Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
BackgroundScreening improves outcomes related to colorectal cancer (CRC); however, suboptimal participation for available screening tests limits the full benefits of screening. Non-invasive screening using a blood based assay may potentially help reach the unscreened population.ObjectiveTo compare the performance of a new Septin9 DNA methylation based blood test with a fecal immunochemical test (FIT) for CRC screening.Design: In this trial, fecal and blood samples were obtained from enrolled patients. To compare test sensitivity for CRC, patients with screening identified colorectal cancer (n = 102) were enrolled and provided samples prior to surgery. To compare test specificity patients were enrolled prospectively (n = 199) and provided samples prior to bowel preparation for screening colonoscopy.MeasurementsPlasma and fecal samples were analyzed using the Epi proColon and OC Fit-Check tests respectively.ResultsFor all samples, sensitivity for CRC detection was 73.3% (95% CI 63.9–80.9%) and 68.0% (95% CI 58.2–76.5%) for Septin9 and FIT, respectively. Specificity of the Epi proColon test was 81.5% (95% CI 75.5–86.3%) compared with 97.4% (95% CI 94.1–98.9%) for FIT. For paired samples, the sensitivity of the Epi proColon test (72.2% –95% CI 62.5–80.1%) was shown to be statistically non-inferior to FIT (68.0%–95% CI 58.2–76.5%). When test results for Epi proColon and FIT were combined, CRC detection was 88.7% at a specificity of 78.8%.ConclusionsAt a sensitivity of 72%, the Epi proColon test is non- inferior to FIT for CRC detection, although at a lower specificity. With negative predictive values of 99.8%, both methods are identical in confirming the absence of CRC.Trial RegistrationClinicalTrials.gov NCT01580540
SUMMARY Sections from 100 cervical biopsy specimens were studied by 12 consultant histopathologists to determine the robustness of the existing pathology terminology and classification. Analysis by K statistics showed good agreement in the diagnosis of CIN 3 and squamous carcinoma but an inability to distinguish accurately between the lesser grades of CIN.It is recommended that the classification be changed to low grade (present CIN 1 and 2) and high grade (present CIN 3) categories alone. There was very poor agreement in the identification ofcellular changes associated with human papilloma virus (HPV) infection.Several novel analytical methods of assessing the severity of uterine cervical intraepithelial neoplasia (CIN) have been proposed,'2 but histological assessment remains the basis for determination oftreatment, clinical management, and subsequent follow up of patients. Although clear criteria for the diagnosis and grading of CIN have been described,3 such assessments are subjective and prone to intra-and interobserver variation.45 The problems of histological assessment have been further complicated by the increasing recognition of human papilloma virus (HPV) infection"7 which may be an aetiological factor in the development of CIN.89 HPV infection may be indicated by koilocytosis and other changes that distort cellular appearances and so may apparently exaggerate the severity of the premalignant appearances ofthe cervical epithelium, particularly in the higher layers-making grading more difficult.It is reasonable that efforts should be made to establish the degree of confidence which can be given to the histological reporting of cervical biopsy lesions by pathologists and to determine the robustness of the existing terminology and classification. We describe the findings of a study of cervical biopsy specimens conducted by a group of 12 pathologists, all of consultant grade, but with varying degrees of experience.Accepted for publication 1 September 1988 Material and methods COMPOSITION OF PANELTwelve histopathologists were invited to join the study with a deliberate attempt by the organisers to obtain a composition representative of Scottish pathology as a whole. The members came from pathology laboratories in Aberdeen (n = 2), Dundee (n = 2), Edinburgh (n = 2), Airdrie (n = 1), Perth (n = 1), Stirling (n = 1) and Glasgow (n = 3) and varied in years of consultant experience (five to 25 years) and nature ofsubstantive post (university staffn = 5: NHS staff n = 7). All the members of the group had undertaken their postgraduate training in Scotland. CLASSIFICATION OF CERVICAL HISTOPATHOLOGYAt the initial meeting current cervical pathology terminology was reviewed and following discussion a proforma was designed for completion after examination of each slide in the circulation. This was modified in a minor way after the first circulation and the final form is shown in the figure. It was decided to keep the classification simple, but to relate it as closely as possible to everyday practice. The following ...
Background: Antibody tests are essential tools to investigate humoral immunity following SARS-CoV-2 infection or vaccination. While first-generation antibody tests have primarily provided qualitative results, accurate seroprevalence studies and tracking of antibody levels over time require highly specific, sensitive and quantitative test setups. Methods: We have developed two quantitative, easy-to-implement SARS-CoV-2 antibody tests, based on the spike receptor binding domain and the nucleocapsid protein. Comprehensive evaluation of antigens from several biotechnological platforms enabled the identification of superior antigen designs for reliable serodiagnostic. Cut-off modelling based on unprecedented large and heterogeneous multicentric validation cohorts allowed us to define optimal thresholds for the tests' broad applications in different aspects of clinical use, such as seroprevalence studies and convalescent plasma donor qualification. Findings: Both developed serotests individually performed similarly-well as fully-automated CE-marked test systems. Our described sensitivity-improved orthogonal test approach assures highest specificity (99.8%); thereby enabling robust serodiagnosis in low-prevalence settings with simple test formats. The inclusion of a calibrator permits accurate quantitative monitoring of antibody concentrations in samples collected at different time points during the acute and convalescent phase of COVID-19 and disclosed antibody level thresholds that correlate well with robust neutralization of authentic SARS-CoV-2 virus. Interpretation: We demonstrate that antigen source and purity strongly impact serotest performance. Comprehensive biotechnology-assisted selection of antigens and in-depth characterisation of the assays allowed us to overcome limitations of simple ELISA-based antibody test formats based on chromometric reporters, to yield comparable assay performance as fully-automated platforms.
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