Physiological and performance effects of live high train low altitude training for elite endurance athletes: A narrative review.

Altitude training has become an important training application for athletes due its potential for altering physiology and enhancing performance. This practice is commonly used by athletes, with a popular choice being the live high - train low approach. This model recommends that athletes live at high altitude (1250-3000 m), but train at low altitude or sea-level (0-1200 m). Exposure to altitude often leads to hypoxic stress and in turn stimulates changes in total haemoglobin mass, erythropoietin, and soluble transferrin receptors, which alter further underlying physiology. Through enhanced physiology, improved exercise performance may arise through enhancement of the oxygen transport system which is important for endurance events. Previous investigations into the effects of altitude training on exercise performance have been completed in a range of contexts, including running, cycling, swimming, and triathlon. Often following a LHTL altitude intervention, athletes realise improvements in maximal oxygen consumption capacity, time trial performance and peak power outputs. Although heterogeneity exists among LHTL methodologies, i.e., exposure durations and altitude ranges, we synthesised this data into kilometre hours, and found that the most common hypoxic doses used in LHTL interventions ranged from ∼578-687 km h. As this narrative review demonstrates, there are potential advantages to using altitude training to enhance physiology and improve performance for endurance athletes.

Regional differences in the reduction in cerebral FDG uptake induced by the ketogenic diet.

BACKGROUND: The postulated benefits of the ketogenic diet in the management of multiple medical conditions have seen more patients who are in therapeutic ketosis attending 18F-FDG PET scans. This study aimed to investigate the effect of ketosis on cerebral glucose metabolism in a clinical PET scanning environment using 18F-FDG uptake as a surrogate marker. METHODS: A retrospective audit was conducted of the brain 18F-FDG uptake in 52 patients who underwent PET scans for possible cardiac sarcoidosis or suspected intracardiac infection, following a ketogenic diet and prolonged fasting. SUVbw for whole brain and separate brain regions was compared with serum glucose and serum ketone body (beta-hydroxybutyrate) levels. RESULTS: The expected negative association between serum glucose levels and whole brain 18F-FDG uptake was confirmed. A reduction in SUVbw due to increasing serum ketones levels was also observed that was independent of and in addition to the effects of glucose. The magnitude of the reduction in SUVbw related to serum glucose level and serum ketone level was found to be greater in the precuneus than in the cerebellum or whole brain. CONCLUSION: In a real-world clinical PET setting, cerebral 18F-FDG uptake appears to be affected by glycaemia and ketonaemia. This means when assessing the brain, both serum glucose and ketone levels need to be considered when SUVs are used to distinguish between pathologic and physiologic states. The magnitude of this effect appears to vary between different brain regions. This regional difference should be taken into consideration when selecting the appropriate brain region for SUV normalisation, particularly when undertaking database comparison in the assessment of dementia.

UK reporting radiographers' perceptions of AI in radiographic image interpretation - Current perspectives and future developments.

INTRODUCTION: Radiographer reporting is accepted practice in the UK. With a national shortage of radiographers and radiologists, artificial intelligence (AI) support in reporting may help minimise the backlog of unreported images. Modern AI is not well understood by human end-users. This may have ethical implications and impact human trust in these systems, due to over- and under-reliance. This study investigates the perceptions of reporting radiographers about AI, gathers information to explain how they may interact with AI in future and identifies features perceived as necessary for appropriate trust in these systems. METHODS: A Qualtrics® survey was designed and piloted by a team of UK AI expert radiographers. This paper reports the third part of the survey, open to reporting radiographers only. RESULTS: 86 responses were received. Respondents were confident in how an AI reached its decision (n = 53, 62%). Less than a third of respondents would be confident communicating the AI decision to stakeholders. Affirmation from AI would improve confidence (n = 49, 57%) and disagreement would make respondents seek a second opinion (n = 60, 70%). There is a moderate trust level in AI for image interpretation. System performance data and AI visual explanations would increase trust. CONCLUSIONS: Responses indicate that AI will have a strong impact on reporting radiographers' decision making in the future. Respondents are confident in how an AI makes decisions but less confident explaining this to others. Trust levels could be improved with explainable AI solutions. IMPLICATIONS FOR PRACTICE: This survey clarifies UK reporting radiographers' perceptions of AI, used for image interpretation, highlighting key issues with AI integration.

Prenatal origins of temperament: Fetal cardiac development & infant surgency, negative affectivity, and regulation/orienting.

Temperament, i.e. individual differences in reactivity and self-regulation, emerges early in infancy; might temperament originate during fetal development? Mixed findings and methodological issues in the literature examining this consideration limit our understanding of the continuity between these fetal indices and infant temperament. The primary aims of the current study were to improve on published studies by (a) using standardized and well-accepted fetal cardiac (actocardiograph) and infant temperament measures (the Infant Behavior Questionnaire-Revised; IBQ-R) (b) expanding fetal assessments to include coupling (the cross correlation of heart rate with movement), and (c) examining a diverse sample to determine if findings of associations between fetal neurobehavior and infant temperament generalize beyond cohorts that are demographically well-resourced and predominantly white. Building on theory and empirical findings, we hypothesized that (1) FHR would be positively associated with Surgency and Negative Affectivity, (2) FHRV would be positively associated with Surgency, and Regulation/Orienting and inversely associated with Negative Affectivity, and (3) fetal coupling would be positively associated with Regulation/Orienting and Surgency and inversely associated with Negative Affectivity. We collected 20 min of fetal data (m gestational age = 34.42 weeks) and mothers completed the IBQ-R (n = 90 women; 60 % non-Caucasian race; 63 % Latina ethnicity). We found that FHR was positively associated with Negative Affectivity but not associated with Surgency (or Regulation/Orienting). FHRV was inversely associated with Surgency but not associated with Negative Affectivity or Regulation/Orienting. Coupling was positively associated with Regulation/Orienting and Surgency but not associated with Negative Affectivity. Our findings, from a more diverse sample and with established measures, provide further evidence that individual differences in reactivity and regulation can be identified in the in-utero period and show theory-based continuity to specific infant temperament constructs.

Altered mapping of sound frequency to cochlear place in ears with endolymphatic hydrops provide insight into the pitch anomaly of diplacusis.

A fundamental property of mammalian hearing is the conversion of sound pressure into a frequency-specific place of maximum vibration along the cochlear length, thereby creating a tonotopic map. The tonotopic map makes possible systematic frequency tuning across auditory-nerve fibers, which enables the brain to use pitch to separate sounds from different environmental sources and process the speech and music that connects us to people and the world. Sometimes a tone has a different pitch in the left and right ears, a perceptual anomaly known as diplacusis. Diplacusis has been attributed to a change in the cochlear frequency-place map, but the hypothesized abnormal cochlear map has never been demonstrated. Here we assess cochlear frequency-place maps in guinea-pig ears with experimentally-induced endolymphatic hydrops, a hallmark of Ménière's disease. Our findings are consistent with the hypothesis that diplacusis is due to an altered cochlear map. Map changes can lead to altered pitch, but the size of the pitch change is also affected by neural synchrony. Our data show that the cochlear frequency-place map is not fixed but can be altered by endolymphatic hydrops. Map changes should be considered in assessing hearing pathologies and treatments.

Dissecting the Role of VicK Phosphatase in Aggregation and Biofilm Formation of Streptococcus mutans.

VicRK (WalRK or YycFG) is a conserved 2-component regulatory system (TCS) that regulates cell division, cell wall biosynthesis, and homeostasis in low-GC Gram-positive bacteria. VicRK is also associated with biofilm formation of Streptococcus mutans on the tooth surface as it directly regulates the extracellular polysaccharide (EPS) synthesis. Of the 2 components, VicK possesses both autokinase and phosphatase activities, which regulate the phosphorylation and dephosphorylation of the regulator VicR in response to environmental cues. However, the dual mechanism of VicK as the autokinase/phosphatase in regulating S. mutans' responses is not well elucidated. Previously, it has been shown that the phosphatase activity depends on the PAS domain and residues in the DHp domain of VicK in S. mutans. Specifically, mutating proline at 222 in the PAS domain inhibits VicK phosphatase activity. We generated a VicKP222A mutant to determine the level of VicR-P in the cytoplasm by Phos-tag sodium dodecyl sulfate polyacrylamide gel electrophoresis. We show that in VicKP222A phosphatase, attenuation increased phosphorylated VicR (VicR-P) that downregulated glucosyltransferases, gtfBC, thereby reducing the synthesis of water-insoluble polysaccharides (WIS-EPS) in the biofilm. In addition, VicKP222A presented as long-rod cells, reduced growth, and displayed asymmetrical division. A major adhesin of S. mutans, SpaP was downregulated in VicKP222A, making it unable to agglutinate in saliva. In summary, we have confirmed that VicK phosphatase activity is critical to maintain optimal phosphorylation status of VicR in S. mutans, which is important for cell growth, cell division, EPS synthesis, and bacterial agglutination in saliva. Hence, VicK phosphatase activity may represent a promising target to modulate S. mutans' pathogenicity.

Racial disparities in pre-operative pain, function and disease activity for patients with rheumatoid arthritis undergoing Total knee or Total hip Arthroplasty: a New York based study.

BACKGROUND: Black and Hispanic patients with osteoarthritis have more pain and worse function than Whites at the time of arthroplasty. Whether this is true for patients with rheumatoid arthritis (RA) is unknown. METHODS: This cross-sectional study used data on RA patients acquired between October 2013 and November 2018 prior to elective total knee (TKA) or hip arthroplasty (THA). Pain, function, and disease activity were assessed using the visual analogue scale (VAS), the Multidimensional Health Assessment Questionnaire (MDHAQ), and the Disease Activity Score (DAS28-ESR). We linked the cases to census tracts using geocoding to determine the community poverty level. Race, education, income, insurance and medications were collected via self-report. Using multivariable linear and logistic models we examined whether minority status predicted pain, function and RA disease activity at the time of arthroplasty. RESULTS: Thirty seven (23%) of the 164 patients were Black or Hispanic (minorities). The MDHAQ and DAS28-ESR were not significantly worse while VAS pain score was significantly worse in minority patients (p = 0.03). There was no significant difference in education between the groups. Insurance varied significantly; 29% of minority patients had Medicaid vs. 0% of Whites (p < 0.0001). In the multivariable analyses minority status was not significantly associated with DAS28-ESR [p = 0.66], MDHAQ [p = 0.26], or VAS pain [p = 0.18]. CONCLUSIONS: For Black and/or Hispanic patients with RA undergoing THA or TKA at a high-volume specialty hospital, unlike Black or Hispanic patients with osteoarthritis (OA), there was no association with worse pain, function, or RA disease activity at the time of elective arthroplasty.

Early Detection of Endolymphatic Hydrops using the Auditory Nerve Overlapped Waveform (ANOW).

Endolymphatic hydrops is associated with low-frequency sensorineural hearing loss, with a large body of research dedicated to examining its putative causal role in low-frequency hearing loss. Investigations have been thwarted by the fact that hearing loss is measured in intact ears, but gold standard assessments of endolymphatic hydrops are made postmortem only; and that no objective low-frequency hearing measure has existed. Yet the association of endolymphatic hydrops with low-frequency hearing loss is so strong that it has been established as one of the important defining features for Ménière's disease, rendering it critical to detect endolymphatic hydrops early, regardless of whether it serves a causal role or is the result of other disease mechanisms. We surgically induced endolymphatic hydrops in guinea pigs and employed our recently developed objective neural measure of low-frequency hearing, the Auditory Nerve Overlapped Waveform (ANOW). Hearing loss and endolymphatic hydrops were assessed at various time points after surgery. The ANOW detected low-frequency hearing loss as early as the first day after surgery, well before endolymphatic hydrops was found histologically. The ANOW detected low-frequency hearing loss with perfect sensitivity and specificity in all ears after endolymphatic hydrops developed, where there was a strong linear relationship between degree of endolymphatic hydrops and severity of low-frequency hearing loss. Further, histological data demonstrated that endolymphatic hydrops is seen first in the high-frequency cochlear base, though the ANOW demonstrated that dysfunction begins in the low-frequency apical cochlear half. The results lay the groundwork for future investigations of the causal role of endolymphatic hydrops in low-frequency hearing loss.

Comparative efficacy of epidural clonidine versus epidural fentanyl for treating breakthrough pain during labor: a randomized double-blind clinical trial.

BACKGROUND: Breakthrough pain during neuraxial labor analgesia is typically alleviated with additional administration of epidural local anesthetics, with or without adjuvants. Sometimes avoiding neuraxial opioids may be warranted and clonidine is an alternative. In a randomized double-blind trial we compared the efficacy of clonidine versus fentanyl, added to bupivacaine, for the management of breakthrough pain. METHODS: Term parturients (n=98) receiving bupivacaine 0.0625% with fentanyl 2 µg/mL at 12 mL/h, a patient-administered bolus of 5 mL at lockout 6-10 min and a maximum of four boluses per hour, and experiencing breakthrough pain ≥5/10, were randomized to receive a 10 mL bolus containing 12.5 mg bupivacaine and either clonidine 100 µg or fentanyl 100 µg. The primary outcome was 'success' of study drug treatment, defined as a pain score reduction ≥4/10 within 15 min of administration. Maternal hemodynamics and fetal heart rate were documented for two hours after treatment. RESULTS: There was no significant difference between groups in success rates (66.0% after clonidine (n=47) vs 74.5% after fentanyl (n=51), P=0.48) or in the incidence of hypotension (systolic blood pressure ≤80% of baseline or <90 mmHg) or sedation at 15 min, with 2/51 and 1/47 subjects in the fentanyl and clonidine groups, respectively, receiving phenylephrine. CONCLUSION: Epidural clonidine 100 µg was not superior to fentanyl 100 µg for decreasing pain scores within 15 min of co-administration with bupivacaine 0.125% for intrapartum breakthrough pain. The analgesic efficacy and hemodynamic side effects did not significantly differ.

Redirecting the immune response towards immunoprotective domains of a DNABII protein resolves experimental otitis media.

The chronicity and recurrence of many bacterial diseases is largely attributable to the presence of a biofilm, and eradication of these structures is confounded by an extracellular DNA-rich matrix. DNABII proteins, including integration host factor (IHF), are critical components of the matrix formed by all human pathogens tested to date. Whereas the natural adaptive immune response to IHF is against non-protective epitopes within the carboxyl-terminal region, antibodies against the DNA-binding "tips" induce biofilm collapse. We designed a "tip-chimer" immunogen to mimic the DNA-binding regions within the α-subunit and ß-subunit of IHF from nontypeable Haemophilus influenzae (IHFNTHi). Re-direction of the natural adaptive immune response toward immunoprotective domains disrupted NTHi biofilms in vitro and in an experimental model of otitis media. Our data support the rational design of a powerful therapeutic approach, and also that of a DNABII-directed vaccine antigen that would avoid augmentation of any pre-existing natural, but nonprotective, immune response.

Hip or spine surgery first?: a survey of treatment order for patients with concurrent degenerative hip and spinal disorders

AIMS: Patients may present with concurrent symptomatic osteoarthritis (OA) of the hip and degenerative disorders of the lumbar spine, with surgical treatment being indicated for both. Whether arthroplasty of the hip or spinal surgery should be performed first remains uncertain. MATERIALS AND METHODS: Clinical scenarios were devised for a survey asking the preferred order of surgery and the rationale for this decision for five fictional patients with both OA of the hip and degenerative lumbar disorders. These were symptomatic OA of the hip and: 1) lumbar spinal stenosis with neurological claudication; 2) lumbar degenerative spondylolisthesis with leg pain; 3) lumbar disc herniation with leg weakness; 4) lumbar scoliosis with back pain; and 5) thoracolumbar disc herniation with myelopathy. This survey was sent to 110 members of The Hip Society and 101 members of the Scoliosis Research Society. The choices of the surgeons were compared among scenarios and between surgical specialties using the chi-squared test. The free-text comments were analyzed using text-mining. RESULTS: Responses were received from 51 hip surgeons (46%) and 37 spine surgeons (37%). The percentages of hip surgeons recommending 'hip first' differed significantly among scenarios: 59% for scenario 1; 73% for scenario 2; 47% for scenario 3; 47% for scenario 4; and 10% for scenario 5 (p < 0.001). The percentages of spine surgeons recommending 'hip first' were 49% for scenario 1; 70% for scenario 2; 19% for scenario 3; 78% for scenario 4; and 0% for scenario 5. There were significant differences between the groups for scenarios 3 (more hip surgeons recommended 'hip first'; p = 0.012) and 4 (more hip surgeons recommended 'spine first'; p = 0.006). CONCLUSION: In patients with coexistent OA of the hip and degenerative disorders of the spine, the question of 'hip or spinal surgery first' elicits relatively consistent answers in some clinical scenarios, but remains controversial in others, even for experienced surgeons. The nature of neurological symptoms can influence surgeons' decision-making. Cite this article: Bone Joint J 2019;101-B(6 Supple B):37-44.

Cytotoxicity of drugs injected into joints in orthopaedics.

OBJECTIVES: Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro. METHODS: Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed. RESULTS: Using LA or GC, especially triamcinolone acetonide, a dilution of 1:100 resulted in only a moderate reduction of viability, while a dilution of 1:10 showed significantly fewer cell counts. TA and CA reduced viability significantly at a dilution of 1:2. Higher dilutions did not affect viability. Notably, HA showed no effects of cytotoxicity in all drug dilutions. CONCLUSION: The toxicity of common intra-articular injectable drugs, assessed by cell viability, is mainly dependent on the dilution of the drug being tested. LA are particularly toxic, whereas HA did not affect cell viability.Cite this article: P. Busse, C. Vater, M. Stiehler, J. Nowotny, P. Kasten, H. Bretschneider, S. B. Goodman, M. Gelinsky, S. Zwingenberger. Cytotoxicity of drugs injected into joints in orthopaedics. Bone Joint Res 2019;8:41-48. DOI: 10.1302/2046-3758.82.BJR-2018-0099.R1.

The vector ecology of introduced Culex quinquefasciatus populations, and implications for future risk of West Nile virus emergence in the Galápagos archipelago.

Culex quinquefasciatus Say (Diptera: Culicidae), an important vector of West Nile virus (WNV) in the U.S.A., was first detected on the Galápagos Islands (Ecuador) in the 1980s. However, little is known of its ecology, distribution or capacity for arbovirus transmission in the Galápagos. We characterize details of lifecycle (including gonotrophic period), temporal abundance, spatial distribution, vector competence and host-feeding behaviour. Culex quinquefasciatus was detected on five islands of the Galápagos during 2006-2011. A period of 7-14 days was required for egg-adult emergence; water salinity above 5 ppt was demonstrated to hinder larval development. Blood-meal analysis indicated feeding on reptiles, birds and mammals. Assessment of WNV vector competency of Galápagos C. quinquefasciatus showed a median infectious dose of 7.41 log10 plaque-forming units per millilitre and evidence of vertical transmission (minimal filial infection rate of 3.7 per 1000 progeny). The distribution of C. quinquefasciatus across the archipelago could be limited by salt intolerance, and its abundance constrained by high temperatures. Feeding behaviour indicates potential to act as a bridge vector for transmission of pathogens across multiple taxa. Vertical transmission is a potential persistence mechanism for WNV on Galápagos. Together, our results can be used for epidemiological assessments of WNV and target vector control, should this pathogen reach the Galápagos Islands.

Metal-on-metal total hip arthroplasty is not associated with cardiac disease.

AIMS: Many case reports and small studies have suggested that cobalt ions are a potential cause of cardiac complications, specifically cardiomyopathy, after metal-on-metal (MoM) total hip arthroplasty (THA). The impact of metal ions on the incidence of cardiac disease after MoM THA has not been evaluated in large studies. The aim of this study was to compare the rate of onset of new cardiac symptoms in patients who have undergone MoM THA with those who have undergone metal-on-polyethylene (MoP) THA. PATIENTS AND METHODS: Data were extracted from the Standard Analytics Files database for patients who underwent MoM THA between 2005 and 2012. Bearing surface was selected using International Classification of Diseases ninth revision codes. Patients with a minimum five-year follow-up were selected. An age and gender-matched cohort of patients who underwent MoP THA served as a comparison group. New diagnoses of cardiac disease were collected during the follow-up period. Comorbidities and demographics were identified and routine descriptive statistics were used. RESULTS: We identified 29 483 patients who underwent MoM THA and 24 175 matched patients who underwent MoP THA. Both groups had a mean Charlson comorbidity index score of 4. There were no statistically significant differences in 30 of 31 pre-existing comorbidities. Patients undergoing MoM THA had a slightly lower incidence of cardiac failure compared with those undergoing MoP THA at three years (6.60% versus 7.06%, odds ratio (OR) 0.93, 95% confidence interval (CI) 0.87 to 0.99) and four years (8.73% versus 9.49%, OR 0.91, 95% CI 0.86 to 0.97) postoperatively, with no difference in the incidence of new cardiac failure in between the groups at five years. There was no statistically significant difference in the incidence of arrhythmia, myocardial infarction and cardiomyopathy at any time between the two groups. CONCLUSION: MoM THA is not associated with cardiac complications. Initial reports may have represented individual instances of cardiac disease in patients with a failing MoM articulation rather than an emerging epidemiological trend. Cite this article: Bone Joint J 2018;100-B:28-32.

An evidence-based guide to the treatment of osteonecrosis of the femoral head.

Non-traumatic osteonecrosis of the femoral head is a potentially devastating condition, the prevalence of which is increasing. Many joint-preserving forms of treatment, both medical and surgical, have been developed in an attempt to slow or reverse its progression, as it usually affects young patients. However, it is important to evaluate the best evidence that is available for the many forms of treatment considering the variation in the demographics of the patients, the methodology and the outcomes in the studies that have been published, so that it can be used effectively. The purpose of this review, therefore, was to provide an up-to-date, evidence-based guide to the management, both non-operative and operative, of non-traumatic osteonecrosis of the femoral head. Cite this article: Bone Joint J 2017;99-B:1267-79.

Novel method for the depletion of cariogenic bacteria using dextranomer microspheres.

Streptococcus mutans is recognized as one of the key contributors to the dysbiotic state that results in dental caries. Existing treatment strategies reduce the incidence of tooth decay, but they also eliminate both the cariogenic and beneficial microbes. Here we introduce a novel treatment alternative using Sephadex, cross-linked dextranomer microspheres (DMs), typically used for gel filtration chromatography. In addition DM beads can be used for affinity purification of glucosyltransferases (GTFs) from S. mutans. In this study we take advantage of the native pathogenic mechanisms used by S. mutans to adhere, form a biofilm and induce dental caries through the expression of surface-associated GTFs. We demonstrate that planktonic and biofilm-grown (adhered to hydroxyapatite-coated pegs to mimic the tooth surface) S. mutans, specifically and competitively attach to DMs. Further investigation demonstrated that DMs are a specific affinity resin for S. mutans and other cariogenic/pathogenic oral streptococci, whereas other commensal and probiotic strains failed to readily adhere to DMs. Using antimicrobial cargo loaded into the DM lumen, we demonstrate that when in co-culture with non-binding to even modestly binding commensal species, S. mutans was selectively killed. This proof of concept study introduces a novel means to safely and effectively reduce the pool of S. mutans and other pathogenic streptococci in the oral cavity with limited disturbance of the necessary commensal (healthy) microbiota when compared with current oral healthcare products.

Radiographic scoring system for the evaluation of stability of cementless acetabular components in the presence of osteolysis.

AIMS: The stability of cementless acetabular components is an important factor for surgical planning in the treatment of patients with pelvic osteolysis after total hip arthroplasty (THA). However, the methods for determining the stability of the acetabular component from pre-operative radiographs remain controversial. Our aim was to develop a scoring system to help in the assessment of the stability of the acetabular component under these circumstances. PATIENTS AND METHODS: The new scoring system is based on the mechanism of failure of these components and the location of the osteolytic lesion, according to the DeLee and Charnley classification. Each zone is evaluated and scored separately. The sum of the individual scores from the three zones is reported as a total score with a maximum of 10 points. The study involved 96 revision procedures which were undertaken for wear or osteolysis in 91 patients between July 2002 and December 2012. Pre-operative anteroposterior pelvic radiographs and Judet views were reviewed. The stability of the acetabular component was confirmed intra-operatively. RESULTS: Intra-operatively, it was found that 64 components were well-fixed and 32 were loose. Mean total scores in the well-fixed and loose components were 2.9 (0 to 7) and 7.2 (1 to 10), respectively (p < 0.001). In hips with a low score (0 to 2), the component was only loose in one of 33 hips (3%). The incidence of loosening increased with increasing scores: in those with scores of 3 and 4, two of 19 components (10.5%) were loose; in hips with scores of 5 and 6, eight of 19 components (44.5%) were loose; in hips with scores of 7 or 8, 13 of 17 components (70.6%) were loose; and for hips with scores of 9 and 10, nine of nine components (100%) were loose. Receiver-operating-characteristic curve analysis demonstrated very good accuracy (area under the curve = 0.90, p < 0.001). The optimal cutoff point was a score of ≥ 5 with a sensitivity of 0.79, and a specificity of 0.87. CONCLUSION: There was a strong correlation between the scoring system and the probability of loosening of a cementless acetabular component. This scoring system provides a clinically useful tool for pre-operative planning, and the evaluation of the outcome of revision surgery for patients with loosening of a cementless acetabular component in the presence of osteolysis. Cite this article: Bone Joint J 2017;99-B:601-6.

Total hip arthroplasty using a monobloc cementless femoral stem for patients with childhood Perthes' disease.

AIMS: Modular or custom-made femoral components have been preferred for total hip arthroplasty (THA) in patients with a history of Perthes' disease because of the distortion in the anatomy of the proximal femur. However, it has not been established whether a monobloc cementless stem will fit the distorted proximal femur or whether the results of the procedure are satisfactory in this group of patients. PATIENTS AND METHODS: We reviewed 68 consecutive patients who had undergone THA for childhood Perthes' disease between June 2003 and December 2008. There were 35 men and 33 women with a mean age of 48 years (16 to 73) at the time of index arthroplasty. Their mean body mass index was 24.4 (18.3 to 32.9). Of the 68 hips, 32 were classified as Stulberg class III and 36 as class IV. The mean pre-operative shortening of the affected leg was 17.2 mm (5 to 34). The minimum follow-up was five years (mean 8.5 years; 5.2 to 10). RESULTS: An intra-operative calcar fracture occurred in eight hips (11.8%) and was successfully treated by cerclage wiring. The mean stem version was 14.6° (-2.3 to 30; standard deviation (sd) 7.3). The mean acetabular component abduction was 40.2° (23.7 to 56.0; sd 6.5) and the mean anteversion 28.3° (6.4 to 43.0; sd 7.6), respectively. The mean follow-up was 8.5 years (5.2 to 10). No dislocations occurred and no hips were revised during the course of the study. At final follow-up, the mean Harris Hip Score was 91 points (59 to 100) and the mean University of California, Los Angeles activity score was 3.2 (2 to 8). CONCLUSION: Monobloc cementless stems reliably restore the anatomy in Perthes' disease at THA without the need for custom-made or modular implants. Cite this article: Bone Joint J 2017;99-B:440-444.

NF-κB as a Therapeutic Target in Inflammatory-Associated Bone Diseases.

Inflammation is a defensive mechanism for pathogen clearance and maintaining tissue homeostasis. In the skeletal system, inflammation is closely associated with many bone disorders including fractures, nonunions, periprosthetic osteolysis (bone loss around orthopedic implants), and osteoporosis. Acute inflammation is a critical step for proper bone-healing and bone-remodeling processes. On the other hand, chronic inflammation with excessive proinflammatory cytokines disrupts the balance of skeletal homeostasis involving osteoblastic (bone formation) and osteoclastic (bone resorption) activities. NF-κB is a transcriptional factor that regulates the inflammatory response and bone-remodeling processes in both bone-forming and bone-resorption cells. In vitro and in vivo evidences suggest that NF-κB is an important potential therapeutic target for inflammation-associated bone disorders by modulating inflammation and bone-remodeling process simultaneously. The challenges of NF-κB-targeting therapy in bone disorders include: (1) the complexity of canonical and noncanonical NF-κB pathways; (2) the fundamental roles of NF-κB-mediated signaling for bone regeneration at earlier phases of tissue damage and acute inflammation; and (3) the potential toxic effects on nontargeted cells such as lymphocytes. Recent developments of novel inhibitors with differential approaches to modulate NF-κB activity, and the controlled release (local) or bone-targeting drug delivery (systemic) strategies, have largely increased the translational application of NF-κB therapy in bone disorders. Taken together, temporal modulation of NF-κB pathways with the combination of recent advanced bone-targeting drug delivery techniques is a highly translational strategy to reestablish homeostasis in the skeletal system.

A bacterial-biofilm-induced oral osteolytic infection can be successfully treated by immuno-targeting an extracellular nucleoid-associated protein.

Periodontal disease exemplifies a chronic and recurrent infection with a necessary biofilm component. Mucosal inflammation is a hallmark response of the host seen in chronic diseases, such as colitis, gingivitis, and periodontitis (and the related disorder peri-implantitis). We have taken advantage of our recently developed rat model of human peri-implantitis that recapitulates osteolysis, the requirement of biofilm formation, and the perpetuation of the bona fide disease state, to test a new therapeutic modality with two novel components. First we used hyperimmune antiserum directed against the DNABII family of proteins, now known to be a critical component of the extracellular matrix of bacterial biofilms. Second we delivered the antiserum as cargo in biodegradable microspheres to the site of the biofilm infection. We demonstrated that delivery of a single dose of anti-DNABII in poly(lactic-co-glycolic acid) (PLGA) microspheres induced significant resolution of experimental peri-implantitis, including marked reduction of inflammation. These data support the continued development of a DNABII protein-targeted therapeutic for peri-implantitis and other chronic inflammatory pathologies of the oral cavity in animals and humans.