Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections.

OBJECTIVES: Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. METHODS: We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. RESULTS: Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. CONCLUSION: IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement.Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179-188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1.

Use of olmesartan and enteropathy outcomes: a multi-database study.

BACKGROUND: Multiple case reports suggest that olmesartan may be linked to sprue-like enteropathy; however, few epidemiological studies have examined this association and results have been mixed. AIM: To assess whether olmesartan is associated with a higher rate of enteropathy vs other angiotensin II receptor blockers (ARBs). METHODS: We conducted a cohort study among ARB initiators in 5 US claims databases representing different health insurance programmes. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for enteropathy-related outcomes, including coeliac disease, malabsorption, concomitant diagnoses of diarrhoea and weight loss, and non-infectious enteropathy, comparing olmesartan initiators to initiators of other ARBs after propensity score (PS) matching. RESULTS: We identified 1 928 469 eligible patients. The unadjusted incidence rates were 0.82, 1.41, 1.66 and 29.20 per 1000 person-years for coeliac disease, malabsorption, concomitant diagnoses of diarrhoea and weight loss, and non-infectious enteropathy respectively. HRs after PS matching comparing olmesartan to other ARBs were 1.21 (95% CI, 1.05-1.40), 1.00 (95% CI, 0.88-1.13), 1.22 (95% CI, 1.10-1.36) and 1.04 (95% CI, 1.01-1.07) for each outcome. HRs were larger for patients aged 65 years and older (eg for coeliac disease, 1.57 [95% CI, 1.20-2.05]), for patients receiving treatment for more than 1 year (1.62 [95% CI, 1.24-2.12]), and for patients receiving higher cumulative olmesartan doses (1.78 [95% CI, 1.33-2.37]). CONCLUSIONS: This large-scale, multi-database study found a higher rate of enteropathy in olmesartan initiators as compared to initiators of other ARBs, although the absolute incidence rate was low in both groups.

Rheumatoid arthritis patients with hip fracture: a nationwide study.

SUMMARY: The study was to investigate the outcomes of rheumatoid arthritis (RA) patients with hip fractures with a large-scale, population-based, nationwide, case-cohort study using the Taiwan National Health Insurance database. The group has hip fractures at a younger age, higher complication, and mortality rate, which indicate that early intervention is necessary. INTRODUCTION: This study seeks to evaluate the incidence, mortality, and complication rates in RA patients with hip fractures, using a nationwide database. METHODS: Data were collected from the National Health Insurance Research Database of Taiwan. The study group included 117,129 patients with hip fractures diagnosed from January 2004 to December 2010. Matching based on the propensity of RA patients was used. In total, 1,088 hip fractures were reported among patients with RA. Patients with hip fractures were divided into two groups: those without RA (controls) and those with RA (RA group). The incidence of hip fracture and mortality and complication rates after the hip fracture were then compared between the two groups. RESULTS: RA patients had a significantly higher incidence of hip fracture (3,260/100,000 person-years) compared with the general population (72/100,000 person-years). Hip fractures occurred significantly earlier among RA patients (70.6±5.3 years) compared with the control group (76.1±6.2 years). Cumulative mortality rates at 6-month and 1-year follow-up were significantly higher among patients in the RA group (9.47 and 18.47%) compared to the controls (8.47 and 13.62%) and among RA patients without hip fractures (3.24 and 6.16%). There was a significantly higher incidence of osteomyelitis after hip fracture among the RA group than among the body mass index-, comorbidity-, age-, and sex-matched patients in the control group. CONCLUSIONS: Compared to patients without RA, those with RA have a higher incidence of hip fractures at a relatively younger age and with higher complication and mortality rates. Steroid and disease-modifying anti-rheumatic drugs, the most common medicine in Taiwanese RA patients, might contribute to the high incidence of fracture and post-op infection. Appropriate early intervention to prevent hip fractures in RA patients is a critical issue in rheumatology care.

Nationwide cohort study of hip fractures: time trends in the incidence rates and projections up to 2035.

SUMMARY: A growing elderly population is expected worldwide, and the burden of hip fractures on health care system will continue to increase. By 2035, there will be a 2.7-fold increase in the number of hip fractures in Taiwan. The study provides quantitative basis for the future distribution of medical resources. INTRODUCTION: Hip fractures have long been recognized as a major public health concern. The study aimed to determine time trends in the incidence of hip fractures and to forecast the number of hip fractures expected in Taiwan up to 2035. METHODS: A nationwide survey was conducted using data from the Taiwan National Health Insurance Research Database from 2004 to 2011. A total of 141,397 hip fractures were identified, with a mean of 17,675 fractures/year. Annual incidences of hip fractures were calculated and tested for trends. Projections of the incidence rates of hip fractures and bed days associated with hip fractures were calculated using Poisson regression on the historical incidence rates in combination with population projections from 2012 to 2035. RESULTS: The incidence rates of hip fracture during 2004-2011 were 317 and 211 per 100,000 person-years among women and men, respectively. Over this 8-year period, the age-standardized incidence of hip fracture decreased by 13.4% among women and 12.2% among men. Despite the decline in the age-standardized incidence, the absolute number of hip fractures increased owing to the aging population. The number of hip fractures is expected to increase from 18,338 in 2010 to 50,421 in 2035-a 2.7-fold increase. The number of bed days for 2010 and 2035 was estimated at 161,248 and 501,995, respectively, representing a 3.1-fold increase. CONCLUSIONS: The socioeconomic impact of hip fractures will be high in the near future. This study provides a quantitative basis for future policy decisions to serve this need.

Liquid antibiotics in bone cement: an effective way to improve the efficiency of antibiotic release in antibiotic loaded bone cement.

OBJECTIVES: The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. METHODS: Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. RESULTS: Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. CONCLUSIONS: Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. Cite this article: Bone Joint Res 2014;3:246-51.

Gentamicin in bone cement: A potentially more effective prophylactic measure of infectionin joint arthroplasty.

OBJECTIVES: The objective of this study is to determine an optimal antibiotic-loaded bone cement (ALBC) for infection prophylaxis in total joint arthroplasty (TJA). METHODS: We evaluated the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with vancomycin, teicoplanin, ceftazidime, imipenem, piperacillin, gentamicin, and tobramycin against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staph. aureus (MRSA), coagulase-negative staphylococci (CoNS), Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Standardised cement specimens made from 40 g PMMA loaded with 1 g antibiotics were tested for elution characteristics, antibacterial activities, and compressive strength in vitro. RESULTS: The ALBC containing gentamicin provided a much longer duration of antibiotic release than those containing other antibiotic. Imipenem-loading on the cement had a significant adverse effect on the compressive strength of the ALBC, which made it insufficient for use in prosthesis fixation. All of the tested antibiotics maintained their antibacterial properties after being mixed with PMMA. The gentamicin-loaded ALBC provided a broad antibacterial spectrum against all the test organisms and had the greatest duration of antibacterial activity against MSSA, CoNS, P. aeruginosa and E. coli. CONCLUSION: When considering the use of ALBC as infection prophylaxis in TJA, gentamicin-loaded ALBC may be a very effective choice. Cite this article: Bone Joint Res 2013;2:220-6.

Risk of heart failure associated with dopamine agonists: a nested case-control study.

BACKGROUND: Recent evidence has emerged that a dopamine agonist, pramipexole, may increase the risk of heart failure among Caucasian patients, but the association has not been examined among Asian patients. The aim of this study was to explore the relationship between use of dopamine agonists and the risk of heart failure. METHODS: Using data from Taiwan's National Health Insurance research database (NHIRD), we identified a population-based cohort comprising 27,135 patients who were prescribed anti-parkinsonian drugs between 2001 and 2010. We conducted a nested case-control study in which 1,707 cases of newly diagnosed heart failure were matched to 3,414 controls (1:2 matched according to age, gender and cohort entry year) within this cohort. Multivariable conditional logistic regressions were used to estimate the association between use of dopamine agonists and heart failure. RESULTS: An increased risk of heart failure was observed with current use of ergot-derived dopamine agonists (adjusted odds ratio [OR] 1.46, 95 % confidence interval [CI] 1.00-2.12) but not with current use of non-ergot-derived dopamine agonists (adjusted OR 1.24, 95 % CI 0.84-1.82). Among non-ergot-derived dopamine agonists, both pramipexole (adjusted OR 1.40, 95 % CI 0.75-2.61) and ropinirole (adjusted OR 1.22, 95 % CI 0.76-1.95) showed a non-significantly increased heart failure risk. Although the findings of our study were limited by lack of statistical power, a clear pattern of an increased duration of pramipexole use and an increased risk of heart failure were observed. CONCLUSION: Use of dopamine agonists, including pramipexole, was associated with non-significantly increased risks of heart failure in this population-based study in Taiwan. Further investigation is needed to clarify this potential association.

The concentration of antibiotic in fresh-frozen bone graft.

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at -80 degrees C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture.Also, in bioassays the bone showed inhibitory effects against bacteria.We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro.

Potential clinical role of 18F FDG-PET/CT in detecting hip prosthesis infection: a study in patients undergoing two-stage revision arthroplasty with an interim spacer.

AIM: We evaluated the potential role of [18F]fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) to identify latent infections at the site of an interim hip spacer after resection arthroplasty for hip prosthesis infection. METHODS: Twelve patients with an interim hip spacer following resection arthroplasty (Group A) were investigated. Twelve patients with painful primary hip prostheses served as controls (Group B). All underwent PET/CT before surgery. Both non-attenuation-corrected (NAC) and attenuation-corrected (AC) images were analyzed. Serum C-reactive protein (CRP) levels were measured in 22 patients. Elevated CRP level was defined as >/=10 mg/L. The diagnosis of infection was based on the results of intraoperative tissue cultures, intraoperative pathology, and clinical follow-up. RESULTS: FDG-PET/CT had 100% sensitivity and 100% negative predictive value for detection of latent infection in both groups. However, there were 4 and 3 false positive cases in Group A and Group B, respectively. Specificity improved from 50% to 62.5% in Group A, and from 62.5% to 87.5% in Group B when using NAC instead of AC. Seventeen patients had CRP values >/=10 mg/L, but only 8 were true positive for infection. FDG-PET/CT ruled out infection in 77.8% (7/9) of false-positive cases identified by CRP levels. CONCLUSION: FDG-PET/CT is highly sensitive to detect latent infections in prosthetic hips and in interim hip spacers. The high negative predictive value of PET/CT scans is useful to rule out infections in patients with persistently elevated CRP levels. PET/CT might serve as an auxiliary tool to exclude latent infections in patients posing a clinical diagnostic dilemma.

Comparison of periacetabular osteotomy and total hip replacement in the same patient: a two- to ten-year follow-up study.

We evaluated 31 patients with bilateral dysplastic hips who had undergone periacetabular osteotomy for early (Tönnis grade 0 or 1) or moderate (Tönnis grade 2) osteoarthritis in one hip and total hip replacement for advanced (Tönnis grade 3) osteoarthritis in the other. At a mean follow-up of 5.5 years (2 to 9) after periacetabular osteotomy and 6.7 years (3 to 10) after total hip replacement, there was no difference in the functional outcome in hips undergoing osteotomy for early or moderate osteoarthritis and those with a total hip replacement, as determined by the Merle d'Aubigné and Postel score and the Western Ontario and McMaster Universities osteoarthritis index. More patients preferred the spherical periacetabular osteotomy to total hip replacement (53% vs 23%; p = 0.029). Osteoarthritis secondary to hip dysplasia is often progressive. Given the results, timely correction of dysplasia by periacetabular osteotomy should be considered whenever possible in young patients since this could produce a favourable outcome which is comparable with that of total hip replacement.

Elevated intraosseous pressure in the intertrochanteric region is associated with poorer results in osteonecrosis of the femoral head treated by multiple drilling.

Multiple drilling is reported to be an effective treatment for osteonecrosis of the head of femur, but its effect on intra-osseous pressure has not been described. We undertook multiple drilling and recorded the intra-osseous pressure in 75 osteonecrotic hips in 60 patients with a mean age of 42 years (19 to 67). At a mean follow-up of 37.1 months (24 to 60), 42 hips (56%) had a clinically successful outcome. The procedure was effective in reducing the mean intra-osseous pressure from 57 mmHg (SD 22) to 16 mmHg (SD 9). Hips with a successful outcome had a mean pressure of 26 mmHg (SD 19). It was less effective in preventing progression of osteonecrosis in hips with considerable involvement and in those with a high intra-osseous pressure in the intertrochanteric region (mean 45 mmHg (SD 25)). This study is not able to answer whether a return of the intra-osseous pressure to normal levels is required for satisfactory healing.

Effects of pulse voltage on inkjet printing of a silver nanopowder suspension.

Inkjet printing of a liquid suspension prepared by dispersing silver powders of size around 4 nm in deionized (DI) water at 30 wt% was investigated in this study. By comparing with the results of pure DI water, the effects of nanoparticles on droplet formation between the nozzle and the substrate were also studied. A bipolar pulse waveform was employed in driving the piezoelectric printhead with pulse voltage set as the primary variable of this study. Observations showed that a higher driving pulse voltage was required for the silver suspension to form droplets than DI water. The liquid column broke up at the nozzle orifice for DI water while the silver suspension broke up further away below the nozzle office. It was also observed that the droplet size of the silver suspension was smaller than that of DI water. For the silver suspension the liquid column formed was thinner and longer and the pinch-off time of the liquid column to form droplets was also longer. However, the characteristic adjustment time for droplet recombination was shorter for the silver suspension than for DI water.

Treatment of deep infection of the hip associated with massive bone loss: two-stage revision with an antibiotic-loaded interim cement prosthesis followed by reconstruction with allograft.

We have carried out in 24 patients, a two-stage revision arthroplasty of the hip for infection with massive bone loss. We used a custom-made, antibiotic-loaded cement prosthesis as an interim spacer. Fifteen patients had acetabular deficiencies, eight had segmental femoral bone loss and one had a combined defect. There was no recurrence of infection at a mean follow-up of 4.2 years (2 to 7). A total of 21 patients remained mobile in the interim period. The mean Merle D'Aubigné and Postel hip score improved from 7.3 points before operation to 13.2 between stages and to 15.8 at the final follow-up. The allograft appeared to have incorporated into the host bone in all patients. Complications included two fractures and one dislocation of the cement prosthesis. The use of a temporary spacer maintains the function of the joint between stages even when there is extensive loss of bone. Allograft used in revision surgery after septic conditions restores bone stock without the risk of recurrent infection.

Effects of glucose, fructose and 5-hydroxymethyl-2-furaldehyde on the presystemic metabolism and absorption of glycyrrhizin in rabbits.

Our previous study reported that co-administration of honey significantly increased the serum levels of glycyrrhetic acid (GA) after oral administration of glycyrrhizin (GZ) in rabbits. The components of honey are sucrose, glucose, fructose and 5-hydroxymethyl-furaldehyde (HMF). To clarify the causative component(s) in honey that altered the metabolic pharmacokinetics of GZ, rabbits were given GZ (150 mg kg(-1)) with and without glucose (5 g/rabbit), fructose (5 g/rabbit) and HMF (1 mg kg(-1)), respectively, in crossover designs. An HPLC method was used to determine concentrations of GZ and GA in serum as well as GA and 3-dehydroglycyrrhetic acid (3-dehydroGA) in faeces suspension. A noncompartment model was used to calculate the pharmacokinetic parameters and analysis of variance was used for statistical comparison. Our results indicated that the area under curve (AUC) of GA was significantly increased by 29% when HMF was coadministered, whereas the pharmacokinetics of GZ and GA were not significantly altered by coadministration of glucose or fructose. An in-vitro study, using faeces to incubate GZ and GA individually, indicated that HMF significantly inhibited the oxidation of GA to 3-dehydroGA and this may explain the enhanced GA absorption in-vivo. It was concluded that HMF is the causative component in honey that affects the presystemic metabolism and pharmacokinetics of GZ in-vivo.

Hip arthroplasty in patients with cirrhosis of the liver.

We retrospectively reviewed 45 hip arthroplasties which were performed over a period of 20 years in 38 patients with cirrhosis of the liver. There was a high perioperative 30-day complication rate (26.7%). Advanced cirrhosis was associated with a higher risk of complications (p = 0.004) as also was increased age, a high level of creatinine, a low level of albumin, a low platelet count, ascites, encephalopathy and an increased operative blood loss. The survival of the prosthesis at five years was 77.8% and infection was a major cause of failure. In view of the high rate of early complications and the limited longevity of the prosthesis, surgeons who perform hip arthroplasty on such patients should counsel them appropriately preoperatively.

Robustness of conditional moments: an application to premium calculation of reinsurance treaties.

In this study, the tail probability of a class of distributions commonly used in assessing the severity of insurance losses was examined. Without specifying any particular distribution, the use of an algebraic functional form Cx(-alpha) to approximate the tail behavior of the distributions in the class was demonstrated. Norwegian fire insurance data were examined, and the algebraic functional form was applied to derive the expected loss of a reinsurance treaty that covers all losses exceeding a retention limit. It was shown that (1) the expected loss is insensitive to the parameter alpha for a high retention limit (e.g., a catastrophe treaty), and (2) with a low retention limit (e.g., a largest claim treaty), a reliable estimate of the parameter alpha and a sound judgment on the maximum potential loss of the treaty could provide useful and defensible summary statistics for pricing the treaty. Thus, when dealing with the losses of certain reinsurance treaties, it was concluded that knowledge of a specific probability distribution is not critical, and the summary statistics derived from the model are robust with respect to a large class of loss distributions.