Imperial College NHS Trust Research Articles

Circulating chromatin conformation signatures to enhance PSA positive predictive value and overall accuracy for prostate cancer detection.

e17016 Background: Prostate cancer (PCa) has a high lifetime prevalence (one out of six men), but currently there is no widely accepted screening programme. Widely used prostate specific antigen (PSA) test at cut-off of 3.0 ng/mL does not have sufficient accuracy for detection of any prostate cancer, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance in some men with PCa. We have recently identified circulating chromosome conformation signatures (CCSs, Episwitch PCa test) allowing PCa detection and risk stratification in line with standards of clinical PCa staging. The purpose of this study was to determine whether combining the Episwitch PCa test with the PSA test will increase its diagnostic accuracy. Methods: n = 109 whole blood samples of men enrolled in the PROSTAGRAM screening pilot study and n = 38 samples of patients with established PCa diagnosis and cancer-negative controls from Imperial College NHS Trust were used. Samples were tested for PSA, and the presence of CCSs in the loci encoding for of DAPK1, HSD3B2, SRD5A3, MMP1, and miRNA98 associated with high-risk PCa identified in our previous work. Results: PSA > 3 ng/mL alone showed a low positive predicted value (PPV) of 0.14 and a high negative predicted value (NPV) of 0.93. EpiSwitch alone showed a PPV of 0.91 and a NPV of 0.32. Combining PSA and Episwitch tests has significantly increased the PPV to 0.81 although reducing the NPV to 0.78. Furthermore, integrating PSA, as a continuous variable (rather than a dichotomised 3 ng/mL cut-off), with EpiSwitch in a new multivariant stratification model, Prostate Screening EpiSwitch (PSE) test, has yielded a remarkable combined PPV of 0.93 and NPV of 0.95 when tested on the independent prospective cohort. Conclusions: Our results demonstrate that combining the standard PSA readout with circulating chromosome conformations (PSE test) allows for significantly enhanced PSA PPV and overall accuracy for PCa detection. The PSE test is accurate, rapid, minimally invasive, and inexpensive, suggesting significant screening diagnostic potential to minimise unnecessary referrals for expensive and invasive MRI and/or biopsy testing, with further extended prospective blinded validation of the new combined signature in a screening cohort with low cancer prevalence as the next step for PSE adoption in PCa screening.

Computerised cognitive assessment in patients with traumatic brain injury: an observational study of feasibility and sensitivity relative to established clinical scales.

Online technology could potentially revolutionise how patients are cognitively assessed and monitored. However, it remains unclear whether assessments conducted remotely can match established pen-and-paper neuropsychological tests in terms of sensitivity and specificity. This observational study aimed to optimise an online cognitive assessment for use in traumatic brain injury (TBI) clinics. The tertiary referral clinic in which this tool has been clinically implemented typically sees patients a minimum of 6 months post-injury in the chronic phase. Between March and August 2019, we conducted a cross-group, cross-device and factor analyses at the St. Mary's Hospital TBI clinic and major trauma wards at Imperial College NHS trust and St. George's Hospital in London (UK), to identify a battery of tasks that assess aspects of cognition affected by TBI. Between September 2019 and February 2020, we evaluated the online battery against standard face-to-face neuropsychological tests at the Imperial College London research centre. Canonical Correlation Analysis (CCA) determined the shared variance between the online battery and standard neuropsychological tests. Finally, between October 2020 and December 2021, the tests were integrated into a framework that automatically generates a results report where patients' performance is compared to a large normative dataset. We piloted this as a practical tool to be used under supervised and unsupervised conditions at the St. Mary's Hospital TBI clinic in London (UK). The online assessment discriminated processing-speed, visual-attention, working-memory, and executive-function deficits in TBI. CCA identified two significant modes indicating shared variance with standard neuropsychological tests (r=0.86, p<0.001 and r=0.81, p=0.02). Sensitivity to cognitive deficits after TBI was evident in the TBI clinic setting under supervised and unsupervised conditions (F (15,555)=3.99; p<0.001). Online cognitive assessment of TBI patients is feasible, sensitive, and efficient. When combined with normative sociodemographic models and autogenerated reports, it has the potential to transform cognitive assessment in the healthcare setting. This work was funded by a National Institute for Health Research (NIHR) Invention for Innovation (i4i) grant awarded to DJS and AH (II-LB-0715-20006).

Circulating Chromosome Conformation Signatures Significantly Enhance PSA Positive Predicting Value and Overall Accuracy for Prostate Cancer Detection.

Prostate cancer (PCa) has a high lifetime prevalence (one out of six men), but currently there is no widely accepted screening programme. Widely used prostate specific antigen (PSA) test at cut-off of 3.0 ng/mL does not have sufficient accuracy for detection of any prostate cancer, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance in some men with PCa. We have recently identified circulating chromosome conformation signatures (CCSs, Episwitch® PCa test) allowing PCa detection and risk stratification in line with standards of clinical PCa staging. The purpose of this study was to determine whether combining the Episwitch PCa test with the PSA test will increase its diagnostic accuracy. n = 109 whole blood samples of men enrolled in the PROSTAGRAM screening pilot study and n = 38 samples of patients with established PCa diagnosis and cancer-negative controls from Imperial College NHS Trust were used. Samples were tested for PSA, and the presence of CCSs in the loci encoding for of DAPK1, HSD3B2, SRD5A3, MMP1, and miRNA98 associated with high-risk PCa identified in our previous work. PSA > 3 ng/mL alone showed a low positive predicted value (PPV) of 0.14 and a high negative predicted value (NPV) of 0.93. EpiSwitch alone showed a PPV of 0.91 and a NPV of 0.32. Combining PSA and Episwitch tests has significantly increased the PPV to 0.81 although reducing the NPV to 0.78. Furthermore, integrating PSA, as a continuous variable (rather than a dichotomised 3 ng/mL cut-off), with EpiSwitch in a new multivariant stratification model, Prostate Screening EpiSwitch (PSE) test, has yielded a remarkable combined PPV of 0.92 and NPV of 0.94 when tested on the independent prospective cohort. Our results demonstrate that combining the standard PSA readout with circulating chromosome conformations (PSE test) allows for significantly enhanced PSA PPV and overall accuracy for PCa detection. The PSE test is accurate, rapid, minimally invasive, and inexpensive, suggesting significant screening diagnostic potential to minimise unnecessary referrals for expensive and invasive MRI and/or biopsy testing. Further extended prospective blinded validation of the new combined signature in a screening cohort with low cancer prevalence would be the recommended step for PSE adoption in PCa screening.

O102 We know about left gastric artery embolisation and will embio provide the next solution to treat obesity?

Abstract Introduction Left gastric artery embolisation (LGAE) is a minimally invasive procedure which has shown promising results for weight loss in recent studies and could play a key role as a treatment option in-between our current tier-3 and tier-4 services. Imperial College NHS Trust will sponsor the EMBIO trial, the first multi-centre double blinded randomised controlled trial comparing LGAE vs Placebo procedure to evaluate its efficacy on weight loss and obesity related comorbidities over a 12 month follow up period. Here, we perform a systematic review of the existing literature. Methods 9 studies were reviewed. Studies which investigated weight loss as a % +- Ghrelin % change at 3,6 and 12 months were included as these pre-defined time points correlate with the EMBIO protocol. 6 studies met our inclusion criteria, 5 single arm studies and 1 single blinded RCT. Results N=62 patients were included in our analysis. Mean weight loss reported was 8.5%, 8.8% and 10% at 3, 6 and 12 months respectively post LGAE. Ghrelin levels reduced by 36%, 16.2% and 16.5% at 3, 6 and 12 months respectively post LGAE. To date, the only reported adverse events recorded include superficial gastric erosions healed on endoscopy by day 90 and one case of subclinical pancreatitis. Conclusion LGAE potentially offers a day case procedure under local anaesthesia and sedation to treat obesity and its metabolic complications. The EMBIO trial will provide level 1 evidence to confirm if LGAE is a viable intervention for obesity and evaluate its safety profile. Take-home message Left gastric artery embolisation could be the perfect solution to treat obesity in between existing tier-3 and tier-4 treatments.

Abstract 3905: A prospective pilot study of desorption electrospray ionisation mass spectrometry (DESI-MS) for the early detection of colorectal adenoma

Abstract Background: Colorectal adenoma detection using non-invasive faecal-based biomarkers is not yet feasible. Our primary aim was to identify differential metabolomic signatures of colorectal adenomas in faecal samples using a Liquid Chromatography Mass Spectrometry (LCMS) assay. The secondary aim was to translate this assay to an Ambient Mass ionization-based technique, DESI, for high throughput, point of care diagnostics. Methods: Patients were prospectively recruited from the colorectal cancer clinic at Imperial College NHS Trust, UK. Patients provided fresh stool samples, prior to taking bowel preparation for colonoscopy. Specimens were collected in Fecotainer (AT Medical BV) and cooled before immediate manual homogenization, aliquoting and storage at -80oC. LCMS untargeted metabolomics was performed using Reversed Phase chromatography (Acquity UPLC, Xevo G2-XS QToF, Waters) in both ElectroSpray Ionization (ESI) modes. Deactivated faecal samples applied to swabs were analysed using DESI-MS (Xevo G2-XS QToF). Multivariate Statistical Analysis was performed using Python. Logistic regression (LR) classification with Leave One patient Out Cross Validation (LOOCV) was applied. Recursive Feature Elimination and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms were used for feature elimination. Results: 36 subjects (17 females, mean age 63.5, range 42-85) were included: 17 controls, 8 adenoma, and 11 cancer patients. Principal Component Analysis of LCMS data from both ESI modes separated the three groups. LR with LOOCV for the adenoma group showed 97% sensitivity and 100% specificity. Receiver Operator Characteristic curve based on a multivariate model of the top 5 significant features showed a diagnostic ability of binary classifiers of adenoma vs cancer 0.997 (Area under the curve (AUC), 95% CI=0.944-1), adenoma v healthy 0.981 (AUC, 95% CI=0.984-1), and healthy v cancer &amp; adenoma 0.995 (AUC, 95% CI=0.931-1). LR with LOOCV after LASSO on the DESI-MS data revealed sensitivity, 84%, and specificity, 95%, for the adenoma group. Specifically, these data suggest increased abundances of N-acyl amino acids, polyunsaturated chain fatty acids (n-3 PUFAs), in the adenoma group. Both species participate in arachidonic and linoleic acid pathways, where upregulation causes prostaglandin overproduction. Glycerophosphoserines, important in cell apoptosis, were significantly increased in cancer vs adenoma/controls (p &amp;lt; 0.01). Conclusion: DESI-MS analysis of faecal samples can detect the presence of colorectal adenomas and distinguish them from cancer. A prospective trial is now under way to validate these findings. Citation Format: Maria Sani, Lauren Ford, Daniel Simon, Yuchen Xiang, James McKenzie, Stefania Manetta Stavrakaki, Petra Paizs, Tausif Huq, Jim Higginson, James Alexander, Zoltan Takats, James Kinross. A prospective pilot study of desorption electrospray ionisation mass spectrometry (DESI-MS) for the early detection of colorectal adenoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3905.

An interactive dashboard to track themes, development maturity, and global equity in clinical artificial intelligence research

An interactive dashboard to track themes, development maturity, and global equity in clinical artificial intelligence research

O68: REDUCING VENOUS CONGESTION FOLLOWING LOWER LIMB RECONSTRUCTION WITH ISOMETRIC CALF EXERCISES: A PROSPECTIVE CLINICAL STUDY

Abstract Introduction Early post-operative dependency aids healing following lower limb reconstruction although increases venostasis and reduces perfusion in the acute setting. The commonest cause of lower limb flap failure is venous congestion and external compression with stockings and pneumatic devices is contraindicated. The aim of this clinical study was to determine whether venous congestion could be reduced through patient-led isometric contractions following lower limb reconstruction. Method A single centre prospective clinical study was conducted at St. Marys Hospital, Imperial College NHS Trust. Combined tissue photospectroscopy and laser Doppler (O2C, LEA, Germany) was used to assess superficial oxygen saturation, venous congestion and flow during standardised training regimens. Haemodynamic parameters were collected in an acute post-operative and outpatient rehabilitation cohort. Result In the acute post-operative cohort, isometric contractions failed to improve superficial flow following dependency on the post-operative day (POD) one (-44% ± 8). Isometric contractions improved superficial flow from POD5 (+11% ± 102) although venous congestion remained higher than measurements taken during rest (+32% ± 54). In the outpatient rehabilitation cohort isometric contractions significantly increased superficial flow following dependency (+16% ± 33, p=0.01) at a mean of 14 weeks since discharge. Conclusion This study provides objective physiological evidence of the haemodynamic changes that occur with dependency and isometric contraction following lower limb reconstruction. These physiological changes evolve following extremity reconstruction and it appears that a continued healing effect exists to accommodate progressive changes in flow dynamics. The present findings could be used to inform enhanced recovery programmes following limb reconstruction. Take-home message Simple patient-led calf contractions reduce venous congestion and improve cutaneous flow following lower extremity reconstruction.

P050 Influence factors in mortality of COVID-19 pateints with underlying rheumatological disorders

Background/Aims Since the outbreak and rapid spread of COVID-19, rheumatologists have sought to provide the best solutions to provide proper shielding of patients vulnerable to COVID-19. Set aside from social distancing and self-isolating, the British Society for Rheumatology proposed pragmatic guidance for different groups of patients for shielding. Clinical presentation, epidemiology, and potential treatment opinions of the management of COVID-19 patients with rheumatic disease had been reported, but a few reports which show a comparison between survivors and non-survivors in relation to their co-morbidities. Methods We collected data from a search identifying 1,200 patients testing positive for SARS-COV-2 with an identified rheumatological condition until 31st April 2020 at Imperial College NHS Trust. A positive laboratory finding is defined as one or more positive result for SARS-COV-2 PCR on nasopharyngeal swab done for inpatients. Results Among 1,200 patients, 39 patients had underlying rheumatological diseases.12 patients died, and 27 patients were discharged. 50% of the patients who died had chronic kidney disease as an existing comorbidity (OR 26, 95%CI ( 2.6-258.1), p value 0.001) compared with only 3% of patients who survived. All the patients with heart failure in this sample died in hospital (33%, OR 29, 95%CI (1.4-597.4, p value 0.006). Regarding drug therapy, 50% of patients who died were receiving more than one immunosuppressant compared with 37% of those who survived. There was a significant association linking non-survivors with a high CRP value (54% , OR 25.2, 95% CI ( 2.44-258.2), p value 0.009) compared with only 4.5% in patients who survived. 70% of patients who died had d-dimer of (>2000ng/ml) compared with 16% of those who survived (OR 11.6, 95% CI ( 1.86-73.06), p value 0.011). Creatinine level also had a significant link with non-survival. 58% patients who died had an initial creatinine (>140umol/l) compared with 18% of survivors (p value 0.0232). Additionally the patients with an elevated creatinine prior to deterioration (which is an indication of acute kidney injury) represented 32% of the total sample and of those, 66% did not survive compared with 13% who did (p value 0.007).We also reviewed the medication adjustment according to NICE guideline. In our study, it was observed that medications were properly adjusted after discussion with rheumatologist. Conclusion Patients with chronic kidney disease and cardiovascular disease should be strictly shielded as a same priority as patient who are taking high dose of immunosuppressive therapy. Follow-up could only be considered for remote consultation in virtual clinic apart from severity of sickness that require for hospital admission. I believe many questions remain for the rheumatology society: How will we continue better rheumatology service during and beyond the pandemic? How particularly important to shield the high-risk patients by widespread adoption of the virtual clinic? Disclosure W.W. Soe: None. F. Hassan: None. W. Phyu: None.

Oncologist-led BRCA \u2018mainstreaming\u2019 in the ovarian cancer clinic: A study of 255 patients and its impact on their management

Although guidelines recommend BRCA testing for all women with non-mucinous epithelial ovarian cancer, there is significant variability in access to testing across the UK. A germline BRCA mutation (BRCAm) in ovarian cancer patients provides prognostic and predictive information and influences clinical management, such as the use of PARP inhibitors, which have demonstrated a progression-free survival benefit in the BRCAm cohort. Additionally, the finding of a BRCAm has significant implications for patients and their families in terms of cancer risk and prevention. We studied the impact of a newly-formed, oncologist-led ‘mainstreaming’ germline BRCA testing pathway in 255 ovarian cancer patients at Imperial College NHS Trust. Prior to the establishment of ‘mainstreaming’, uptake of germline BRCA testing was 14% with a mean turnaround time of 148.2 calendar days. The ‘mainstreaming’ approach led to a 95% uptake of germline BRCA testing and a mean turnaround time of 20.6 days. Thirty-four (13.33%) BRCAm patients were identified. At the time of data collection nine BRCAm patients had received a PARP inhibitor off-trial, three had entered a PARP inhibitor trial and 5 were receiving platinum-based chemotherapy with a plan to receive PARP inhibitor maintenance. This study provides further evidence of the impact of oncologist-led ‘mainstreaming’ programs.

A41 Deep sequencing of respiratory syncytial virus links viral diversity to disease severity

Respiratory syncytial virus (RSV) is a common virus that can cause bronchiolitis in infants and pneumonia in immunocompromised and elderly people. RSV belongs to the Pneumoviridae family and consists of a genome of 15 kb. Its genome contains ten genes that code for eleven proteins, with M2 coding for two different proteins in overlapping open reading frames. It is unclear why some infected children have severe disease and others have mild or asymptomatic disease. In this project, methods for complete genome sequencing of RSV via Sanger and Illumina MiSeq platforms were optimized. One hundred and twenty-four community samples (59 RSV A and 65 RSV B) from 2014 to 2018 were collected (in collaboration with the Royal College of General Practitioners) and sequenced. Samples were selected based on viral load (e.g. Ct values had to be < 30). The genotype of each sample was determined by constructing phylogenetic trees with reference sequences from all genotypes. Trees were reconstructed using the maximum likelihood method. Furthermore, Illumina sequencing was used to deep sequence seven community samples and four hospital samples that were spatiotemporally matched (obtained via Imperial College NHS Trust hospitals). Variants were studied to investigate if certain variants influence disease severity (e.g. cause mild (community samples) or severe infection (hospital samples)). Analysis so far showed that ON1 (with a seventy-two nucleotide duplication in attachment protein G) is the most common genotype in both community and hospitalized samples (90% and 75% of samples, respectively), with GA2 (without duplication) as the next most common genotype for RSV A subtypes (7% and 25%). Three per cent of community samples were of the GA5 genotype. Samples from the RSV B subgroup all belong to the BA genotypes with a 60-nucleotide duplication in G. Samples that were selected for Illumina sequencing had a Ct value between 19.0 and 29.1, while hospital samples had a Ct value of 18.3 to 29.1. Viral load, therefore, did not explain disease severity in these selected samples. The Shannon entropy from Illumina sequenced samples averaged at 22.78 in community samples (ranges from 15 to 28) and 38.78 in hospitalized samples (ranges from 31 to 57). This indicated that diversity of the virus pool might influence disease severity; however, more samples need to be analyzed. There are no specific variants that could explain disease severity. Diversity of the virus pool could explain the link between higher viral loads and disease severity, which is sometimes found but cannot always be confirmed. Higher viral loads can harbor more diverse viral particles compared to lower viral loads. Future work will focus on more in-depth variation and diversity analysis and on evolutionary analysis of both community and hospital samples. We will also investigate intra-host evolution of RSV in acute infections using consecutive samples and its possible implications on the host response.

P85 Waiting time for operative management of degenerative cervical myelopathy (DCM) and its impact on outcome

ObjectivesTo audit the waiting time for patients with degenerative cervical myelopathy (DCM ) and its impact on outcome in the Imperial College NHS Trust (ICNHST) against the latest AO standard.DesignRetrospective analysis.Subjects1. Waiting time for surgery and impact on outcome for DCM. 2. Operative approach.MethodsThe medical records of 107 patients who had undergone surgery for DCM at ICNHST in 2016 to 2017 was reviewed. Central tendency analysis of nominal and ordinal variables such as surgery waiting time and demographics were assessed using Microsoft excel.ResultsThe mean age reviewed was 58.2 years. Male to female ratio was 1:1. The mean wait time was 10.22 overall. However, 58% of cases were moderate with mean wait time in that stratum at 4 weeks. Most patients improved at 3–6 months by 2 points on the mJOA regardless of approach done although 63% of cases were anterior. The results were compatible with the latest AO recommendations except for mild patients where it seemed more efficient to converse about morbidity of surgery vs myelopathy in the first instance, since disease burden is tolerable and plated in most hence risk may outweigh benefit. The approach chosen should be individually chosen based on a gestalt of patient and disease factors since results are equivocal.ConclusionsThe approach to the cervical myelopathy must be taken at the merit of each patient based on a gestalt of the individual clinical factors involved. However, default approach to limiting wait to under 4 weeks is reasonable.

Care planning post transcatheter aortic valve implantation (TAVI)

Background: As the transcatheter aortic valve implantation (TAVI) procedure continues to advance, the post-procedure care needs of patients are also changing. This is a high-risk patient population and there is variation between levels of post-procedure care needs for each patient. Previously, at Imperial College NHS Trust, all patients had gone directly to level 3 care. Aim: The aim of the current work was to develop an assessment tool to predict the level of care required post procedure. Methods: A screening tool was implemented pre procedure to predict the level of care patients would require post procedure. Findings: The system correctly identified 94% of patients able to go to the coronary care unit (CCU) rather than requiring a cardiac intenstive care unit (CICU) bed. Conclusion: Levels of care required vary between patients undergoing TAVI; in the majority of cases, this can be predicted in advance by the procedure type, level of sedation and individual comorbidities of the patient. Further research into the post-care needs of patients over 90 years of age is needed.

Defining Phenotypes in Diabetic Nephropathy: a novel approach using a cross-sectional analysis of a single centre cohort

The global increase in Diabetes Mellitus (DM) has led to an increase in DM-Chronic Kidney Disease (DM-CKD). In this cross-sectional observational study we aimed to define phenotypes for patients with DM-CKD that in future may be used to individualise treatment We report 4 DM-CKD phenotypes in 220 patients recruited from Imperial College NHS Trust clinics from 2004–2012. A robust principal component analysis (PCA) was used to statistically determine clusters with phenotypically different patients. 163 patients with complete data sets were analysed: 77 with CKD and 86 with DM-CKD. Four different clusters were identified. Phenotypes 1 and 2 are entirely composed of patients with DM-CKD and phenotypes 3 and 4 are predominantly CKD (non-DM-CKD). Phenotype 1 depicts a cardiovascular phenotype; phenotype 2: microvascular complications with advanced DM-CKD; phenotype 3: advanced CKD with less anaemia, lower weight and HbA1c; phenotype 4: hypercholesteraemic, younger, less severe CKD. We are the first group to describe different phenotypes in DM-CKD using a PCA approach. Identification of phenotypic groups illustrates the differences and similarities that occur under the umbrella term of DM-CKD providing an opportunity to study phenotypes within these groups thereby facilitating development of precision/personalised targeted medicine.

Microbiological and functional outcomes after open extremity fractures sustained overseas: The experience of a UK level I trauma centre

BackgroundOpen extremity fractures carry a high risk of limb loss and poor functional outcomes. Transfer of extremity trauma patients from developing countries and areas of conflict adds further layers of complexity due to challenges in the delivery of adequate care. The combination of extensive injuries, transfer delays and complex microbiology presents unique challenges. MethodsA retrospective review was conducted to analyse the surgical and microbiological themes of patients with open extremity fractures transferred from overseas to our institution (Imperial College NHS Trust) between January 2011 and January 2016. ResultsTwenty civilian patients with 21 open extremity fractures were referred to our unit from 11 different countries. All patients had poly-microbial wound contamination on initial surveillance cultures. Five patients (25%) underwent amputation depending on the extent of osseous injury; positive surveillance cultures did not preclude limb reconstruction, with seven patients undergoing complex reconstruction and eight undergoing simple reconstruction to achievewound coverage. Hundred percent of patients demonstrated infection-free fracture union on discharge. ConclusionPatients with open extremity fractures transferred from overseas present the unique challenge of poly-microbial infection in addition to extensive traumatic wounds. Favourable outcomes can be achieved despite positive microbiological findings on tissue culture with adequate antimicrobial therapy. The decision to salvage the limb and the complexity of reconstruction used should be based on the chance of achieving meaningful functional recovery, mainly determined by the extent of bony injury. The complexity of reconstruction was based on the predicted long-term functionality of the salvaged limb.

Ultrasound-Guided Laparoscopic Ovarian Wedge Resection in Recurrent Serous Borderline Ovarian Tumours.

The aim of this study was to demonstrate the use of intraoperative ultrasound-guided ovarian wedge resection in the treatment of recurrent serous borderline ovarian tumors (sBOTs) that are too small to be visualized laparoscopically. This was a prospective analysis of all women with recurrent sBOTs that were not visible laparoscopically, who underwent intraoperative ultrasound-guided ovarian wedge resection between January 2015 and December 2016 at the West London Gynaecological Cancer Centre, Imperial College NHS Trust, London, United Kingdom. We evaluated 7 patients, with a median age of 35 years (range, 28-39 years). Six women were nulliparous, whereas 1 woman had a single child. Previous surgical intervention left 5 women with a single ovary, whereas the remaining 2 had previous ovarian-sparing surgery. The median size of recurrence was 18 mm (range, 12-37 mm). All women underwent uncomplicated intraoperative guided ovarian wedge resections. Histological assessment confirmed sBOT in all 7 cases. Six of the women remain disease-free. One woman recurred postoperatively with her third recurrence, who previously had bilateral disease and noninvasive implants with microinvasive disease and micropapillary pattern. No cases progressed to invasive disease. The median follow-up time was 12 months (range, 1-20 months). One pregnancy has been achieved postoperatively but resulted in miscarriage. Continuous intraoperative ultrasound can be used to facilitate complete tumor excision in recurrent sBOT while minimizing the removal of ovarian tissue in women with recurrent sBOT. It is essential that surgical techniques evolve simultaneously with diagnostic imaging modalities to enable surgeons to treat such pathology.

An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomised placebo-controlled trial (AARDVARK).

Although data are inconsistent, angiotensin-converting enzyme inhibitors (ACE-Is) have been associated with a reduced incidence of abdominal aortic aneurysm (AAA) rupture in analysis of administrative databases. (1) To investigate whether or not the ACE-I perindopril (Coversyl arginine, Servier) reduces small AAA growth rate and (2) to evaluate blood pressure (BP)-independent effects of perindopril on small AAA growth and to compare the repeatability of measurement of internal and external aneurysm diameters. A three-arm, multicentre, single-blind, randomised placebo-controlled trial. Fourteen hospitals in England. Men or women aged ≥ 55 years with an AAA of 3.0-5.4 cm in diameter by internal or external measurement according to ultrasonography and who met the trial eligibility criteria. Patients were randomised to receive 10 mg of perindopril arginine daily, 5 mg of the calcium channel blocker amlodipine daily or placebo daily. The primary outcome was AAA diameter growth using external measurements in the longitudinal plane, which in-trial studies suggested was the preferred measure. Secondary outcome measures included AAA rupture, AAA repair, modelling of the time taken for the AAA to reach the threshold for intervention (5.5 cm) or referral for surgery, tolerance of study medication (measured by compliance, adverse events and quality of life) and a comparison of the repeatability of measures of internal and external AAA diameter. Patients were followed up every 3-6 months over 2 years. In total, 227 patients were recruited and randomised into the three groups, which were generally well matched at baseline. Multilevel modelling was used to determine the maximum likelihood estimates for AAA diameter growth. No significant differences in the estimates of annual growth were apparent [1.68 (standard error 0.02) mm, 1.77 (0.02) mm and 1.81 (0.02) mm in the placebo, perindopril and amlodipine groups, respectively]. Similarly, no significant differences in the slopes of modelled growth over time were apparent between perindopril and placebo (p = 0.78) or between perindopril and amlodipine (p = 0.89). The results were essentially unaffected by adjustment for potential confounders. Compliance, measured by pill counts, was good throughout (> 80% at all visit time points). There were no significant in-trial safety concerns. Six patients withdrew because of adverse events attributed to the study medications (n = 2 perindopril, n = 4 amlodipine). No patients ruptured their AAA and 27 underwent elective surgery during the trial (n = 9 placebo, n = 10 perindopril, n = 8 amlodipine). We were unable to demonstrate a significant impact of perindopril compared with placebo or amlodipine on small AAA growth over a 2-year period. Furthermore, there were no differences in the times to reach a diameter of 5.5 cm or undergo surgery among the three groups. Perindopril and amlodipine were well tolerated by this population. External AAA measurements were found to be more repeatable than internal measurements. The observed AAA growth measurement variability was greater than that expected pre trial. This, combined with slower than expected mean growth rates, resulted in our having limited power to detect small differences between growth rates and hence this adds uncertainty to the interpretation of the results. Several further analyses are planned including a multivariate analysis of determinants of AAA growth, an evaluation of the possible differential effect of perindopril on fast AAA growth and an investigation into the roles of central BP and BP variability on AAA growth. Current Controlled Trials ISRCTN51383267. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 59. See the NIHR Journals Library website for further project information. The NIHR Biomedical Research Centre based at Imperial College NHS Trust supported the trial. Servier provided perindopril at no charge.

Frequent attendances to National Health Service general practitioner-led urgent care centres in London: an observational study

BackgroundSome patients attend emergency departments more frequently than others and account for a disproportionate number of attendances. However, little is known about repeat attenders at National Health Service urgent care centres. We aimed to describe the volume and characteristics of repeat attenders at such centres. MethodsIn an observational study, we analysed routine attendance data at two urgent care centres in London. We included all adult patients (aged 18 years and older) who attended either centre at least once between Jan 1, 2010, and Dec 31, 2012. We used Poisson regression models to predict the characteristics of frequent attenders. For each patient, the outcome variable was the numbers of repeat visits, and the exposure variable was length of follow-up. The predictors were age, sex, and risk factors recorded at the first visit (socioeconomic status, ethnicity, centre attended, referral to an accident and emergency [A&E] department, referral to a non-A&E service, mental health indication, number of diagnoses, and general practitioner [GP] registration status). We also estimated population attributable fractions for the non-base levels of each risk factor. Findings189 614 attendances were made by 108 677 patients. Although only 3116 (2·9%) attended more than five times, they accounted for a disproportionate number (26 826, 14·1%) of the total attendances. The strongest predictor of frequent attendance was low socioeconomic status (population attributable fraction for men 0·501, 95% CI 0·446–0·550; women 0·353, 0·281–0·418). Frequent attendees were commonly of non-white ethnicity (men 0·057, 0·038–0·076; women 0·030, 0·017–0·044) and unregistered with a GP (men 0·021, 0·015–0·027; women 0·017, 0·013–0·020). Patients referred to non-A&E services at their first visit were less likely to re-attend (men −0·020, −0·024 to −0·015; women −0·011, −0·015 to −0·007). InterpretationAlthough very few patients attended the centres frequently, they contributed disproportionally to the workload of the centres. Patients of low socioeconomic status, non-white ethnicity, and unregistered with a GP were more likely to attend frequently. Interventions to reduce repeat attendances could target these populations via educational programmes or enhanced access to community-based services. The generalisability of these findings is limited because data come from only two urgent care centres in London. FundingThis study was funded by a grant from the Imperial College NHS Trust Healthcare Charity and National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Northwest London.

P69 A Study Of The Effect Of The 2013 'be Clear On Lung Cancer' Campaign On 2 Week Wait Referrals To An Inner North West London Cancer Centre

Introduction The first national ‘Be Clear on Cancer’ lung cancer campaign ran for 6 weeks from May 2012 with the message ‘Been coughing for 3 weeks? Tell your doctor’. During this time there was a 32% increase in 2 week wait (2 WW) referrals, with approximately 700 additional cancers diagnosed compared to 2011. Method We studied the effect of the 6 week campaign in 2013 on 2 WW referrals to Imperial College NHS trust, comparing with referrals in the 6 week period prior to the campaign. We assessed quality of the referral based on completeness of the 2 WW proforma (scored out of 10), and the outcome of the referral. Direct radiology referrals were not included. Results The campaign period was 2nd July to mid-August 2013. We studied from 15th May until 15th August 2013. Our referrals increased by 52% during the campaign (25 vs 38). The referral quality was unchanged (average score 6.24 pre-campaign and 6.65 during the campaign, p = 0.41). The proforma was used in 20/25 referrals pre-campaign and 30/38 during the campaign. Table 1 shows the results of the patient information section. Patients received less information during the campaign (p=ns). Diagnoses There were more referrals diagnosed with lung cancer pre-campaign than during it (37.5% vs 13.9% p = 0.055). One patient in the campaign group was diagnosed with lymphoma. The pre-campaign group had normal investigations in 16.7% patients, with other diagnoses made in 45.8% compared to the campaign group which had 22.2% (p = 0.6) and 61.1% (p = 0.25) respectively. There was no significant increase in referrals with a cough as the only symptom (7/25 vs 11/38 p = 0.95). In the campaign group, in patients diagnosed with lung cancer, we found a significant improvement in referral score compared to those without cancer (8 vs 4.87, p = 0.01). There was no change in the pre-campaign group. Conclusion Our 2 WW referrals increased during the campaign but fewer patients were diagnosed with lung cancer and more received a non-cancer diagnosis. During the campaign, referral forms for those without cancer were poorly completed which may represent pressure on GPs to refer coughs through the 2 WW pathway despite low suspicion.

Trends and usage in a London National Health Service Sperm Bank for cancer patients

Sperm cryopreservation is the only method currently available that offers men with cancer insurance against sterilising iatrogenic treatments. We carried out two cohort and cross-sectional audits to identify trends with sperm cryopreservation referral rates and sample usage rates for men diagnosed with cancer and who banked sperm at The Andrology Laboratory, Hammersmith Hospital, Imperial College NHS Trust. These retrospective audits revealed that a total of 4362 men with cancer successfully banked sperm between 1976 and 2013. Truncating the dataset to 2009 to allow for lag times between storage and use, the overall sample usage rate for cancer patients was 6.0% with 75 live births. Increased median age at referral influences the cancer profile of men seen at the bank, which is highlighted by a disproportionate rise in the number of men with prostate cancer. Among men who use banked sperm, a large rise in the use of intracytoplasmic sperm injection has occurred over time. The number of patients requiring the service is sharply increasing year on year as are the number of patients who go on to use their sample in assisted conception. The historical use rates of frozen sperm are likely to be significant underestimations of future use.

Ventricular remodelling post-bariatric surgery: is the type of surgery relevant? A prospective study with 3D speckle tracking.

The aim of the study was to examine ventricular remodelling in patients free of cardiac risk factors, before, and 6 months post-bariatric surgery with the new imaging modality of three-dimensional (3D) strain and the comparison of two surgical techniques: sleeve gastrectomy vs. gastric bypass. Fifty-two consecutive patients referred to the Bariatric Services of Imperial College NHS Trust were examined with conventional 2D and 3D strain echocardiography, prior to and 6 months after bariatric surgery. They were all free from cardiac disease. The study cohort's mean age was 44.2 ± 8.7 years and body mass index of 42.4 ± 4.6 g/m(2) prior to surgery. Eighteen patients (34.6%) underwent laparoscopic sleeve gastrectomy, and 34 laparoscopic gastric bypass. On 3D speckle tracking, there was significant reverse remodelling post-bariatric surgery [left ventricular (LV) ejection fraction (EF): pre-surgery: 59 ± 8% vs. post-surgery: 67 ± 7%, P < 0.001 and right ventricular (RV) EF: pre-surgery: 60 ± 9% vs. post-surgery: 68 ± 8.2%, P = 0.0001]. Furthermore, there was significant regression of mass (LV mass: pre-surgery: 111 ± 23.5 g vs. post-surgery: 92.8 ± 15.5 g and RV mass: pre-surgery: 95.2 ± 19.8 vs. post-surgery: 67.3 ± 16.3, P < 0.001). RV and LV global strain improved 6 months post-bariatric surgery: global RV strain: pre-surgery -11.7 ± 4 vs. post-surgery -17.52 ± 3.7, P < 0.001; global LV strain: pre-surgery: -20.2 ± 1.7 vs. post-surgery: -26.5 ± 1.86, P < 0.001. Sleeve gastrectomy and gastric bypass had comparable effects. Bariatric surgery has an important effect in reverse LV and RV remodelling and it substantially improves RV longitudinal strain.