Systematic review of the evidence relating FEV1 decline to giving up smoking

<p>Abstract</p> <p>Background</p> <p>The rate of forced expiratory volume in 1 second (FEV₁) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta.</p> <p>Methods</p> <p>Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors.</p> <p>Results</p> <p>Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex.</p> <p>Conclusion</p> <p>The available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV₁decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products.</p

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Autologous Chondrocyte Implantation: Second-Look Arthroscopy

Background: A known complication following autologous chondrocyte implantation (ACI) for the repair of cartilage defects is graft hypertrophy. Although hypertrophic tissue can sometimes be asymptomatic, it may cause pain, catching, or effusion prompting a debridement operation—the most common cause for reoperation. Indications: Second-look arthroscopy is required for debridement of symptomatic hypertrophic or delaminated tissue. Technique Description: First, the graft is distinguished from the surrounding tissue. Visually, the graft has a lighter white color than the surrounding egg-shell-colored native cartilage. With a probe, it can be appreciated that the graft also has a softer texture than the firmer surrounding cartilage. Once the graft is identified, hypertrophy can be appreciated by the extent of raised margins from the surrounding cartilage. Delamination can also be seen by visualizing separated strands of graft on the surface or separation of the graft at the margins. A probe may then be used to gently assess the extent of the delamination. After diagnosing hypertrophy or delamination, a shaver is used to gently debride the tissue back so that it becomes flush with the surrounding tissue. Special care must be taken as to not over-debride the tissue, as this can subsequently lead to recurrent cartilage defect. Results: Patients are expected to have resolved pain, catching, and clicking sensations as well as resolved graft-associated effusion following this procedure. Discussion/Conclusion: Due to the incidence of symptomatic graft hypertrophy and delamination following ACI, second-look arthroscopy may be necessary to evaluate and possibly treat a cartilage defect following its repair. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication

Osteoarthritis Classification Scales: Interobserver Reliability and Arthroscopic Correlation

The MARS Group* Background: Osteoarthritis of the knee is commonly diagnosed and monitored with radiography. However, the reliability of radiographic classification systems for osteoarthritis and the correlation of these classifications with the actual degree of confirmed degeneration of the articular cartilage of the tibiofemoral joint have not been adequately studied. Methods: As the Multicenter ACL (anterior cruciate ligament) Revision Study (MARS) Group, we conducted a multicenter, prospective longitudinal cohort study of patients undergoing revision surgery after anterior cruciate ligament reconstruction. We followed 632 patients who underwent radiographic evaluation of the knee (an anteroposterior weight-bearing radiograph, a posteroanterior weight-bearing radiograph made with the knee in 45°of flexion [Rosenberg radiograph], or both) and arthroscopic evaluation of the articular surfaces. Three blinded examiners independently graded radiographic findings according to six commonly used systems-the Kellgren-Lawrence, International Knee Documentation Committee, Fairbank, Brandt et al., Ahlbäck, and Jäger-Wirth classifications. Interobserver reliability was assessed with use of the intraclass correlation coefficient. The association between radiographic classification and arthroscopic findings of tibiofemoral chondral disease was assessed with use of the Spearman correlation coefficient. Results: Overall, 45°posteroanterior flexion weight-bearing radiographs had higher interobserver reliability (intraclass correlation coefficient = 0.63; 95% confidence interval, 0.61 to 0.65) compared with anteroposterior radiographs (intraclass continue