Imperial College Healthcare NHS Trust
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The evaluation of joint disease using synovial fluid is an emerging field of metabolic profiling. The analysis is challenged by multiple macromolecules which can obscure the small molecule chemistry. The use of protein precipitation and extraction has been evaluated previously, but not in synovial fluid. We systematically review the published NMR spectroscopy methods of synovial fluid analysis and investigated the efficacy of three different protein precipitation techniques: methanol, acetonitrile and trichloroacetic acid. The trichloroacetic wash removed the most protein. However, metabolite recoveries were universally very poor. Acetonitrile liquid/liquid extraction gave metabolite gains from four unknown compounds with spectral peaks at δ = 1.91 ppm, 3.64 ppm, 3.95 ppm & 4.05 ppm. The metabolite recoveries for acetonitrile were between 1.5 and 7 times higher than the methanol method, across all classes of metabolite. The methanol method was more effective in removing protein as reported by the free GAG undefined peak (44 % vs 125 %). However, qualitative evaluation showed that acetonitrile and methanol provided good restoration of the spectra to baseline. The methanol extraction has issues of a gelatinous substrate in the samples. All metabolite recoveries had a CV of > 15 %. A recommendation of acetonitrile liquid/liquid extraction was made for human synovial fluid (HSF) analysis. This is due to consistency, effective protein precipitation, recovery of metabolites and additional compounds not previously visible.
Introduction. As surgical site infections (SSIs) after joint arthroplasty contribute to increased morbidity and mortality, they require further surgical intervention, prolonged hospitalisation, and antimicrobial treatment. Te aim of our study is to examine the association between preoperative quality of life (QoL) and other predictive factors on the development of SSIs after primary arthroplasty. Methods. Tis is a prospective study that enrolled 56 patients with hip and knee primary osteoarthritis who underwent joint replacement. Data were collected from January to March 2017, including patient demographic characteristics, comorbidities, laboratory results, and perioperative clinical data. Te patients' QoL was evaluated preoperatively by applying the knee injury and osteoarthritis outcome score (KOOS) and the hip disability and osteoarthritis outcome score (HOOS) for total knee replacement (TKR) and total hip replacement (THR), respectively. A 5-year follow-up was conducted to assess the clinical status of the patients. Results. 66.1% of patients underwent TKR, with 4.9 ± 1.2 days of hospitalisation, 16% of them required autologous blood transfusion, while 33.9% of patients were treated with THR, with 5.7 ± 1 days hospitalisation and 36.8 of them required this type of transfusion. 16 patients were diagnosed with SSIs, with the older of them (>65 years old) presenting lower probability (odds ratio: 0.13, 95% CI: 0.03-0.62) requiring treatment with additional antibiotics, while revision surgery was performed in 3 of these cases, following periprosthetic joint infection (PJI). Overall preoperative QoL was not statistically associated with SSIs, but low QoL scores were associated with higher rates of SSIs and increased levels of postoperative pain (p � 0.009 < 0.05). Conclusions. Te duration of each operation (>90 min), the length of hospitalisation (>4 days), and the presence of comorbidities including hypothyroidism and recurrent urinary tract infections were associated with a high risk for SSIs following arthroplasties. On the contrary, this study revealed no association between other comorbidities, including heart coronary disease, hypertension, and diabetes mellitus, with close monitoring of plasma glucose and SSIs. Moreover, the younger the patients, the more likely they were to require treatment with antibiotics. Overall, high QoL index scores were mainly accompanied by low rates of postoperative SSIs and pain.
MR imaging has a high diagnostic accuracy and reproducibility to classify adnexal masses as benign or malignant, using a risk stratification scoring system, the Ovarian-Adnexal Reporting and Data System (O-RADS) MR imaging score. The first step in achieving high accuracy is to ensure high technical quality of the MR scan. The sequences needed are clearly described in this article, with tips for handling difficult cases. This information will assist in obtaining the best possible images, to allow for accurate use of the O-RADS MR imaging risk score.
Objectives The optimal endovascular treatment for tandem occlusion in anterior circulation ischaemic stroke remains unknown. The aim of this study was to examine how the aetiology of carotid pathology, dissection versus atherothrombosis, affects clinical outcomes. Materials and Methods Data was obtained from prospectively collected registries from two stroke centres between April 2016 and December 2020. Tandem cases with complete cervical internal carotid artery (ICA) occlusion or near-total occlusion (≥90% stenosis) were included. Patients were divided into two groups based on carotid pathology: dissection versus atherothrombosis. Results A total of 134 patients were included: 36 were dissection and 98 were atherothrombosis. The dissection group had better clinical outcomes compared to the atherothrombosis group, although after adjusting for age and stroke risk factors differences were non-significant. In the non-stented cohort, the dissection patients achieved a better outcome (modified Rankin scale 0-2) than atherothrombotic patients (57% vs. 34%, p=0.04) at 90-days. Conclusion Dissection-related tandem occlusions appear to have different clinical features from atherothrombotic tandem occlusions which suggests different management strategies are needed.
Infertility affects 15% of couples worldwide and in approximately 50% of cases the cause is secondary to an abnormality of the sperm. However, treatment options for male infertility are limited and empirical use of hormone stimulation has been utilised. We review the contemporary data regarding the application of hormone stimulation to treat male infertility. There is strong evidence supporting the use of hormone stimulation in hypogonadotropic hypogonadism but there is inadequate evidence for all other indications.
Background Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Methods Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Findings Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R²X 0.25, R²Y 0.26, Q² 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithocholate and taurodeoxycholate were associated with poorer response. Interpretation Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response. Funding JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) (grant number MC_PC_12025) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care.
214 Background: The bacteriome and mycobiome, collectively referred to as the microbiome, is a key player in CRC pathogenesis, progression and response to chemotherapy, radiotherapy and immunotherapy. Microbial modulation and exacerbation in CRC is likely attributable to alterations of composition and diversity of the microbiome rather than to a single microbial species. We therefore systematically investigated alterations in the bacteriome and mycobiome of CRC patients in tumours and matched adjacent mucosa resulting in the identification of microbiome-based subtypes associated with host clinico-pathological and molecular characteristics. Methods: We estimated bacterial and fungal composition from RNA sequencing experiments using a validated subtractive method ( PathSeq) in in-house and publicly available cohorts. We evaluated the quality of the microbial estimates with two sets of orthogonal analysis determining i) the agreement with composition from an independent method and ii) retrieval of expected clinically-relevant microbial signatures. Diversity and composition of bacteriome and mycobiome of tumour and adjacent mucosa, and resulting subtypes were computationally deconvoluted using > 10,000 samples. Results: The bacteriome of tumours had higher dominance and lower ɑ-diversity compared to matched adjacent local and distant mucosa. Tumours were enriched with Proteobacteria (Gammaproteobacteria class), Fusobacteria (including Fusobacterium Nucleatum species) and Basidiomycota fungi (Malasseziaceae family). Tumours were depleted of Bacteroidetes (Bacteroidia class), Firmicutes (Clostridia class) and Ascomycota (Sordariomycetes and Saccharomycotina). Tumours and adjacent mucosa samples were classified into 4 microbial subtypes, termed C1 to C4, based on the bacteriome and mycobiome composition. The bacterial Propionibacteriaceae, Enterobacteriaceae, Fusobacteriaceae, Bacteroidaceae and Ruminococcaceae along with the fungal Malasseziaceae, Saccharomycetaceae and Aspergillaceae were among the key families driving the microbial subtyping. Microbial subtypes were associated with distinct tumour histology and patient phenotypes and served as independent prognostic marker for disease-free survival. Key associations between microbial subtypes and alterations in host immune response and signalling pathways were validated in the TCGA pan-cancer cohort. The microbial subtyping demonstrated stratification value in the pan-cancer settings beyond merely representing differences in survival by cancer type. Conclusions: This study demonstrates the translational potential of microbial subtyping in CRC patient stratification, and provides avenues to design tailored microbiota modulation therapy to further precision oncology.
Objective: Socioeconomic and health inequalities persist in multicultural western countries. Here, we compared outcomes following an acute stroke amongst ethnic minorities with Caucasian patients. Methods: Data were prospectively collected (2014-2016) from the Sentinel Stroke National Audit Programme for 3309 patients who were admitted with an acute stroke in four UK hyperacute stroke units. Associations between variables were examined by chi-squared tests and multivariable logistic regression, adjusted for age, sex, prestroke functional limitations and co-morbidities, presented as odds ratios (OR) with 95% CI. Results: There were 3046 Caucasian patients, 95 from ethnic minorities (mostly South Asians, Blacks, mixed race and a few in other ethnic groups) and 168 not stated. Compared with Caucasian patients, those from ethnic minorities had a proportionately higher history of diabetes (33.7% vs 15.4%, P < 0.001), but did not differ in other chronic conditions, functional limitations or sex distribution. Their age of stroke onset was younger both in women (76.8 year vs 83.2 year, P < 0.001) and in men (69.5 year vs 75.9 year, P = 0.002). They had greater risk for having a stroke before the median age of 79.5 year: OR = 2.15 (1.36-3.40) or in the first age quartile (< 69 year): OR = 2.91 (1.86-4.54), requiring palliative care within the first 72 h: OR = 3.88 (1.92-7.83), nosocomial pneumonia or urinary tract infection within the first 7 days of admission: OR = 1.86 (1.06-3.28), and in-hospital mortality: OR = 2.50 (1.41-4.44). Conclusions: Compared with Caucasian patients, those from ethnic minorities had earlier onset of an acute stroke by about 5 years and a 2- to fourfold increase in many stroke-related adverse outcomes and death.
Background: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to medical management may differ between clinician specialties. Methods: We conducted an international survey (1/1/22-3/31/22) regarding management strategies in acute BAO prior to the announcement of 2 trials indicating superiority of EVT, and compared responses between interventionalists (INT) and non-interventionalists (nINT). Selection practices for routine EVT based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. Results: Among the 1245 respondents (nINT=702), INT more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p<0.01). A similar proportion of INT and nINT responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific circumstances (p=0.45). Among respondents who would recommend EVT, there was no difference in the maximum pre-stroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p>0.05), although nINT more commonly preferred perfusion imaging (24.2% vs. 19.7%, p=0.04). Among respondents who indicated they would randomize to medical management, INT were more likely to randomize when the NIHSS was ≥10 (15.9% vs. 6.9%, p<0.01). Conclusions: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a patient to medical treatment. There were small differences in preference of advanced neuroimaging, although these preferences were unsupported by clinical trial data.
Background: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. Objectives: We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. Methods: In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. Results: Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers. Conclusions: SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).
Objective: To investigate serum human epididymis-4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH). Design: Prospective prognostic factor study. Setting: Consecutive sample of women attending a tertiary gynaecological oncology centre in the North West of England. Population: Women with AEH or early stage, low grade endometrial cancer who were unfit or declined primary surgical management. Methods: A total of 76 women, 32 with AEH and 44 with endometrial cancer, were treated with a levonorgestrel intrauterine system (LNG-IUS) for 12 months. Endometrial biopsies and imaging were performed to assess treatment response. Pre-treatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses performed. Main outcome measure: Progestin response at 12 months defined by histology and imaging. Results: The median age and BMI of the final cohort were 52 years (IQR:33-62) and 46kg/m2 (IQR:38-54), respectively. Baseline serum HE4 was significantly higher in non-responders than responders [119.2pmol/L (IQR:94.0-208.4) vs 71.8pmol/L (IQR:56.1-84.2), p<0.001]. Older age [OR=0.96 (95%CI:0.93-0.99), p=0.02], baseline serum HE4 [OR=0.97 (95%CI:0.96-0.99), p=0.001] and endometrial cancer histology [OR=0.22 (95%CI:0.72-0.68), p=0.009] were associated with a lower likelihood of progestin treatment response. Serum HE4 remained independently associated with progestin treatment failure when adjusted for age and histology [aHR=0.97 (95%CI:0.96-0.99), p=0.008]. Conclusion: Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH.
Background Patients with Inflammatory bowel disease (IBD) receiving anti-TNF or JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the currently dominant Omicron BA.4/5 variants. Methods We prospectively recruited 329 adults (68 healthy controls (HC) and 261 IBD) who had received three doses of COVID-19 vaccine at nine UK centres. The IBD population was established (>12 weeks therapy) on either thiopurine (n=60), infliximab (IFX) (n=43), thiopurine & IFX combination (n=46), ustekinumab (n=43), vedolizumab (n=46) or tofacitinib (n=23). Pseudoneutralisation assays were performed and the half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARS-CoV-2 neutralising response against wild-type (WT) virus and the BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, ethnicity, vaccine type and age. Results Heterologous (two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both WT SARS-CoV-2 virus and the BA.4/5 variants in HCs and IBD (fig 1). Antibody titres against BA.4/5 were significantly lower than antibodies against WT virus in both groups (Geometric Mean Ratio (GMR) [95% CI], 0.11 [0.09, 0.15], P<0.0001 in healthy participants; GMR 0.07 [0.06, 0.08], P<0.0001 in IBD patients). Multivariable models showed that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in IBD patients on IFX (GMR 0.44 [0.20, 0.97], P=0.042), IFX and thiopurine combination (GMR 0.34 [0.15, 0.77], P=0.0098) or tofacitinib (GMR 0.37 [0.15, 0.92], P=0.032), but not in patients on thiopurine monotherapy, ustekinumab or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against WT and BA.4/5 (P<0.05). Conclusion A third dose of COVID-19 vaccine based on the WT spike glycoprotein boosts neutralising antibody titres in patients with IBD. However, responses are lower against the currently dominant variant BA.4/5, particularly in patients taking anti-TNF or JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed IBD patients may receive additional benefit from bivalent vaccine boosters which target Omicron variants. Financial support was provided as an Investigator Sponsored Research Grant from Pfizer Limited.
This CIRSE Standards of Practice document is aimed at healthcare professionals (including interventional radiologists) performing endovascular procedures to provide best practices for performing arterial access for interventions. It has been developed by an expert writing group under the guidance of the CIRSE Standards of Practice Committee. This paper encompasses up-to-date clinical and technical aspects in performing safe and appropriate arterial access for interventions.
Functional Electrical Stimulation (FES) has been used to support mobility for people with upper motor neuron conditions such as stroke and multiple sclerosis for over 25 years. Recent development and publication of clinical practice guidelines (CPGs) provide evidence to guide clinical decision making for application of FES to improve mobility. Understanding key barriers to the implementation of these CPGs is a critical initial step necessary to create tailored knowledge translation strategies. A public involvement and engagement consultation was conducted with international stakeholders including researchers, clinicians and engineers working with FES to inform implementation strategies for CPG use internationally. Reflexive thematic analysis of the consultation transcripts revealed themes including inconsistent use of CPGs, barriers to implementation such as limited access to FES and low clinician confidence, and the need for a tiered education approach with ongoing support. Insights derived from this consultation will inform the development of knowledge translation strategies to support the next steps to implementing FES use for mobility.
Background Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID. Methods People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis. Results We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID. Conclusion This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.
Introduction: Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed bariatric operations worldwide. Leaks following RYGB are rare, but the consequences can be devastating. Although most leaks occur at the gastrojejunostomy (GJ) anastomosis, there is a lack of data on modifiable technical factors that can reduce the risk of leaks. Therefore, we evaluated whether the leak pressure of a GJ linear stapled anastomosis is dependent on the closure technique. Methods: Two expert surgeons constructed gastric pouches and GJ anastomoses on ex vivo porcine models in a laparoscopic simulator using 30-mm and 45-mm endoscopic staplers. The GJ anastomosis was closed using either a single layer suture, double layer suture or stapler. The endpoints were leak pressure to air insufflation, measured by two independent observers, site of leak and internal circumference of the GJ anastomosis. Results: In total, 30 GJ anastomoses were constructed (30 mm, n = 15; 45 mm, n = 15). The GJ anastomosis was closed using single layer (n = 9), double layer (n = 9) and stapled techniques (n = 12). Inter-observer agreement was high. Stapled and double layer closures were more resilient than a single layer closure, with 75% (9/12) stapled closures remaining intact at < 70 mmHg. GJ stoma circumference was lower using a 30-mm stapler (64.8 mm vs 80.2 mm; p < 0.05) but independent of closure technique. The most common leak site was the corner of the closure (67%). Conclusion: In summary, the GJ anastomosis closure technique may be a modifiable factor to prevent anastomotic leak.
Real-time continuous glucose monitoring (CGM) in hospital holds promise; however, further evidence is required on its use to guide adjustment of variable rate intravenous insulin infusion (VRIII). We retrospectively analysed data from 20 women with type 1 diabetes (T1D) during the peripartum period who were commenced on VRIII. Data were analysed for CGM accuracy (Dexcom G6) using point-of-care (POC) glucose-CGM matched pairs. Twenty women were included; median age 30 (26-35) years with first HbA1c in pregnancy of 57 (49 - 60) mmol/mol. Overall median absolute relative difference was 6.1 (1.6 - 17.3)%. The total simulated CGM adjusted VRIII was 2.5 units per hour, compared to 2.4 units per hour with CBG adjusted VRIII. In this retrospective analysis of CGM adjustment of maternal VRIII, we demonstrate early feasibility and considerable accuracy. Further prospective studies are required to confirm the safety and potential efficacy of CGM-based insulin titration.
Ablation of ventricular tachycardia (VT) has been shown to reduce VT recurrence more favourably than drug therapy in a number of trials This article is protected by copyright. All rights reserved.
Background The CC genotype of the IFNL4 gene is known to be associated with increased Hepatitis C (HCV) cure rates with interferon-based therapy and may contribute to cure with direct acting antivirals. The Genedrive® IFNL4 is a CE marked Point of Care (PoC) molecular diagnostic test, designed for in vitro diagnostic use to provide rapid, real-time detection of IFNL4 genotype status for SNP rs12979860. Methods 120 Participants were consented to a substudy comparing IFNL4 genotyping results from a buccal swab analysed on the Genedrive® platform with results generated using the Affymetix UK Biobank array considered to be the gold standard. Results Buccal swabs were taken from 120 participants for PoC IFNL4 testing and a whole blood sample for genetic sequencing. Whole blood genotyping vs. buccal swab PoC testing identified 40 (33%), 65 (54%), and 15 (13%) had CC, CT and TT IFNL4 genotype respectively. The Buccal swab PoC identified 38 (32%) CC, 64 (53%) CT and 18 (15%) TT IFNL4 genotype respectively. The sensitivity and specificity of the buccal swab test to detect CC vs non-CC was 90% (95% CI 76–97%) and 98% (95% CI 91–100%) respectively. Conclusions The buccal swab test was better at correctly identifying non-CC genotypes than CC genotypes. The high specificity of the Genedrive® assay prevents CT/TT genotypes being mistaken for CC, and could avoid patients being identified as potentially ‘good responders’ to interferon-based therapy.
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Frank Dor
  • Division of Renal Medicine and Transplantation
Faisal Ahmed
  • Division of Medical and Surgical Ophthalmology
Jiten Jaipuria
  • Division of Urological Surgery
Nick D Francis
  • Division of Histopathology Cytology and Immunology
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Paul Abel