• Recurrent chilblains in a child with neurological impairment.

      Mohandas, Padma; Bowker, R; Ravenscroft, J; Bleiker, T (2017-12)
    • Regional Variation in Acute Kidney Injury Requiring Dialysis in the English National Health Service from 2000 to 2015 - A National Epidemiological Study.

      Kolhe, Nitin; Fluck, Richard; Taal, Maarten (2016-10)
      BACKGROUND: The absence of effective interventions in presence of increasing national incidence and case-fatality in acute kidney injury requiring dialysis (AKI-D) warrants a study of regional variation to explore any potential for improvement. We therefore studied regional variation in the epidemiology of AKI-D in English National Health Service over a period of 15 years. METHOD: We analysed Hospital Episode Statistics data for all patients with a diagnosis of AKI-D, using ICD-10-CM codes, in English regions between 2000 and 2015 to study temporal changes in regional incidence and case-fatality. RESULTS: Of 203,758,879 completed discharges between 1st April 2000 and 31st March 2015, we identified 54,252 patients who had AKI-D in the nine regions of England. The population incidence of AKI-D increased variably in all regions over 15 years; however, the regional variation decreased from 3·3-fold to 1·3-fold (p<0·01). In a multivariable adjusted model, using London as the reference, in the period of 2000-2005, the North East (odd ratio (OR) 1·38; 95%CI 1·01, 1·90), East Midlands (OR 1·38; 95%CI 1·01, 1·90) and West Midlands (OR 1·38; 95%CI 1·01, 1·90) had higher odds for death, while East of England had lower odds for death (OR 0·66; 95% CI 0·49, 0·90). The North East had higher OR in all three five-year periods as compared to the other eight regions. Adjusted case-fatality showed significant variability with temporary improvement in some regions but overall there was no significant improvement in any region over 15 years. CONCLUSIONS: We observed considerable regional variation in the epidemiology of AKI-D that was not entirely attributable to variations in demographic or other identifiable clinical factors. These observations make a compelling case for further research to elucidate the reasons and identify interventions to reduce the incidence and case-fatality in all regions.
    • Relation of Aortic Stiffness to Left Ventricular Remodelling in Younger Adults with Type 2 Diabetes.

      Wilmot, Emma (2018-04)
      Individuals with type 2 diabetes have a three-to-five-fold increased risk of developing heart failure. Diabetic cardiomyopathy is typified by left ventricular (LV) concentric remodelling, which is a recognised predictor of adverse cardiovascular events. Although the mechanisms underlying LV remodelling in type 2 diabetes are unclear, progressive aortic stiffening may be a key determinant. The aim of this study was to assess the relationship between aortic stiffness and LV geometry in younger adults with type 2 diabetes, using multiparametric cardiovascular magnetic resonance imaging. We prospectively recruited 80 adults (aged 18-65 years) with type 2 diabetes and no cardiovascular disease and 20 age- and sex-matched healthy controls. All subjects underwent comprehensive bio-anthropometric assessment and cardiac magnetic resonance imaging, including measurement of aortic stiffness by aortic distensibility (AD). Type 2 diabetes was associated with increased LV mass, concentric LV remodelling and lower AD compared with controls. On multivariable linear regression, AD was independently associated with concentric LV remodelling in type 2 diabetes. Aortic stiffness may therefore be a potential therapeutic target to prevent the development of heart failure in type 2 diabetes.
    • Remote ischaemic conditioning-therapeutic opportunities in renal medicine.

      Crowley, Lisa; McIntyre, Christopher (2013-12)
      Following ischaemic insult, tissue damage is extended after reperfusion, known as an ischaemia reperfusion injury. Ischaemic conditioning-the application of transient, non-lethal, episodes of ischaemia-reduces the effect of a larger ischaemic insult, and limits the reperfusion injury. How this phenomenon might be exploited as a therapeutic treatment is now the subject of a number of clinical trials. From initial trials focusing on the mitigation of cardiac injury, interest has expanded to examine the potential for its use as an adjunctive therapy in different clinical scenarios, including renal medicine. In this Review, we discuss different forms of conditioning, potential molecular mechanisms underpinning its effect, and potential applications in the setting of acute kidney injury, chronic kidney disease and end-stage renal disease.
    • Renal arcuate vein microthrombi-associated AKI.

      Redfern, Andrew; Selby, Nicholas (2015-02)
      BACKGROUNDS AND OBJECTIVES: This report describes six patients with AKI stages 2-3 (median admission creatinine level, 2.75 mg/dl [range, 1.58-5.44 mg/dl]), hematuria (five with hemoproteinuria), and unremarkable imaging with an unusual and unexplained histologic diagnosis on renal biopsy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The patients were young adults who presented to two neighboring United Kingdom nephrology centers over a 40-month period (between July 2010 and November 2013). Four were male, and the median age was 22.5 years (range, 18-27 years). Their principal symptoms were flank pain or lower back pain. All had consumed alcohol in the days leading up to admission. RESULTS: Renal biopsy demonstrated microthrombi in the renal arcuate veins with a corresponding stereotypical, localized inflammatory infiltrate at the corticomedullary junction. All patients recovered to baseline renal function with supportive care (median, 17 days; range, 6-60 days), and none required RRT. To date, additional investigations have not revealed an underlying cause for these histopathologic changes. Investigations have included screening for thrombophilic tendencies, renal vein Doppler ultrasonographic studies, and testing for recreational drugs and alcohol (including liquid chromatography-mass spectrometry of urine) to look for so-called designer drugs. Inquiries to the United Kingdom National Poisons Information Centre have identified no other cases with similar presentation or histologic findings. CONCLUSIONS: Increased awareness and additional study of future cases may lead to a greater understanding of the underlying pathophysiologic mechanisms that caused AKI in these patients.
    • Repeatability of Contrast-Enhanced Ultrasound to Determine Renal Cortical Perfusion.

      Pham, A; Williams, John P
      Alterations in renal perfusion play a major role in the pathogenesis of renal diseases. Renal contrast-enhanced ultrasound (CEUS) is increasingly applied to quantify renal cortical perfusion and to assess its change over time, but comprehensive assessment of the technique's repeatability is lacking. Ten adults attended two renal CEUS scans within 14 days. In each session, five destruction/reperfusion sequences were captured. One-phase association was performed to derive the following parameters: acoustic index (AI), mean transit time (mTT), perfusion index (PI), and wash-in rate (WiR). Intra-individual and inter-operator (image analysis) repeatability for the perfusion variables were assessed using intra-class correlation (ICC), with the agreement assessed using a Bland-Altman analysis. The 10 adults had a median (IQR) age of 39 years (30-46). Good intra-individual repeatability was found for mTT (ICC: 0.71) and PI (ICC: 0.65). Lower repeatability was found for AI (ICC: 0.50) and WiR (ICC: 0.56). The correlation between the two operators was excellent for all variables: the ICCs were 0.99 for PI, 0.98 for AI, 0.87 for mTT, and 0.83 for WiR. The Bland-Altman analysis showed that the mean biases (± SD) between the two operators were 0.03 ± 0.16 for mTT, 0.005 ± 0.09 for PI, 0.04 ± 0.19 for AI, and -0.02 ± 0.11 for WiR.
    • Report from the kick-off meeting of the Cochrane Skin Group Core Outcome Set Initiative (CSG-COUSIN).

      Sharma, Maulina (2016-02)
      A major obstacle of evidence-based clinical decision making is the use of nonstandardized, partly untested outcome measurement instruments. Core Outcome Sets (COSs) are currently developed in different medical fields to standardize and improve the selection of outcomes and outcome measurement instruments in clinical trials, in order to pool results of trials or to allow indirect comparison between interventions. A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. The international, multidisciplinary Cochrane Skin Group Core Outcome Set Initiative (CSG-COUSIN) aims to develop and implement COSs in dermatology, thus making trial evidence comparable and, herewith, more useful for clinical decision making. The inaugural meeting of CSG-COUSIN was held on 17-18 March 2015 in Dresden, Germany, as the exclusive theme of the Annual Cochrane Skin Group Meeting. In total, 29 individuals representing a broad mix of different stakeholder groups, professions, skills and perspectives attended. This report provides a description of existing COS initiatives in dermatology, highlights current methodological challenges in COS development, and presents the concept, aims and structure of CSG-COUSIN.
    • Response to the NCEPOD report: development of a care bundle for patients admitted with decompensated cirrhosis-the first 24 h.

      Austin, Andrew (2016-01)
      Recently, there has been a significant increase in the prevalence of chronic liver disease in the UK, and as a result, hospital admissions and deaths due to liver disease have also increased. The 2013 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) of patients with alcohol-related liver disease (ARLD) found that less than half the number of patients who died from ARLD received 'good care', and avoidable deaths were identified. In order to improve the care of patients admitted with ARLD, the NCEPOD report recommended that a 'toolkit' for the acute management of patients admitted with decompensated ARLD be developed and made widely available. As a result, we have developed a 'care bundle' for patients admitted with decompensated cirrhosis (of all aetiologies) to ensure that effective evidence-based treatments are delivered within the first 24 h. This care bundle provides a checklist to ensure that all appropriate investigations are undertaken when a patient with decompensated cirrhosis presents and provides clinicians with clear guidance on the initial management of alcohol withdrawal, infection, acute kidney injury, gastrointestinal bleeding and encephalopathy. The first 24 h are particularly important, as early intervention can reduce mortality and shorten hospital stay, and specialist gastroenterology/liver advice is not always available during this period. This review will discuss the care bundle and the evidence base behind the treatment recommendations made.
    • Retrograde Fixation of the Ulna in Pediatric Forearm Fractures Treated With Elastic Stable Intramedullary Nailing.

      Rajan, Rohan (2020-05)
      Introduction This study analyzes the outcomes of retrograde fixation of the ulna in pediatric forearm fractures treated with elastic stable intramedullary nailing (ESIN). Materials and Methods A retrospective analysis was conducted by reviewing patient records of forearm fractures treated with ESIN by retrograde fixation. The study included 30 children (26 boys and 4 girls). The mean age at the time of injury was 11.7 years (range: 6.6 to 14.3 years). The technique is described. All patients were followed up until hardware removal. Results The mean time for fracture healing was 5.3 weeks (range: 4 to 8.8 weeks). The mean time for nail removal was 6.6 months (range: 5 to 10 months). There were five cases with rotation deficits, one of which was a re-fracture. Conclusions When antegrade nailing is performed, the ulna is sometimes complicated by non-union as well as entry point irritation. We did not encounter such complications. Retrograde fixation of the ulna in pediatric forearm fractures treated with ESIN is a safe and effective alternative to common fixation (antegrade ulnar fixation) and offers technical advantages.
    • Review article: coeliac disease in later life must not be missed.

      Holmes, Geoffrey (2018-01)
      BACKGROUND: The presenting symptoms of coeliac disease are often subtle and the diagnosis is frequently delayed or overlooked. Therefore, especially elderly patients may be denied the benefits conferred by gluten free diet which can be dramatically life-changing. AIM: To review the occurrence, clinical features, diagnosis and management in coeliac patients detected later in life. METHODS: To review manuscripts concerned with coeliac disease in the elderly and to derive subgroups of elderly people from publications on the disorder. RESULTS: Approximately a quarter of all diagnoses are now made at the age of 60 years or more and a fifth at 65 years or over. About 4% are diagnosed at 80 years or above. Around 60% remain undetected, since their symptoms are often subtle: tiredness, indigestion, reduced appetite. Good compliance with gluten free diet, resolution of symptoms and improvement in laboratory indices can be achieved in over 90% of patients. CONCLUSIONS: Coeliac disease not uncommonly presents for the first time in older patients and is an important diagnosis to make.
    • Rheumatoid cachexia and cardiovascular disease.

      Summers, Greg (2010-08)
      Both cachexia and cardiovascular disease are strongly associated with rheumatoid arthritis (RA) and linked to the chronic inflammatory process. Typically, rheumatoid cachexia occurs in individuals with normal or increased BMI (reduced muscle mass and increased fat mass). Classic cachexia (reduced muscle mass and reduced fat mass) is rare in RA but is associated with high inflammatory activity and aggressive joint destruction in patients with a poor cardiovascular prognosis. Conversely, obesity is linked to hypertension and dyslipidemia but, paradoxically, lower RA disease activity and less cardiovascular disease-related mortality. Rheumatoid cachexia might represent the 'worst of both worlds' with respect to cardiovascular outcome, but until diagnostic criteria for this condition are agreed upon, its effect on cardiovascular disease risk remains controversial.
    • Risk factors and survival outcome for non-elective referral in non-small cell lung cancer patients--analysis based on the National Lung Cancer Audit.

      Beckett, Paul (2014-03)
      Survival after diagnosis of lung cancer is poor and seemingly lower in the UK than other Western countries, due in large part to late presentation with advanced disease precluding curative treatment. Recent research suggests that around one-third of lung cancer patients reach specialist care after emergency presentation and have a worse survival outcome. Confirmation of these data and understanding which patients are affected may allow a targeted approach to improving outcomes. Methods: We used data from the UK National Lung Cancer Audit in a multivariate logistic regression model to quantify the association of non-elective referral in non-small cell lung cancer patients with covariates including age, sex, stage, performance status, co-morbidity and socioeconomic status and used the Kaplan-Meier method and Cox proportional hazards model to quantify survival by source of referral. Results: In an analysis of 133,530 cases of NSCLC who presented 2006-2011, 19% of patients were referred non-electively (following an emergency admission to hospital or following an emergency presentation to A&E). This route of referral was strongly associated with more advanced disease stage (e.g. in Stage IV - OR: 2.34, 95% CI: 2.14-2.57, p< 0.001) and worse performance status (e.g. in PS 4 - OR: 7.28, 95% CI: 6.75-7.86, p< 0.001), but was also independently associated with worse socioeconomic status, and extremes of age. These patients were more likely to have died within 1 year of diagnosis (hazard ratio of 1.51 (95% CI: 1.49-1.54) after adjustment for key clinical variables. Conclusion: Our data confirm and quantify poorer survival in lung cancer patients who are referred non-electively to specialist care, which is more common in patients with poorer performance status, higher disease stage and less advantaged socioeconomic status. Work to tackle this late presentation should be urgently accelerated, since its realisation holds the promise of improved outcomes and better healthcare resource utilisation.
    • Risk of statin-induced rhabdomyolysis in patients with hepatic impairment.

      Kolhe, Nitin (2014-09)
      We describe a case of a 54-year-old man with a 2-month history of biliary colic associated with a common bile duct stone. He underwent laparoscopic cholecystectomy and developed postoperative acute kidney injury stage 3. A renal biopsy was performed and demonstrated myoglobin in the renal tubules. Retrospective creatine kinase analysis was suggestive of rhabdomyolysis. It is thought this was precipitated by simvastatin accumulation in the context of a period of hepatic impairment and elevated liver enzymes.
    • Risk Prediction for Acute Kidney Injury in Acute Medical Admissions in the UK.

      Selby, Nicholas (2018-11)
      Background: Acute Kidney Injury (AKI) is associated with adverse outcomes; therefore identifying patients who are at risk of developing AKI in hospital may lead to targeted prevention. Aim: We undertook a UK-wide study in acute medical units (AMUs) to define those who develop hospital-acquired AKI (hAKI); to determine risk factors associated with hAKI and to assess the feasibility of developing a risk prediction score. Design: Prospective multicentre cohort study across 72 acute medical units in the UK. Methods: Data collected from all patients who presented over a 24-hour period. Chronic dialysis, community-acquired AKI (cAKI) and those with fewer than two creatinine measurements were excluded. Primary outcome was the development of h-AKI. Results: 2,446 individuals were admitted to the 72 participating centres. 384 patients (16%) sustained AKI of whom 287 (75%) were cAKI and 97 (25%) were hAKI. After exclusions, chronic kidney disease (OR 3.08, 95% CI 1.96-4.83), diuretic prescription (OR 2.33, 95% CI 1.5-3.65), a lower haemoglobin concentration and elevated serum bilirubin were independently associated with development of hAKI. Multivariable model discrimination was only moderate (c-statistic 0.75).Conclusions: AKI in AMUs is common and associated with worse outcomes, with the majority of cases community acquired. Only a small proportion of patients develop hAKI. Prognostic risk factor modelling demonstrated only moderate discrimination implying that widespread adoption of such an AKI clinical risk score across all AMU admissions is not currently justified. More targeted risk assessment or automated methods of calculating individual risk may be more appropriate alternatives.
    • Risk profile in chronic kidney disease stage 3: older versus younger patients.

      McIntyre, Christopher; Fluck, Richard; McIntyre, Natasha; Taal, Maarten (2011-09)
      BACKGROUND: The prevalence of chronic kidney disease (CKD) increases with age, but its significance in older patients is uncertain and is regarded by some as part of 'normal aging'. Moreover, subjects ≥75 years are often excluded from research studies. We therefore undertook a prospective study of patients with CKD stage 3 in primary care to compare the risk profile of older versus younger subjects. METHODS: Subjects with an estimated glomerular filtration rate (eGFR) 59-30 ml/min/1.73 m(2) on two measurements were recruited from 32 primary care practices. Medical history and demographic data were obtained and participants underwent clinical assessment as well as urine and serum biochemistry tests. RESULTS: 1,741 participants were recruited: mean age 72.9 ± 9 years; 60% female; 98% white; 17% diabetic. Mean eGFR was 52.5 ± 10 ml/min/1.73 m(2) and 16.9% had albuminuria. Subjects ≥75 years had a significantly lower eGFR than younger subjects and a higher risk profile characterised by greater albuminuria, more arterial stiffness and higher serum uric acid levels. CONCLUSION: Older subjects with CKD stage 3 evidenced a higher risk profile for CKD progression and cardiovascular events than younger patients. This implies that CKD is not a benign condition in all elderly patients, but further investigation is required to identify those at greatest risk who may benefit from intervention.
    • ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

      Holmes, Geoffrey (2017-09)
      OBJECTIVES: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. DESIGN: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. RESULTS: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. CONCLUSION: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence.
    • The Role of Risk Prediction Models in Prevention and Management of AKI.

      Selby, Nicholas (2019-09)
      Acute kidney injury is a major health care problem. Improving recognition of those at risk and highlighting those who have developed AKI at an earlier stage remains a priority for research and clinical practice. Prediction models to risk-stratify patients and electronic alerts for AKI are two approaches that could address previously highlighted shortcomings in management and facilitate timely intervention. We describe and critique available prediction models and the effects of the use of AKI alerts on patient outcomes are reviewed. Finally, the potential for prediction models to enrich population subsets for other diagnostic approaches and potential research, including biomarkers of AKI, are discussed.
    • Role of routine oesophago-gastroduodenoscopy before cholecystectomy.

      Rashid, Farhan; Waraich, Naseem; Ahmed, Javed; Iftikhar, Syed (2010)
      INTRODUCTION: A proportion of patients do not get symptomatic relief after cholecystectomy because there is an overlap in the symptomology of biliary and gasroduodenal pathologies. In our unit all the patients are offered gastroscopy prior to Cholecystectomy. Aim of this study was to evaluate the efficacy of gastroscopy in all patients with upper abdominal pain irrespective of ultrasound findings. MATERIAL AND METHODS: This retrospective study was carried out, between Jan 2001-Oct 2003. All the patients undergoing laparoscopic cholecystectomy by a single surgeon were studied. Group 1 (n = 61) were not endoscoped before the operation (Jan 2001-May 2002). Group 2 (n = 60) had routine endoscopy carried out before surgery (June 2002-October 2003). The results were entered in a database and analyzed. RESULTS: Total of 240 laparoscopic cholecystectomies were carried out. Female to male ratio was 4:1. In Group 1, the recurrence or persistence of symptoms was 20/61 (32.78%) patients who were not scoped. In Group 2, all patients were scoped with positive findings in 35% of the patients. All were treated for the pathology and only 2(3.3%) had recurrence or persistence of symptoms. CONCLUSION: The routine use of gastroscopy before laparoscopic cholecystectomy helps to reduce persistence of symptoms and is recommended.