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Constantinos Kallis,1– 3 Amit Kaura,1,3 Nathan A Samuel,4 Abdulrahim Mulla,3 Ben Glampson,3 Kevin O’Gallagher,5 Jim Davies,4 Dimitri Papadimitriou,3 Kerrie J Woods,4 Anoop D Shah,6,7 Bryan Williams,6,7 Folkert W Asselbergs,6,7 Erik K Mayer,3,8 Richard W Lee,1,9 Christopher Herbert,10 Stuart W Grant,11 Nick Curzen,12 Iain B Squire,13 Thomas Johnson,14 Ajay M Shah,15 Divaka Perera,5 Rajesh K Kharbanda,4 Riyaz S Patel,6 Keith M Channon,4 Jamil Mayet,1,3 Jennifer K Quint1– 3 1National Heart and Lung Institute, Imperial College London, London, UK; 2School of Public Health, Imperial College London, London, UK; 3NIHR Imperial Biomedical Research Centre, Imperial College London and Imperial College Healthcare NHS Trust, London, UK; 4NIHR Oxford Biomedical Research Centre, University of Oxford and Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 5NIHR King’s Biomedical Research Centre, King’s College London and King’s College Hospital NHS Foundation Trust, London, UK; 6NIHR University College London Biomedical Research Centre, University College London and University College London Hospitals NHS Foundation Trust, London, UK; 7Institute of Health Informatics, University College London, London, UK; 8Imperial Clinical Analytics, Research & Evaluation (iCARE) and Department of Surgery & Cancer, Imperial College London, London, UK; 9Early Diagnosis and Detection Centre, NIHR BRC at The Royal Marsden and Institute of Cancer Research, London, UK; 10NIHR Leeds Clinical Research Facility, Leeds Teaching Hospitals Trust and University of Leeds, Leeds, UK; 11NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust and the University of Manchester, Manchester, UK; 12NIHR Southampton Clinical Research Facility and Biomedical Research Centre, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK; 13NIHR Leicester Biomedical Research Centre, Glenfield Hospital, and Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; 14NIHR Bristol Biomedical Research Centre, University of Bristol and University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 15NIHR Guys & St Thomas’ Hospital Clinical Research Facility, King’s College Hospital, and King’s College London British Heart Foundation Centre of Excellence, London, UKCorrespondence: Jennifer K Quint, School of Public Health, Imperial College London, Floor 9, Sir Michael Uren Building, 86 Wood Ln, London, W12 0BZ, United Kingdom, Email j.quint@imperial.ac.ukBackground: No single biomarker currently risk stratifies chronic obstructive pulmonary disease (COPD) patients at the time of an exacerbation, though previous studies have suggested that patients with elevated troponin at exacerbation have worse outcomes. This study evaluated the relationship between peak cardiac troponin and subsequent major adverse cardiac events (MACE) including all-cause mortality and COPD hospital readmission, among patients admitted with COPD exacerbation.Methods: Data from five cross-regional hospitals in England were analysed using the National Institute of Health Research Health Informatics Collaborative (NIHR-HIC) acute coronary syndrome database (2008– 2017). People hospitalised with a COPD exacerbation were included, and peak troponin levels were standardised relative to the 99th percentile (upper limit of normal). We used Cox Proportional Hazard models adjusting for age, sex, laboratory results and clinical risk factors, and implemented logarithmic transformation (base-10 logarithm). The primary outcome was risk of MACE within 90 days from peak troponin measurement. Secondary outcome was risk of COPD readmission within 90 days from peak troponin measurement.Results: There were 2487 patients included. Of these, 377 (15.2%) patients had a MACE event and 203 (8.2%) were readmitted within 90 days from peak troponin measurement. A total of 1107 (44.5%) patients had an elevated troponin level. Of 1107 patients with elevated troponin at exacerbation, 256 (22.8%) had a MACE event and 101 (9.0%) a COPD readmission within 90 days from peak troponin measurement. Patients with troponin above the upper limit of normal had a higher risk of MACE (adjusted HR 2.20, 95% CI 1.75– 2.77) and COPD hospital readmission (adjusted HR 1.37, 95% CI 1.02– 1.83) when compared with patients without elevated troponin.Conclusion: An elevated troponin level at the time of COPD exacerbation may be a useful tool for predicting MACE in COPD patients. The relationship between degree of troponin elevation and risk of future events is complex and requires further investigation.Keywords: COPD, CVD, exacerbation

Background: Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data., Methods: 2,187 patients admitted to five UK hospitals with a diagnosis of HF and a left ventricular ejection fraction ≥ 40% were identified from the NIHR Health Informatics Collaborative database. Partition-based, model-based, and density-based machine learning clustering techniques were applied. Cox Proportional Hazards and Fine-Gray competing risks models were used to compare outcomes (all-cause mortality and hospitalisation for HF) across phenogroups., Results: Three phenogroups were identified: (1) Younger, predominantly female patients with high prevalence of cardiometabolic and coronary disease; (2) More frail patients, with higher rates of lung disease and atrial fibrillation; (3) Patients characterised by systemic inflammation and high rates of diabetes and renal dysfunction. Survival profiles were distinct, with an increasing risk of all-cause mortality from phenogroups 1 to 3 (p < 0.001). Phenogroup membership significantly improved survival prediction compared to conventional factors. Phenogroups were not predictive of hospitalisation for HF., Conclusions: Applying unsupervised machine learning to routinely collected electronic health record data identified phenogroups with distinct clinical characteristics and unique survival profiles., (© 2024. The Author(s).)

Background: Cardiac troponin is commonly raised in patients presenting with malignancy. The prognostic significance of raised troponin in these patients is unclear., Objectives: We sought to investigate the relation between troponin and mortality in a large, well characterised cohort of patients with a routinely measured troponin and a primary diagnosis of malignancy., Methods: We used the National Institute for Health Research (NIHR) Health Informatics Collaborative data of 5571 patients, who had troponin levels measured at 5 UK cardiac centres between 2010 and 2017 and had a primary diagnosis of malignancy. Patients were classified into solid tumour or haematological malignancy subgroups. Peak troponin levels were standardised as a multiple of each laboratory's 99th -percentile upper limit of normal (xULN)., Results: 4649 patients were diagnosed with solid tumours and 922 patients with haematological malignancies. Raised troponin was an independent predictor of mortality in all patients (Troponin > 10 vs. <1 adjusted HR 2.01, 95% CI 1.73 to 2.34), in solid tumours (HR 1.84, 95% CI 1.55 to 2.19), and in haematological malignancy (HR 2.72, 95% CI 1.99 to 3.72). There was a significant trend in increasing mortality risk across troponin categories in all three subgroups (p < 0.001)., Conclusion: Raised troponin level is associated with increased mortality in patients with a primary diagnosis of malignancy regardless of cancer subtype. Mortality risk is stable for patients with a troponin level below the ULN but increases as troponin level increases above the ULN in the absence of acute coronary syndrome., (© 2024. The Author(s).)

Competing Interests: Declarations of competing interest Dr Papadimitriou: None. Dr Korompoki: None. Dr Ntaios: None.

Objective: The COVID-19 pandemic was associated with a reduction in the incidence of myocardial infarction (MI) diagnosis, in part because patients were less likely to present to hospital. Whether changes in clinical decision making with respect to the investigation and management of patients with suspected MI also contributed to this phenomenon is unknown., Methods: Multicentre retrospective cohort study in three UK centres contributing data to the National Institute for Health Research Health Informatics Collaborative. Patients presenting to the Emergency Department (ED) of these centres between 1st January 2020 and 1st September 2020 were included. Three time epochs within this period were defined based on the course of the first wave of the COVID-19 pandemic: pre-pandemic (epoch 1), lockdown (epoch 2), post-lockdown (epoch 3)., Results: During the study period, 10,670 unique patients attended the ED with chest pain or dyspnoea, of whom 6,928 were admitted. Despite fewer total ED attendances in epoch 2, patient presentations with dyspnoea were increased ( p  < 0.001), with greater likelihood of troponin testing in both chest pain ( p  = 0.001) and dyspnoea ( p  < 0.001). There was a dramatic reduction in elective and emergency cardiac procedures (both p  < 0.001), and greater overall mortality of patients ( p  < 0.001), compared to the pre-pandemic period. Positive COVID-19 and/or troponin test results were associated with increased mortality ( p  < 0.001), though the temporal risk profile differed., Conclusions: The first wave of the COVID-19 pandemic was associated with significant changes not just in presentation, but also the investigation, management, and outcomes of patients presenting with suspected myocardial injury or MI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chammas, Yuan, Little, Roadknight, Varnai, Chang, Sze, Davies, Tsui, Salih, Glampson, Papadimitriou, Mulla, Woods, O'Gallagher, Shah, Williams, Asselbergs, Mayer, Lee, Herbert, Johnson, Grant, Curzen, Shah, Perera, Patel, Channon, Kaura, Mayet, Eyre, Squire, Kharbanda, Lewis and Wijesurendra.)

Introduction: Ejection fraction (EF) is widely used to evaluate heart function during heart failure (HF) due to its simplicity compared but it may misrepresent cardiac function during ventricular hypertrophy, especially in heart failure with preserved EF (HFpEF). To resolve this shortcoming, we evaluate a correction factor to EF, which is equivalent to computing EF at the mid-wall layer (without the need for mid-layer identification) rather than at the endocardial surface, and thus better complements other complex metrics., Method: The retrospective cohort data was studied, consisting of 2,752 individuals (56.5% male, age 69.3 ± 16.4 years) admitted with a request of a troponin test and undergoing echocardiography as part of their clinical assessment across three centres. Cox-proportional regression models were constructed to compare the adjusted EF (EFa) to EF in evaluating risk of heart failure admissions., Result: Comparing HFpEF patients to non-HF cases, there was no significant difference in EF (62.3 ± 7.6% vs. 64.2 ± 6.2%, p  = 0.79), but there was a significant difference in EFa (56.6 ± 6.4% vs. 61.8 ± 9.9%, p  = 0.0007). Both low EF and low EFa were associated with a high HF readmission risk. However, in the cohort with a normal EF (EF ≥ 50%), models using EFa were significantly more associative with HF readmissions within 3 years, where the leave one out cross validation ROC analysis showed a 18.6% reduction in errors, and Net Classification Index (NRI) analysis showed that risk increment classification of events increased by 12.2%, while risk decrement classification of non-events decreased by 16.6%., Conclusion: EFa is associated with HF readmission in patients with a normal EF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Chan, Kaura, Mulla, Papadimitriou, Glampson, Mayer, Shah, Mayet and Yap.)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and the most common motor neuron disease. ALS shows substantial clinical and molecular heterogeneity. In vitro and in vivo models coupled with multiomic techniques have provided important contributions to unraveling the pathomechanisms underlying ALS. To date, despite promising results and accumulating knowledge, an effective treatment is still lacking. Here, we provide an overview of the literature on the use of genomics, epigenomics, transcriptomics and microRNAs to deeply investigate the molecular mechanisms developing and sustaining ALS. We report the most relevant genes implicated in ALS pathogenesis, discussing the use of different high-throughput sequencing techniques and the role of epigenomic modifications. Furthermore, we present transcriptomic studies discussing the most recent advances, from microarrays to bulk and single-cell RNA sequencing. Finally, we discuss the use of microRNAs as potential biomarkers and promising tools for molecular intervention. The integration of data from multiple omic approaches may provide new insights into pathogenic pathways in ALS by shedding light on diagnostic and prognostic biomarkers, helping to stratify patients into clinically relevant subgroups, revealing novel therapeutic targets and supporting the development of new effective therapies., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (alanine transferase [ALT] and HBV viral load)., Methods: We used anonymized electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK National Health Service (NHS) Trusts., Results: We report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID-19 years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient., Conclusions: These results demonstrate the real-time utility of HIC data in monitoring health-care provision, and support interventions to provide catch-up services to minimise the impact of the pandemic. Further investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes., Competing Interests: Competing interests: GC reports personal fees from Gilead and Merck Sharp & Dohme outside the submitted work. BG reports other from Imperial National Institute for Health Research (NIHR) Biomedical Research Centres (BRC), during the conduct of the study. EN reports grants from ViiV healthcare, grants from GlaxoSmithKline (GSK), grants from Gilead, outside the submitted work. Other authors have no conflict of interest., (Copyright: © 2023 Campbell C et al.)

Background: In Greece, nearly a third of savory baked goods (SBGs) exceeded the limit of 2 g of nonruminant or industrial trans fatty acids (i-TFA) per 100 g fat in 2015. The impact of the Commission Regulation (European Union) 2019/649 on exposure to trans fatty acids (TFA), i-TFA, and saturated fatty acid (SFA) from SBGs has not been previously evaluated., Objectives: The study aimed to explore fatty acid reformulation of SBG products and assess differences in TFA, i-TFA, and SFA intakes using a sample of Greek SBG consumers from a nationally representative survey., Methods: In 2021, 140 samples of SBGs were collected in the greater metropolitan area of Athens, and their fat profile and content were compared to those from 2015. Based on these measurements, food consumption substitution models were employed to examine TFA and SFA intake differences, and the percent contribution from SBG among consumers was calculated (N = 1008). Nutrient densities were calculated by adjusting all fat intakes by individual mean energy intake (percentage of daily total energy intake)., Results: The 2% i-TFA legislative limit/100 g of fat in measured SBGs was exceeded by 11.4% in 2021 compared to 31.1% in 2015 (19.7% increase in compliance). Median i-TFA and TFA intakes from SBGs were reduced from 0.05 (0.01, 0.12)% and 0.13 (0.03, 0.27)% in 2015 to 0.03 (0.01, 0.09) and 0.06 (0.03, 0.13)% in 2021, respectively. In terms of SFA, a mean increase/100 g was calculated, resulting in an increased intake in 2021 compared to 2015 [5.18% (2.78, 8.37) and 3.55 (1.99, 5.73), respectively]., Conclusions: Despite the reductions seen in i-TFA content of SBGs, food product reformulation efforts in Greece should focus not only on TFA content but also on SFA reduction to improve public health., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest There is no conflict of interest.

Introduction Triple-negative breast cancer (TNBC) comprises a heterogeneous group of tumors with a single trait in common: an evident aggressive nature with higher rates of relapse and lower overall survival in the metastatic context when compared to other subtypes of breast cancer. To date, not a single targeted therapy has been approved for the treatment of TNBC, and cytotoxic chemotherapy remains the standard treatment. In the present experimental study, we examine the effects of the chemotherapeutic docetaxel and the bcr/abl kinase inhibitor dasatinib on TNBC cell lines (in vitro) and on TNBC tumor xenograft mouse models (in vivo). Materials and methods TNBC cell lines were cultivated and treated with various concentrations of docetaxel and dasatinib (5 nM to 100 nM). Cell death and apoptosis were studied by flow cytometry. TNBC cell lines were then injected in BALB/c athymic nude mice to express the tumor in vivo. Four groups of mice were created (group A: control; group B: DOC; group C: DAS; group D: DOC + DAS) and treated, respectively, with the drugs and their combination. Tumors were obtained, maintained in a 10% formaldehyde solution, embedded in paraffin, and sent for further histological evaluation (hematoxylin-eosin staining and immune-histochemical analysis) to assess the tumor growth inhibition. Results The cytotoxic effects of docetaxel seem statistically important, with little effect on apoptosis. The effect of dasatinib in vitro and vivo is statistically important, in terms of apoptosis and tumor reduction, with little adverse effects. Conclusions TNBC is a difficult-to-treat oncologic condition, even in an experimental setting. Promising results concerning the addition of targeted therapies (dasatinib) to the conventional cytotoxic ones (docetaxel) have been shown, awaiting further evaluation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Passos et al.)

Background: Microglial activation is considered to assume a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). To date, the relationship between ALS and the rs3865444 polymorphism of the cluster of differentiation 33 (CD33) has not been explored. The current report aimed to investigate the potential connection between CD33 rs3865444 and ALS., Methods: Patients diagnosed with sporadic ALS according to the revised El Escorial criteria, as well as age and sex matched community controls, were enrolled. Two evenly numbered, age and sex matched groups of 155 participants each were genotyped., Results: No association was found between rs3865444 and ALS [log-additive odds ratio (OR) = 0.83 (0.57, 1.22), over-dominant OR = 0.86 (0.55, 1.36), recessive OR = 0.73 (0.25, 2.17), dominant OR = 0.82 (0.52, 1.29), co-dominant OR1 = 0.68 (0.23, 2.05) and co-dominant OR2 = 0.84 (0.53, 1.33)]. Moreover, no relationship was established between rs3865444 and the age of ALS onset based on both unadjusted and sex adjusted Cox-proportional hazards models. Finally, no association between rs3865444 and ALS was found in subgroup analyses based on the site of ALS onset (bulbar or spinal) and sex., Conclusions: The current analysis is the first to report that rs3865444 is not linked to ALS. Larger multi-racial studies are required to confirm these findings., Competing Interests: The authors declare no conflict of interest. Vasileios Siokas, Christos Bakirtzis, Efthimios Dardiotis, and Ioannis Liampas are serving as one of the Guest editors of this journal. We declare that Vasileios Siokas, Christos Bakirtzis, Efthimios Dardiotis, and Ioannis Liampas had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Gernot Riedel., (© 2023 The Author(s). Published by IMR Press.)

Background: The role of blood uric acid as a biomarker in symptomatic motor PD has been increasingly established in the literature., Objective: Our present study assessed the role of serum uric acid as a putative biomarker in a prodromal PD cohort [REM Sleep Behavior disorder (RBD) and Hyposmia] followed longitudinally., Methods: Longitudinal 5-year serum uric acid measurement data of 39 RBD patients and 26 Hyposmia patients with an abnormal DATSCAN imaging were downloaded from the Parkinson's Progression Markers Initiative database. These cohorts were compared with 423 de novo PD patients and 196 healthy controls enrolled in the same study., Results: After adjusting for age, sex, body mass index, and concomitant disorders (hypertension/gout), baseline and longitudinal serum uric acid levels were higher in the RBD subgroup as compared to the established PD cohort (p = 0.004 and p = 0.001). (Baseline RBD 6.07±1.6 vs. Baseline PD 5.35±1.3 mg/dL and Year-5 RBD 5.7±1.3 vs. Year-5 PD 5.26±1.33). This was also true for longitudinal measurements in the Hyposmic subgroup (p = 0.008) (Baseline Hyposmic 5.7±1.6 vs. PD 5.35±1.3 mg/dL and Year-5 Hyposmic 5.58±1.6 vs. PD 5.26±1.33)., Conclusion: Our results indicate that serum uric acid levels are higher in prodromal PD subjects with ongoing dopaminergic degeneration compared to those with manifest PD. These data indicate that the well-established decrease in the levels of serum uric acid occurs with the transition from prodromal to clinical PD. Whether the higher levels of serum uric acid observed in prodromal PD may provide protection against conversion to full-blown clinical PD will require further study.

Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction(NIHR Health Informatics Collaborative:TROP-CABG study). Benedetto et al. BACKGROUND: The optimal timing of coronary artery bypass grafting (CABG) in patients with non-ST elevation myocardial infarction (NSTEMI) and the utility of pre-operative troponin levels in decision-making remains unclear. We investigated (a) the association between peak pre-operative troponin and survival post-CABG in a large cohort of NSTEMI patients and (b) the interaction between troponin and time-to-surgery. METHODS AND RESULTS: Our cohort consisted of 1746 patients (1684 NSTEMI; 62 unstable angina) (mean age 69 ± 11 years,21% female) with recorded troponins that had CABG at five United Kingdom centers between 2010 and 2017. Time-segmented Cox regression was used to investigate the interaction of peak troponin and time-to-surgery on early (within 30 days) and late (beyond 30 days) survival. Average interval from peak troponin to surgery was 9 ± 15 days, with 1466 (84.0%) patients having CABG during the same admission. Sixty patients died within 30-days and another 211 died after a mean follow-up of 4 ± 2 years (30-day survival 0.97 ± 0.004 and 5-year survival 0.83 ± 0.01). Peak troponin was a strong predictor of early survival (adjusted P = 0.002) with a significant interaction with time-to-surgery (P interaction = 0.007). For peak troponin levels <100 times the upper limit of normal, there was no improvement in early survival with longer time-to-surgery. However, in patients with higher troponins, early survival increased progressively with a longer time-to-surgery, till day 10. Peak troponin did not influence survival beyond 30 days (adjusted P = 0.64). CONCLUSIONS: Peak troponin in NSTEMI patients undergoing CABG was a significant predictor of early mortality, strongly influenced the time-to-surgery and may prove to be a clinically useful biomarker in the management of these patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Despite several advances in the field, pharmacodynamic outcome measures reflective of LRRK2 kinase activity in clinical biofluids remain urgently needed. A variety of targets and approaches have been utilized including assessments of LRRK2 itself (levels, phosphorylation), or its substrates (e.g. Rab10 or other Rab GTPases). We have previously shown that intrinsic kinase activity of LRRK2 isolated from PBMCs of G2019S carriers is elevated, irrespective of disease status. In the present study we find that phosphorylation of Rab10 is also elevated in G2019S carriers, but only those with PD. Additionally, phosphorylation of this substrate is also elevated in two separate idiopathic PD cohorts, but not in carriers of the A53T mutation in α-synuclein. In contrast, Rab29 phosphorylation was specifically reduced in urinary exosomes from A53T and idiopathic PD patients. Taken together, our findings highlight the need for the assessment of multiple complimentary targets for a more comprehensive picture of the disease., (© 2022. The Author(s).)

Objective: Colorectal cancer is a common cause of death and morbidity. A significant amount of data are routinely collected during patient treatment, but they are not generally available for research. The National Institute for Health Research Health Informatics Collaborative in the UK is developing infrastructure to enable routinely collected data to be used for collaborative, cross-centre research. This paper presents an overview of the process for collating colorectal cancer data and explores the potential of using this data source., Methods: Clinical data were collected from three pilot Trusts, standardised and collated. Not all data were collected in a readily extractable format for research. Natural language processing (NLP) was used to extract relevant information from pseudonymised imaging and histopathology reports. Combining data from many sources allowed reconstruction of longitudinal histories for each patient that could be presented graphically., Results: Three pilot Trusts submitted data, covering 12 903 patients with a diagnosis of colorectal cancer since 2012, with NLP implemented for 4150 patients. Timelines showing individual patient longitudinal history can be grouped into common treatment patterns, visually presenting clusters and outliers for analysis. Difficulties and gaps in data sources have been identified and addressed., Discussion: Algorithms for analysing routinely collected data from a wide range of sites and sources have been developed and refined to provide a rich data set that will be used to better understand the natural history, treatment variation and optimal management of colorectal cancer., Conclusion: The data set has great potential to facilitate research into colorectal cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lipid profiles in biological fluids from patients with Parkinson's disease (PD) are increasingly investigated in search of biomarkers. However, the lipid profiles in genetic PD remain to be determined, a gap of knowledge of particular interest in PD associated with mutant α-synuclein (SNCA), given the known relationship between this protein and lipids. The objective of this research is to identify serum lipid composition from SNCA A53T mutation carriers and to compare these alterations to those found in cells and transgenic mice carrying the same genetic mutation. We conducted an unbiased lipidomic analysis of 530 lipid species from 34 lipid classes in serum of 30 participants with SNCA mutation with and without PD and 30 healthy controls. The primary analysis was done between 22 PD patients with SNCA+ (SNCA+/PD+) and 30 controls using machine-learning algorithms and traditional statistics. We also analyzed the lipid composition of human clonal-cell lines and tissue from transgenic mice overexpressing the same SNCA mutation. We identified specific lipid classes that best discriminate between SNCA+/PD+ patients and healthy controls and found certain lipid species, mainly from the glycerophosphatidylcholine and triradylglycerol classes, that are most contributory to this discrimination. Most of these alterations were also present in human derived cells and transgenic mice carrying the same mutation. Our combination of lipidomic and machine learning analyses revealed alterations in glycerophosphatidylcholine and triradylglycerol in sera from PD patients as well as cells and tissues expressing mutant α-Syn. Further investigations are needed to establish the pathogenic significance of these α-Syn-associated lipid changes., (© 2022. The Author(s).)

Background: Cortical demyelination and meningeal inflammation have been detected neuropathologically in multiple sclerosis (MS) and recently in myelin oligodendrocyte glycoprotein antibody disease (MOGAD)., Objectives: To assess in vivo cortical and leptomeningeal involvement in MOGAD., Methods: We prospectively evaluated 11 MOGAD and 12 relapsing-remitting MS (RRMS) patients combining three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) and 3D-T1-weighted (3D-T1w) sequences at 3-Tesla magnetic resonance imaging (MRI). Leptomeningeal contrast enhancement (LMCE) was assessed on 3D-FLAIR post-gadolinium (3D-FLAIRGd). Cerebral cortical lesions (CCLs) were classified as either intracortical-subpial (IC-SP) or leukocortical (LC)., Results: CCLs were present in 8/11 MOGAD and 12/12 RRMS patients, with the number of CCLs being significantly lower in MOGAD (median (interquartile range (IQR)) 3 (0.5-4) vs 12 (4.75-19), p  = 0.0032). In MOGAD, IC-SP lesions were slightly more prevalent than LC lesions (2 (0-2.5) vs 1 (0-2), p  = 0.6579); whereas in RRMS, IC-SP lesions were less prevalent than LC lesions (3.5 (2.75-5.5) vs 9 (2-12.75), p  = 0.27). LMCE was observed in 3/11 MOGAD and 1/12 RRMS patients; MOGAD with LMCE showed an increased median number of CCLs compared with MOGAD without LMCE (8 (4-9) vs 2.5 (0.75-3.25), p  = 0.34). No correlation was observed between MOGAD MRI findings and (a) MOGAD duration, (b) serum MOG-immunoglobulin G1 titers, and (c) oligoclonal band presence., Conclusion: We described cortical lesion topography and detected for the first time LMCE using 3D-FLAIRGd sequences in MOGAD patients.

Objective: It is increasingly recognized that patient safety requires heterogeneous insights from a range of stakeholders, yet incident reporting systems in health care still primarily rely on staff perspectives. This paper examines the potential of combining insights from patient complaints and staff incident reports for a more comprehensive understanding of the causes and severity of harm., Methods: Using five years of patient complaints and staff incident reporting data at a large multi-site hospital in London (in the United Kingdom), this study conducted retrospective patient-level data linkage to identify overlapping reports. Using a combination of quantitative coding and in-depth qualitative analysis, we then compared level of harm reported, identified descriptions of adjacent events missed by the other party and examined combined narratives of mutually identified events., Results: Incidents where complaints and incident reports overlapped (n = 446, reported in 7.6%' of all complaints and 0.6% of all incident reports) represented a small but critical area of investigation, with significantly higher rates of Serious Incidents and severe harm. Linked complaints described greater harm from safety incidents in 60% of cases, reported many surrounding safety events missed by staff (n = 582), and provided contesting stories of why problems occurred in 46% cases, and complementary accounts in 26% cases., Conclusions: This study demonstrates the value of using patient complaints to supplement, test, and challenge staff reports, including to provide greater insight on the many potential factors that may give rise to unsafe care. Accordingly, we propose that a more holistic analysis of critical safety incidents can be achieved through combining heterogeneous data from different viewpoints, such as through the integration of patient complaints and staff incident reporting data.

Background and Objectives : To date, only one study has investigated the association between the rs616147 polymorphism of the Myelin-associated Oligodendrocyte Basic Protein (MOBP) locus and Amyotrophic Lateral Sclerosis (ALS). Materials and Methods : A case-control study was performed. Patients with definite sporadic ALS were prospectively and consecutively recruited from the inpatient and outpatient clinics of the Neurology Department of the General University Hospital of Larissa, Central Greece. Community based, age and sex matched healthy individuals with a free personal and family history constituted the control group. Results : A total of 155 patients with definite sporadic ALS and an equal number of healthy controls were genotyped. The power of our sample size was slightly above 80% and MOBP rs616147 was determined to be in Hardy-Weinberg Equilibrium among healthy participants ( p = 1.00). According to the univariate analysis, there was no significant relationship between rs616147 and ALS [log-additive OR = 0.85 (0.61, 1.19), over-dominant OR = 0.73 (0.46, 1.15), recessive OR = 1.02 (0.50, 2.09), dominant OR = 0.74 (0.47, 1.16), co-dominant OR 1 = 0.71 (0.44, 1.14) and co-dominant OR 2 = 0.88 (0.42, 1.84). Additionally, the effect of rs616147 on the age of ALS onset was determined insignificant using both unadjusted and adjusted (sex, site of onset) cox-proportional models. Finally, rs616147 was not related to the site of ALS onset. Conclusions : Our study is the first to report the absence of an association between MOBP rs616147 and ALS among individuals of Greek ancestry. Additional, larger nationwide and multi-ethnic studies are warranted to shed light on the connection between rs616147 and ALS.