Recent Submissions

  • Plasma Soluble Tumor Necrosis Factor Receptor Concentrations and Clinical Events After Hospitalization: Findings From the ASSESS-AKI and ARID Studies.

    Packington, Rebecca
    RATIONALE & OBJECTIVE: The role of plasma soluble tumor necrosis factor receptor (sTNFR)1 and sTNFR2 in the prognosis of clinical events after hospitalization with or without acute kidney injury (AKI) is unknown. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: Hospital survivors from the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) and AKI Risk in Derby (ARID) with and without AKI during the index hospitalization who had baseline serum samples for biomarker measurements. PREDICTORS: We measured sTNFR1 and sTNFR2 obtained 3 months post-discharge. OUTCOMES: The associations between biomarkers with longitudinal kidney disease incidence and progression, heart failure and death were evaluated. ANALYTICAL APPROACH: Cox proportional hazard models. RESULTS: Among 1474 participants with plasma biomarker measurements, 19% developed kidney disease progression, 14% had later heart failure, and 21% died over a median follow-up of 4.4 years. For the kidney outcome, the adjusted HRs per doubling in concentration were 2.9 (2.2-3.9) for sTNFR1 and 1.9 (1.5-2.5) for sTNFR2. AKI during the index hospitalization did not modify the association between biomarkers and kidney events. For heart failure, the adjusted HRs per doubling in concentration were 1.9 (1.4-2.5) for sTNFR1 and 1.5 (1.2-2.0) for sTNFR2. For mortality, the adjusted HRs were 3.3 (2.5-4.3) for sTNFR1 and 2.5 (2.0-3.1) for sTNFR2. The findings in ARID were qualitatively similar for the magnitude of association between biomarkers and outcomes. LIMITATIONS: Different biomarker platforms, AKI definitions, limited generalizability to other ethnic groups. CONCLUSION: Plasma sTNFR1 and sTNFR2 measured 3 months after discharge were independently associated with clinical events, regardless of AKI status during the index admission. sTNFR1 and sTNFR2 may assist with the risk stratification of patients during follow-up.
  • Promoting simulation-based training in radiology: a homemade phantom for the practice of ultrasound-guided procedures.

    Jethwa, K
    OBJECTIVE: Ultrasound-guided intervention is an essential skill for many radiologists and critical for accurate diagnosis and treatment in many radiology subspecialties. Simulation using phantoms have demonstrated statistically significant benefits for trainees within the literature. We propose a novel phantom model which the authors feel is ideal for training clinical radiology trainees in the performance of ultrasound-guided procedures. METHODS: The recipe to prepare a homemade phantom is described. Results of a local survey from trainees preparing and using the phantom are also presented. RESULTS: This realistic training simulation model can be adapted to suit a variety of biopsy devices and procedures including soft tissue biopsy and cyst aspiration. The phantom mimics the sonographic appearances of soft tissue and biopsy targets can be concealed within. The phantom was easily prepared by 22 trainees (Likert score 4.5) and it functioned well (Likert score of 4.7). CONCLUSION: In summary, our phantom model is ideal for training clinical radiology trainees in the performance of ultrasound-guided core biopsy. The availability and low cost of the model, combined with the ease of preparation and reproducibility, make this an efficient and effective addition to the training process. ADVANCES IN KNOWLEDGE: A low cost easily handmade phantom recipe is described that could be easily implemented in training schemes.
  • Opportunities in digital health and electronic health records for acute kidney injury care.

    Selby, Nicholas
    PURPOSE OF REVIEW: The field of digital health is evolving rapidly with applications relevant to the prediction, detection and management of acute kidney injury (AKI). This review will summarize recent publications in these areas. RECENT FINDINGS: Machine learning (ML) approaches have been applied predominantly for AKI prediction, but also to identify patients with AKI at higher risk of adverse outcomes, and to discriminate different subgroups (subphenotypes) of AKI. There have been multiple publications in this area, but a smaller number of ML models have robust external validation or the ability to run in real-time in clinical systems. Recent studies of AKI alerting systems and clinical decision support systems continue to demonstrate variable results, which is likely to result from differences in local context and implementation strategies. In the design of AKI alerting systems, choice of baseline creatinine has a strong effect on performance of AKI detection algorithms. SUMMARY: Further research is required to overcome barriers to the validation and implementation of ML models for AKI care. Simpler electronic systems within the electronic medical record can lead to improved care in some but not all settings, and careful consideration of local context and implementation strategy is recommended.
  • Promoting simulation-based training in radiology: A homemade phantom for the practice of ultrasound-guided procedures.

    Jethwa, K
    OBJECTIVES: Ultrasound-guided intervention is an essential skill for many radiologists and critical for accurate diagnosis and treatment in many radiology sub specialties. Simulation using phantoms have demonstrated statistically significant benefits for trainees within the literature. We propose a novel phantom model which the authors feel is ideal for training clinical radiology trainees in the performance of ultrasound-guided procedures. METHODS: The recipe to prepare a homemade phantom is described. Results of a local survey from trainees preparing and using the phantom are also presented. RESULTS: This realistic training simulation model can be adapted to suit a variety of biopsy devices and procedures including soft tissue biopsy and cyst aspiration. The phantom mimics the sonographic appearances of soft tissue and biopsy targets can be concealed within. The phantom was easily prepared by 22 trainees (Likert score 4.5) and it functioned well (Likert score of 4.7). CONCLUSIONS: In summary, our phantom model is ideal for training clinical radiology trainees in the performance of ultrasound-guided core biopsy. The availability and low cost of the model, combined with the ease of preparation and reproducibility, make this an efficient and effective addition to the training process. ADVANCES IN KNOWLEDGE: A low cost easily handmade phantom recipe is described that could be easily implemented in training schemes.
  • Defining improvement in chronic kidney disease: regression and remission.

    Taal, Maarten
    PURPOSE OF REVIEW: International definitions exist for chronic kidney disease (CKD) progression and kidney failure but despite evidence that kidney function may improve, there are no agreed definitions for regression and remission of CKD. In the light of recent novel kidney protective therapies and the promise of regenerative medicine to reverse kidney damage, it is time to critically examine these neglected aspects of CKD epidemiology. RECENT FINDINGS: We propose that CKD regression is viewed as a process of improvement defined as a sustained increase in glomerular filtration rate (GFR) by ≥25% and an improvement in GFR category or increase in GFR of 1≥ml/min/year, whereas remission is considered a category of improvement defined as GFR ≥60 ml/min/1.73m2 and urine albumin to creatinine ratio <30 mg/g. Several recent studies have reported improvement in kidney function in populations with CKD, even in the absence of specific therapy. Regression and remission of CKD are associated with increased likelihood of sustained improvement in kidney function as well as improved survival. SUMMARY: Further research is warranted to validate the proposed definitions and investigate associated mechanisms. We look to a future in which the goal of therapy is not merely to slow CKD progression but to improve kidney function and seek a cure.
  • Room for improvement: diagnosing and managing acute coronary syndromes in persons with reduced eGFR.

    Horne, Kerry; Taal, Maarten; Selby, Nicholas
    Cardiovascular events are the leading cause of death in chronic kidney disease. A recent analysis from the High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome trial focused on results in those with reduced estimated glomerular filtration rate. This commentary discusses aspects of acute coronary syndrome diagnosis in this group and the differential approach to acute coronary syndrome management that was observed between those with normal and reduced kidney function.
  • Infections in relapsed myeloma patients treated with isatuximab plus pomalidomide and dexamethasone during the COVID-19 pandemic: Initial results of a UK-wide real-world study.

    Firas, AK
    OBJECTIVES: There are no real-world data describing infection morbidity in relapsed/refractory myeloma (RRMM) patients treated with anti-CD38 isatuximab in combination with pomalidomide and dexamethasone (IsaPomDex). In this UK-wide retrospective study, we set out to evaluate infections experienced by routine care patients who received this novel therapy across 24 cancer centres during the COVID-19 pandemic. METHODS: The primary endpoint was infection morbidity (incidence, grading, hospitalization) as well as infection-related deaths. Secondary outcomes were clinical predictors of increased incidence of any grade (G2-5) and high grade (≥G3) infections. RESULTS: In a total cohort of 107 patients who received a median (IQR) of 4 cycles (2-8), 23.4% of patients experienced ≥1 any grade (G2-5) infections (total of 31 episodes) and 18.7% of patients experienced ≥1 high grade (≥G3) infections (total of 22 episodes). Median time (IQR) from start of therapy to first episode was 29 days (16-75). Six patients experienced COVID-19 infection, of whom 5 were not vaccinated and 1 was fully vaccinated. The cumulative duration of infection-related hospitalizations was 159 days. The multivariate (MVA) Poisson Regression analysis demonstrated that a higher co-morbidity burden with Charlson Co-morbidity Index (CCI) score ≥4 (incidence rate ratio (IRR) = 3, p = 0.012) and sub-optimal myeloma response less than a partial response.
  • Burnout in diabetes and endocrinology specialist registrars across England, Scotland and Wales in the pre-COVID era.

    Agha, A
    BACKGROUND: Presence of either emotional exhaustion, depersonalization or lack of personal accomplishment define Burnout Syndrome which may lead to decreased workforce productivity, increased absenteeism, depression and medical errors as well as decreased patient satisfaction. OBJECTIVE: The aim of this study was to assess the frequency of burnout syndrome among Diabetes Specialist Registrars across England, Scotland and Wales and to identify any self-reported factors which may be contributory to burnout. METHODS: Over 430 Diabetes Specialist Registrars were invited to anonymously participate in an electronic survey which used Maslach Burnout Inventory and selfreporting questionnaire to identify burnout and contributory factors. RESULTS: In this pre-pandemic times study, Burnout was identified in 61 (57.5%; n = 106) respondents using Maslach burnout cut-off scores. 45.2% (48/106) participants had scored high in Emotional Exhaustion, while lack of personal accomplishment and depersonalization was seen in 24.5% (26/106) and 21.6% (23/106) of the respondents respectively. The commonest self-reported stressors by participants were "General Internal Medicine workload" 60.4% (64/106) followed by "Lack of specialty training" 36.8% (39/106) and "Lack of audit/research/Continuing Professional Development time" 10.8% (11/106) CONCLUSION: Burnout syndrome is frequent among the participating Diabetes Specialist Registrars and urgent steps may be required address this problem nationally to ensure that these physicians remain physically and mentally healthy, especially after the pandemic.
  • Excellent outcomes with combined single stage Physica ZUK medial unicompartment knee replacement and anterior cruciate ligament reconstruction results in young, active patients with instability and osteoarthritis with a mean follow up of 5 years.

    Kurien, T; Stragier, B; Senevirathna, S; Geutjens, G
    BACKGROUND (INCLUDING THE AIM OF THE STUDY): Young and more active patients with medial compartment osteoarthritis (OA) in conjunction with anterior cruciate ligament (ACL) deficiency are difficult to treat. The aim of this study was to explore the outcomes of combined fixed bearing Physica ZUK medial unicompartmental knee replacement (UKR) (Lima Corporate, Udine Italy) with ACL reconstruction for patients presenting with isolated medial compartment OA and symptomatic ACL deficiency. METHODS: Patients who underwent simultaneous single stage ACL reconstruction and medial UKR between 2012 and 2020 by a single surgeon (GG) were included. Preoperative outcome measures including Lysholm, Tegner, Oxford Knee Score and VAS pain score were evaluated and were repeated postoperatively at the most recent follow up appointment. RESULTS: Twenty four patients underwent simultaneous combined ACL and ZUK Medial UKR with a mean follow up of 5.1 years. Significant improvements in Lysholm (p < 0.001), Tegner (p < 0.001), Oxford Knee Score (p < 0.001) and VAS pain scores (p < 0.001) were seen with this combined approach with all patients returning to sport. Two patients had a minor peri-operative complication, which was treated conservatively. There were no revision procedures, and no evidence of implant loosening, however one patient had deceased due to an unrelated illness. CONCLUSION: UKR combined with ACL reconstruction can be an effective treatment option for selected patients suffering from medial unicompartmental knee osteoarthritis and symptomatic ACL deficiency. This allowed active patients to return to sports, addressing both instability and OA pain in a specific patient population.
  • 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.
  • Management of Inpatient macroscopic haematuria: a typical urology emergency with a high mortality.

    Pavithran, A
    OBJECTIVE: To review the in-patient (IP) management patterns and 30-day outcomes of patients admitted with macroscopic haematuria (MH) over a 1-year-period in a single-institution, aiming to clarify management for such cases in the future. METHODS: Retrospective cohort study was conducted on all patients admitted with MH in a single-institution over 1-year, excluding patients not requiring an overnight stay. A case note review was performed for patient demographics, MH investigations, and management. RESULTS: A total of 120 patients were admitted with MH over a span of 1-year. 89% (107/120) were males, with an average age of 78 years (36-97 years), an average ASA of 3, mean length-of-stay (LOS) was 5 days (1-31days) and 68% (82/120) had pre-existing urological conditions. 62% (74/120) required bladder irrigation for a mean duration of 3 days (1-16days). 10% (12/120) required an emergency rigid cystoscopy and washout to manage the bleeding, of which 4% (5/12) had malignancy noted. Over 8% (10/120) patients discharged had unplanned readmissions within 30 days. The 1-year mortality for this cohort was 23% (28/120) of which 21% (6/28) died within 30 days from discharge. CONCLUSION: IP MH affects a vulnerable patient cohort. There is no specific pathway guiding the inpatient management of MH; therefore, research is required to produce standardized pathways for managing MH, considering the high-risk patient cohort, the prolonged LOS, and high one-year mortality rate.
  • Pressor therapy in acute ischaemic stroke: an updated systematic review.

    England, Tim
    BACKGROUND: Low blood pressure (BP) in acute ischaemic stroke (AIS) is associated with poor functional outcome, death, or severe disability. Increasing BP might benefit patients with post-stroke hypotension including those with potentially salvageable ischaemic penumbra. This updated systematic review considers the present evidence regarding the use of vasopressors in AIS. METHODS: We searched the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and trial databases using a structured search strategy. We examined reference lists of relevant publications for additional studies examining BP elevation in AIS. RESULTS: We included 27 studies involving 1886 patients. Nine studies assessed increasing BP during acute reperfusion therapy (intravenous thrombolysis, mechanical thrombectomy, intra-arterial thrombolysis or combined). Eighteen studies tested BP elevation alone. Phenylephrine was the most commonly used agent to increase BP (n = 16 studies), followed by norepinephrine (n = 6), epinephrine (n = 3) and dopamine (n = 2). Because of small patient numbers and study heterogeneity, a meta-analysis was not possible. Overall, BP elevation was feasible in patients with fluctuating or worsening neurological symptoms, large vessel occlusion with labile BP, sustained post-stroke hypotension and ineligible for intravenous thrombolysis or after acute reperfusion therapy. The effects on functional outcomes were largely unknown and close monitoring is advised if such intervention is undertaken. CONCLUSION: Although theoretical arguments support increasing BP to improve cerebral blood flow and sustain the ischaemic penumbra in selected AIS patients, the data are limited and results largely inconclusive. Large, randomised controlled trials are needed to identify the optimal BP target, agent, duration of treatment and effects on clinical outcomes.
  • Efficacy of Isatuximab With Pomalidomide and Dexamethasone in Relapsed Myeloma: Results of a UK-Wide Real-World Dataset.

    Al-Kaisi, F
    Real-world data on the efficacy and tolerability of isatuximab with pomalidomide and dexamethasone (IsaPomDex) in relapsed/refractory myeloma patients have not been reported. In this UK-wide retrospective study, IsaPomDex outcomes were evaluated across 24 routine care cancer centers. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DOR) for patients who achieved an objective response (≥partial response [PR]), and adverse events (AEs). In a total cohort 107 patients, median follow up (interquartile range [IQR]) was 12.1 months (10.1-18.6 mo), median age (IQR) was 69 years (61-77). Median (IQR) Charlson Comorbidity Index (CCI) score was 3 (2-4); 43% had eGFR <60 mL/min. Median (IQR) number of prior therapies was 3 (3-3). Median (IQR) number of IsaPomDex cycles administered was 7 (3-13). ORR was 66.4%, with responses categorized as ≥ very good partial response: 31.8%, PR: 34.6%, stable disease: 15.9%, progressive disease: 15%, and unknown 2.8%. Median PFS was 10.9 months. Median DOR was 10.3 months. There was no statistical difference in median PFS by age (<65: 10.2 versus 65-74 13.2 versus ≥75: 8.5 mo, log-rank P = 0.4157), by CCI score (<4: 10.2 mo versus ≥4: 13.2, log-rank P = 0.6531), but inferior PFS was observed with renal impairment (≥60: 13.2 versus <60: 7.9 mo, log-rank P = 0.0408). Median OS was 18.8 months. After a median of 4 cycles, any grade AEs were experienced by 87.9% of patients. The most common ≥G3 AEs were neutropenia (45.8%), infections (18.7%), and thrombocytopenia (14%). Our UK-wide IsaPomDex study demonstrated encouraging efficacy outcomes in the real world, comparable to ICARIA-MM trial.
  • Effects of late, repetitive remote ischaemic conditioning on myocardial strain in patients with acute myocardial infarction.

    Chitkara, Kamal
    Late, repetitive or chronic remote ischaemic conditioning (CRIC) is a potential cardioprotective strategy against adverse remodelling following ST-segment elevation myocardial infarction (STEMI). In the randomised Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction (DREAM) trial, CRIC following primary percutaneous coronary intervention (P-PCI) did not improve global left ventricular (LV) systolic function. A post-hoc analysis was performed to determine whether CRIC improved regional strain. All 73 patients completing the original trial were studied (38 receiving 4 weeks' daily CRIC, 35 controls receiving sham conditioning). Patients underwent cardiovascular magnetic resonance at baseline (5-7 days post-STEMI) and after 4 months, with assessment of LV systolic function, infarct size and strain (longitudinal/circumferential, in infarct-related and remote territories). At both timepoints, there were no significant between-group differences in global indices (LV ejection fraction, infarct size, longitudinal/circumferential strain). However, regional analysis revealed a significant improvement in longitudinal strain in the infarcted segments of the CRIC group (from - 16.2 ± 5.2 at baseline to - 18.7 ± 6.3 at follow up, p = 0.0006) but not in corresponding segments of the control group (from - 15.5 ± 4.0 to - 15.2 ± 4.7, p = 0.81; for change: - 2.5 ± 3.6 versus + 0.3 ± 5.6, respectively, p = 0.027). In remote territories, there was a lower increment in subendocardial circumferential strain in the CRIC group than in controls (- 1.2 ± 4.4 versus - 2.5 ± 4.0, p = 0.038). In summary, CRIC following P-PCI for STEMI is associated with improved longitudinal strain in infarct-related segments, and an attenuated increase in circumferential strain in remote segments. Further work is needed to establish whether these changes may translate into a reduced incidence of adverse remodelling and clinical events. Clinical Trial Registration: http://clinicaltrials.gov/show/NCT01664611 .
  • Injectable semaglutide and reductions in HbA1c and weight in the real-world in people switched from alternative glucagon-like peptide 1 receptor agonists.

    Crabtree, Thomas; Idris, Iskandar
    The ABCD semaglutide audit was designed to capture the routine clinical outcomes of people commenced on semaglutide in the UK. Previous work demonstrated differential reductions in HbA1c and weight dependent on previous GLPRA exposure. The analysis, in this research letter, demonstrates decreases in HbA1c and weight associated with semaglutide occur irrespective of previous GLP1RA use. However, HbA1c reductions were less if switched from dulaglutide or liraglutide and weight changes were attenuated if switched from dulaglutide or exenatide - potentially suggesting differing potencies between GLP1RAs. Dedicated studies with head-to-head comparisons are needed to confirm these findings. This article is protected by copyright. All rights reserved.
  • Treatment and Outcome of Autoimmune Hepatitis (AIH): Audit of 28 UK centres.

    Hooper, Patricia
    BACKGROUND: With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities. METHODS: Patients with AIH were identified in 14 University and 14 District General hospitals; incident cases during 2007-2015 and prevalent cases, presenting 2000-2015. Treatment and outcomes were analysed. RESULTS: In 1267 patients with AIH, followed-up for 3.8(0-15) years, 5- and 10-year death/transplant rates were 7.1+0.8% and 10.1+1.3% (all-cause) and 4.0+0.6% and 5.9+1% (liver-related) respectively. Baseline parameters independently associated with death/transplantation for all-causes were: older age, vascular/respiratory co-morbidity, cirrhosis, decompensation, platelet count, attending transplant centre and for liver-related: the last four of these and peak bilirubin All-cause and liver-related death/transplantation was independently associated with: non-treatment with corticosteroids, non-treatment with a steroid-sparing agent (SSA), non-treatment of asymptomatic or non-cirrhotic patients and initial dose of Prednisolone >35mg/0.5mg/kg/day (all-cause only), but not with type of steroid (Prednisolone versus Budesonide) or steroid duration beyond 12-months. Subsequent all-cause and liver-death/transplant rates showed independent associations with smaller percentage fall in serum ALT after 1 and 3-months, but not with failure to normalise levels over 12-months. CONCLUSIONS: We observed higher death/transplant rates in patients with AIH who were untreated with steroids (including asymptomatic or non-cirrhotic sub-groups), those receiving higher Prednisolone doses and those who did not receive an SSA. Similar death/transplant rates were seen in those receiving Prednisolone or Budesonide, those continuing steroids after 12-months and patients attaining normal ALT within 12-months versus not.
  • Contribution of NOTCH1 genetic variants to bicuspid aortic valve and other congenital lesions.

    Elamin, Mohamed
    INTRODUCTION: Bicuspid aortic valve (BAV) affects 1% of the general population. NOTCH1 was the first gene associated with BAV. The proportion of familial and sporadic BAV disease attributed to NOTCH1 mutations has not been estimated. AIM: The aim of our study was to provide an estimate of familial and sporadic BAV disease attributable to NOTCH1 mutations. METHODS: The population of our study consisted of participants of the University of Leicester Bicuspid aoRtic vAlVe gEnetic research-8 pedigrees with multiple affected family members and 381 sporadic patients. All subjects underwent NOTCH1 sequencing. A systematic literature search was performed in the NCBI PubMed database to identify publications reporting NOTCH1 sequencing in context of congenital heart disease. RESULTS: NOTCH1 sequencing in 36 subjects from 8 pedigrees identified one variant c.873C>G/p.Tyr291* meeting the American College of Medical Genetics and Genomics criteria for pathogenicity. No pathogenic or likely pathogenic NOTCH1 variants were identified in 381 sporadic patients. Literature review identified 64 relevant publication reporting NOTCH1 sequencing in 528 pedigrees and 9449 sporadic subjects. After excluding families with syndromic disease pathogenic and likely pathogenic NOTCH1 variants were detected in 9/435 (2.1%; 95% CI: 0.7% to 3.4%) of pedigrees and between 0.05% (95% CI: 0.005% to 0.10%) and 0.08% (95% CI: 0.02% to 0.13%) of sporadic patients. Incomplete penetrance of definitely pathogenic NOTCH1 mutations was observed in almost half of reported pedigrees. CONCLUSIONS: Pathogenic and likely pathogenic NOTCH1 genetic variants explain 2% of familial and <0.1% of sporadic BAV disease and are more likely to associate with tetralogy of Fallot and hypoplastic left heart.
  • Provision and standards of care for treatment and follow-up of patients with Autoimmune Hepatitis (AIH).

    Hooper, Patricia
    BACKGROUND: Autoimmune hepatitis (AIH) is a substantial UK health burden, but there is variation in care, facilities and in opinion regarding management. We conducted an audit of service provision and care of patients with AIH in 28 UK hospitals. METHODS: Centres provided information about staffing, infrastructure and patient management (measured against predefined guideline-based standards) via a web-based data collection tool. RESULTS: Hospitals (14 university hospitals (UHs), 14 district general hospitals (DGHs)) had median (range) of 8 (3-23) gastroenterologists; including 3 (0-10) hepatologists. Eight hospitals (29%, all DGHs) had no hepatologist. In individual hospital departments, there were 50% (18-100) of all consultants managing AIH: in DGH's 92% (20-100) vs 46% (17-100) in UHs. Specialist nurses managed AIH in only 18%. Seventeen (61%) hospitals had a histopathologist with a liver interest, these were more likely to find rosettes than those without (172/795 vs 50/368; p<0.001).Of 999 steroid-treated patients with ≥12 months follow-up, 25% received steroids for <12 months. After 1 year of treatment, 82% of patients achieved normal serum alanine aminotransaminase (ALT); this was higher in UHs than DGHs. Three-monthly liver blood tests were inadequately recorded in 26%. Of potentially eligible patients with liver decompensation, transplantation was apparently not considered in 5% (n=7). The same standards were attained in different types of hospital. CONCLUSION: Management of AIH in UK hospitals is often shared between most gastroenterologists. Blood test monitoring and treatment duration are not always in line with recommendations. Some eligible patients with decompensation are not discussed with transplant teams. Care might be improved by expanding specialist input and management by fewer designated consultants.
  • Pneumomediastinum in COVID-19: a phenotype of severe COVID-19 pneumonitis? The results of the United Kingdom (POETIC) survey.

    Lawrence, Hannah; Saville, Rachel
    BACKGROUND: There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalised with COVID-19 in the United Kingdom and describe factors associated with outcome. METHODS: A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality. RESULTS: 377 cases of pneumomediastinum in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p<0.001) along with increasing age (p<0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality. CONCLUSIONS: Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis.

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