrospective Outcome Study.

Background:There have been many reported benefits of the usage of acellular dermal matrices (ADMs) in breast reconstruction. ADM reduces the need for rectus abdominis muscle and serratus anterior coverage by providing an inferolateral coverage of the implant/tissue expander. ADM can provide patients with a 1-staged reconstruction. This study was designed to look at the complication rates of 2 major hospitals in the United Kingdom.Methods:A large, 2-center retrospective cohort review of patients, who underwent implant-based breast reconstruction using Strattice (LifeCell Corp., Branchburg, N.J.) between March 2009 and November 2017, was performed. One-way analysis of variance was done to compare outcome significance between groups. Independent t test was performed to compare outcomes of 2 cohorts and regression analysis to include confounding factors using SPSS Statistics for Windows (Version 22.0. Armonk, NY: IBM Corp.).Results:A total of 450 and 400 breast reconstructions were carried out in University Hospital of South Manchester (UHSM) and Royal Free London Hospital (RFH), respectively. We recorded a total complication of 37.8% in RFH cohort and 28% in UHSM cohort. The seroma rate was 11.25% and 13.33% in the UHSM and RFH cohort, respectively. Other complications reported were major and minor infections, implant loss, skin necrosis, hematomas, and implant exposure. Multiple linear regression analysis reported that confounding factors affected certain outcomes.Conclusion:Our 2-center complication rates were comparable to other articles. Results were comparable despite being in 2 different breast units in the United Kingdom.

Clinical audit of the completion of CT scan request forms.

Objective: To pilot study an audit looking at whether CT scan request forms are completed to an appropriate level. This was based on the adequacy of the detail provided and the use of abbreviations based on local trust guidance. Methods: 60 CT scan requests were retrospectively analysed at University Hospital South Manchester. The following factors were considered: clinical information provided, the offering of a differential diagnosis and use of abbreviations in requests. Results: Of the scan requests analysed, 44 (73%) were adequately completed according to the criteria set. The adequacy of requests and use of appropriate abbreviations varied between the types of scan being requested. There were 59 different abbreviations used in 34 of the requests (57%). Of these, only two (3%) were considered inappropriate. Conclusion: There is still room for improvement in the completion of CT scan requests at University Hospital South Manchester. The poor completion of the forms and use of poor abbreviations can have a detrimental effect on the reporting and therefore, care of the patient. It is important that this problem is tackled appropriately. Advances in Knowledge: There is scope for improvement in the completion of CT request forms. This audit highlights this issue and provides the basis for implementing larger studies looking at completion of radiological request forms.

Idiopathic unilateral persistent hypoglossal nerve palsy – literature review and illustrative case

AbstractThe motor nerve innervation of the extrinsic and intrinsic muscles of the tongue is through the hypoglossal nerve. Hypoglossal nerve palsy arising as a result of injury to the nerve can occur anywhere along its course from the hypoglossal nuclei, medulla oblongata to the tongue itself. Idiopathic isolated and unilateral persistent hypoglossal nerve palsy is an extremely rare condition with only four cases ever reported. In this article, we review reported cases in the literature with comparison to a recent case in the oral and maxillofacial department of University Hospital South Manchester, which highlight the necessity of a segmental and stepwise approach in the diagnosis and management of this condition.

Abstract CN08-03: Liquid biopsies for the management of cancer patient treatment and for early detection of cancer

Abstract Molecular profiling to aid treatment selection is becoming routine in major cancer centers across the globe. Liquid biopsies for this purpose are increasing because of the challenges that tumor biopsies can present, especially for particular tumor types (e.g., pancreas and lung cancer), for patients with multiple metastases, and when serial sampling is needed to monitor tumor evolution and acquired drug resistance. In Manchester, we have pioneered this approach within the TARGET protocol to support selection of the most appropriate phase I trial for patients at the Christie Hospital. Within the TARGET study, we are profiling DNA from tumor biopsies (archival and/or fresh) and circulating tumor DNA. I will describe the TARGET feasibility study with results from the first 100 patients that focused on the development of our robust ctDNA workflow and bioinformatics pipeline, how ctDNA data correlate with those derived from tumor biopsy, and the matching of molecular profiles with actionable alterations to available trials. I will also describe our biweekly Molecular Tumor Board and the current initiative to provide a "virtual tumor board," where board members can access and discuss laboratory and clinical data remotely. Our ongoing and future goals are to expand TARGET to a further 450 Christie Hospital patients and across the CRUK Experimental Medicines Centres North (ECMC North), bringing opportunities for patients to travel to the most appropriate trial for them across the region. I will then discuss how we are approaching the harder challenge of liquid biopsy for the early detection of cancer, focusing on lung cancer where earlier detection that results in surgery with curative intent would transform patient outcomes. The subject cohort study that will maximize the success of liquid biopsy discovery for lung cancer is termed the "hard to reach, high risk" and typically reside in socially deprived areas, only seeking medical attention when their cancer is at an advanced and usually incurable stage. To address this challenge, we have worked closely with the University Hospital of South Manchester to set up a parallel blood test discovery program alongside the Manchester Community Lung Health Study. Subjects receive invitations from their GP to attend a free Lung Health Check in their communities (in shopping mall carparks), part of which for many subjects is a CT scan in a purpose-built van. This summer (and ongoing) we have collected &amp;gt;600 subject blood samples in vans parked adjacent to the CT scanner van. Samples are brought to our laboratory ED for processing and storage prior to analysis of circulating tumor cells (CTCs) using new technology platforms that examine every cell within the sample, and of ctDNA. Liquid biopsy results will be mapped to CT scan results and with clinical follow-up. Last summer, the CT scan data led to earlier detection of lung cancer cases allowing curative-intent surgery, but this is expensive and generates false-positive calls. Unlike liquid biopsy, multiple repeat CT scanning cannot be offered. We are therefore asking whether liquid biopsies that provide a molecular confirmation of cancer (single CTC or ctDNA profiling) can identify those subjects with a positive CT scan who have a cancer diagnosis and whether liquid biopsies yield earlier detection of cancer. Citation Format: Caroline Dive. Liquid biopsies for the management of cancer patient treatment and for early detection of cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr CN08-03.

119 - Patient experience on a rapid lung cancer diagnostic pathway at University Hospital South Manchester

119 - Patient experience on a rapid lung cancer diagnostic pathway at University Hospital South Manchester

Prevalence of nodal metastases in lymph node stations 8 & 9 in a large UK lung cancer surgical centre without routine pre-operative EUS nodal staging

IntroductionEndoscopic ultrasound (EUS) allows access to the inferior mediastinal lymph node stations (8 and 9) which are beyond the reach of endobronchial ultrasound (EBUS). The addition of EUS to EBUS procedures requires cost and resource investment. This study sought to describe the prevalence of station 8/9 nodal metastases from intra-operative lymph node sampling in a UK region where routine pre-operative EUS is not available. MethodsA retrospective review of all lung cancer resections at the University Hospital South Manchester from 2011 to 2014. Surgical variables, pre-operative PET variables and survival outcomes were collected and analysed. Results1421 surgical resections were performed in the study period. Lymph node stations 8 and/or 9 were sampled in 52% (736/1421) of patients. Overall, there were 34 patients with lymph node metastases at station 8/9. This represents 2.4% of the study populations and 4.6% of patients in whom stations 8/9 were sampled intra-operatively. Of those patients with station 8/9 metastases, 65% (22/34) had multi-station N2 disease and the majority of the additional N2 disease was present in EBUS-accessible areas (lymph node stations 2, 4 and 7). Two percent (16/736) of patients in whom station 8/9 lymph nodes were sampled intra-operatively had N2 disease that was only accessible endoscopically with EUS. There was no significant difference in overall survival in patients with pathological N2 disease stratified according to whether stations 8/9 were involved or not. ConclusionsThe prevalence of lymph node metastases in stations 8/9 in this UK surgical centre where routine pre-operative EUS is not performed is low at approximately 5%. Given the identification of N2 disease in two-thirds of these patients can potentially be achieved through EBUS alone, this questions whether the resource implications of EUS are justified by the impact on patient management.

Role of the multidisciplinary team in the care of the tracheostomy patient

Tracheostomies are used to provide artificial airways for increasingly complex patients for a variety of indications. Patients and their families are dependent on knowledgeable multidisciplinary staff, including medical, nursing, respiratory physiotherapy and speech and language therapy staff, dieticians and psychologists, from a wide range of specialty backgrounds. There is increasing evidence that coordinated tracheostomy multidisciplinary teams can influence the safety and quality of care for patients and their families. This article reviews the roles of these team members and highlights the potential for improvements in care.

Peer-assisted learning: something to feel confident about.

Peer-assisted learning (PAL) enables senior medical students to assist in the training and learning of junior medical students. Senior medical students from Manchester Medical School (MMS) developed a PAL scheme (PALS) for students training at University Hospital of South Manchester (UHSM). Senior medical students were trained as examiners and junior medical students acted as candidates in a series of mock OSCE examination stations.

Peer-assisted learning: something to feel confident about

Peer-assisted learning (PAL) enables senior medical students to assist in the training and learning of junior medical students. Senior medical students from Manchester Medical School (MMS) developed a PAL scheme (PALS) for students training at University Hospital of South Manchester (UHSM). Senior medical students were trained as examiners and junior medical students acted as candidates in a series of mock OSCE examination stations.

Degradation Phenomena on Second Generation of Explanted Aortic Textile Endografts

s 403 3 Department of Vascular and Endovascular Surgery, Manchester Royal Infirmary, United Kingdom Department of Vascular and Endovascular Surgery, University Hospital South Manchester, Manchester, United Kingdom Introduction: We previously reported our early experience using the firstgeneration multi-layer flow modulating stent (MFMS) for patients with thoraco-abdominal (TAAA) and perirenal aneurysms (PAA) who were unsuitable for conventional EVAR and unfit for open repair. We encountered continued aneurysm growth, device component dislocation and re-intervention. Our study patients have now completed at least 3 years follow-up and we report the outcomes. Methods: Patients with TAAA and PAA unfit for open surgery and with no conventional options for endovascular repair were recruited by two UK vascular units. Follow-up included CTA at 1, 3, 6, and 12 months, then annually until 3 years. Outcome measures included 30 day mortality, growth-free survival, branch vessel patency, complications, re-intervention and maximal aortic diameter. Results: MFMS were implanted in 14 patients (6 PAA, 8 TAAA) between October 2011 and March 2014 with one (7%) 30 day death and 11 (79%) surviving to 12 months. The median aneurysm growth was 9 mm in the first 12 months following implantation. At current follow-up to death or at least 3 years, eleven patients (79%) have died including four confirmed ruptures, one presumed rupture, one confirmed dissection with rupture, one MI post-op (procedure related), one multi-organ failure following re-intervention (procedure related) one myocardial infarction (MI) (out of hospital e unrelated), one pneumonia (not device or procedure related), and one decompensated liver failure (unrelated). Continued aneurysm growth occurred in all patients who suffered rupture or dissection. AAA diameter remains stable in two of the three surviving patients. Fifty of 51 covered aortic branches remained patent with no embolic episodes or symptoms of ischaemia in any patient. MFMS dislocation occurred in four patients, leading to re-intervention in two. A total of six re-interventions were performed in five patients (35%) with one post re-intervention death. Conclusion: These first-generation MFMS were unstable and dislocated frequently. It is uncertain whether MFMS implantation influenced the natural history of these aneurysms as none decreased in size, but two remain stable after a mean of 42.5 months. Although side branch patency was maintained, rupture or dissection occurred in 43% of patients and our results do not support the continued use of these first-generation devices. Further development is needed as this technology has potential as demonstrated by the control of aneurysm rupture in three and growth in two patients. Disclosure of Interest: None Declared. SESSION 4 e MISCELLANEOUS (1) THU, 29 SEPT, 8:00e9:00

Book Review

University Hospital of South Manchester, NHS Foundation Trust, Greater Manchester, UK [email protected] Conflicts of interest and sources of funding: none declared.

WS01.3 A ‘surprising’ pair: the synergistic antimicrobial activity of polymyxin B in combination with the cystic fibrosis drug ivacaftor against polymyxin-resistant P. aeruginosa

WS01.1 Discontinuation of routine anti-staphylococcal prophylaxis has no adverse effect on a paediatric CF patient population A. Shawcross, J. Holman, A. Maitra, A. Horsley, L.B. Patel, J. Panickar. Royal Manchester Childrens Hospital, Department of Paediatric Respiratory Medicine, Manchester, United Kingdom; University of Manchester, Institute of Inflammation and Repair, University Hospital of South Manchester, Wythenshawe, Manchester, United Kingdom; Manchester Adult Cystic Fibrosis Centre, University Hospital of South Manchester, Wythenshawe, Manchester, United Kingdom; SKMC Hospital, Department of Paediatric Respiratory Medicine, Abu Dhabi, United Arab Emirates

Q&A: Peter Whorwell.

Peter Whorwell is Director of the South Manchester Neurogastroenterology Service and a gastroenterologist at the University Hospital of South Manchester, UK. He has been researching and treating patients with irritable bowel syndrome (IBS) for more than 35 years, and has seen the depths of despair that this condition can cause.

Inhaled Mannitol (Bronchitol) for Cystic Fibrosis

Sarah J. Nolan *, Judith Thornton , Clare S. Murray , Tiffany Dwyer 4 Department of Biostatistics, The University of Liverpool, Liverpool, UK Centre for Clinical Practice, National Institute for Health and Care Excellence, Manchester, UK Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, UK 4 Sydney Medical School, University of Sydney, Sydney, Australia

Professor Jørgen Vestbo: advances on the management of COPD.

Professor Jorgen Vestbo ( Figure 1 ) is a Professor of Respiratory Medicine at the University of Manchester and an Honorary Consultant at the North West Lung Centre, University Hospital South Manchester NHS Foundation Trust. His professional training consisted of specialist training in Internal Medicine and Respiratory Medicine in university hospitals in Copenhagen. He obtained a DrMedSci degree from the University of Copenhagen in 1992.

A comparison of low and high dose atorvastatin on lipoproteins and inflammatory cytokines: The protection against nephropathy in diabetes with atorvastatin (panda) trial

s / Atherosclerosis 241 (2015) e149ee229 e202 treatments for key risk factors, such as hypertension, diabetes, and lipid abnormalities is critical to reduce future complications. Objective: To identify prevalence of lipid abnormalities and unmet needs among ACS patients in Germany currently receiving lipid lowering therapy (LLT) in light of aggressive goals recommended by new guidelines. Methods: DYSIS II is a multicenter, observational cross-sectional study conducted fromMay 2013-July 2014 in 22 German hospitals. Eligible adult patients were hospitalized for an ACS event, had full lipid profile available within 24 hours of admission, on LLT 3 months or not treated at all, not participating in randomized clinical trials involving medication, and were alive at discharge. Patient characteristics, risk factors, treatment patterns, and laboratory values were collected. Low density lipoprotein cholesterol (LDL-C) target achievement was assessed based on 2011 ESC/EAS guidelines. Results: Among 461 ACS patients (75.5% male, mean age 64.1 years), 80.9% had hypertension, 63.5% hypercholesterolemia, 56.9% history of coronary heart disease, 29.0% type 2 diabetes, and 27.3% were current smokers. 270 patients were on LLT, with only 21.9% reaching <70 mg/dl LDL-C target. Mean atorvastatin-equivalent dose was 18±11mg/day and 5.2% of treated patients received ezetimibe plus statin. Conclusion: More than three-fourths of LLT treated ACS patients in Germany were unable to achieve LDL-C target. Additional effective lipid lowering strategies are needed among these very high risk patients for LDL-C target achievement. Table 1 Comparison of lipid-lowering therapy in individuals receiving statin + PPI and those taking only statin Statin (N1⁄4700) Statin + PPI (N1⁄455) N, % Median dose, mg N, % Median dose, mg Atorvastatin 42 20 36 20 Rosuvastatin 31 20 36 10 Simvastatin 22 40 26 40 Fluvastatin 4 80 2 80 Ezetimibe 21 10 24 10 EAS-0434. A COMPARISON OF LOW AND HIGH DOSE ATORVASTATIN ON LIPOPROTEINS AND INFLAMMATORY CYTOKINES: THE PROTECTION AGAINST NEPHROPATHY IN DIABETES WITH ATORVASTATIN (PANDA) TRIAL H. Soran , Y. Liu , T. Siahmansur , J. Schofield , S. Kwok , V. CharltonMenys , M. Gittins , M. Gibson , N. Younis , M. France , P.N. Durrington , M.K. Rutter . 1 Lipoprotein Research Group, University of Manchester, Manchester, United Kingdom; Cardiovascular Trials Unit, Central Manchester University Hospitals, Manchester, United Kingdom; Manchester Diabetes Centre, Central Manchester University Hospitals, Manchester, United Kingdom; Diabetes & Endocrinology, Salford Royal NHS Foundation Trust, Manchester, United Kingdom; Diabetes & Endocrinology, University Hospital South Manchester, Manchester, United Kingdom; Clinical Biochemistry, Central Manchester University Hospitals, Manchester, United Kingdom * Corresponding author. Aim: To investigate the frequency with which recommended treatment goals are met in high risk diabetic patients with conventional dose as opposed to high dose statin therapy and their different effects on lipoproteins and other cardiovascular disease (CVD) risk factors. Methods: Patients with type 2 diabetes and optimally treated hypertension were randomized to receive atorvastatin 10mg (n1⁄459) or 80mg (n1⁄460) daily. Data at baseline and after one year are reported. Results: Patients in the study were at high CVD risk (observed annual event rate of 4.8%). The non-high density lipoprotein cholesterol (nonHDL-C) therapeutic goal of <2.6mmol/l was achieved by 72% of participants receiving 80mg daily, but only 40% on 10mg (p<0.005). Serum total cholesterol, low density lipoprotein cholesterol (LDL-C), apolipoprotein B100, glycated apolipoprotein B100 and lipoprotein-associated phospholipase A2 decreased significantly more on the higher dose. Serum apolipoprotein E and amyloid A decreased significantly only on 80mg daily. Both doses reduced triglycerides and oxidized LDL, and increased adiponectin, but these effects were not dose-dependent. Neither dose significantly affected cholesterol efflux, HDL-C, apolipoprotein A1, myeloperoxidase, high-sensitivity C-reactive protein (hsCRP), glycated hemoglobin (HbA1c) concentrations or the activities of paraoxonase-1, lecithin:cholesterol acyl transferase and cholesteryl ester transfer protein. Conclusions: High dose atorvastatin is necessary to achieve non-HDL-C therapeutic goals in a substantial proportion of patients. Atorvastatin is effective, generally in a dose-dependent manner, in modifying LDL-related CVD risk factors. It has no effect on HDL-related parameters or hsCRP, but evidence that therapeutic modification of these is beneficial is currently largely lacking. EAS-0440. PROTON PUMP INHIBITORS AND STATINS: A COMBINATION THAT FAVORS LDL-C REDUCTION? F. Barkas, E. Liberopoulos, M. Kostapanos, C. Rizos, E. Klouras, M. Elisaf. Internal Medicine, School of Medicine University of Ioannina,