Abstract
Background
Smoking is a risk factor for most respiratory infections, but it may protect against SARS-CoV-2 infection. The objective was to assess whether smoking and e-cigarette use were ...associated with severe COVID-19.
Methods
This cohort ran from 24 January 2020 until 30 April 2020 at the height of the first wave of the SARS-CoV-2 epidemic in England. It comprised 7 869 534 people representative of the population of England with smoking status, demographic factors and diseases recorded by general practitioners in the medical records, which were linked to hospital and death data. The outcomes were COVID-19-associated hospitalization, intensive care unit (ICU) admission and death. The associations between smoking and the outcomes were assessed with Cox proportional hazards models, with sequential adjustment for confounding variables and indirect causal factors (body mass index and smoking-related disease).
Results
Compared with never smokers, people currently smoking were at lower risk of COVID-19 hospitalization, adjusted hazard ratios (HRs) were 0.64 (95% confidence intervals 0.60 to 0.69) for <10 cigarettes/day, 0.49 (0.41 to 0.59) for 10–19 cigarettes/day, and 0.61 (0.49 to 0.74) for ≥20 cigarettes/day. For ICU admission, the corresponding HRs were 0.31 (0.24 to 0.40), 0.15 (0.06 to 0.36), and 0.35 (0.17 to 0.74) and death were: 0.79 (0.70 to 0.89), 0.66 (0.48 to 0.90), and 0.77 (0.54 to 1.09) respectively. Former smokers were at higher risk of severe COVID-19: HRs: 1.07 (1.03 to 1.11) for hospitalization, 1.17 (1.04 to 1.31) for ICU admission, and 1.17 (1.10 to 1.24) for death. All-cause mortality was higher for current smoking than never smoking, HR 1.42 (1.36 to 1.48). Among e-cigarette users, the adjusted HR for e-cigarette use and hospitalization with COVID-19 was 1.06 (0.88 to 1.28), for ICU admission was 1.04 (0.57 to 1.89, and for death was 1.12 (0.81 to 1.55).
Conclusions
Current smoking was associated with a reduced risk of severe COVID-19 but the association with e-cigarette use was unclear. All-cause mortality remained higher despite this possible reduction in death from COVID-19 during an epidemic of SARS-CoV-2. Findings support investigating possible protective mechanisms of smoking for SARS-CoV-2 infection, including the ongoing trials of nicotine to treat COVID-19.
Conflicting evidence has emerged regarding the relevance of smoking on risk of COVID-19 and its severity.
We undertook large-scale observational and Mendelian randomisation (MR) analyses using UK ...Biobank. Most recent smoking status was determined from primary care records (70.8%) and UK Biobank questionnaire data (29.2%). COVID-19 outcomes were derived from Public Health England SARS-CoV-2 testing data, hospital admissions data, and death certificates (until 18 August 2020). Logistic regression was used to estimate associations between smoking status and confirmed SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death. Inverse variance-weighted MR analyses using established genetic instruments for smoking initiation and smoking heaviness were undertaken (reported per SD increase).
There were 421 469 eligible participants, 1649 confirmed infections, 968 COVID-19-related hospitalisations and 444 COVID-19-related deaths. Compared with never-smokers, current smokers had higher risks of hospitalisation (OR 1.80, 95% CI 1.26 to 2.29) and mortality (smoking 1-9/day: OR 2.14, 95% CI 0.87 to 5.24; 10-19/day: OR 5.91, 95% CI 3.66 to 9.54; 20+/day: OR 6.11, 95% CI 3.59 to 10.42). In MR analyses of 281 105 White British participants, genetically predicted propensity to initiate smoking was associated with higher risks of infection (OR 1.45, 95% CI 1.10 to 1.91) and hospitalisation (OR 1.60, 95% CI 1.13 to 2.27). Genetically predicted higher number of cigarettes smoked per day was associated with higher risks of all outcomes (infection OR 2.51, 95% CI 1.20 to 5.24; hospitalisation OR 5.08, 95% CI 2.04 to 12.66; and death OR 10.02, 95% CI 2.53 to 39.72).
Congruent results from two analytical approaches support a causal effect of smoking on risk of severe COVID-19.
Previous studies suggested that the prevalence of chronic respiratory disease in patients hospitalised with COVID-19 was lower than its prevalence in the general population. The aim of this study was ...to assess whether chronic lung disease or use of inhaled corticosteroids (ICS) affects the risk of contracting severe COVID-19.
In this population cohort study, records from 1205 general practices in England that contribute to the QResearch database were linked to Public Health England's database of SARS-CoV-2 testing and English hospital admissions, intensive care unit (ICU) admissions, and deaths for COVID-19. All patients aged 20 years and older who were registered with one of the 1205 general practices on Jan 24, 2020, were included in this study. With Cox regression, we examined the risks of COVID-19-related hospitalisation, admission to ICU, and death in relation to respiratory disease and use of ICS, adjusting for demographic and socioeconomic status and comorbidities associated with severe COVID-19.
Between Jan 24 and April 30, 2020, 8 256 161 people were included in the cohort and observed, of whom 14 479 (0·2%) were admitted to hospital with COVID-19, 1542 (<0·1%) were admitted to ICU, and 5956 (0·1%) died. People with some respiratory diseases were at an increased risk of hospitalisation (chronic obstructive pulmonary disease COPD hazard ratio HR 1·54 95% CI 1·45–1·63, asthma 1·18 1·13–1·24, severe asthma 1·29 1·22–1·37; people on three or more current asthma medications, bronchiectasis 1·34 1·20–1·50, sarcoidosis 1·36 1·10–1·68, extrinsic allergic alveolitis 1·35 0·82–2·21, idiopathic pulmonary fibrosis 1·59 1·30–1·95, other interstitial lung disease 1·66 1·30–2·12, and lung cancer 2·24 1·89–2·65) and death (COPD 1·54 1·42–1·67, asthma 0·99 0·91–1·07, severe asthma 1·08 0·98–1·19, bronchiectasis 1·12 0·94–1·33, sarcoidosis 1·41 0·99–1·99), extrinsic allergic alveolitis 1·56 0·78–3·13, idiopathic pulmonary fibrosis 1·47 1·12–1·92, other interstitial lung disease 2·05 1·49–2·81, and lung cancer 1·77 1·37–2·29) due to COVID-19 compared with those without these diseases. Admission to ICU was rare, but the HR for people with asthma was 1·08 (0·93–1·25) and severe asthma was 1·30 (1·08–1·58). In a post-hoc analysis, relative risks of severe COVID-19 in people with respiratory disease were similar before and after shielding was introduced on March 23, 2020. In another post-hoc analysis, people with two or more prescriptions for ICS in the 150 days before study start were at a slightly higher risk of severe COVID-19 compared with all other individuals (ie, no or one ICS prescription): HR 1·13 (1·03–1·23) for hospitalisation, 1·63 (1·18–2·24) for ICU admission, and 1·15 (1·01–1·31) for death.
The risk of severe COVID-19 in people with asthma is relatively small. People with COPD and interstitial lung disease appear to have a modestly increased risk of severe disease, but their risk of death from COVID-19 at the height of the epidemic was mostly far lower than the ordinary risk of death from any cause. Use of inhaled steroids might be associated with a modestly increased risk of severe COVID-19.
National Institute for Health Research Oxford Biomedical Research Centre and the Wellcome Trust.
Neuroendocrine neoplasms (NEN) are a class of tumours heterogeneous in terms of their anatomical sites of origin and clinical behaviour. Outdated perspectives of indolence have been superseded by ...appreciation for their myriad clinical challenges, such as the high rates of regional and distant metastases at initial diagnosis, lack of clarity on optimal treatment strategies/sequencing, and incompletely elucidated genetic/other pathophysiological drivers. The first randomised controlled trials in this arena were published approximately a decade ago – since then, increased understanding of the genetic drivers and signalling pathway perturbations in these tumours have suggested promise for precision therapy influenced by an individual tumour’s molecular sub-type, but this is yet to be realised for manifold reasons. In this article, the authors review the genetic landscapes as currently understood for selected forms of NEN and discuss the current and developing evidence to support the use of genetic information to influence therapy. They provide a critical assessment of the potential limitations of using such approaches and also posit avenues for future developments in this arena.
OBJECTIVE:To discover serum-based microRNA (miRNA) biomarkers for small-bowel neuroendocrine tumors (SBNET) to help guide clinical decisions.
BACKGROUND:MiRNAs are small noncoding RNA molecules ...implicated in the initiation and progression of many cancers. MiRNAs are remarkably stable in bodily fluids, and can potentially be translated into clinically useful biomarkers. Novel biomarkers are needed in SBNET to determine disease aggressiveness, select patients for treatment, detect early recurrence, and monitor response.
METHODS:This study was performed in 3 stages (discovery, validation, and a prospective, longitudinal assessment). Discovery comprised of global profiling of 376 miRNA in sera from SBNET patients (n = 11) versus healthy controls (HCs; n = 3). Up-regulated miRNAs were subsequently validated in additional SBNET (n = 33) and HC sera (n = 14); and then longitudinally after SBNET resection (n = 12), with serial serum sampling (preoperatively day 0; postoperatively at 1 week, 1 month, and 12 months).
RESULTS:Four serum miRNAs (miR-125b-5p, -362–5p, -425–5p and -500a-5p) were significantly up-regulated in SBNET (P < 0.05; fold-change >2) based on multiple normalization strategies, and were validated by RT-qPCR. This combination was able to differentiate SBNET from HC with an area under the curve of 0.951. Longitudinal assessment revealed that miR-125b-5p returned towards HC levels at 1 month postoperatively in patients without disease, whereas remaining up-regulated in those with residual disease (RSD). This was also true at 12 months postoperatively. In addition, miR-362–5p appeared up-regulated at 12 months in RSD and recurrent disease (RCD).
CONCLUSIONS:Our study represents the largest global profiling of serum miRNAs in SBNET patients, and the first to evaluate ongoing serum miRNA expression changes after surgical resection. Serum miR-125b-5p and miR-362–5p have potential to be used to detect RSD/RCD.
Introduction: Appendiceal neuroendocrine neoplasms are rare, clinically challenging tumours that are typically incidentally diagnosed, have a poorly understood biology and have controversy ...surrounding their management. Most are adequately treated with appendectomy, and although distant metastases are rare, the threat of disease dissemination remains and current guidelines possess poor accuracy in terms of selecting patients requiring more extensive surgery, i.e. oncological right-hemicolectomy.
Areas covered: In this article, we discuss the presentation and diagnostic work-up of patients with appendiceal neuroendocrine neoplasms, and also examine the evidence base for existing management strategies. We highlight controversies within the management of these tumours, and anticipate avenues for further progress. Although no longer classified as neuroendocrine neoplasms, we also discuss two related forms of tumours with neuroendocrine features - goblet cell cancers and mixed adeno-neuroendocrine carcinomas.
Expert commentary: Existing guidelines for the treatment of appendiceal neuroendocrine neoplasms are derived from a limited evidence base and are unable to accurately predict which patients require extensive attempts at surgical disease control. Future advances in the field of improved patient selection for more extensive surgery may be possible with multi-factorial tumour assessment integrating morphological and molecular analyses.
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