Oxford University Hospitals NHS Trust

BACKGROUND: The Surgical CAse REport (SCARE) guidelines were first published in 2016 as a tool for surgeons to document and report their surgical cases in a standardised and comprehensive manner. However, with advances in technology and changes in the healthcare landscape, it is important to revise and update these guidelines to ensure they remain relevant and valuable for surgeons. MATERIALS AND METHODS: The updated guidelines were produced through a Delphi consensus exercise. Members of the SCARE 2020 guidelines Delphi group, editorial board members, and peer reviewers were invited to participate. Potential contributors were contacted by e-mail. An online survey was completed to indicate their agreement with the proposed changes to the guideline items. RESULTS: A total of 54 participants were invited to participate and 44 (81.5%) completed the survey. There was a high degree of agreement among reviewers, with 36 items (83.7%) meeting the threshold for inclusion. CONCLUSION: Through a completed Delphi consensus exercise we present the SCARE 2023 guidelines. This will provide surgeons with a comprehensive and up-to-date tool for documenting and reporting their surgical cases while highlighting the importance of patient-centred care.

Instantaneous contact tracing New analyses indicate that severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is more infectious and less virulent than the earlier SARS-CoV-1, which emerged in China in 2002. Unfortunately, the current virus has greater epidemic potential because it is difficult to trace mild or presymptomatic infections. As no treatment is currently available, the only tools that we can currently deploy to stop the epidemic are contact tracing, social distancing, and quarantine, all of which are slow to implement. However imperfect the data, the current global emergency requires more timely interventions. Ferretti et al. explored the feasibility of protecting the population (that is, achieving transmission below the basic reproduction number) using isolation coupled with classical contact tracing by questionnaires versus algorithmic instantaneous contact tracing assisted by a mobile phone application. For prevention, the crucial information is understanding the relative contributions of different routes of transmission. A phone app could show how finite resources must be divided between different intervention strategies for the most effective control. Science , this issue p. eabb6936

BACKGROUND: Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis. METHODS: For this retrospective cohort study and time-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism. FINDINGS: Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17-34·07), with 12·84% (12·36-13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78-48·09) and for a first diagnosis was 25·79% (23·50-28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50-0·63) for intracranial haemorrhage, 2·10% (1·97-2·23) for ischaemic stroke, 0·11% (0·08-0·14) for parkinsonism, 0·67% (0·59-0·75) for dementia, 17·39% (17·04-17·74) for anxiety disorder, and 1·40% (1·30-1·51) for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24-3·16) for intracranial haemorrhage, 6·92% (6·17-7·76) for ischaemic stroke, 0·26% (0·15-0·45) for parkinsonism, 1·74% (1·31-2·30) for dementia, 19·15% (17·90-20·48) for anxiety disorder, and 2·77% (2·31-3·33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40-1·47, for any diagnosis; 1·78, 1·68-1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14-1·17, for any diagnosis; 1·32, 1·27-1·36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58, 1·50-1·67, for any diagnosis; 2·87, 2·45-3·35, for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events. INTERPRETATION: Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings. FUNDING: National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.

These guidelines are intended for use by infectious disease specialists, orthopedists, and other healthcare professionals who care for patients with prosthetic joint infection (PJI). They include evidence-based and opinion-based recommendations for the diagnosis and management of patients with PJI treated with debridement and retention of the prosthesis, resection arthroplasty with or without subsequent staged reimplantation, 1-stage reimplantation, and amputation.

Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.

INTRODUCTION: The STROCSS guideline was developed in 2017 to improve the reporting quality of observational studies in surgery. Building on its impact and usefulness, we sought to update the guidelines two years after its publication. METHODS: A steering group was formed to review the existing guideline and propose amendments to the 17-item checklist. A Delphi consensus exercise was utilised to determine agreement across a list of proposed modifications to the STROCSS 2017 guideline. An expert panel of 46 surgeons were invited to assess the proposed updates via Google Forms. RESULTS: The response rate was 91% (n = 42/46). High agreement was reached across all the items and the guideline was finalised in the first round. The checklist maintained 17-items, with modifications primarily considered to improve content and readability. CONCLUSIONS: The STROCSS 2019 guideline is hereby presented as a considered update to improve reporting of cohort, cross-sectional and case-control studies in surgery.

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia.

Breast cancer is now the most commonly diagnosed cancer in the world. The most recent global cancer burden figures estimate that there were 2.26 million incident breast cancer cases in 2020 and the disease is the leading cause of cancer mortality in women worldwide. The incidence is strongly correlated with human development, with a large rise in cases anticipated in regions of the world that are currently undergoing economic transformation. Survival, however, is far less favourable in less developed regions. There are a multitude of factors behind disparities in the global survival rates, including delays in diagnosis and lack of access to effective treatment. The World Health Organization's new Global Breast Cancer Initiative was launched this year to address this urgent global health challenge. It aims to improve survival across the world through three pillars: health promotion, timely diagnosis, and comprehensive treatment and supportive care. In this article, we discuss the key challenges of breast cancer care and control in a global context.

BACKGROUND: Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce. We aimed to assess temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014. METHODS: For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months. For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates. We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages (>0 years). FINDINGS: From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91-0·94). However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age. The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616). Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years [SD 12·0] to 77·0 years [12·9], adjusted difference 0·79 years, 95% CI 0·37-1·20; mean number of comorbidities 3·4 [SD 1·9] vs 5·4 [2·5]; adjusted difference 2·0, 95% CI 1·9-2·1). Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58-1·64), and did so earlier in life than those from the most affluent group (adjusted difference -3·51 years, 95% CI -3·77 to -3·25). From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened. Socioeconomically deprived individuals also had more comorbidities, despite their younger age. INTERPRETATION: Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined. The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled. FUNDING: British Heart Foundation and National Institute for Health Research.

The race to produce vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began when the first sequence was published, and this forms the basis for vaccines currently deployed globally. Independent lineages of SARS-CoV-2 have recently been reported: UK, B.1.1.7; South Africa, B.1.351; and Brazil, P.1. These variants have multiple changes in the immunodominant spike protein that facilitates viral cell entry via the angiotensin-converting enzyme-2 (ACE2) receptor. Mutations in the receptor recognition site on the spike are of great concern for their potential for immune escape. Here, we describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor-binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K, although K417N and N501Y act together against some important antibody classes. In a number of cases, it would appear that convalescent and some vaccine serum offers limited protection against this variant.

BACKGROUND: Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS: In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. RESULTS: By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003). CONCLUSIONS: In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

BACKGROUND: Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat. A novel imaging biomarker-the perivascular fat attenuation index (FAI)-captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA). However, the ability of the perivascular FAI to predict clinical outcomes is unknown. METHODS: In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort). Perivascular fat attenuation mapping was done around the three major coronary arteries-the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery. We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features. FINDINGS: Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17-89]). Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19-87]). Median follow-up was 72 months (range 51-109) in the derivation cohort and 54 months (range 4-105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33-3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50-2·83; p<0·0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as -70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35-24·40; p<0·0001 for cardiac mortality; 2·55, 1·65-3·92; p<0·0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90-10·88; p<0·0001 for cardiac mortality; 3·69, 2·26-6·02; p<0·0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality. INTERPRETATION: The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation. High perivascular FAI values (cutoff ≥-70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients. FUNDING: British Heart Foundation, and the National Institute of Health Research Oxford Biomedical Research Centre.

BACKGROUND: Patients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease. METHODS: We randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [no upper limit] indicating more complex coronary anatomy). The primary end point was the rate of a composite of death from any cause, stroke, or myocardial infarction at 3 years, and the trial was powered for noninferiority testing of the primary end point (noninferiority margin, 4.2 percentage points). Major secondary end points included the rate of a composite of death from any cause, stroke, or myocardial infarction at 30 days and the rate of a composite of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. RESULTS: At 3 years, a primary end-point event had occurred in 15.4% of the patients in the PCI group and in 14.7% of the patients in the CABG group (difference, 0.7 percentage points; upper 97.5% confidence limit, 4.0 percentage points; P=0.02 for noninferiority; hazard ratio, 1.00; 95% confidence interval, 0.79 to 1.26; P=0.98 for superiority). The secondary end-point event of death, stroke, or myocardial infarction at 30 days occurred in 4.9% of the patients in the PCI group and in 7.9% in the CABG group (P<0.001 for noninferiority, P=0.008 for superiority). The secondary end-point event of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years occurred in 23.1% of the patients in the PCI group and in 19.1% in the CABG group (P=0.01 for noninferiority, P=0.10 for superiority). CONCLUSIONS: In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776 .).

OBJECTIVE: To systematically examine the design, reporting standards, risk of bias, and claims of studies comparing the performance of diagnostic deep learning algorithms for medical imaging with that of expert clinicians. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, and the World Health Organization trial registry from 2010 to June 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trial registrations and non-randomised studies comparing the performance of a deep learning algorithm in medical imaging with a contemporary group of one or more expert clinicians. Medical imaging has seen a growing interest in deep learning research. The main distinguishing feature of convolutional neural networks (CNNs) in deep learning is that when CNNs are fed with raw data, they develop their own representations needed for pattern recognition. The algorithm learns for itself the features of an image that are important for classification rather than being told by humans which features to use. The selected studies aimed to use medical imaging for predicting absolute risk of existing disease or classification into diagnostic groups (eg, disease or non-disease). For example, raw chest radiographs tagged with a label such as pneumothorax or no pneumothorax and the CNN learning which pixel patterns suggest pneumothorax. REVIEW METHODS: Adherence to reporting standards was assessed by using CONSORT (consolidated standards of reporting trials) for randomised studies and TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) for non-randomised studies. Risk of bias was assessed by using the Cochrane risk of bias tool for randomised studies and PROBAST (prediction model risk of bias assessment tool) for non-randomised studies. RESULTS: Only 10 records were found for deep learning randomised clinical trials, two of which have been published (with low risk of bias, except for lack of blinding, and high adherence to reporting standards) and eight are ongoing. Of 81 non-randomised clinical trials identified, only nine were prospective and just six were tested in a real world clinical setting. The median number of experts in the comparator group was only four (interquartile range 2-9). Full access to all datasets and code was severely limited (unavailable in 95% and 93% of studies, respectively). The overall risk of bias was high in 58 of 81 studies and adherence to reporting standards was suboptimal (<50% adherence for 12 of 29 TRIPOD items). 61 of 81 studies stated in their abstract that performance of artificial intelligence was at least comparable to (or better than) that of clinicians. Only 31 of 81 studies (38%) stated that further prospective studies or trials were required. CONCLUSIONS: Few prospective deep learning studies and randomised trials exist in medical imaging. Most non-randomised trials are not prospective, are at high risk of bias, and deviate from existing reporting standards. Data and code availability are lacking in most studies, and human comparator groups are often small. Future studies should diminish risk of bias, enhance real world clinical relevance, improve reporting and transparency, and appropriately temper conclusions. STUDY REGISTRATION: PROSPERO CRD42019123605.

Measurable residual disease (MRD; previously termed minimal residual disease) is an independent, postdiagnosis, prognostic indicator in acute myeloid leukemia (AML) that is important for risk stratification and treatment planning, in conjunction with other well-established clinical, cytogenetic, and molecular data assessed at diagnosis. MRD can be evaluated using a variety of multiparameter flow cytometry and molecular protocols, but, to date, these approaches have not been qualitatively or quantitatively standardized, making their use in clinical practice challenging. The objective of this work was to identify key clinical and scientific issues in the measurement and application of MRD in AML, to achieve consensus on these issues, and to provide guidelines for the current and future use of MRD in clinical practice. The work was accomplished over 2 years, during 4 meetings by a specially designated MRD Working Party of the European LeukemiaNet. The group included 24 faculty with expertise in AML hematopathology, molecular diagnostics, clinical trials, and clinical medicine, from 19 institutions in Europe and the United States.

Early detection of vascular inflammation would allow deployment of targeted strategies for the prevention or treatment of multiple disease states. Because vascular inflammation is not detectable with commonly used imaging modalities, we hypothesized that phenotypic changes in perivascular adipose tissue (PVAT) induced by vascular inflammation could be quantified using a new computerized tomography (CT) angiography methodology. We show that inflamed human vessels release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex vivo, and in vivo. We developed a three-dimensional PVAT analysis method and studied CT images of human adipose tissue explants from 453 patients undergoing cardiac surgery, relating the ex vivo images with in vivo CT scan information on the biology of the explants. We developed an imaging metric, the CT fat attenuation index (FAI), that describes adipocyte lipid content and size. The FAI has excellent sensitivity and specificity for detecting tissue inflammation as assessed by tissue uptake of 18F-fluorodeoxyglucose in positron emission tomography. In a validation cohort of 273 subjects, the FAI gradient around human coronary arteries identified early subclinical coronary artery disease in vivo, as well as detected dynamic changes of PVAT in response to variations of vascular inflammation, and inflamed, vulnerable atherosclerotic plaques during acute coronary syndromes. Our study revealed that human vessels exert paracrine effects on the surrounding PVAT, affecting local intracellular lipid accumulation in preadipocytes, which can be monitored using a CT imaging approach. This methodology can be implemented in clinical practice to noninvasively detect plaque instability in the human coronary vasculature.

November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses.

BACKGROUND: Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues. METHODS AND FINDINGS: We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score-matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan-Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms. CONCLUSIONS: Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.

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BACKGROUND: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. METHODS: -mutation cohort), and the intention-to-treat population. RESULTS: -mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall. CONCLUSIONS: Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by AbbVie; VELIA/GOG-3005 ClinicalTrials.gov number, NCT02470585.).