Feasibility testing of a standardised virtual clinic for follow-up of patients after hip and knee arthroplasty.

INTRODUCTION: Over 200,000 hip and knee total joint arthroplasties (TJAs) are performed annually in England and Wales. UK guidelines recommend regular follow-up because missed early failure can result in complex revision surgery, which places additional burden on overstretched orthopaedic services. This study evaluated the feasibility and acceptability of an expert, consensus-based, standardised virtual clinic (VC) approach for TJA follow-up. METHODS: Five UK secondary care orthopaedic centres implemented a standardised VC. Feedback was obtained through patient satisfaction questionnaires and telephone interviews with arthroplasty care practitioners. Key stakeholders subsequently attended an expert discussion forum to achieve consensus on the final VC format and to address obstacles identified during testing. RESULTS: From 19 June 2018 to 11 December 2018, 561 TJA patients [mean age (SD) 70 (9.4) years, 57.8% female, 69.0% hip TJA, 1-28 years postsurgery (median 5 years)] completed a VC. Of these 561 patients, 82.2% were discharged without attending an outpatient appointment and 46 (8.8%) required early face-to-face consultant review. Patient satisfaction with the VC was high (156/188; 83.0%); over 70% of patients indicated a preference for the VC. DISCUSSION: This feasibility study suggested significant resource savings, including time spent by consultant orthopaedic surgeons in outpatient clinics, hospital transport and an estimated saving of up to two-thirds of usual clinic-allotted time. The expert discussion forum provided helpful feedback for supporting more efficient implementation of the VC. CONCLUSIONS: A standardised VC is a feasible alternative to outpatient clinics for the follow-up of hip and knee TJA patients, and is acceptable to key stakeholders, including patients.

Predictive factors for the development of surgical site infection in adults undergoing initial open inguinal hernia repair.

INTRODUCTION: Despite being one of the most commonly performed general surgery procedures, surgical site infection (SSI) is still seen in primary, elective, open inguinal hernia repair. Studies have reported a wide range of infection rates, yet predictive risk factors have not been definitely identified leading to variability and controversy in the use of pre-operative antibiotics. In this study, the authors seek to identify factors predictive of SSI development in a large cohort of patients undergoing initial unilateral open inguinal repair. METHODS: The American College of Surgery National Surgical Quality Improvement Program (ACS NSQIP) personal use file (PUF) database was queried for initial, open, reducible inguinal hernia repair cases in adults with clean surgical sites performed from 2012 to 2015 (CPT 49,505 and class one wound). Patient data were analyzed using univariate and multivariate analysis to identify factors predictive of surgical site infection. RESULTS: 57,951 cases were identified. 90.8% were men with an average age of 58.2 years and a median operative time of 53.0 min. Of all variables evaluated with univariate logistic regression, 17 demonstrated an association with surgical site infection. Performing multiple logistic regression on those 17 variables yielded 3 factors independently associated with surgical site infection: diabetes (OR 2.017, 95% CI 1.012-4.023), BMI ≥ 35 kg/m2 (OR 2.587, 95% CI 1.123-5.964), and current smoking (OR 2.071, 95% CI 1.126-3.811). CONCLUSION: Diabetes, BMI ≥ 35 kg/m2, and current smoking are significantly associated with an increased odds surgical site infection after initial, open, reducible inguinal hernia repair in adults with clean surgical sites.

Reverse hybrid total hip arthroplasty.

Aims: This study aimed to evaluate implant survival of reverse hybrid total hip arthroplasty (THA) at medium-term follow-up. Patients and Methods: A consecutive series of 1082 THAs in 982 patients with mean follow-up of 7.9 years (5 to 11.3) is presented. Mean age was 69.2 years (21 to 94). Of these, 194 (17.9%) were in patients under 60 years, 663 (61.3%) in female patients and 348 (32.2%) performed by a trainee. Head size was 28 mm in 953 hips (88.1%) or 32 mm in 129 hips (11.9%). Survival analysis was performed and subgroups compared using log rank tests. Results: Ten-year survival (122 hips at risk) was 97.2% (95% confidence interval (CI) 95.77 to 98.11) for all-cause revision. There was no difference in survival by age (p = 0.50), gender (p = 0.78), head size (p = 0.63) or surgeon grade (p = 0.36). No acetabular components underwent revision for aseptic loosening in the entire series. Four (0.4%) aseptic stem failures occurred early at a mean of 2.5 years (0.6 to 4.8) and were associated with age under 60 years (p = 0.015). There was no difference in survival by gender (p = 0.12), head size (p = 0.43) or surgeon grade (p = 0.77) for stem revision. Conclusion: This is the largest reported study into reverse hybrid THA and it confirms successful outcomes, irrespective of age, gender, head size and surgeon grade. Cite this article: Bone Joint J 2018;100-B:1010-17.

Three cases of localized cutaneous nodular amyloidosis in patients with limited systemic sclerosis and a brief literature review.

Localized cutaneous nodular amyloidosis (LCNA) is the rarest form of localized cutaneous amyloidosis. In patients with LCNA, local plasma cells secrete immunoglobulin light chains called amyloid L via an unknown mechanism. LCNA has been associated with autoimmune connective tissue diseases such as most commonly Sjögren syndrome. A few reported cases of LCNA are associated with limited systemic sclerosis (LSSc). We report three cases of LCNA in patients with LSSc to add to the existing literature, discuss the disease association and proposed pathophysiology, and briefly review the existing information in current literature. It is important to closely follow patients with LCNA to monitor progression to systemic amyloidosis.

Inhibitors of DNA Methylation, Histone Deacetylation, and Histone Demethylation: A Perfect Combination for Cancer Therapy.

Epigenetic silencing and inappropriate activation of gene expression are frequent events during the initiation and progression of cancer. These events involve a complex interplay between the hypermethylation of CpG dinucleotides within gene promoter and enhancer regions, the recruitment of transcriptional corepressors and the deacetylation and/or methylation of histone tails. These epigenetic regulators act in concert to block transcription or interfere with the maintenance of chromatin boundary regions. However, DNA/histone methylation and histone acetylation states are reversible, enzyme-mediated processes and as such, have emerged as promising targets for cancer therapy. This review will focus on the potential benefits and synergistic/additive effects of combining DNA-demethylating agents and histone deacetylase inhibitors or lysine-specific demethylase inhibitors together in epigenetic therapy for solid tumors and will highlight what is known regarding the mechanisms of action that contribute to the antitumor response.

Is a questionnaire and radiograph-based follow-up model for patients with primary hip and knee arthroplasty a viable alternative to traditional regular outpatient follow-up clinic?

AIMS: Increasing demand for total hip and knee arthroplasty (THA/TKA) and associated follow-up has placed huge demands on orthopaedic services. Feasible follow-up mechanisms are therefore essential. METHODS: We conducted an audit of clinical follow-up decision-making for THA/TKA based on questionnaire/radiograph review compared with local practice of Arthroplasty Care Practitioner (ACP)-led outpatient follow-up. In all 599 patients attending an ACP-led THA/TKA follow-up clinic had a pelvic/knee radiograph, completed a pain/function questionnaire and were reviewed by an ACP. An experienced orthopaedic surgeon reviewed the same radiographs and questionnaires, without patient contact or knowledge of the ACP's decision. Each pathway classified patients into: urgent review, annual monitoring, routine follow-up or discharge. RESULTS: In total, 401 hip and 198 knee patients were included. There was substantial agreement between the ACP and surgeon for both hip (kappa = 0.69, 95% confidence interval (CI) 0.62 to 0.76) and knee (kappa = 0.81, 95% CI 0.74 to 0.88). Positive agreement was very high for discharge and routine follow-up; however the ACP was more likely to select annual monitoring and the surgeon urgent review. DISCUSSION: Review of the questionnaire/radiograph together identified all patients in need of increased surveillance, with good agreement for on-going patient management. However, review of the radiograph or questionnaire alone missed some patients with potential problems. A radiograph in conjunction with a questionnaire as a review may represent a cost effective THA/TKA follow-up mechanism. TAKE HOME MESSAGE: A questionnaire and radiograph-based remote review may represent a cost-effective total joint arthroplasty follow-up mechanism; thereby reducing the considerable burden that follow-up currently places on the NHS.

Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis.

OBJECTIVE: To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS). METHOD: We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon-intron boundaries, and 5 kb flanking DNA in the 5' and 3' UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p<0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into 'mild' and 'severe' groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration. RESULTS: Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10(-5)), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10(-3)). There was no observed association between radiographic severity and HLA-B*27. CONCLUSIONS: These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.

Hyperpharmacotherapy in ageing cystic fibrosis patients: The first report of an atypical hip fracture.

Cystic fibrosis (CF) is a common autosomal recessive disorder in Caucasian populations with respiratory, gastrointestinal and endocrine manifestations. Thanks to recent advances in medical therapies and infection control, life expectancy of a patient with CF has significantly increased from less than 5 years in the mid-1900s to almost 50 years nowadays. However, as CF patients are living longer, multimorbidity and Hyperpharmacotherapy are becoming more common. This case illustrates a cascade of problems that ensued from medication side-effects, highlighting the increasing challenge of managing an ageing CF population.

Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: efficacy and safety results from a randomized open-label study.

Denosumab has been shown to reduce new vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis. In subjects who were treatment-naïve or previously treated with alendronate, denosumab was associated with greater gains in bone mineral density (BMD) and decreases in bone turnover markers when compared with alendronate-treated subjects. This trial was designed to compare the efficacy and safety of denosumab with risedronate over 12 months in postmenopausal women who transitioned from daily or weekly alendronate treatment and were considered to be suboptimally adherent to therapy. In this randomized, open-label study, postmenopausal women aged ≥55 years received denosumab 60 mg subcutaneously every 6 months or risedronate 150 mg orally every month for 12 months. Endpoints included percentage change from baseline in total hip BMD (primary endpoint), femoral neck, and lumbar spine BMD at month 12, and percentage change from baseline in sCTX-1 at months 1 and 6. Safety was also assessed. A total of 870 subjects were randomized (435, risedronate; 435, denosumab) who had a mean (SD) age of 67.7 (6.9) years, mean (SD) BMD T-scores of -1.6 (0.9), -1.9 (0.7), and -2.2 (1.2) at the total hip, femoral neck, and lumbar spine, respectively, and median sCTX-1 of 0.3 ng/mL at baseline. At month 12, denosumab significantly increased BMD compared with risedronate at the total hip (2.0% vs 0.5%), femoral neck (1.4% vs 0%), and lumbar spine (3.4% vs 1.1%; p<0.0001 at all sites). Denosumab significantly decreased sCTX-1 compared with risedronate at month 1 (median change from baseline of -78% vs -17%; p<0.0001) and month 6 (-61% vs -23%; p<0.0001). Overall and serious adverse events were similar between groups. In postmenopausal women who were suboptimally adherent to alendronate therapy, transitioning to denosumab was well tolerated and more effective than risedronate in increasing BMD and reducing bone turnover.

Inelastic neutron scattering study of a nonmagnetic collapsed tetragonal phase in nonsuperconducting CaFe2As2: evidence of the impact of spin fluctuations on superconductivity in the iron-arsenide compounds.

The relationship between antiferromagnetic spin fluctuations and superconductivity has become a central topic of research in studies of superconductivity in the iron pnictides. We present unambiguous evidence of the absence of magnetic fluctuations in the nonsuperconducting collapsed tetragonal phase of CaFe2As2 via inelastic neutron scattering time-of-flight data, which is consistent with the view that spin fluctuations are a necessary ingredient for unconventional superconductivity in the iron pnictides. We demonstrate that the collapsed tetragonal phase of CaFe2As2 is nonmagnetic, and discuss this result in light of recent reports of high-temperature superconductivity in the collapsed tetragonal phase of closely related compounds.

Olfactory cues increase avoidance behavior and induce Fos expression in the amygdala, hippocampus and prefrontal cortex of socially defeated mice.

Genes and proteins of the Fos family are used as markers of neuronal activity and can be modulated by stress. This study investigated whether social defeat (SD) or exposure to an olfactory cue associated with the SD experience activated Fos and FosB/DeltaFosB (ΔFosB) expression in brain regions implicated in the development of post-traumatic stress disorder. Mice exposed to acute SD showed more Fos positive cells in the basolateral amygdala (BLA), CA1 of the hippocampus and the medial prefrontal cortex (mPFC) 1h after SD, and had greater expression of the more persistent FosB/ΔFosB protein in the BLA 24 h after SD compared to controls. Mice exposed to an olfactory cue 24 h or 7 days after SD had higher levels of Fos expression in all three regions 1h after exposure to the cue, and displayed increased avoidance behavior compared to controls. While the avoidance response dissipated with time (less at 7 day vs 24 h after social defeat), Fos expression in the mPFC and CA1 in response to an olfactory cue was greater at 7 days relative to 24 h after social defeat. The results suggest additional processing of the cue-stress association and may provide further support for a role of the mPFC in fear inhibition. These findings may have implications for brain regions and circuitry involved in the avoidance of cues associated with a stressful event that may lead to context-dependent adaptive or maladaptive behavior.

Litigation after hip and knee replacement in the National Health Service.

The results of hip and knee replacement surgery are generally regarded as positive for patients. Nonetheless, they are both major operations and have recognised complications. We present a review of relevant claims made to the National Health Service Litigation Authority. Between 1995 and 2010 there were 1004 claims to a value of £41.5 million following hip replacement surgery and 523 claims to a value of £21 million for knee replacement. The most common complaint after hip surgery was related to residual neurological deficit, whereas after knee replacement it was related to infection. Vascular complications resulted in the highest costs per case in each group.Although there has been a large increase in the number of operations performed, there has not been a corresponding relative increase in litigation. The reasons for litigation have remained largely unchanged over time after hip replacement. In the case of knee replacement, although there has been a reduction in claims for infection, there has been an increase in claims for technical errors. There has also been a rise in claims for non-specified dissatisfaction. This information is of value to surgeons and can be used to minimise the potential mismatch between patient expectation, informed consent and outcome.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

SUMMARY: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). CONCLUSION: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

Perioperative management of patients with cardiac implantable electronic devices.

Many anaesthesia practitioners caring for patients with a cardiac implantable electronic device (CIED) lack the knowledge, experience, and requisite programming devices to independently manage these patients perioperatively. A recently updated ASA task force Practice Advisory presents expert opinion regarding the perioperative management of patients with CIEDs, and the Heart Rhythm Society (HRS) recently published a consensus statement on this subject in collaboration with the ASA, American Heart Association (AHA), and Society of Thoracic Surgeons (STS). The main intent of these documents is to provide recommendations that promote safe management of patients with CIEDs throughout the perioperative period and reduce the likelihood of adverse outcomes. Reviews of this topic focusing on the actions of the anaesthesiologist have been published, but a multidisciplinary approach to the perioperative management is now advocated. In emergent situations, however, or when there is no time for the requisite consultations, and in practice settings where the suggested multidisciplinary approach is simply not feasible, the anaesthesia team must still provide effective, safe perioperative management. Thus, all anaesthesiologists should become familiar with the basics of the current CIED technology and the essential tenets of perioperative CIED management. This review discusses relevant advances in CIED technology and practical perioperative management as outlined in the 2011 ASA Practice Advisory and HRS consensus statement.

Promoting discussions and decisions about dogs' quality-of-life.

OBJECTIVE: The objective of this paper is to report the formulation and preliminary testing of a participatory tool in order to encourage discussions and decisions about dogs' quality-of-life. MATERIALS AND METHODS: A tool was designed in which owners rated aspects of their dog's quality-of-life. Two randomised controlled trials were conducted: one with a veterinary surgeon who was involved in the tool design, the second with other veterinary surgeons. In each, owners either were given the tool before a veterinary consultation or underwent normal consultations. After each consultation, owners were asked to report what they had discussed and what decisions they had made. RESULTS: The study involved a total of 170 consultations, of which 91 were randomly allocated to the tool group and 79 into the control group. In both trials, using the tool was associated with a significant increase in the frequency of discussions. In the first trial, using the tool was also associated with an increase in the number of decisions made, but this was not found in the second trial with practitioners who were not involved in the trial design. CLINICAL SIGNIFICANCE: These data suggest that the use of a participatory tool has the potential to enhance the effectiveness of consultations, especially if the practitioner is familiar with the tool design.

Ultrathin aluminum sample cans for single crystal inelastic neutron scattering.

Single crystal inelastic neutron scattering measurements are often performed using a sample environment for controlling sample temperature. One difficulty associated with this is establishing appropriate thermal coupling from the sample to the temperature controlled portion of the sample environment. This is usually accomplished via a sample can which thermally couples the sample environment to the sample can and the sample can to the sample via an exchange gas. Unfortunately, this can will contribute additional background signal to one's measurement. We present here the design of an ultrathin aluminum sample can based upon established technology for producing aluminum beverage cans. This design minimizes parasitic sample can scattering. Neutron scattering measurements comparing a machined sample can to our beverage can design clearly indicate a large reduction in scattering intensity and texture when using the ultrathin sample can design. We also examine the possibility of using standard commercial beverage cans as sample cans.

Topoisomerase IIalpha maintains genomic stability through decatenation G(2) checkpoint signaling.

Topoisomerase IIalpha (topoIIalpha) is an essential mammalian enzyme that topologically modifies DNA and is required for chromosome segregation during mitosis. Previous research suggests that inhibition of topoII decatenatory activity triggers a G(2) checkpoint response, which delays mitotic entry because of insufficient decatenation of daughter chromatids. Here we examine the effects of both topoIIalpha and topoIIbeta on decatenatory activity in cell extracts, DNA damage and decatenation G(2) checkpoint function, and the frequencies of p16(INK4A) allele loss and gain. In diploid human fibroblast lines, depletion of topoIIalpha by small-interfering RNA was associated with severely reduced decatenatory activity, delayed progression from G(2) into mitosis and insensitivity to G(2) arrest induced by the topoII catalytic inhibitor ICRF-193. Furthermore, interphase nuclei of topoIIalpha-depleted cells showed increased frequencies of losses and gains of the tumor suppressor genetic locus p16(INK4A). This study shows that the topoIIalpha protein is required for decatenation G(2) checkpoint function, and inactivation of decatenation and the decatenation G(2) checkpoint leads to abnormal chromosome segregation and genomic instability.