Objectives The aims of this study were to determine the spectrum and prevalence of “background genetic noise” in the arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) genetic test and ...to determine genetic associations that can guide the interpretation of a positive test result. Background ARVC is a potentially lethal genetic cardiovascular disorder characterized by myocyte loss and fibrofatty tissue replacement of the right ventricle. Genetic variation among the ARVC susceptibility genes has not been systematically examined, and little is known about the background noise associated with the ARVC genetic test. Methods Using direct deoxyribonucleic acid sequencing, the coding exons/splice junctions of PKP2 , DSP , DSG2 , DSC2 , and TMEM43 were genotyped for 93 probands diagnosed with ARVC from the Netherlands and 427 ostensibly healthy controls of various ethnicities. Eighty-two additional ARVC cases were obtained from published reports, and additional mutations were included from the ARVD/C Genetic Variants Database. Results The overall yield of mutations among ARVC cases was 58% versus 16% in controls. Radical mutations were hosted by 0.5% of control individuals versus 43% of ARVC cases, while 16% of controls hosted missense mutations versus a similar 21% of ARVC cases. Relative to controls, mutations in cases occurred more frequently in non-Caucasians, localized to the N-terminal regions of DSP and DSG2, and localized to highly conserved residues within PKP2 and DSG2. Conclusions This study is the first to comprehensively evaluate genetic variation in healthy controls for the ARVC susceptibility genes. Radical mutations are high-probability ARVC-associated mutations, whereas rare missense mutations should be interpreted in the context of race and ethnicity, mutation location, and sequence conservation.
Abstract Background This study aimed at identifying preoperative predictors of patient-reported outcomes after total knee arthroplasty (TKA) and at investigating their association with the outcomes ...over time. Methods We used data from 2080 patients from the Knee Arthroplasty Trial who received primary TKA in the United Kingdom between July 1999 and January 2003. The primary outcome measure was the Oxford knee score (OKS) collected annually over 10 years after TKA. Preoperative predictors included a range of patient characteristics and clinical conditions. Mixed-effects linear regression model analysis of repeated measurements was used to identify predictors of overall OKS, and pain and function subscale scores over 10 years, separately. Results Worse preoperative OKS, worse mental well-being, body mass index greater than 35 kg/m2 , living in the most deprived areas, higher American Society of Anesthesiologists grade, presence of comorbidities, and history of previous knee surgery were associated with worse overall OKS over 10 years after surgery. The same predictors were identified for pain and function subscale scores, and for both long-term (10 years) and short-to-medium-term outcomes (1 and 5 years). However, fitted models explained more variations in function and shorter-term outcomes than in pain and longer-term outcomes, respectively. Conclusion The same predictors were identified for pain and functional outcomes over both short-to-medium term and long term after TKA. Within the factors identified, functional and shorter-term outcomes were more predictable than pain and longer-term outcomes, respectively. Regardless of their preoperative characteristics, on average, patients achieved substantial improvement in pain over time, although improvement for function was less prominent.
Background The relationship between myopenia, nutritional status, and long-term oncologic outcomes remains poorly characterized in patients with clinically resectable pancreatic cancer. We sought to ...reliably quantify prognostic indicators of preoperative cachexia in a manner applicable to any clinical setting. Methods Preoperative computed tomographies were available electronically and suitable for analysis in 73 of 82 consecutive patients with pancreatic cancer undergoing pancreatoduodenectomy between November 2010 and February 2014. The psoas index was computed from the cross-sectional area of the psoas muscles normalized to vertebral body area at the third lumbar vertebra. Correlation and proportional hazards analyses were performed to identify relationships between muscularity, preoperative nutritional markers, clinicopathologic parameters, and long-term survival. Results The psoas index correlated strongly with preoperative hemoglobin and albumin levels ( P = .001 and .014, respectively) identifying a pattern of preoperative frailty. High psoas index and the albumin and hemoglobin levels were associated with improved long-term survival (hazard ratio 0.014, P < .001; hazard ratio 0.43, P < .001; and hazard ratio = 0.80, P = .014); however, on multivariate analysis, the psoas index proved to be the only independent predictor of survival (hazard ratio 0.021; P = .003). Rapid decreases in the psoas index during neoadjuvant chemotherapy were associated with poor postoperative outcomes, as were decreases in the psoas index during the postoperative period. Conclusion The data indicate that the psoas index, a calculation derived from a clinically mandated, preoperative computed tomography, is a statistically powerful and easily calculated predictor of survival in pancreatic cancer when compared to tumor grade and stage as well as previously validated nutritional parameters.
Summary Background Total knee replacement (TKR) or unicompartmental knee replacement (UKR) are options for end-stage osteoarthritis. However, comparisons between the two procedures are confounded by ...differences in baseline characteristics of patients undergoing either procedure and by insufficient reporting of endpoints other than revision. We aimed to compare adverse outcomes for each procedure in matched patients. Methods With propensity score techniques, we compared matched patients undergoing TKR and UKR in the National Joint Registry for England and Wales. The National Joint Registry started collecting data in April 1, 2003, and is continuing. The last operation date in the extract of data used in our study was Aug 28, 2012. We linked data for multiple potential confounders from the National Health Service Hospital Episode Statistics database. We used regression models to compare outcomes including rates of revision, revision/reoperation, complications, readmission, mortality, and length of stay. Findings 25 334 UKRs were matched to 75 996 TKRs on the basis of propensity score. UKRs had worse implant survival both for revision (subhazard ratio SHR 2·12, 95% CI 1·99–2·26) and for revision/reoperation (1·38, 1·31–1·44) than TKRs at 8 years. Mortality was significantly higher for TKR at all timepoints than for UKR (30 day: hazard ratio 0·23, 95% CI 0·11–0·50; 8 year: 0·85, 0·79–0·92). Length of stay, complications (including thromboembolism, myocardial infarction, and stroke), and rate of readmission were all higher for TKR than for UKR. Interpretation In decisions about which procedure to offer, the higher revision/reoperation rate of UKR than of TKR should be balanced against a lower occurrence of complications, readmission, and mortality, together with known benefits for UKR in terms of postoperative function. If 100 patients receiving TKR received UKR instead, the result would be around one fewer death and three more reoperations in the first 4 years after surgery. Funding Royal College of Surgeons of England and Arthritis Research UK.
Summary Knee-replacement surgery is frequently done and highly successful. It relieves pain and improves knee function in people with advanced arthritis of the joint. The most common indication for ...the procedure is osteoarthritis. We review the epidemiology of and risk factors for knee replacement. Because replacement is increasingly considered for patients younger than 55 years, improved decision making about whether a patient should undergo the procedure is needed. We discuss assessment of surgery outcomes based on data for revision surgery from national joint-replacement registries and on patient-reported outcome measures. Widespread surveillance of existing implants is urgently needed alongside the carefully monitored introduction of new implant designs. Developments for the future are improved delivery of care and training for surgeons and clinical teams. In an increasingly ageing society, the demand for knee-replacement surgery will probably rise further, and we predict future trends. We also emphasise the need for new strategies to treat early-stage osteoarthritis, which will ultimately reduce the demand for joint-replacement surgery.
Objectives The aim of this study was to determine if exercise testing could expose a latent electrical substrate of arrhythmogenic right ventricular cardiomyopathy (ARVC) in asymptomatic gene ...carriers. Background Management of asymptomatic ARVC gene carriers is challenging because of variable penetrance of disease and the recognition that sudden cardiac death may be the first clinical manifestation. Methods Exercise-induced abnormalities during exercise treadmill testing (ETT) were initially compared in 60 subjects: 30 asymptomatic ARVC gene carriers and 30 healthy controls. In phase 2 of the study, ETT results of 25 patients with ARVC with histories of sustained ventricular arrhythmia or cardiac arrest were evaluated to determine if ETT abnormalities in asymptomatic gene carriers were common to patients with a malignant electrical form of the disease. Results Depolarization abnormalities during ETT were found to develop more frequently in asymptomatic gene carriers compared with healthy controls: epsilon waves appeared in 4 of 28 (14%) compared with 0 of 30 (0%) (p = 0.048), premature ventricular contractions in 17 of 30 (57%) compared with 3 of 30 (10%) (p = 0.0003), and new QRS terminal activation duration ≥55 ms in 7 of 22 (32%) compared with 2 of 29 (7%) (p = 0.03). Superior axis premature ventricular contractions occurred only in gene carriers. In the second phase of the study, the frequency of these abnormalities was found to be high in patients with symptomatic ARVC: new epsilon waves appeared in 3 of 18 (17%), superior axis premature ventricular contractions in 21 of 25 (84%), and new terminal activation duration ≥55 ms in 8 of 12 (67%). Conclusions Exercise testing exposes a latent electrical substrate in asymptomatic ARVC gene carriers that is shared by patients with ARVC with histories of ventricular arrhythmia. ETT may be useful in guiding treatment decisions, exercise prescription, and prioritizing medical surveillance in asymptomatic ARVC gene carriers.
Abstract The OHS/OKS are PROMs for assessing symptomatic pain and function following TJA. However, actual change in pre-operative/post-operative scores cannot distinguish patients of varying baseline ...symptom severity. The percentage of potential change (PoPC) is a simple method that accounts for this, expressing the actual change attained, as a percentage of the potential change possible. Measures are described using OHS/OKS at baseline and 6-months (1784 – TKA, 1523 – THA) from the Elective Orthopaedic Centre. Each method identified different proportions of patients as satisfied and importantly, the measures identified different patients. PoPC overcomes floor and ceiling effects and standardises measures to an easy to interpret − 100 to + 100 scale. In addition to actual change, we recommend using PoPC to assess the overall outcome of patients.
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