Sheffield Teaching Hospitals NHS Foundation Trust
Recent publications
Background Fabry disease (FD) is a treatable X-linked condition leading to progressive cardiac disease, arrhythmia and premature death. We aimed to increase awareness of the arrhythmogenicity of Fabry cardiomyopathy, by comparing device usage in patients with Fabry cardiomyopathy and sarcomeric HCM. All Fabry patients with an implantable cardioverter defibrillator (ICD) implanted in the UK over a 17 year period were included. A comparator group of HCM patients, with primary prevention ICD implantation, were captured from a regional registry database. Results Indications for ICD in FD varied with 72% implanted for primary prevention based on multiple potential risk factors. In FD and HCM primary prevention devices, arrhythmia occurred more frequently in FD over shorter follow-up (HR 4.2, p < 0.001). VT requiring therapy was more common in FD (HR 4.5, p = 0.002). Immediate shock therapy for sustained VT was also more common (HR 2.5, p < 0.001). There was a greater burden of AF needing anticoagulation and NSVT in FD (AF: HR 6.2, p = 0.004, NSVT: HR 3.1, p < 0.001). Conclusion This study demonstrates arrhythmia burden and ICD usage in FD is high, suggesting that Fabry cardiomyopathy may be more ‘arrhythmogenic’ than previously thought. Existing risk models cannot be mutually applicable and further research is needed to provide clarity in managing Fabry patients with cardiac involvement.
Background Right atrial (RA) area predicts mortality in patients with pulmonary hypertension, and is recommended by the European Society of Cardiology/European Respiratory Society pulmonary hypertension guidelines. The advent of deep learning may allow more reliable measurement of RA areas to improve clinical assessments. The aim of this study was to automate cardiovascular magnetic resonance (CMR) RA area measurements and evaluate the clinical utility by assessing repeatability, correlation with invasive haemodynamics and prognostic value. Methods A deep learning RA area CMR contouring model was trained in a multicentre cohort of 365 patients with pulmonary hypertension, left ventricular pathology and healthy subjects. Inter-study repeatability (intraclass correlation coefficient (ICC)) and agreement of contours (DICE similarity coefficient (DSC)) were assessed in a prospective cohort (n = 36). Clinical testing and mortality prediction was performed in n = 400 patients that were not used in the training nor prospective cohort, and the correlation of automatic and manual RA measurements with invasive haemodynamics assessed in n = 212/400. Radiologist quality control (QC) was performed in the ASPIRE registry, n = 3795 patients. The primary QC observer evaluated all the segmentations and recorded them as satisfactory, suboptimal or failure. A second QC observer analysed a random subcohort to assess QC agreement (n = 1018). Results All deep learning RA measurements showed higher interstudy repeatability (ICC 0.91 to 0.95) compared to manual RA measurements (1st observer ICC 0.82 to 0.88, 2nd observer ICC 0.88 to 0.91). DSC showed high agreement comparing automatic artificial intelligence and manual CMR readers. Maximal RA area mean and standard deviation (SD) DSC metric for observer 1 vs observer 2, automatic measurements vs observer 1 and automatic measurements vs observer 2 is 92.4 ± 3.5 cm ² , 91.2 ± 4.5 cm ² and 93.2 ± 3.2 cm ² , respectively. Minimal RA area mean and SD DSC metric for observer 1 vs observer 2, automatic measurements vs observer 1 and automatic measurements vs observer 2 was 89.8 ± 3.9 cm ² , 87.0 ± 5.8 cm ² and 91.8 ± 4.8 cm ² . Automatic RA area measurements all showed moderate correlation with invasive parameters (r = 0.45 to 0.66), manual (r = 0.36 to 0.57). Maximal RA area could accurately predict elevated mean RA pressure low and high-risk thresholds (area under the receiver operating characteristic curve artificial intelligence = 0.82/0.87 vs manual = 0.78/0.83), and predicted mortality similar to manual measurements, both p < 0.01. In the QC evaluation, artificial intelligence segmentations were suboptimal at 108/3795 and a low failure rate of 16/3795. In a subcohort (n = 1018), agreement by two QC observers was excellent, kappa 0.84. Conclusion Automatic artificial intelligence CMR derived RA size and function are accurate, have excellent repeatability, moderate associations with invasive haemodynamics and predict mortality.
This case report proposes the use of pulsed methylprednisolone in a patient with lymphangioleiomyomatosis (LAM) who was invasively ventilated. A 38-year-old, East Indian gravida 4, para 1 ⁺² , patient with worsening respiratory function with spontaneous pneumothoraxes and hypoxemia was pulsed with methylprednisolone leading to rapid resolution of respiratory failure. The author proposes pulsed methylprednisolone in ventilated LAM patients, which gives another option to patients which resulted in alleviation of hypoxemia and maintaining foetal viability.
Background Paravalvular leak (PVL) is uncommon but can lead to severe complications after surgical or transcatheter aortic valve implantation. Conditions associated with PVLs such as heart failure, hemolysis, and infective endocarditis can lead to catastrophic results if not treated promptly; the therapeutic goals differ according to the presentation. It is vital that PVLs are diagnosed early using various imaging modalities. Different approaches have been studied in managing PVLs; there is an increased interest in the transcatheter aortic valve closure procedure as it is minimally invasive and decreases the occurrence of further reinterventions. Aim To discuss the classification of PVLs, diagnostic approaches, and available management options. Method A literature review was performed using 28 studies. Results This review evaluated the relationship between the time of diagnosis, management of PVL and the resulting outcomes. Discussion Patients with PVL should be assessed through a multidisciplinary team approach and a patient‐selective plan should be in place. Conclusion Open surgical intervention is reserved for complex cases where minimally invasive techniques cannot be utilized.
Objectives The objective of this review was to determine the rate and risk factors of paratracheal lymph node (PTLN) involvement during total laryngectomy (TL) or total pharyngolaryngectomy (TPL). In addition, we aimed to assess its prognostic significance in terms of survival and peristomal recurrence. Methods A comprehensive electronic search was performed on PubMed, EMBASE, and CENTRAL databases. We searched for studies reporting outcomes of PTLN dissection during radical laryngeal surgery for squamous cell carcinoma of the larynx, hypopharynx or cervical oesophagus. Results We included a total of ten studies (838 patients). The overall rate of PTLN dissection positivity was 18.6% (20.7% for primary TL, 8.7% for salvage TL). Random-effects meta-analysis identified T4 stage, N+ stage of the lateral neck, subglottis involvement and primary tumour arising from the hypopharynx or cervical oesophagus as significant risk factors for PTLN involvement. Conclusions This meta-analysis allowed to better define the risk of PTLN involvement during TL or TPL, in a bid to guide indication for PTLN dissection. There is a need for further large studies reporting rigorously the outcomes of PTLN dissection in order to establish stronger evidence-based recommendations.
Background Women with stress urinary incontinence (SUI) experience urine leakage with physical activity. Currently, the interventional treatments for SUI are surgical, or endoscopic bulking injection(s). However, these procedures are not always successful, and symptoms can persist or come back after treatment, categorised as recurrent SUI. There are longstanding symptoms and distress associated with a failed primary treatment, and currently, there is no consensus on how best to treat women with recurrent, or persistent, SUI. Methods A two-arm trial, set in at least 20 National Health Service (NHS) urology and urogynaecology referral units in the UK, randomising 250 adult women with recurrent or persistent SUI 1:1 to receive either an endoscopic intervention (endoscopic bulking injections) or a standard NHS surgical intervention, currently colposuspension, autologous fascial sling or artificial urinary sphincter. The aim of the trial is to determine whether surgical treatment is superior to endoscopic bulking injections in terms of symptom severity at 1 year after randomisation. This primary outcome will be measured using the patient-reported International Consultation on Incontinence Questionnaire - Urinary Incontinence - Short Form (ICIQ-UI-SF). Secondary outcomes include assessment of longer-term clinical impact, improvement of symptoms, safety, operative assessments, sexual function, cost-effectiveness and an evaluation of patients’ and clinicians’ views and experiences of the interventions. Discussion There is a lack of high-quality, randomised, scientific evidence for which treatment is best for women presenting with recurrent SUI. The PURSUIT study will benefit healthcare professionals and patients and provide robust evidence to guide further treatment and improve symptoms and quality of life for women with this condition . Trial registration International Standard Randomised Controlled Trials Number (ISRCTN) registry ISRCTN12201059. Registered on 09 January 2020
The practice and clinical outcomes of peritoneal dialysis (PD) have demonstrated significant improvement over the past 20 years. The aim of this review is to increase awareness and update healthcare professionals on current PD practice, especially with respect to patient and technique survival, patient modality selection, pathways onto PD, understanding patient experience of care and use prior to kidney transplantation. These improvements have been impacted, at least in part, by greater emphasis on shared decision-making in dialysis modality selection, the use of advanced laparoscopic techniques for PD catheter implantation, developments in PD connecting systems, glucose-sparing strategies, and modernising technology in managing automated PD patients remotely. Evidence-based clinical guidelines such as those prepared by national and international societies such as the International Society of PD have contributed to improved PD practice underpinned by a recognition of the place of continuous quality improvement processes.
Introduction: Recent guidelines suggest obstructive sleep apnoea (OSA) is not an absolute contraindication for same day discharge following surgery. The aim of this systematic review was to examine the feasibility and safety of day case nasal and/or palatopharyngeal surgery in patients with OSA. Methods: We performed a systematic search of PubMed, EMBASE and the Cochrane library. Quality assessment of included studies was done. The protocol of this systematic review was registered with PROSPERO (CRD42021273451). Results: A total of 1836 patients from ten observational studies were included. There were 268 (15.4%) nasal surgeries, 738 palatopharyngeal surgeries (42.4%) and 735 (42.2%) combined nasal and palatopharyngeal surgery. The majority of patients had moderate to severe OSA. A total of 860 patients (49.8%) were successfully discharged as day cases. There were no standard criteria for daycase surgery. Post-anaesthetic respiratory events were reported in 86/1750 (4.9%) patients. Oxygen desaturation was the most common respiratory event (83.7%, n = 72). There was no mortality reported. Conclusion: Current data suggests day surgery is feasible in carefully selected patients with OSA undergoing nasal and/or palatopharyngeal surgery. Further well-designed prospective studies with an emphasis on the systematic assessment of complications are required to establish safety and daycase criteria.
In recent years considerable variations in conditioning protocols for allogeneic hematopoietic cell transplantation (allo-HCT) protocols have been introduced for higher efficacy, lower toxicity, and better outcomes. To overcome the limitations of the classical definition of reduced intensity and myeloablative conditioning, a transplantation conditioning intensity (TCI) score had been developed. In this study, we compared outcome after two frequently used single alkylator-based conditioning protocols from the intermediate TCI score category, fludarabine/melphalan 140 mg/m2 (FluMel) and fludarabine/treosulfan 42 g/m2 (FluTreo) for patients with acute myeloid leukemia (AML) in complete remission (CR). This retrospective analysis from the registry of the Acute Leukemia Working Party (ALWP) of the European Society of Bone Marrow Transplantation (EBMT) database included 1427 adult patients (median age 58.2 years) receiving either Flu/Mel (n = 1005) or Flu/Treo (n = 422). Both groups showed similar 3-year overall survival (OS) (54% vs 51.2%, p value 0.49) for patients conditioned with FluMel and FluTreo, respectively. However, patients treated with FluMel showed a reduced 3-year relapse incidence (32.4% vs. 40.4%, p value < 0.001) and slightly increased non-relapse mortality (NRM) (25.7% vs. 20.2%, p value = 0.06) compared to patients treated with FluTreo. Our data may serve as a basis for further studies examining the role of additional agents/ intensifications in conditioning prior to allo-HCT.
Intramural Hematoma (IMH) forms part of the acute aortic syndrome, aortic dissection, and penetrating aortic ulcer. It is a life-threatening aortic disease that warrants prompt diagnosis and management. Like aortic dissections, it is classified using the Stanford classification system as type A (proximal to the origin of the left subclavian artery) and type B (distal to the origin of the left subclavian artery). Patients with type A IMH is generally managed surgically, and uncomplicated type B IMH is managed medically. The right subclavian artery arises typically from the brachiocephalic trunk. Aberrant right subclavian arteries (ARSA) are rare and derive directly from the aortic arch distal to the left subclavian artery. In this case report, a 73-year-old female presented with right-sided chest pain and shortness of breath. On examination, her heart rate was 100 bpm and blood Pressure was 185/85 and her ECG showed sinus rhythm. Following a CT scan, she was found to have a type B Aortic IMH with an ARSA. She was medically managed with vigorous blood pressure control. After a period of intravenous blood pressure treatment, she was treated with oral medication. Her subsequent CT scan showed that the hematoma was stable. She was followed up with MRI scanning 1 year later, which showed complete healing of the aorta with no changes in diameter. This case illustrates the importance of strict blood pressure management and follow-up imaging in patients presenting with type B IMH. It is important to monitor these patients regularly and where blood pressure control alone is not sufficient, further intervention may be required. Even though the complete resolution may be achieved as in this case, these patients will need to be kept under surveillance with repeated scans to monitor for any changes.
The recombination-activating genes (RAG) 1 and 2 are indispensable for diversifying the primary B cell receptor repertoire and pruning self-reactive clones via receptor editing in the bone marrow; however, the impact of RAG1/RAG2 on peripheral tolerance is unknown. Partial RAG deficiency (pRD) manifesting with late-onset immune dysregulation represents an ‘experiment of nature’ to explore this conundrum. By studying B cell development and subset-specific repertoires in pRD, we demonstrate that reduced RAG activity impinges on peripheral tolerance through the generation of a restricted primary B cell repertoire, persistent antigenic stimulation and an inflammatory milieu with elevated B cell-activating factor. This unique environment gradually provokes profound B cell dysregulation with widespread activation, remarkable extrafollicular maturation and persistence, expansion and somatic diversification of self-reactive clones. Through the model of pRD, we reveal a RAG-dependent ‘domino effect’ that impacts stringency of tolerance and B cell fate in the periphery.
Aims The primary aim of this study was to assess the reliability, intra- and inter-observer variation of the SPICE, Mucosal protrusion angle (MPA) and SHYUNG scores in differentiating a subepithelial mass (SEM) from a bulge. Methods This retrospective multicentre study analysed the 3 scores, radiological studies, enteroscopy and/or surgical findings. Results 100 patients with a potential SEM (mean age 57.6years) were recruited with 75 patients having pathology. In patients with a SEM the mean SPICE score was 2.04 (95% CI 1.82–2.26) as compared to 1.16 (95% CI 0.81–1.51) without any pathology (AUC 0.74, p<0.001), with a fair intra-observer agreement (Kappa 0.3, p<0.001) and slight inter-observer agreement (Kappa 0.14, p<0.05). SPICE had a 37.3% sensitivity and 92.0% specificity in distinguishing between a SEM and bulge, whereas MPA<90˚ had 58.7% and 76.0% respectively, with poor intra-observer(p = 0.05) and interobserver agreement (p = 0.64). The SHYUNG demonstrated a moderate intra-observer (Kappa 0.44, p<0.001) and slight inter-observer reliability (Kappa 0.18, p<0.001). The sensitivity of an elevated SHYUNG score (≥4) in identifying a SEM was 18.7% with a specificity of 92.0% (AUC 0.71, p = 0.002). Conclusions Though these scores are easy to use, they have, at best, slight to moderate intra and inter-observer agreement. Their overall diagnostic performances are limited.
Background The success of total ankle replacement (TAR) must be based on restoring reasonable mechanical balance with anatomical structures that can produce mechanical joint work through elastic (eg, tendons, fascia) or viscoelastic (eg, heel pad) mechanisms, or by active muscle contractions. Yet, quantifying the work distribution across the affected joint and the neighboring foot joints after TAR is lacking. Therefore, the objective of this study was to investigate if there is a change in the joint work distribution across the Ankle, Chopart, Lisfranc and Metatarsophalangeal joints during level walking before and after patients undergo TAR. Methods Fifteen patients with end-stage ankle osteoarthritis scheduled for primary TAR for pain relief were recruited and peer-matched with a sample of 15 control subjects. All patients underwent a 3D gait analysis before and after surgery, during which a kinetic multisegment foot model was used to quantify intersegmental joint work. Results The contribution of the Ankle joint ( P = .007) to the total foot and ankle positive work increased significantly after TAR. In contrast, a significant decrease in the contribution to the total foot and ankle joint positive work ( P < .001) were found at the Chopart joint after TAR. The foot joints combined produced a significant increase in a net mechanical work from +0.01 J/kg before surgery to +0.05 J/kg after TAR ( P = .006). Conclusion The findings of this study corroborate the theoretical rationale that TAR reduces significantly the compensatory strategy in the Chopart joint in patients with end-stage ankle osteoarthritis after TAR. However, the findings also showed that the contribution of the ankle joint of patients after TAR to the total foot and ankle joint positive work remained impaired compared to the control group.
The aim of this study is to investigate the relationships between psychological/social factors and transfer readiness from paediatric to adult rheumatology services in pre- and post-transfer young people (YP) with juvenile idiopathic arthritis (JIA). Participants completed questionnaires measuring a broad range of psychological/social factors (generalised anxiety, pain-specific anxiety, pain-related thoughts, depression, prosocial behaviours, problem behaviours, arthritis-related quality of life (QoL), social support, family functioning) and transfer readiness (transfer-related knowledge and skills, health-related self-efficacy). JIA disease activity was measured on the same day as the questionnaires. This study received all relevant ethical and regulatory approvals, and informed consent was received from or on behalf of all participants. In total, 40 pre-transfer YP with JIA aged 10-16 years (M = 13.54 years, 26 females) and their parents/guardians participated at Sheffield Children's NHS Foundation Trust, and 40 post-transfer YP with JIA aged 16-24 years (M = 20.16 years, 26 females) participated at Sheffield Teaching Hospitals NHS Foundation Trust. For both pre- and post-transfer YP, greater transfer readiness was associated with lower generalised anxiety levels, lower pain-specific anxiety levels, fewer pain-related thoughts, lower depression levels, fewer problem behaviours, better arthritis-related QoL, better social support, and better family functioning. Greater transfer readiness was also associated with less JIA disease activity for post-transfer YP only. A broad range of psychological/social factors were associated with transfer readiness in pre- and post-transfer YP with JIA. This highlights the importance of assessing and addressing YP's psychological/social well-being during their transition to adult services. Key Points • A wide range of psychological and social factors may be associated with how ready young people with juvenile idiopathic arthritis feel to move from paediatric to adult rheumatology services. • Transition outcomes may be improved by comprehensively assessing and addressing young people's psychological and social well-being.
NIHR (National Institute for Health Research) Devices for Dignity MedTech Cooperative (D4D) and NIHR Children and Young People MedTech Cooperative (CYPMedTech) have established track records in keeping patient and public involvement (PPI) at the core of medical technology development, evaluation and implementation. The 2020 global COVID-19 pandemic presented significant challenges to maintaining this crucial focus. In this paper we describe prior successful methodologies and share examples of the adaptations made in order to continue to engage with patients and the public throughout the pandemic and beyond. We reflect on learning gained from these experiences, and new areas of scope and focus relating to broadening the reach of engagement and representation, along with associated resource requirements and impact metrics.
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1,174 members
Badri Man Shrestha
  • Sheffield Kidney Institute (Northern General Hospital)
Pradip Sarkar
  • cardiothoracic surgery
Ricardo Mohammed-Ali
  • Oral and Maxillofacial Surgery (Royal Hallamshire Hospital)
Muzzammil Nusrath
  • Oral and Maxillofacial Surgery (Royal Hallamshire Hospital)
Sirwan M Hadad
  • Breast and Plastic Surgery
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