Unraveling the link between cardiorespiratory fitness and cancer: a state-of-the-art review.

Cardiorespiratory fitness (CRF) not only reflects an individual's capacity to perform physical activities but also encapsulates broader effects on the basic biology of aging. This review aims to summarize the evidence on the influence of CRF on overall and site-specific cancer risks. It delves into the biological mechanisms through which CRF may exert its effects, explores the clinical implications of these findings, identifies gaps in the current evidence base, and suggests directions for future research. The synthesis of findings reveals that higher CRF levels (general threshold of > 7 METs) are consistently associated with a reduced risk of a range of cancers, including head and neck, lung, breast, gastrointestinal, particularly pancreatic and colorectal, bladder, overall cancer incidence and mortality, and potentially stomach and liver, bile duct, and gall bladder cancers. These inverse associations between CRF and cancer risk do not generally differ across age groups, sex, race, or adiposity, suggesting a universal protective effect of CRF. Nonetheless, evidence linking CRF with skin, mouth and pharynx, kidney, and endometrial cancers is limited and inconclusive. Conversely, higher CRF levels may be potentially linked to an increased risk of prostate cancer and hematological malignancies, such as leukemia and myeloma, although the evidence is still not conclusive. CRF appears to play a significant role in reducing the risk of several cancers through various biological mechanisms, including inflammation reduction, immune system enhancement, hormonal regulation, and metabolic improvements. Overall, enhancing CRF through regular physical activity offers a vital, accessible strategy for reducing cancer risk and extending the health span. Future research should aim to fill the existing evidence gaps regarding specific cancers and elucidate the detailed dose-response relationships between CRF levels and cancer risk. Studies are also needed to elucidate the causal relationships and mechanistic pathways linking CRF to cancer outcomes.

Self-reported smoking, urine cotinine, and risk of type 2 diabetes: Findings from the PREVEND prospective cohort study.

BACKGROUND: Smoking is a major risk factor for type 2 diabetes (T2D), but the evidence has mostly relied on self-reports. We aimed to compare the associations of smoking exposure as assessed by self-reports and urine cotinine with T2D. METHODS: Using the PREVEND prospective study, smoking status was assessed at baseline by self-reports and urine cotinine in 4708 participants (mean age, 53 years) without a history of diabetes. Participants were classified as never, former, light current and heavy current smokers according to self-reports and analogous cut-offs for urine cotinine. Hazard ratios (HRs) with 95% CIs were estimated for T2D. RESULTS: During a median follow-up of 7.3 years, 259 participants developed T2D. Compared with self-reported never smokers, the multivariable adjusted HRs (95% CI) of T2D for former, light current, and heavy current smokers were 1.02 (0.75-1.4), 1.41 (0.89-2.22), and 1.30 (0.88-1.93), respectively. The corresponding adjusted HRs (95% CI) were 0.84 (0.43-1.67), 1.61 (1.12-2.31), and 1.58 (1.08-2.32), respectively, as assessed by urine cotinine. Urine cotinine-assessed but not self-reported smoking status improved T2D risk prediction beyond established risk factors. CONCLUSION: Urine cotinine assessed smoking status may be a stronger risk indicator and predictor of T2D compared to self-reported smoking status.

Focal resurfacing of the knee - A systematic review and meta-analysis.

PURPOSE: In order to assess the published validity of focal resurfacing of the knee, a systematic review and meta-analysis were conducted to (i) evaluate revision rates and implant survival of focal resurfacing of the knee; (ii) explore surgical complications; and (iii) evaluate patient reported clinical outcome measures. METHODS: PubMED, Cochrane Library and Medline databases were searched by 2 independent reviewers in February 2022 for prospective and retrospective cohort studies evaluating any of the following implant types: HemiCAP®, UniCAP®, Episealer® or BioBoly®. Data on incidence of revision, complications and various patient reported outcome measures, such as Knee Society Score (KSS) or Knee Injury and Osteoarthritis Outcome Score (KOOS) was sourced. RESULTS: A total of 24 published studies were identified with a total of 1465 enrolled patients. A revision rate of 12.97% over a 5.9 year weighted mean follow-up period was observed across all implant types. However, in one series a Kaplan-Meir survival as high as 92.6% at a 10-year follow-up period was noted. A statistically significant improvement was documented across multiple subjective clinical outcomes scores, for example a mean 4.56 point improvement of the VAS (0-10) pain score. The Kellgren-Lawrence score was used to evaluate the radiological progression of osteoarthritis and showed a small significant reduction in all anatomical locations, hence not supporting the hypothesis that focal femoral implants can lead to the progression of osteoarthritis in the affected compartment. There was a low reported incidence of post-operative complications such as aseptic loosening or deep wound infection. CONCLUSIONS: Focal femoral resurfacing appears to be a viable treatment option for focal symptomatic chondral lesions in patients beyond biological reconstruction, with low revision rates and high patient satisfaction especially at short and medium length follow-up.

Urine cotinine versus self-reported smoking and the risk of chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Evidence on the role of smoking in the development of chronic kidney disease (CKD) has mostly relied on self-reported smoking status. We aimed to compare the associations of smoking status as assessed by self-reports and urine cotinine with CKD risk. METHODS: Using the PREVEND prospective study, smoking status was assessed at baseline using self-reports and urine cotinine in 4333 participants (mean age, 52 years) without a history of CKD at baseline. Participants were classified as never, former, light current and heavy current smokers according to self-reports and comparable cut-offs for urine cotinine. Hazard ratios (HRs) with 95% CIs were estimated for CKD. RESULTS: The percentages of self-reported and cotinine-assessed current smokers were 27.5% and 24.0%, respectively. During a median follow-up of 7.0 years, 593 cases of CKD were recorded. In analyses adjusted for established risk factors, the HRs (95% CI) of CKD for self-reported former, light current, and heavy current smokers compared with never smokers were 1.17 (0.95-1.44), 1.48 (1.10-2.00), and 1.48 (1.14-1.93), respectively. On further adjustment for urinary albumin excretion (UAE), the HRs (95% CI) were 1.07 (0.87-1.32), 1.26 (0.93-1.70), and 1.20 (0.93-1.57), respectively. For urine cotinine-assessed smoking status, the corresponding HRs (95% CI) were 0.81 (0.52-1.25), 1.17 (0.92-1.49), and 1.32 (1.02-1.71), respectively, in analyses adjusted for established risk factors plus UAE. CONCLUSION: Self-reported current smoking is associated with increased CKD risk, but dependent on UAE. The association between urine cotinine-assessed current smoking and increased CKD risk is independent of UAE. Urine cotinine-assessed smoking status may be a more reliable risk indicator for CKD incidence than self-reported smoking status.

Outcomes of Octogenarian Patients Treated with Tafamidis for Transthyretin Amyloid Cardiomyopathy.

Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) benefit from disease-modifying agents such as tafamidis. However, the survival benefit of tafamidis in elderly patients (age ≥80 years) is not reported. This study aimed to assess the survival of patients with ATTR-CM aged 80 years and older who were treated with tafamidis compared with patients aged <80 years. We conducted a retrospective analysis of patients with ATTR-CM who underwent tafamidis treatment, aged 45 to 97 years at the time of diagnosis between January 1, 2008, and May 31, 2021. A total of 484 patients were included, with 208 in the ≥80 years group and 276 in the <80 years group. The cohort was followed up for mortality outcomes, and hazard ratios with 95% confidence intervals were calculated. After a median follow-up of 18.5 months, 72 deaths were recorded in the entire cohort. Kaplan-Meier curves showed no differences in survival probability between the 2 groups at 30 months (p for log-rank test = 0.76). The survival rates for patients aged ≥80 years who underwent treatment at 1, 2, 3, 4, and 5 years were 94.7%, 86.0%, 77.0%, 77.0%, and 38.5%, respectively. The corresponding rates for patients aged <80 years who underwent treatment were 93.2, 84.8, 74.4, 68.2, and 64.6%, respectively. In the multivariable analysis, the hazard ratio (95% confidence interval) of the mortality comparing treatment patients aged ≥80 years with those aged <80 years was 0.81 (0.41 to 1.61). In conclusion, tafamidis treatment is associated with similar reductions in mortality in older and younger patients with ATTR-CM.

Sex disparities in physical activity domains and hypertension prevalence.

BACKGROUND: This study aimed to examine the associations of leisure time physical activity (LTPA) and occupational physical activity (OPA) with the prevalence of hypertension, while exploring the sex disparities in these associations. METHODS: A cross-sectional study was conducted using data from the Korea National Health and Nutrition Examination Survey between 2014 and 2019 (n = 26,534). Hypertension was defined as the use of antihypertensive drugs or systolic and diastolic blood pressure ≥ 140/90 mm Hg. Self-reported physical activity (PA), assessed by the global PA questionnaire, was categorized into three domains: total PA, LTPA and OPA. Each PA domain was classified based on METs-min/wk and intensity. RESULTS: In a multivariable adjusted model, the odds ratio (OR) with 95% confidence intervals (CIs) for the prevalence of hypertension in the active versus inactive group, based on METs, was 0.92 (95% CI 0.85-0.99) for total PA, 0.90 (95% CI 0.83-0.98) for LTPA and 1.21 (95% CI 1.05-1.38) for OPA. Compared to the inactive group, moderate to vigorous intensity was associated with a lower odds of hypertension for total PA and LTPA (total PA: OR 0.95, 95% CI 0.89-1.00 and LTPA: OR 0.92, 95% CI 0.86-0.98), but a higher odd for OPA (OR 1.17, 95% CI 1.05-1.30). Subgroup analyses showed significant evidence of effect modification by sex on the associations of total PA and LTPA (METs and intensity) with hypertension prevalence (p-values for interaction < 0.01); the associations were generally stronger for women. OPA was associated with a higher prevalence of hypertension in women, but not in men (p-value for interaction > 0.05). CONCLUSIONS: Higher levels of total PA and LTPA were associated with lower prevalence of hypertension in both men and women, with slightly stronger associations for women. However, higher OPA was associated with a higher prevalence of hypertension in women. These findings support the PA health paradox hypothesis and highlight the sex disparities in the association between OPA and hypertension prevalence.

Association between Serum Testosterone and Aortic Valve Stenosis: A Prospective Cohort Study.

Serum testosterone is associated with atherosclerotic cardiovascular disease, which shares risk factors with aortic stenosis (AS). The association between serum testosterone and AS has not been previously investigated. We aimed to assess the prospective association between serum testosterone and risk of AS. Serum testosterone was determined at baseline using a radioimmunoassay kit in 2577 men aged 42-61 years recruited into the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) with 95% confidence intervals (Cis) were estimated for AS. After a median follow-up of 27.2 years, 119 cases of AS were recorded. The risk of AS increased continuously with increasing serum testosterone across the range 25-39 nmol/L (p-value for nonlinearity = 0.49). In an analysis adjusted for age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking status, history of type 2 diabetes, history of coronary heart disease, and alcohol consumption, the HR (95% CI) for AS was 1.39 (1.10-1.76) per 10 nmol/L increase in serum testosterone. When alcohol consumption was replaced with physical activity, the HR (95% CI) was 1.38 (1.09-1.74). Comparing the bottom versus top third of serum testosterone, the corresponding (adjusted) risk estimates were 1.76 (1.11-2.81) and 1.76 (1.10-2.80), respectively. In middle-aged and older Finnish men, elevated levels of serum testosterone were associated with an increased risk of AS. Further research is needed to replicate these findings and assess any potential relevance of serum testosterone in AS prevention.

High Cardiorespiratory Optimal Point Values Are Related to Cardiovascular Mortality in Men Aged 46 to 70 Years: a Prospective Cohort Study

Abstract Background: Several hemodynamic and respiratory variables measured during cardiopulmonary exercise testing (CPX) have been shown to predict survival. One such measure is the cardiorespiratory optimal point (COP) that reflects the best possible circulation-respiration interaction, but there are still limited data on its relationship with adverse outcomes. Objective: To assess the association between COP and cardiovascular mortality in men aged 46 to 70 years. Methods: A sample of 2201 men who had anthropometric, clinical, and COP data obtained during cycling CPX between 1995 and 2022 was extracted from the CLINIMEX Exercise cohort. COP was identified as the minimal minute-to-minute VE/VO2 during CPX. Vital data were censored on October 31, 2022 for ICD-10-identified cardiovascular deaths. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: The mean ± standard deviation age was 57 ± 6 years and the median COP value was 24 (interquartile range = 21.2 to 27.4). During a mean follow-up of 4688 ± 2416 days, 129 (5.6%) patients died from cardiovascular causes. The death rates for low (< 28), high (28 to 30), and very high (> 30) categories of COP were 3.2%, 9.6%, and 18.7%, respectively. Following adjustment for age, history of myocardial infarction, diagnosis of coronary artery disease, and diabetes mellitus, the HR (95% CI) for cardiovascular mortality comparing very high versus low COP was 2.76 (1.87 to 4.07; p < 0.001). Conclusions: Our data indicate that, for a general population-based sample of men, COP > 30 represents a considerably higher risk for cardiovascular death. Information on COP could assist cardiovascular risk assessment in men.

Mortality and re-revision following single-stage and two-stage revision surgery for the management of infected primary hip arthroplasty in England and Wales.

We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty. Patients with a periprosthetic joint infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies. In total, 535 primary hip arthroplasties were revised with single-stage procedure (1,525 person-years) and 1,605 with two-stage procedure (5,885 person-years). All-cause re-revision was higher following single-stage revision, especially in the first three months (HR at 3 months = 1.98 (95% confidence interval (CI) 1.14 to 3.43), p = 0.009). The risks were comparable thereafter. Re-revision for PJI was higher in the first three postoperative months for single-stage revision and waned with time (HR at 3 months = 1.81 (95% CI 1.22 to 2.68), p = 0.003; HR at 6 months = 1.25 (95% CI 0.71 to 2.21), p = 0.441; HR at 12 months = 0.94 (95% CI 0.54 to 1.63), p = 0.819). Patients initially managed with a single-stage revision received fewer revision operations (mean 1.3 (SD 0.7) vs 2.2 (SD 0.6), p < 0.001). Mortality rates were comparable between these two procedures (29/10,000 person-years vs 33/10,000). The risk of unplanned re-revision was lower following two-stage revision, but only in the early postoperative period. The lower overall number of revision procedures associated with a single-stage revision strategy and the equivalent mortality rates to two-stage revision are reassuring. With appropriate counselling, single-stage revision is a viable option for the treatment of hip PJI.

Life's Essential 8 and the risk of cardiovascular disease death and all-cause mortality in Finnish men.

AIMS: The aim of the study was to examine the association between Life's Essential 8 (LE8) and the risk of cardiovascular and all-cause mortality. METHODS AND RESULTS: The LE8 was computed for 1662 men, aged 42-60 years, without pre-existing history of cardiovascular disease (CVD) at baseline in the Kuopio Ischaemic Heart Disease study. The LE8 factors include diet, physical activity, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and lipids. Each LE8 factor was scored between 0 and 100 points. The summation of all points generated the total LE8 score, which was categorized into quartiles ≤-420, >420-485, >485-550, and >550. Multivariable Cox regression models were used to estimate hazard ratios and 95% confidence intervals of LE8 scores for the outcomes. During a median follow-up of 30 years, 402 and 987 men died from CVD and any cause, respectively. The total LE8 score among participants ranged from 185 to 750. The higher the LE8 scores, the lower the risk of dying from CVD and all-cause. Following adjustment for age, alcohol consumption, and socio-economic status, every 50-unit increase in LE8 score was associated with 17% and 14% lower risk of CVD and all-cause deaths, respectively. Men within LE8 top quartile had 60% lower risk of CVD mortality when compared with those within the bottom quartile. CONCLUSION: Life's Essential 8 was strongly and inversely associated with the risk of CVD death and all-cause mortality among ageing men. Measures that promote optimal LE8 scores should be encouraged among the general population.

The association between the American Heart Association's Life's Essential 8 (LE8) and the risk of cardiovascular and all-cause mortality was examined using the Kuopio Ischaemic Heart Disease Risk Factor Study in Finland. The result supports continuous improvement in healthy behaviours and factors used in generating LE8 score, which may lower future risk of dying from heart disease. In this paper: • Men who had total LE8 score more than 550 had lower risk of dying from heart disease or any cause of death compared with those with LE8 score ≤ 420. • Increasing LE8 score by 50 can lower risk of dying from heart disease or any other cause.

Serum C-reactive protein-to-albumin ratio may be a potential risk indicator for venous thromboembolism: Findings from a prospective cohort study.

BACKGROUND AND AIMS: Circulating C-reactive protein (CRP) and albumin are commonly used inflammatory biomarkers. C-reactive protein-to-albumin ratio (CAR), a novel inflammatory biomarker, has been suggested to be a more reliable risk indicator compared to CRP or albumin alone. An inflammatory hypothesis has been postulated in VTE aetiology, but the association between CAR and VTE has not been investigated. We aimed to assess the prospective association of CAR with VTE risk. METHODS AND RESULTS: C-reactive protein and albumin were measured in serum samples at baseline from 2479 men aged 42-61 years. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. During a median follow-up of 27.0 years, 168 VTE cases were recorded. In analysis adjusted for potential confounders, the HR (95% CI) for VTE comparing extreme tertiles of CAR was 1.49 (1.01-2.21), which was minimally attenuated on further adjustment for prevalent cancer, a potential mediator 1.48 (1.00-2.19). Serum CRP and albumin were each modestly associated with VTE risk in the same set of participants. CONCLUSION: In middle-aged and older men, elevated serum CAR may be associated with an increased risk of VTE. Further research is needed to replicate or refute these findings in other populations and assess if CAR may be of potential value in VTE management.

Rehabilitation for revision total knee replacement: survey of current service provision and systematic review.

BACKGROUND: Revision total knee replacement (TKR) is a major operation with a long recovery period and many patients report suboptimal outcomes. Rehabilitation has the potential to improve outcomes. The aim of this study was to understand current provision of rehabilitation for revision TKR in England and evaluate the existing evidence. METHODS: Phase 1: An online national survey of education and rehabilitation provision for patients receiving revision TKR was completed by physiotherapy staff at 22 hospitals across England that were high volume for revision TKR (response rate of 34%). Phase 2: Systematic review to identify studies evaluating rehabilitation programmes for revision joint replacement. Searches were conducted in MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane databases from inception to 15th June 2022. Randomised controlled trials (RCTs) and observational studies that evaluated post-operative rehabilitation for adults undergoing revision joint replacement were included. Screening, data extraction and quality assessment was undertaken by two reviewers. RESULTS: Phase 1: Pre-operative education which aimed to prepare patients for surgery and recovery was provided in most hospitals, predominately involving a single session delivered by a multidisciplinary team. Inpatient physiotherapy commonly commenced on post-operative day 1 and was provided twice daily, with most hospitals also providing occupational therapy. Rehabilitation was often provided in the first four weeks after hospital discharge, either in an outpatient, community or home setting. In most hospitals, the education and rehabilitation provided to patients receiving revision TKR was the same as that provided to patients undergoing primary TKR. Phase 2: Of the 1,445 articles identified, three retrospective cohort studies based on hospital records review were included. The studies evaluated intensive inpatient rehabilitation programmes, consisting of 2-3 h of daily group or individual physiotherapy, with additional occupational therapy in one study. All three studies reported improvement in functional outcomes for patients undergoing rehabilitation after revision TKR. All studies were limited by their retrospective design, short duration of follow-up and lack of sample size calculation. No RCTs evaluating effectiveness of rehabilitation for revision TKR were identified. CONCLUSION: This study identified the need for future research to develop and evaluate tailored rehabilitation to optimise patient outcomes following revision TKR.

A Meta-Analysis of the Incidence and Temporal Trends of Postoperative Dislocation in Revision Total Hip Arthroplasty Utilizing Constrained Acetabular Components or Dual Mobility Implants.

BACKGROUND: The incidence of dislocation after revision total hip arthroplasty (rTHA) is reported to be up to 25% and remains a common source of failure. Constrained acetabular components and dual mobility implants are two implant classes being utilized to alleviate this burden in patients who have recurrent instability or major intraoperative instability. This meta-analysis evaluated the incidence and temporal trends of dislocation after implantation with constrained acetabular components and dual mobility implants in rTHA. METHODS: Longitudinal studies reporting dislocation after the use of constrained acetabular components or dual mobility implants in rTHA were sought from Medline and Embase to October 2022. Secondary outcomes included re-revision surgery for dislocation and all causes. A total of 75 relevant citations were identified comprising 36 datasets of 3,784 constrained acetabular components and 47 datasets of 10,216 dual mobility implants. RESULTS: For constrained acetabular components, the pooled incidence of dislocation was 9% (95% confidence interval: 7.2, 11.7) (range 0.0%-35.3%) over a weighted mean follow-up of 6 years, in contrast to 3% (95% confidence interval: 2.2, 4.4) (range 0.0%-21.4%) over 5 years for dual mobility implants. Re-revision rates for dislocation after using constrained acetabular components were around 9%, in contrast to 2% for dual mobility implants. Re-revision rates for all causes after using constrained acetabular components were around 19%, in contrast to 8% for dual mobility implants. CONCLUSION: Dual mobility implants in the context of rTHA demonstrate lower incidences of dislocation (3% versus 9%), re-revision for dislocation (2% versus 9%), and rer-evision for any cause (8% versus 19%) in contrast to constrained acetabular components. This must be considered by surgeons when implanting such devices, often selected to treat instability.

Associations of Cardiorespiratory Fitness With Estimated Remnant Cholesterol and Non-High-Density Lipoprotein Cholesterol in Healthy Men.

Remnant cholesterol (RC) and non-high-density lipoprotein cholesterol (non-HDL-C) may contribute to the residual risk for atherosclerotic cardiovascular disease. High cardiorespiratory fitness (CRF) is associated with favorable traditional lipid profiles, but its relation with RC and non-HDL-C remains unclear. We analyzed cross-sectional data on 4,613 healthy men (mean age 49 years). CRF was measured using peak oxygen uptake during incremental exercise testing and categorized into quartiles. RC was estimated as total cholesterol minus HDL-C and low-density lipoprotein cholesterol, and elevated RC was defined as ≥38 mg/100 ml (90 percentile). Non-HDL-C was calculated as total cholesterol minus HDL-C, and high non-HLD-C was defined as ≥190 mg/100 ml. CRF was inversely associated with RC (ß -0.31, 95% confidence interval [CI] -0.39 to -0.24) and non-HDL-C (ß -0.34, 95% CI -0.57 to -0.11) after adjustment for several risk factors. Each metabolic equivalent increment in CRF was associated with lower odds of having elevated RC (odds ratio [OR] 0.85, 95% CI 0.77 to 0.93) and non-HDL-C (OR 0.93, 95% CI 0.85 to 1.00) in multivariable analysis. Compared with the bottom quartile, the top quartile of CRF had significantly lower odds of elevated RC (OR 0.63, 95% CI 0.45 to 0.88) and non-HDL-C (OR 0.68, 95% CI 0.51 to 0.91). In conclusion, higher CRF was independently associated with lower levels of RC and non-HDL-C and lower odds of the prevalence of elevated RC and non-HDL-C in healthy men.

How long do revised and multiply revised hip replacements last? A retrospective observational study of the National Joint Registry.

Background: Hip replacements are common and effective operations but patients that undergo this intervention are at risk of the replacements failing, requiring costly and often complex revision surgery with poorer outcomes than primary surgery. There is paucity of reliable data examining the treatment pathway for hip replacements over the life of the patient in terms of risk of revision and re-revisions. We aim to provide detailed information on the longevity of hip revision surgery. Methods: We did a retrospective observational registry-based study of the National Joint Registry, using data on hip replacements from all participating hospitals in England and Wales, UK. We included data on all first revisions, with an identifiable primary procedure, with osteoarthritis as the sole indication for the original primary procedure. Kaplan-Meier estimates were used to determine the cumulative probability of revision and subsequent re-revision after primary hip replacement. Analyses were stratified by age and gender, and the influence of time from first to second revision on the risk of further revision was explored. Findings: Between April 1, 2003, and Dec 31, 2019, there were 29 010 revision hip replacements with a linked primary episode. Revision rates of revision hip replacements were higher in patients younger than 55 years than in older age groups. After revision of primary total hip replacement, 21·3% (95% CI 18·6-24·4) of first revisions were revised again within 15 years, 22·3% (20·3-24·4) of second revisions were revised again within 7 years, and 22·3% (18·3-27·0) of third revisions were revised again within 3 years. After revision of hip resurfacing, 23·7% (95% CI 19·6-28·5) of these revisions were revised again within 15 years, 21·0% (17·0-25·8) of second revisions were revised again within 7 years, and 19·3% (11·9-30·4) of third revisions were revised again within 3 years. A shorter time between revision episodes was associated with earlier subsequent revision. Interpretation: Younger patients are at an increased risk of multiple revisions. Patients who undergo a revision have a steadily increasing risk of further revision the more procedures they undergo, and each subsequent revision lasts for approximately half the time of the previous one. Although hip replacements are effective for improving pain and function and usually last a remarkably long time, if they are revised, successive revisions are progressively and markedly less successful. Funding: NIHR Biomedical Research Centre at the University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Healthcare Quality Improvement Partnership; and the National Joint Registry.

Clinical effectiveness of patellar resurfacing, no resurfacing and selective resurfacing in primary total knee replacement: systematic review and meta-analysis of interventional and observational evidence.

BACKGROUND: Patellar resurfacing is optional during total knee replacement (TKR). Some surgeons always resurface the patella, some never resurface, and others selectively resurface. Which resurfacing strategy provides optimal outcomes is unclear. We assessed the effectiveness of patellar resurfacing, no resurfacing, and selective resurfacing in primary TKR. METHODS: A systematic review and meta-analysis was performed. MEDLINE, Embase, Web of Science, The Cochrane Library, and bibliographies were searched to November 2021 for randomised-control trials (RCTs) comparing outcomes for two or more resurfacing strategies (resurfacing, no resurfacing, or selective resurfacing) in primary TKR. Observational studies were included if limited or no RCTs existed for resurfacing comparisons. Outcomes assessed were patient reported outcome measures (PROMs), complications, and further surgery. Study-specific relative risks [RR] were aggregated using random-effects models. Quality of the evidence was assessed using GRADE. RESULTS: We identified 33 RCTs involving 5,540 TKRs (2,727 = resurfacing, 2,772 = no resurfacing, 41 = selective resurfacing). One trial reported on selective resurfacing. Patellar resurfacing reduced anterior knee pain compared with no resurfacing (RR = 0.65 (95% CI = 0.44-0.96)); there were no significant differences in PROMs. Resurfacing reduced the risk of revision surgery (RR = 0.63, CI = 0.42-0.94) and other complications (RR = 0.54, CI = 0.39-0.74) compared with no resurfacing. Quality of evidence ranged from high to very low. Limited observational evidence (5 studies, TKRs = 215,419) suggested selective resurfacing increased the revision risk (RR = 1.14, CI = 1.05-1.22) compared with resurfacing. Compared with no resurfacing, selective resurfacing had a higher risk of pain (RR = 1.25, CI = 1.04-1.50) and lower risk of revision (RR = 0.92, CI = 0.85-0.99). CONCLUSIONS: Level 1 evidence supports TKR with patellar resurfacing over no resurfacing. Resurfacing has a reduced risk of anterior knee pain, revision surgery, and complications, despite PROMs being comparable. High-quality RCTs involving selective resurfacing, the most common strategy in the UK and other countries, are needed given the limited observational data suggests selective resurfacing may not be effective over other strategies.

Clinical effectiveness and safety of spinal anaesthesia compared with general anaesthesia in patients undergoing hip fracture surgery using a consensus-based core outcome set and patient-and public-informed outcomes: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: We conducted a systematic review and meta-analysis of contemporary RCTs to determine the clinical effectiveness of spinal vs general anaesthesia (SA vs GA) in patients undergoing hip fracture surgery using a consensus-based core outcome set, and outcomes defined as important by patient and public involvement (PPI) initiatives. METHODS: RCTs comparing any of the core outcomes (mortality, time from injury to surgery, acute coronary syndrome, hypotension, acute kidney injury, delirium, pneumonia, orthogeriatric input, being out of bed at day 1 postoperatively, and pain) or PPI-defined outcomes (return to preoperative residence, quality of life, and mobility status) between SA and GA were identified from MEDLINE, Embase, Cochrane Library, and Web of Science (2000 to February 2022). Pooled relative risks (RRs) and mean differences (95% confidence intervals [CIs]) were estimated. RESULTS: There was no significant difference in the risk of delirium comparing SA vs GA (RR=1.07; 95% CI, 0.90-1.29). Comparing SA vs GA, the RR for mortality was 0.56 (95% CI, 0.22-1.44) in-hospital, 1.07 (95% CI, 0.52-2.23) at 30 days, and 1.08 (95% CI, 0.55-2.12) at 90 days. Spinal anaesthesia reduced the risk of acute kidney injury compared with GA: RR=0.59 (95% CI, 0.39-0.89). There were no significant differences in the risk of other outcomes. Few studies reported PPI-defined outcomes, with most studies reporting on one to three core outcomes. CONCLUSIONS: Except for acute kidney injury, there were no differences between SA and GA in hip fracture surgery when using a consensus-based core outcome set and patient and public involvement-defined outcomes. Most studies reported limited outcomes from the core outcome set, and few reported outcomes important to patients, which should be considered when designing future RCTs. PROSPERO REGISTRATION: CRD42021275206.

Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM): pragmatic, parallel group, open label, randomised controlled trial.

OBJECTIVES: To determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures. DESIGN: Pragmatic, parallel group, open label, randomised controlled trial. SETTING: High volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018. PARTICIPANTS: 140 adults (aged ≥18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision). INTERVENTIONS: A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure. MAIN OUTCOME MEASURES: The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included surgical complications and joint infection. The economic evaluation (only assessed in UK participants) compared quality adjusted life years and costs between the randomised groups. RESULTS: The mean age of participants was 71 years (standard deviation 9) and 51 (36%) were women. WOMAC scores did not differ between groups at 18 months (mean difference 0.13 (95% confidence interval -8.20 to 8.46), P=0.98); however, the single stage procedure was better at three months (11.53 (3.89 to 19.17), P=0.003), but not from six months onwards. Intraoperative events occurred in five (8%) participants in the single stage group and 20 (27%) in the two stage group (P=0.01). At 18 months, nine (14%) participants in the single stage group and eight (11%) in the two stage group had at least one marker of possible ongoing infection (P=0.62). From the perspective of healthcare providers and personal social services, single stage revision was cost effective with an incremental net monetary benefit of £11 167 (95% confidence interval £638 to £21 696) at a £20 000 per quality adjusted life years threshold (£1.0; $1.1; €1.4). CONCLUSIONS: At 18 months, single stage revision compared with two stage revision for prosthetic joint infection of the hip showed no superiority by patient reported outcome. Single stage revision had a better outcome at three months, fewer intraoperative complications, and was cost effective. Patients prefer early restoration of function, therefore, when deciding treatment, surgeons should consider patient preferences and the cost effectiveness of single stage surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN10956306.

Mortality and re-revision following single-stage and two-stage revision surgery for the management of infected primary knee arthroplasty in England and Wales : evidence from the National Joint Registry.

AIMS: We compared the risks of re-revision and mortality between two-stage revision surgery and single-stage revision surgery among patients with infected primary knee arthroplasty. METHODS: Patients with a periprosthetic joint infection (PJI) of their primary knee arthroplasty, initially revised with a single-stage or a two-stage procedure in England and Wales between 2003 and 2014, were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HR) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies. RESULTS: A total of 489 primary knee arthroplasties were revised with single-stage procedure (1,390 person-years) and 2,377 with two-stage procedure (8,349 person-years). The adjusted incidence rates of all-cause re-revision and for infection were comparable between these strategies (HR overall five years, 1.15 (95% confidence interval (CI) 0.87 to 1.52), p = 0.308; HR overall five years, 0.99 (95% CI 0.70 to 1.39), p = 0.949, respectively). Patients initially managed with single-stage revision received fewer revision procedures overall than after two-stage revision (1.2 vs 2.2, p < 0.001). Mortality was lower for single-stage revision between six and 18 months postoperative (HR at six months, 0.51 (95% CI 0.25 to 1.00), p = 0.049 HR at 18 months, 0.33 (95% CI 0.12 to 0.99), p = 0.048) and comparable at other timepoints. CONCLUSION: The risk of re-revision was similar between single- and two-stage revision for infected primary knee arthroplasty. Single-stage group required fewer revisions overall, with lower or comparable mortality at specific postoperative periods. The single-stage revision is a safe and effective strategy to treat infected knee arthroplasties. There is potential for increased use to reduce the burden of knee PJI for patients, and for the healthcare system.Cite this article: Bone Joint Res 2022;11(10):690-699.