Enhancing cancer prediction in challenging screen-detected incident lung nodules using time-series deep learning.

Lung cancer screening (LCS) using annual computed tomography (CT) scanning significantly reduces mortality by detecting cancerous lung nodules at an earlier stage. Deep learning algorithms can improve nodule malignancy risk stratification. However, they have typically been used to analyse single time point CT data when detecting malignant nodules on either baseline or incident CT LCS rounds. Deep learning algorithms have the greatest value in two aspects. These approaches have great potential in assessing nodule change across time-series CT scans where subtle changes may be challenging to identify using the human eye alone. Moreover, they could be targeted to detect nodules developing on incident screening rounds, where cancers are generally smaller and more challenging to detect confidently. Here, we show the performance of our Deep learning-based Computer-Aided Diagnosis model integrating Nodule and Lung imaging data with clinical Metadata Longitudinally (DeepCAD-NLM-L) for malignancy prediction. DeepCAD-NLM-L showed improved performance (AUC = 88%) against models utilizing single time-point data alone. DeepCAD-NLM-L also demonstrated comparable and complementary performance to radiologists when interpreting the most challenging nodules typically found in LCS programs. It also demonstrated similar performance to radiologists when assessed on out-of-distribution imaging dataset. The results emphasize the advantages of using time-series and multimodal analyses when interpreting malignancy risk in LCS.

Plasma fibrinogen and risk of vascular recurrence after ischaemic stroke: An individual participant and summary-level data meta-analysis of 11 prospective studies.

INTRODUCTION: Inflammation is an emerging target for secondary prevention after stroke and randomised trials of anti-inflammatory therapies are ongoing. Fibrinogen, a putative pro-inflammatory marker, is associated with first stroke, but its association with major adverse cardiovascular events (MACE) after stroke is unclear. MATERIALS AND METHODS: We did a systematic review investigating the association between fibrinogen and post-stroke vascular recurrence. Authors were invited to provide individual-participant data (IPD) and where available we did within-study multivariable analyses with adjustment for cardiovascular risk factors and medications. Adjusted summary-level data was extracted from published reports from studies that did not provide IPD. We pooled risk ratios (RR) by random-effects meta-analysis by comparing supra-median with sub-median fibrinogen levels and performed pre-specified subgroup analysis according to timing of phlebotomy after the index event. RESULTS: Eleven studies were included (14,002 patients, 42,800 follow-up years), of which seven provided IPD. Fibrinogen was associated with recurrent MACE on unadjusted (RR 1.35, 95% CI 1.17-1.57, supra-median vs sub-median) and adjusted models (RR 1.21, 95% CI 1.06-1.38). Fibrinogen was associated with recurrent stroke on univariate analysis (RR 1.19, 95% CI 1.03-1.39), but not after adjustment (RR 1.11, 95% CI 0.94-1.31). The association with recurrent MACE was consistently observed in patients with post-acute (⩾14 days) fibrinogen measures (RR 1.29, 95% CI 1.16-1.45), but not in those with early phlebotomy (<14 days) (RR 0.98, 95% CI 0.82-1.18) (Pinteraction = 0.01). Similar associations were observed for recurrent stroke. DISCUSSION AND CONCLUSION: Fibrinogen was independently associated with recurrence after stroke, but the association was modified by timing of phlebotomy. Fibrinogen measurements might be useful to identify patients who are more likely to derive benefit from anti-inflammatory therapies after stroke.

A comparison of available guidelines for the detection of cauda equina syndrome and assessing the need for further clinical guidance in Ireland.

The cauda equina syndrome (CES) is a rare but critical disorder, which can result in devastating motor weakness and sensory deficit, alongside often irreversible bladder, bowel and sexual dysfunction. In addition to the clinical burden of disease, this syndrome results in a disproportionately high medicolegal strain due to missed or delayed diagnoses. Despite being an emergency diagnosis, often necessitating urgent surgical decompression to treat, we believe there is a lack of clarity for clinicians in the current literature, with no published Irish guideline concerning screening or detection. The current study aims to identify and analyse appropriate guidelines in relation to CES screening which are available to clinicians in Ireland. The study design included a comprehensive literature review and comparison of existing guidelines. The review identified 13 sources of appropriate guidance for clinicians working in Ireland. These resources included textbooks, websites and guidelines developed in the UK. No Irish guidelines or advice were available on CES screening/treatment at the time of review. This review demonstrated the lack of consensus and guidance for clinicians in Ireland on how to effectively screen for CES, judge who requires further imaging and investigations and how to rule out the condition. A national consensus on thorough screening and prompt investigation for CES is necessary, and the formulation of new CES guidelines would be a welcome addition to what is available to clinicians currently.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis

BACKGROUND AND OBJECTIVES: Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention. METHODS: Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack. The prespecified coprimary end points were (1) any recurrent MACE (first major coronary event, recurrent stroke, or vascular death) and (2) any recurrent stroke (ischemic, hemorrhagic, or unspecified) after sample measurement. Analyses were performed stratified by stroke mechanism, per quarter and per biomarker unit increase after loge transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed. RESULTS: IPD was obtained from 10 studies (8,420 patients). After adjustment for vascular risk factors and statins/antithrombotic therapy, IL-6 was associated with recurrent MACE in stroke caused by large artery atherosclerosis (LAA) (risk ratio [RR] 2.30, 95% CI 1.21-4.36, p = 0.01), stroke of undetermined cause (UND) (RR 1.78, 1.19-2.66, p = 0.005), and small vessel occlusion (SVO) (RR 1.71, 0.99-2.96, p = 0.053) (quarter 4 [Q4] vs quarter 1 [Q1]). No association was observed for stroke due to cardioembolism or other determined cause. Similar results were seen for recurrent stroke and when analyzed per loge unit increase for MACE (LAA, RR 1.26 [1.06-1.50], p = 0.009; SVO, RR 1.22 [1.01-1.47], p = 0.04; UND, RR 1.18 [1.04-1.34], p = 0.01). High-sensitivity CRP was associated with recurrent MACE in UND stroke only (Q4 vs Q1 RR 1.45 [1.04-2.03], p = 0.03). Findings were consistent on study-level meta-analysis of the IPD results with 2 other comparable studies (20,136 patients). DISCUSSION: Our data provide new evidence for the selection of patients in future RCTs of anti-inflammatory therapy in stroke due to large artery atherosclerosis, small vessel occlusion, and undetermined etiology according to inflammatory marker profile.

Targeting inflammation to reduce recurrent stroke.

BACKGROUND: Approximately one in four stroke patients suffer from recurrent vascular events, underlying the necessity to improve secondary stroke prevention strategies. Immune mechanisms are causally associated with coronary atherosclerosis. However, stroke is a heterogeneous disease and the relative contribution of inflammation across stroke mechanisms is not well understood. The optimal design of future randomized control trials (RCTs) of anti-inflammatory therapies to prevent recurrence after stroke must be informed by a clear understanding of the prognostic role of inflammation according to stroke subtype and individual patient factors. AIM: In this narrative review, we discuss (1) inflammatory pathways in the etiology of ischemic stroke subtypes; (2) the evidence on inflammatory markers and vascular recurrence after stroke; and (3) review RCT evidence of anti-inflammatory agents for vascular prevention. SUMMARY OF REVIEW: Experimental work, genetic epidemiological data, and plaque-imaging studies all implicate inflammation in atherosclerotic stroke. However, emerging evidence also suggests that inflammatory mechanisms are also important in other stroke mechanisms. Advanced neuroimaging techniques support the role of neuroinflammation in blood-brain barrier dysfunction in cerebral small vessel disease (cSVD). Systemic inflammatory processes also promote atrial cardiopathy, incident and recurrent atrial fibrillation (AF). Although several inflammatory markers have been associated with recurrence after stroke, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) are presently the most promising markers to identify patients at increased vascular risk. Several RCTs have shown that anti-inflammatory therapies reduce vascular risk, including stroke, in coronary artery disease (CAD). Some, but not all of these trials, selected patients on the basis of elevated hsCRP. Although unproven after stroke, targeting inflammation to reduce recurrence is a compelling strategy and several RCTs are ongoing. CONCLUSION: Evidence points toward the importance of inflammation across multiple stroke etiologies and potential benefit of anti-inflammatory targets in secondary stroke prevention. Taking the heterogeneous stroke etiologies into account, the use of serum biomarkers could be useful to identify patients with residual inflammatory risk and perform biomarker-led patient selection for future RCTs.

Novel Targets for Molecular Imaging of Inflammatory Processes of Carotid Atherosclerosis: A Systematic Review.

Computed tomography angiography (CTA), magnetic resonance angiography (MRA) and 18F-FDG-PET have proven clinical value when evaluating patients with carotid atherosclerosis. In this systematic review, we will focus on the role of novel molecular imaging tracers in that assessment and their potential strengths to stratify stroke risk. We systematically searched PubMed, Embase, the Web of Science Core Collection, and Cochrane Library for articles reporting on molecular imaging to noninvasively detect or characterize inflammation in carotid atherosclerosis. As our focus was on nonclassical novel targets, we omitted reports solely on 18F-FDG and 18F-NaF. We summarized and mapped the selected studies to provide an overview of the current clinical development in molecular imaging in relation to risk factors, imaging and histological findings, diagnostic and prognostic performance. We identified 20 articles in which the utilized tracers to visualize carotid wall inflammation were somatostatin subtype-2- (SST2-) (n = 5), CXC-motif chemokine receptor 4- (CXCR4-) (n = 3), translocator protein- (TSPO-) (n = 2) and aVß3 integrin-ligands (n = 2) and choline-tracers (n = 2). Tracer uptake correlated with traditional cardiovascular risk factors, that is, age, gender, diabetes, hypercholesterolemia, and hypertension as well as prior cardiovascular disease. We identified discrepancies between tracer uptake and grade of stenosis, plaque calcification, and 18F-FDG uptake, suggesting the importance of alternative characterization of atherosclerosis beyond classical neuroimaging features. Immunohistochemical analysis linked tracer uptake to markers of macrophage infiltration and neovascularization. Symptomatic carotid arteries showed higher uptake compared to asymptomatic (including contralateral, nonculprit) arteries. Some studies demonstrated a potential role of these novel molecular imaging as a specific intermediary (bio)marker for outcome. Several novel tracers show promise for identification of high-risk plaque inflammation. Based on the current evidence we cautiously propose the SST2-ligands and the choline radiotracers as viable candidates for larger prospective longitudinal outcome studies to evaluate their predictive use in clinical practice.

Effect of Fluoride Release on Enamel Demineralization Adjacent to Orthodontic Brackets.

INTRODUCTION AND AIM: This study aimed to evaluate the ability of fluoride-releasing adhesives to inhibit enamel demineralization surrounding orthodontic brackets. METHODS: Two groups of 40 sound human premolars were sectioned mesio-distally. The halves were varnished, and orthodontic brackets were bonded with different adhesive materials. An area 1 mm wide surrounding the brackets was left exposed. Each specimen was immersed daily in a pH cycle for 28 days. In the second group, the specimens were exposed daily to a fluoride solution (250 ppm F-) at 37°C. The fluoride release from different groups was measured. Quantitative light-induced fluorescence (QLF) was used to quantify fluorescence loss of enamel surfaces adjacent to the brackets. Results were statistically analyzed using ANOVA at (p<0.05). RESULTS: Fluoride released from the three fluoride-releasing adhesives was significantly higher (p<0.001) in the group with daily fluoride exposures than in the group without fluoride exposures. Enamel adjacent to brackets bonded with Fuji Ortho LC, Ketac Cem, and Dyract Cem showed significantly less (p<0.001) changes in (ΔQ) value (less demineralization) than enamel bonded with Transbond, the control adhesive material. CONCLUSIONS: Using fluoride-releasing adhesives significantly reduced the level of demineralization adjacent to orthodontic brackets.

Imaging Carotid Plaque Inflammation Using Positron Emission Tomography: Emerging Role in Clinical Stroke Care, Research Applications, and Future Directions.

Atherosclerosis is a chronic systemic inflammatory condition of the vasculature and a leading cause of stroke. Luminal stenosis severity is an important factor in determining vascular risk. Conventional imaging modalities, such as angiography or duplex ultrasonography, are used to quantify stenosis severity and inform clinical care but provide limited information on plaque biology. Inflammatory processes are central to atherosclerotic plaque progression and destabilization. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a validated technique for quantifying plaque inflammation. In this review, we discuss the evolution of FDG-PET as an imaging modality to quantify plaque vulnerability, challenges in standardization of image acquisition and analysis, its potential application to routine clinical care after stroke, and the possible role it will play in future drug discovery.

Symptomatic Carotid Atheroma Inflammation Lumen-stenosis score compared with Oxford and Essen risk scores to predict recurrent stroke in symptomatic carotid stenosis.

BACKGROUND: The Oxford Carotid Stenosis tool (OCST) and Essen Stroke Risk Score (ESRS) are validated to predict recurrent stroke in patients with and without carotid stenosis. The Symptomatic Carotid Atheroma Inflammation Lumen stenosis (SCAIL) score combines stenosis and plaque inflammation on fluorodeoxyglucose positron-emission tomography (18FDG-PET). We compared SCAIL with OCST and ESRS to predict ipsilateral stroke recurrence in symptomatic carotid stenosis. PATIENTS AND METHODS: We pooled three prospective cohort studies of patients with recent (<30 days) non-severe ischaemic stroke/TIA and internal carotid artery stenosis (>50%). All patients had carotid 18FDG-PET/CT angiography and late follow-up, with censoring at carotid revascularisation. RESULTS: Of 212 included patients, 16 post-PET ipsilateral recurrent strokes occurred in 343 patient-years follow-up (median 42 days (IQR 13-815)).Baseline SCAIL predicted recurrent stroke (unadjusted hazard ratio [HR] 1.96, CI 1.20-3.22, p = 0.007, adjusted HR 2.37, CI 1.31-4.29, p = 0.004). The HR for OCST was 0.996 (CI 0.987-1.006, p = 0.49) and for ESRS was 1.26 (CI 0.87-1.82, p = 0.23) (all per 1-point score increase). C-statistics were: SCAIL 0.66 (CI 0.51-0.80), OCST 0.52 (CI 0.40-0.64), ESRS 0.61 (CI 0.48-0.74). Compared with ESRS, addition of plaque inflammation (SUVmax) to ESRS improved risk prediction when analysed continuously (HR 1.51, CI 1.05-2.16, p = 0.03) and categorically (ptrend = 0.005 for risk increase across groups; HR 3.31, CI 1.42-7.72, p = 0.006; net reclassification improvement 10%). Findings were unchanged by further addition of carotid stenosis. CONCLUSIONS: SCAIL predicted recurrent stroke, had discrimination better than chance, and improved the prognostic utility of ESRS, suggesting that measuring plaque inflammation may improve risk stratification in carotid stenosis.

The contribution of competing mechanisms in stroke despite anticoagulation in patients with atrial fibrillation.

BACKGROUND: For reasons poorly understood, strokes frequently occur in patients with atrial fibrillation (AF) despite oral anticoagulation. Better data are needed to inform randomised trials (RCTs) of new strategies to prevent recurrence in these patients. We investigate the relative contribution of competing stroke mechanisms in patients with AF who have stroke despite anticoagulation (OAC+) compared with those who are anticoagulant naïve (OAC-) at the time of their event. PATIENTS AND METHODS: We performed a cross-sectional study leveraging data from a prospective stroke registry (2015-2022). Eligible patients had ischemic stroke and AF. Stroke classification was performed by a single stroke-specialist blinded to OAC status using TOAST criteria. The presence of atherosclerotic plaque was determined using duplex ultrasonography, computerised tomography (CT) or magnetic resonance (MR) angiography. Imaging was reviewed by a single reader. Logistic regression was used to identify independent predictors of stroke despite anticoagulation. RESULTS: Of 596 patients included, 198 (33.2%) were in the OAC+ group. A competing cause for stroke was more frequent in patients with OAC+ versus OAC- (69/198 (34.8%)) versus 77/398 (19.3%), p < 0.001). After adjustment, both small vessel occlusion (odds ratio (OR): 2.46, 95% CI: 1.20-5.06) and arterial atheroma (⩾50% stenosis) (OR: 1.78, 95% CI: 1.07-2.94) were independently associated with stroke despite anticoagulation. DISCUSSION AND CONCLUSION: Patients with AF-associated stroke despite OAC are much more likely than patients who are OAC-naïve to have competing stroke mechanisms. Rigorous investigation for alternative stroke causes in stroke despite OAC has a high diagnostic yield. These data should be used to guide patient selection for future RCTs in this population.

A novel scoring system incorporating sarcopenia to predict postoperative survival in spinal metastasis.

BACKGROUND CONTEXT: As the prevalence of spinal metastasis rises, methods to predict survival will become increasingly important for clinical decision-making. Sarcopenia may be used to predict survival in these patients. PURPOSE: The purpose of this study to develop a prediction model incorporating sarcopenia for postoperative survival in patients with spinal metastasis. DESIGN: Retrospective cohort study. PATIENT SAMPLE: This study included 200 patients who underwent operative intervention for spinal metastasis in our institution, a tertiary, academic spine center. OUTCOME MEASURES: The primary outcome measure was 1-year postoperative survival. The secondary outcome measures were 3-month and 6-month postoperative survival. METHODS: Clinicopathological and survivorship data was collated. Sarcopenia was defined using the L3 Psoas/Vertebral Body Ratio on cross-sectional CT. Independent predictors of postoperative survival were assessed by multiple logistic regression. RESULTS: Overall 1-year postoperative survival was 50%. L3/Psoas ratio ≥1.5 (OR 6.2), albumin ≥35g/l (OR 3.0) and primary tumor type were found to be independent predictors of 3 month, 6 month and 1 year postoperative survival on multivariable analysis. Age at surgery, ambulatory status and mode of presentation were not independent predictors of survival. Variables were used to generate a new scoring system, ProgMets, to predict postoperative survival. The ProgMets system had greater correlation and higher area under the curve (AUC, 0.80) for 1-year survival than other scoring systems. CONCLUSIONS: This is the first model to incorporate sarcopenia to predict survival in spinal metastasis patients and has good prediction of survival compared to previous models. This tool may be increasingly useful for informed decision making for patients and surgeons.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis.

BACKGROUND: Anti-inflammatory therapies reduce recurrent vascular events in coronary disease. Existing studies have reported highly conflicting findings for the association of blood inflammatory markers with vascular recurrence after stroke leading to uncertainty about the potential of anti-inflammatory therapies after stroke and no consensus about the utility of measurement of inflammatory markers in current guidelines. METHODS: We investigated the association between hsCRP (high-sensitivity C-reactive protein), IL-6 (interluekin-6), and recurrent major adverse cardiovascular events (MACE), and stroke from individual participant data from 8420 patients with ischemic stroke/transient ischemic attack from 10 prospective studies. We did within-study multivariable regression analyses and then combined adjusted risk ratio (RR) by random-effects meta-analysis. RESULTS: During 18 920 person-years of follow-up, 1407 (16.7% [95% CI, 15.9-17.5]) patients had MACE and 1191 (14.1% [95% CI, 13.4-14.9]) patients had recurrent stroke. On bivariate analysis, baseline IL-6 was associated with MACE (RR, 1.26 [95% CI, 1.10-1.43]) and recurrent stroke (RR, 1.18 [95% CI, 1.05-1.32]), per unit increase logeIL-6. Similar associations were observed for hsCRP (MACE RR, 1.19 [95% CI, 1.09-1.29]; recurrent stroke RR, 1.12 [95% CI, 1.04-1.21], per unit increase logehsCRP). After adjustment for vascular risk factors and treatment, independent associations remained with MACE (IL-6, RR, 1.12 [95% CI, 1.04-1.21]; hsCRP, RR, 1.09 [95% CI, 1.04-1.15]) and recurrent stroke (IL-6, RR, 1.09 [95% CI, 1.00-1.19]; hsCRP, RR, 1.05 [95% CI, 1.00-1.11]). Comparing the top with the bottom quarters (Q4 versus Q1), IL-6 (RR, 1.35 [95% CI, 1.09-1.67]) and hsCRP (RR, 1.31 [95% CI, 1.07-1.61]) were associated with MACE after adjustment. Similar results were observed for recurrent stroke for IL-6 (RR, 1.33 [95% CI, 1.08-1.65]) but not hsCRP (RR, 1.16 [95% CI, 0.93-1.43]). CONCLUSIONS: Blood markers of inflammation were independently associated with vascular recurrence after stroke, strengthening the rationale for randomized trials of anti-inflammatory therapies for secondary prevention after ischemic stroke/TIA.

Thermal Generation in Spinal Surgery: Does Rate of Irrigation Matter During Anterior Cervical Discectomy?

BACKGROUND: High-speed rotational burring is considered the mainstay of modern spinal decompression surgery. However, high-energy burrs generate significant heat due to the friction between the bone and the rotating burr. This study determines the effects of automated irrigation rate on burr tip temperatures either with a serrated steel burr or diamond-coated burr during anterior cervical discectomy and fusion (ACDF). METHODS: This is an observational study of the routine practice of a single surgeon for 20 patients aged 18 years or older undergoing elective single- or multilevel ACDF. Various continuous irrigation rates of 0, 0.5, 1.0, or 2.0 cc/min were used. Forward-looking infrared thermography was used to measure the burr tip temperatures. The Midas Rex Legend EHS (Medtronic, PLC, Minneapolis, MN) stylus high-speed surgical drill was used with 3-mm burrs (diamond-coated and carbide-serrated steel) paired to the Medtronic Integrated Power Console set at 60,000 rpm. RESULTS: The 0.5-cc/min irrigation rate kept the maximum burr temperatures below 45°C (P < .001). With no irrigation (0 cc/min), the steel burrs reached a maximum of 141°C, and the diamond-coated burrs reached 177°C, which was the only significant difference related to the burr materials (P = 0.0354). With irrigation rates of 0.5 cc/min and above, the maximum recorded temperature for steel burrs was 40.6°C, and the maximum temperature for diamond-coated burrs was 38.9°C. Irrigation rates greater than 0.5 cc/min yielded little additional benefit. CONCLUSION: This study highlights the importance of adequate irrigation during high-speed burr drilling. Continuous irrigation is recommended even as low as 0.5 cc/min. It is good operative practice to reduce the risk of heat transmission to surrounding tissues, especially considering the proximity of cervical spinal nerve roots during uncoforaminal decompression.

The SUMMIT Study: Utilising a written 'Next Steps' information booklet to prepare participants for potential lung cancer screening results and follow-up.

OBJECTIVES: Low-Dose Computed Tomography (LDCT) screening for lung cancer can result in several potential outcomes of varying significance. Communication methods used in Lung Cancer Screening (LCS) programmes must, therefore, ensure that participants are prepared for the range of possible results and follow-up. Here, we assess perceptions of a written preparatory information booklet provided to participants in a large LCS cohort designed to convey this information. MATERIALS AND METHODS: All participants in the SUMMIT Study (NCT03934866) were provided with a results preparation information booklet, entitled 'The SUMMIT Study: Next Steps' at their baseline appointment which outlined potential results, their significance, and timelines for follow up. Results from the LDCT scan and Lung Health Check were subsequently sent by letter. Perceptions of this booklet were assessed among participants with indeterminate pulmonary findings when they attended a face-to-face appointment immediately before their three-month interval scan. Specifically, questions assessed the perceived usefulness of the booklet and the amount of information contained in it. RESULTS: 70.1% (n = 1,412/2,014) participants remembered receiving the booklet at their appointment. Of these participants, 72.0% (n = 1,017/1,412) found it quite or very useful and 68.0% (n = 960/1,412) reported that it contained the right amount of information. Older participants, those from the least deprived socioeconomic quintile and those of Black ethnicity were less likely to report finding the booklet either quite or very useful, or that it contained the right amount of information. Participants who remembered receiving the booklet were more likely to be satisfied with the process of results communication by letter. CONCLUSION: Providing written information that prepares participants for possible LDCT results and their significance appears to be a useful resource and a helpful adjunct to a written method of results communication for large scale LCS programmes.

Uptake of invitations to a lung health check offering low-dose CT lung cancer screening among an ethnically and socioeconomically diverse population at risk of lung cancer in the UK (SUMMIT): a prospective, longitudinal cohort study.

BACKGROUND: Lung cancer screening with low-dose CT reduces lung cancer mortality, but screening requires equitable uptake from candidates at high risk of lung cancer across ethnic and socioeconomic groups that are under-represented in clinical studies. We aimed to assess the uptake of invitations to a lung health check offering low-dose CT lung cancer screening in an ethnically and socioeconomically diverse cohort at high risk of lung cancer. METHODS: In this multicentre, prospective, longitudinal cohort study (SUMMIT), individuals aged 55-77 years with a history of smoking in the past 20 years were identified via National Health Service England primary care records at practices in northeast and north-central London, UK, using electronic searches. Eligible individuals were invited by letter to a lung health check offering lung cancer screening at one of four hospital sites, with non-responders re-invited after 4 months. Individuals were excluded if they had dementia or metastatic cancer, were receiving palliative care or were housebound, or declined research participation. The proportion of individuals invited who responded to the lung health check invitation by telephone was used to measure uptake. We used univariable and multivariable logistic regression analyses to estimate associations between uptake of a lung health check invitation and re-invitation of non-responders, adjusted for sex, age, ethnicity, smoking, and deprivation score. This study was registered prospectively with ClinicalTrials.gov, NCT03934866. FINDINGS: Between March 20 and Dec 12, 2019, the records of 2 333 488 individuals from 251 primary care practices across northeast and north-central London were screened for eligibility; 1 974 919 (84·6%) individuals were outside the eligible age range, 7578 (2·1%) had pre-existing medical conditions, and 11 962 (3·3%) had opted out of particpation in research and thus were not invited. 95 297 individuals were eligible for invitation, of whom 29 545 (31·0%) responded. Due to the COVID-19 pandemic, re-invitation letters were sent to only a subsample of 4594 non-responders, of whom 642 (14·0%) responded. Overall, uptake was lower among men than among women (odds ratio [OR] 0·91 [95% CI 0·88-0·94]; p<0·0001), and higher among older age groups (1·48 [1·42-1·54] among those aged 65-69 years vs those aged 55-59 years; p<0·0001), groups with less deprivation (1·89 [1·76-2·04] for the most vs the least deprived areas; p<0·0001), individuals of Asian ethnicity (1·14 [1·09-1·20] vs White ethnicity; p<0·0001), and individuals who were former smokers (1·89 [1·83-1·95] vs current smokers; p<0·0001). When ethnicity was subdivided into 16 groups, uptake was lower among individuals of other White ethnicity than among those with White British ethnicity (0·86 [0·83-0·90]), whereas uptake was higher among Chinese, Indian, and other Asian ethnicities than among those with White British ethnicity (1·33 [1·13-1·56] for Chinese ethnicity; 1·29 [1·19-1·40] for Indian ethnicity; and 1·19 [1·08-1·31] for other Asian ethnicity). INTERPRETATION: Inviting eligible adults for lung health checks in areas of socioeconomic and ethnic diversity should achieve favourable participation in lung cancer screening overall, but inequalities by smoking, deprivation, and ethnicity persist. Reminder and re-invitation strategies should be used to increase uptake and the equity of response. FUNDING: GRAIL.

Growing small solid nodules in lung cancer screening: safety and efficacy of a 200 mm3 minimum size threshold for multidisciplinary team referral.

The optimal management of small but growing nodules remains unclear. The SUMMIT study nodule management algorithm uses a specific threshold volume of 200 mm3 before referral of growing solid nodules to the multidisciplinary team for further investigation is advised, with growing nodules below this threshold kept under observation within the screening programme. Malignancy risk of growing solid nodules of size >200 mm3 at initial 3-month interval scan was 58.3% at a per-nodule level, compared with 13.3% in growing nodules of size ≤200 mm3 (relative risk 4.4, 95% CI 2.17 to 8.83). The positive predictive value of a combination of nodule growth (defined as percentage volume change of ≥25%), and size >200 mm3 was 65.9% (29/44) at a cancer-per-nodule basis, or 60.5% (23/38) on a cancer-per-participant basis. False negative rate of the protocol was 1.9% (95% CI 0.33% to 9.94%). These findings support the use of a 200 mm3 minimum volume threshold for referral as effective at reducing unnecessary multidisciplinary team referrals for small growing nodules, while maintaining early-stage lung cancer diagnosis.

Emergency Urology procedures during the COVID-19 pandemic in the UK: A 3-month prospective study.

OBJECTIVE: COVID-19 resulted in Regional tiered restrictions being introduced across the UK with subsequent implications for planned and emergency surgical care. Specific to Merseyside, Tier 4, Tier 2 and Tier 5 restrictions were introduced in late 2020 and early 2021. The purpose of this study was to examine the nature and workload of emergency urological procedures during three different national lockdown Tiers in the North West of England. METHOD: A 3-month prospective study examining all emergency urological activity was conducted from November 2020 when Tier 4 restrictions were introduced and included Tier 2 restrictions in December and then concluded at the end of January 2021 when Tier 5 restrictions were in place. Data was obtained by identifying patients using the electronic theatre listing system. RESULTS: A total of 71 emergency cases were performed (24 in November (Tier 4), 28 in December (Tier 2), 19 in January 2021 (Tier 5)) with 15 different types of procedures performed. The most frequently performed procedure was stent insertion (36), followed by scrotal exploration (10). The least commonly performed procedure was suprapubic catheter insertion under general anaesthesia (1). One patient required transfer to a different hospital. In total 6 calls were made by general surgery and 3 by gynaecology for urgent urological assistance in theatre. Three urology patients returned to the theatre as emergencies following elective procedures. CONCLUSION: Unlike the Spring lockdown, acute urological presentations requiring operative intervention still presented daily. Of the 71 cases performed, most occurred in Tier 2. Stent insertion was the most commonly performed procedure, with the majority of the cases performed by registrars.

Phenotypes associated with genetic determinants of type I interferon regulation in the UK Biobank: a protocol.

Background: Type I interferons are cytokines involved in innate immunity against viruses. Genetic disorders of type I interferon regulation are associated with a range of autoimmune and cerebrovascular phenotypes. Carriers of pathogenic variants involved in genetic disorders of type I interferons are generally considered asymptomatic. Preliminary data suggests, however, that genetically determined dysregulation of type I interferon responses is associated with autoimmunity, and may also be relevant to sporadic cerebrovascular disease and dementia. We aim to determine whether functional variants in genes involved in type I interferon regulation and signalling are associated with the risk of autoimmunity, stroke, and dementia in a population cohort. Methods: We will perform a hypothesis-driven candidate pathway association study of type I interferon-related genes using rare variants in the UK Biobank (UKB). We will manually curate type I interferon regulation and signalling genes from a literature review and Gene Ontology, followed by clinical and functional filtering. Variants of interest will be included based on pre-defined clinical relevance and functional annotations (using LOFTEE, M-CAP and a minor allele frequency <0.1%). The association of variants with 15 clinical and three neuroradiological phenotypes will be assessed with a rare variant genetic risk score and gene-level tests, using a Bonferroni-corrected p-value threshold from the number of genetic units and phenotypes tested. We will explore the association of significant genetic units with 196 additional health-related outcomes to help interpret their relevance and explore the clinical spectrum of genetic perturbations of type I interferon. Ethics and dissemination: The UKB has received ethical approval from the North West Multicentre Research Ethics Committee, and all participants provided written informed consent at recruitment. This research will be conducted using the UKB Resource under application number 93160. We expect to disseminate our results in a peer-reviewed journal and at an international cardiovascular conference.