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.

ObjectiveTo examine the role of the variants of the PTPN22 and HLA–DRB1 genes as predictors of mortality in inflammatory polyarthritis (IP) and rheumatoid arthritis (RA).MethodsPatients were recruited from a primary care–based inception cohort of patients with IP and were followed up prospectively. For patients who died, the cause and date of death was obtained. Cox proportional hazards regression models were used to assess the association of the HLA–DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti–cyclic citrullinated peptide (anti-CCP) status, adjusted by age at symptom onset and sex.ResultsDNA samples were available from 1,022 IP patients. During followup, 751 of them (74%) satisfied the American College of Rheumatology 1987 criteria for RA, and 242 of them (24%) died. Carriage of 2 copies of SE alleles predicted death from all causes (hazard ratio [HR] 1.57 [95% confidence interval (95% CI) 1.1–2.2]) and from CVD (HR 1.68 [95% CI 1.1–2.7]). This effect was most marked for individuals with the HLA–DRB1*01/*04 combination. An interaction of smoking, SE alleles, and anti-CCP antibodies was observed and was associated with the greatest risk of death from CVD (HR 7.81 [95% CI 2.6–23.2]). No association of the PTPN22 gene with mortality was detected.ConclusionSE alleles, particularly compound heterozygotes, are associated with death from all causes and from CVD, independently of autoantibody status. However, the combination of SE, smoking, and anti-CCP antibodies is associated with a high risk of premature death in patients with IP and RA, which raises the possibility of a targeted strategy to prevent CVD in these patients.

ObjectiveAnti–cyclic citrullinated peptide (anti-CCP) antibodies are a stronger predictor of the severity of rheumatoid arthritis than is rheumatoid factor (RF). Their role in predicting outcome in unselected patients with new-onset inflammatory polyarthritis (IP) has not been examined. The aims of this study were to examine the role of baseline RF and anti-CCP antibodies in determining the likelihood of patients having erosions at presentation or in predicting future radiologic damage, and to determine whether anti-CCP antibodies or RF is sufficiently robust to be clinically useful in guiding treatment decisions in early IP.MethodsPatients were recruited from the Norfolk Arthritis Register. Logistic regression models were fitted to test the ability of anti-CCP antibodies and RF to predict erosions. Further models were investigated to examine the role of anti-CCP antibodies in patients stratified by RF status.ResultsThe presence of anti-CCP antibodies at baseline was strongly associated with both prevalent erosions (odds ratio [OR] 2.53 [95% confidence interval (95% CI) 1.48–4.30]) and developing erosions at 5 years (OR 10.2 [95% CI 6.2–16.9]). These ORs were higher than those for RF (OR 1.63 [95% CI 0.94–2.82] and OR 3.4 [95% CI 2.2–5.2], respectively). The likelihood ratio (LR) for the prediction of prevalent erosions and erosions at 5 years was highest in the RF−subgroup (LR 2.2 and 5.8, respectively). However, 27% of anti-CCP−patients had developed erosions by 5 years.ConclusionDespite their strong association with the presence, development, and extent of erosions, anti-CCP antibodies alone are not a sufficiently accurate measure upon which to base clinical treatment decisions. Knowledge of anti-CCP antibody status is most informative in RF−negative patients.

BackgroundPolymorphisms of the peptidylarginine deiminase type 4 (PADI4) gene confer susceptibility to rheumatoid arthritis (RA) in East Asian people. However, studies in European populations have produced conflicting results. This study explored the association of the PADI4 genotype with RA in a large UK Caucasian population.MethodsThe PADI4_94 (rs2240340) single nucleotide polymorphism (SNP) was directly genotyped in a cohort of unrelated UK Caucasian patients with RA (n=3732) and population controls (n=3039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was used to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1859) and controls (n=10 599). A further 56 SNPs spanning the PADI4 gene were investigated for association with RA using data from the WTCCC study.ResultsThe PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all the cases of RA (n=5591) and controls (n=13 638) gave an overall OR of 1.01 (95% CI 0.96 to 1.05, p=0.72). No association with anti-CCP antibodies and no interaction with either shared epitope or PTPN22 was detected. No evidence for association with RA was identified for any of the PADI4 SNPs investigated. Meta-analysis of previously published studies and our data confirmed no significant association between the PADI4_94 genotype and RA in people of European descent (OR 1.06, 95% CI 0.99 to 1.13, p=0.12).ConclusionIn the largest study performed to date, the PADI4 genotype was not a significant risk factor for RA in people of European ancestry, in contrast to Asian populations.

SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality ). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.

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Background Several aspects of slipped capital femoral epiphysis (SCFE) treatment remain controversial. Loder's work has been instrumental in changing our understanding and approach to the management of the condition when he introduced the concept of ''slip instability'' and showed that avascular necrosis (AVN) developed in 47% of unstable slips but none of the stable slips. As the two types of SCFE behave differently in terms of presentation, progress and complications, we approached them as two different conditions to highlight these differences. This paper focuses on treatments of stable SCFE. Materials and methods An extensive literature search was carried out from multiple databases. One thousand six hundred and twenty-three citations were screened. Three hundred and sixteen full publications were obtained for further scrutiny. Fifty-eight studies (2262 hips) were included in the review. These studies evaluated 6 interventions. AVN was chosen as a surrogate for bad outcome. Secondary outcomes were chondrolysis (CL), femoro-acetabular impingement (FAI), osteoarthritis (OA) and patients' reported outcomes. The latter were pooled when they met our predefined criteria. Results The type of surgical intervention was an important risk factor. Pinning in situ (PIS) was associated with the lowest AVN rate (1.4%). Moreover, the CL, FAI and OA rates were relatively low in patients who underwent PIS.

We assessed the association between breast cancer (BC) and colorectal cancer (CRC) from referral pattern to the Regional Genetics Service including molecular analysis. Hospital computer records and/or department referral books were used to identify cases referred to the Regional Genetic Service during a 16-year period (1990-2005 inclusive). All files were reviewed along with associated demographic data, risk assessments, referral details and results from mutation testing. Families were assessed for hereditary breast and colorectal cancer (HBCC) criteria, and all families with eligible individuals were tested for the 1100delC mutation in CHEK2. A total of 8,612 families were identified. One hundred and sixteen of 1,631 (7.5%) families with a primary referral for CRC fulfilled the criteria for HBCC, whereas only 68/6981 (1%) BC referrals fulfilled these criteria. Blood samples were obtained from 113 individuals from 83/184 families. Only 1/113 (1%) has screened positive for the CHEK2 mutation, whereas 14 (17%) families segregate BRCA1/2 mutations and at least 7 (8.5%) carry MLH1/MSH2 mutations. HBCC syndrome, if it exists as a separate entity, is not likely to be due to CHEK2 mutations. Many families are explicable by existing high-penetrance genes, and further work is necessary to elucidate whether the remainder is due to chance or as yet undiscovered genes.