Examining short interval intracortical inhibition with different transcranial magnetic stimulation-induced current directions in ALS.

Objective: To establish if induced current direction across the motor cortex alters the sensitivity of transcranial magnetic stimulation (TMS)-evoked short-interval intracortical inhibition (SICI) as an ALS biomarker. Methods: Threshold tracking-TMS was undertaken in 35 people with ALS and 39 controls. Using a coil orientation which induces posterior-anterior (PA)-directed current across the motor cortex, SICI (1 ms and 3 ms interstimulus intervals) and intracortical facilitation (ICF, 10 ms interstimulus interval) were recorded. SICI3ms was also recorded using a coil orientation which induces anterior-posterior (AP)-directed current across the motor cortex. Results: At group level, SICI3ms-PA (AUROC = 0.7), SICI3ms-AP (AUROC = 0.8) and SICI1ms (AUROC = 0.66) were substantially lower in those with ALS, although there was considerable interindividual heterogeneity. Averaging across interstimulus intervals (ISIs) marginally improved SICIPA sensitivity (AUROC = 0.76). Averaging SICI values across ISIs and orientations into a single SICI measure did not substantially improve sensitivity (AUROC = 0.81) compared to SICI3ms-AP alone. SICI3ms-AP and SICI3ms-PA did not significantly correlate (rho = 0.19, p = 0.313), while SICI1ms-PA and SICI3ms-PA did (rho = 0.37, p = 0.006). Further, those with ALS with the lowest SICI3ms-PA were not those with the lowest SICI3ms-AP. ICF was similar between groups (AUROC = 0.50). Conclusions: SICIPA and SICIAP are uncorrelated measures of motor cortical inhibitory functions which are useful as distinct, unequally affected, measures of disinhibition in ALS. Significance: Examining both SICIPA and SICIAP may facilitate more comprehensive characterisation of motor cortical disinhibition in ALS.

Influence of humeral position of the Affinis Short stemless shoulder arthroplasty system on long-term survival and clinical outcome.

BACKGROUND: The purpose of this study was to evaluate the influence of humeral position of the Affinis Short implant in stemless anatomic total shoulder arthroplasties (STSAs) on clinical and radiologic results and mid- to long-term survival in the treatment of primary osteoarthritis (OA) of the shoulder. METHODS: Eighty patients treated with a stemless shoulder arthroplasty for OA of the shoulder were evaluated with a mean follow-up of 92 ± 14 months (range 69-116 months) by the Constant Score (CS), Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH), and active range of motion (ROM). Radiographic assessment for bone adaptations and humeral implant position was performed by plain radiographs. Comparison of the pre- and postoperative centers of rotation (CORs) was used to assess the restoration of the geometry of the humeral head. The appraisal of proper humeral component positioning was correlated with the functional outcomes. A Kaplan-Meier analysis was performed to investigate the influence of humeral implant position compared to survival time. Complications were noted. RESULTS: The ROM (P < .001), CS (P < .001), and DASH scores (P < .001) showed significant improvements after surgery for the entire series. The COR restoration was anatomic in 75% (n = 60) of all implants and in 25% (n = 20) nonanatomic implants (pre- and postoperative COR deviation of 2.7 ± 1.8 mm vs. 5.1 ± 3.2 mm, P = .0380). The humeral component position did not affect the functional outcome whereas the 10-year unadjusted cumulative survival rate for the anatomic group was significantly higher in comparison with the nonanatomic group (96.7% vs. 75%, P = .002). The radiologic evaluation revealed minor periprosthetic bone adaptions in various forms without clinical significance or further intervention. No revision was necessary because of a failed fixation of the stemless humeral component. CONCLUSIONS: Regarding the treatment of primary OA of the shoulder, STSA shows excellent long-term survival and clinical outcomes. In particular, STSA implants are able to restore the geometry of the humeral head. Nonanatomic reconstruction may influence the survival over the long term in different pathways. Further studies are necessary to elucidate the effect of humeral component position in STSA on function, pain, and implant survival rates.

Injection of autologous conditioned plasma combined with a collagen scaffold may improve the clinical outcome in shoulder impingement syndrome: a prospective study.

BACKGROUND: Shoulder impingement syndrome (SIS) is one of the most common diseases of the shoulder and can be addressed with various therapeutic concepts. Orthobiological agents such as platelet rich plasma with a low side effect rate gain importance in the conservative treatment of SIS. Currently, the knowledge about success rate influencing factors, such as the growth factors (GF) concentration or acromion type, is limited. The aim of this study was to analyze the clinical outcome in the therapy of external SIS using autologous conditioned plasma combined with recombinant human collagen scaffold (ACP/STR) injection in comparison with a corticosteroid-local anesthetic (CSA) injection. Additionally, the influence of potential limiting factors such as GF concentration, age and acromial morphology was proved. MATERIALS AND METHODS: This prospective pseudo-randomized trial recruited 58 patients with external SIS who received an ultrasound-guided subacromial injection either an ACP/STR or a CSA followed by physical therapy. Follow-up (FU) was performed at 6 weeks, 3 and 6 months. The outcome was assessed with Constant-Murley score, disability of arm, shoulder and hand score and simple shoulder test. The concentration of GF was measured using ELISA. RESULTS: During the FU, the improvement of outcome measures was observed with no differences between both groups. Shoulder force was significantly increased in the ACP/STR group (p < 0.01). We found no correlation between the amount of GF and age or gender in the ACP/STR patients. An acromion Bigliani type III predisposes for therapy failure (p < 0.001, OR = 56) in both treatment groups. CONCLUSIONS: Patients with SIS benefit regarding to PROMs after both ACP/STR and CSA injection and physical therapy. Patients who received ACP/STR obtained superior improvement in force. The quantity of GF did not vary depending on the age, so that ACP/STR can be a treatment option for SIS in elderly patients with multimorbidity. The presence of an acromion type III seems to be a predictive factor for limited effectivity of injections in the clinical management of SIS.

Fast acquisition of resting motor threshold with a stimulus-response curve - Possibility or hazard for transcranial magnetic stimulation applications?

OBJECTIVE: Previous research has suggested that transcranial magnetic stimulation (TMS) related cortical excitability measures could be estimated quickly using stimulus-response curves with short interstimulus intervals (ISIs). Here we evaluated the resting motor threshold (rMT) estimated with these curves. METHODS: Stimulus-response curves were measured with three ISIs: 1.2-2 s, 2-3 s, and 3-4 s. Each curve was formed with 108 stimuli using stimulation intensities ranging from 0.75 to 1.25 times the rMTguess, which was estimated based on motor evoked potential (MEP) amplitudes of three scout responses. RESULTS: The ISI did not affect the rMT estimated from the curves (F = 0.235, p = 0.683) or single-trial MEP amplitudes at the group level (F = 0.90, p = 0.405), but a significant subject by ISI interaction (F = 3.64; p < 0.001) was detected in MEP amplitudes. No trend was observed which ISI was most excitable, as it varied between subjects. CONCLUSIONS: At the group level, the stimulus-response curves are unaffected by the short ISI. At the individual level, these curves are highly affected by the ISI. SIGNIFICANCE: Estimating rMT using stimulus-response curves with short ISIs impacts the rMT estimate and should be avoided in clinical and research TMS applications.

Long-term survival and failure analysis of anatomical stemmed and stemless shoulder arthroplasties.

AIMS: The purpose of this study was to compare clinical results, long-term survival, and complication rates of stemless shoulder prosthesis with stemmed anatomical shoulder prostheses for treatment of osteoarthritis and to analyze radiological bone changes around the implants during follow-up. METHODS: A total of 161 patients treated with either a stemmed or a stemless shoulder arthroplasty for primary osteoarthritis of the shoulder were evaluated with a mean follow-up of 118 months (102 to 158). The Constant score (CS), the Disabilities of the Arm, Shoulder and Hand (DASH) score, and active range of motion (ROM) were recorded. Radiological analysis for bone adaptations was performed by plain radiographs. A Kaplan-Meier survivorship analysis was calculated and complications were noted. RESULTS: The ROM (p < 0.001), CS (p < 0.001), and DASH score (p < 0.001) showed significant improvements after shoulder arthroplasty for both implants. There were no differences between the groups treated with stemmed or stemless shoulder prosthesis with respect to the mean CS (79.2 (35 to 118) vs 74.4 (31 to 99); p = 0.519) and DASH scores (11.4 (8 to 29) vs 13.2 (7 to 23); p = 0.210). The ten-year unadjusted cumulative survival rate was 95.3% for the stemmed anatomical shoulder prosthesis and 91.5% for the stemless shoulder prosthesis and did not differ between the treatment groups (p = 0.251). The radiological evaluation of the humeral components in both groups did not show loosening of the humeral implant. The main reason for revision for each type of arthroplasties were complications related to the glenoid. CONCLUSION: The use of anatomical stemless shoulder prosthesis yielded good and reliable results and did not differ from anatomical stemmed shoulder prosthesis over a mean period of ten years. The differences in periprosthetic humeral bone adaptations between both implants have no clinical impact during the follow-up. Cite this article: Bone Joint J 2021;103-B(7):1292-1300.

Surgical site, gender, and place of residence influence the time to resume driving after total joint arthroplasty.

BACKGROUND: For a large proportion of the population, especially those residing in the countryside, the use of a car for daily activities is indispensable. Following a TKA or THA procedure, the overseeing physician will usually recommend refraining from driving, sometimes up to 12 weeks after surgery with a major social and economical impact on patient's life. OBJECTIVE: Considering the legal stipulations in Germany regarding fitness to drive a motor vehicle, the aim of this study is to determine the time point when patients after total knee arthroplasty (TKA) or total hip arthroplasty (THA) take up driving again postoperatively. Further, we assessed the replaced joint, side, gender, place of residence and physician's recommendations influencing the patient in making the decision to start driving again. METHODS: 92 eligible participants, contained within the frame of a prospective experimental observational study, were contacted via telephone 12 weeks after surgery and interviewed using a structured questionnaire. The answers were statistically analysed using SPSS® Version 26 for Windows. RESULTS: Male participants resumed driving between the 6th and 7th week post-surgery, female participants resumed driving between the 8th and 9th week post-surgery. For 58.6% of patients the reason for the first post-operative use of a vehicle was medical: the journey to physical therapy or to a doctor's appointment. There were statistically significant differences regarding operated side, gender and place of residence. TKA impaired patients the most. Patients recovering from a TKA drove considerably later. Patients recovering from a right sided TKA had an increased risk (9 times) not to become an "early driver". Female patients who underwent TKA had an increased risk by a factor of 21 of becoming a "late driver". In the ageing population, surgeons, physical therapists and rehabilitation professionals need to consider new approaches in providing options for patients' mobility. Interestingly, there is a different need for early use of own vehicle in rural regions whereas in cities patients start driving later. There are clear differences between gender and surgical site. CONCLUSIONS: The rehabilitation following a right sided TKA proved a challenge with regard to the reuptake of driving. This should be taken into account when planning the course of therapy for patients who are driving regulary. Female patients could benefit from special training. TRIAL REGISTRATION: retrospectively registered, DRKS00018693 https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&TRIAL_ID=DRKS00018693.

Associations of Medications With Lower Odds of Typical COVID-19 Symptoms: Cross-Sectional Symptom Surveillance Study.

BACKGROUND: As the COVID-19 pandemic continues to spread across the globe, the search for an effective medication to treat the symptoms of COVID-19 continues as well. It would be desirable to identify a medication that is already in use for another condition and whose side effect profile and safety data are already known and approved. OBJECTIVE: The objective of this study was to evaluate the effect of different medications on typical COVID-19 symptoms by using data from an online surveillance survey. METHODS: Between early April and late-July 2020, a total of 3654 individuals in Lower Saxony, Germany, participated in an online symptom-tracking survey conducted through the app covid-nein-danke.de. The questionnaire comprised items on typical COVID-19 symptoms, age range, gender, employment in patient-facing healthcare, housing status, postal code, previous illnesses, permanent medication, vaccination status, results of reverse transcription polymerase chain reaction (RT-PCR) and antibody tests for COVID-19 diagnosis, and consequent COVID-19 treatment if applicable. Odds ratio estimates with corresponding 95% CIs were computed for each medication and symptom by using logistic regression models. RESULTS: Data analysis suggested a statistically significant inverse relationship between typical COVID-19 symptoms self-reported by the participants and self-reported statin therapy and, to a lesser extent, antihypertensive therapy. When COVID-19 diagnosis was based on restrictive symptom criteria (ie, presence of 4 out of 7 symptoms) or a positive RT-PCR test, a statistically significant association was found solely for statins (odds ratio 0.28, 95% CI 0.1-0.78). CONCLUSIONS: Individuals taking statin medication are more likely to have asymptomatic COVID-19, in which case they may be at an increased risk of transmitting the disease unknowingly. We suggest that the results of this study be incorporated into symptoms-based surveillance and decision-making protocols in regard to COVID-19 management. Whether statin therapy has a beneficial effect in combating COVID-19 cannot be deduced based on our findings and should be investigated by further study. TRIAL REGISTRATION: German Clinical Trials Register DRKS00022185; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022185; World Health Organization International Clinical Trials Registry Platform U1111-1252-6946.

The Genetic Variations Associated With Time to Aseptic Loosening After Total Joint Arthroplasty.

BACKGROUND: Total joint arthroplasty (TJA) is one of the most frequent surgical procedures performed in modern hospitals, and aseptic loosening is the most common indication for revision surgeries. We conducted a systemic exploration of potential genetic determinants for early aseptic loosening. METHODS: Data from 423 patients undergoing TJA were collected and analyzed. Three analytical groups were formed based on joint arthroplasty status. Group 1 were TJA patients without symptoms of aseptic loosening of at least 1 year, group 2 were patients with primary TJA, and group 3 were patients receiving revision surgery because of aseptic loosening. Genome-wide genotyping comparing genotype frequencies between patients with and without aseptic loosening (group 3 vs groups 1 and 2) was conducted. A case-control association analysis and linear modeling were applied to identify the impact of the identified genes on implant survival with time to the revision as an outcome measure. RESULTS: We identified 52 single-nucleotide polymorphisms (SNPs) with a genome-wide suggestive P value less than 10-5 to be associated with the implant loosening. The most remarkable odds ratios (OR) were found with the variations in the IFIT2/IFIT3 (OR, 21.6), CERK (OR, 12.6), and PAPPA (OR, 14.0) genes. Variations in the genotypes of 4 SNPs-rs115871127, rs16823835, rs13275667, and rs2514486-predicted variability in the time to aseptic loosening. The time to aseptic loosening varied from 8 to 16 years depending on the genotype, indicating a substantial effect of genetic variance. CONCLUSION: Development of the aseptic loosening is associated with several genetic variations and we identified at least 4 SNPs with a significant effect on the time for loosening. These data could help to develop a personalized approach for TJA and loosening management.

Screw Track Osteolysis in the Cementless Total Knee Replacement Design.

BACKGROUND: There is a paucity of reports on osteolysis associated with tibial screw fixation in cementless total knee arthroplasty (TKA), and the pathophysiology is not clear. This study aimed to describe the pathology related to screw track osteolysis around the tibia in cementless TKA. METHODS: The study cohort comprised 100 revised cementless TKAs with tibial screw fixation. Screw track osteolysis and various screw angles were analyzed radiologically. Tissue samples from the joint capsule and the osteolytic cavity were investigated for metal/polyethylene wear. The type of tissue response was determined using immunohistochemistry. Retrieved tibial polyethylene inserts were analyzed for screw hole impression and mode of wear. Tissue metal content was measured by inductively coupled plasma optical emission spectrometry. Electrochemical reactions between the tibial tray and the cancellous screws were investigated. RESULTS: Radiological analysis showed screw track osteolysis predominantly at the medial aspect of the tibial component, and the severity of osteolysis positively correlated with smaller medial proximal tibial screw angles. Osteolysis was associated with high titanium concentrations but not with polyethylene particles. An open circuit potential between the screw and the tibial base plate was measured. Necrosis, osteolytic cyst formation and macrophages, T and B cells, and dendritic cells were present. CONCLUSION: The present study highlights the risk for screw track osteolysis in cementless TKA with screw fixation. Our data collectively suggest that titanium wear may contribute to screw track osteolysis in the cementless TKA design. The contribution of screw angles is difficult to prove.

Ionic cobalt but not metal particles induces ROS generation in immune cells in vitro.

Total joint replacement is one of the most successful procedures in orthopedic surgery today. However, metal implant materials undergo wear and corrosion processes. Generated particles and ions can cause a variety of cellular reactions. Cobalt-containing alloys are used frequently in implant materials. Some studies suggest that cobalt exhibits potential cytotoxic effects, for example, via generation of reactive oxygen species (ROS). To further elucidate the effects of cobalt on human cells, we determined cell viability and cytosolic and mitochondrial superoxide formation after incubation of either ions or particles with different cells. MM-6 and Jurkat cell lines were treated for 24, 48 and 72 h with either CoCrMo particles or cobalt ions (supplied as CoCl2 ). A total of 24 h exposure of both forms of cobalt did not induce cell death using terminal deoxynucleotidyl transferase (TUNEL) and trypan blue assay. Interestingly, the formation of superoxide (O2.- ) is evoked mainly by ionic CoCl2 but not cobalt particles. Cobalt alloy particles are likely to even suppress O2.- formation in mitochondria in both used cell lines. Furthermore, we did not observe any effect of cobalt particles on O2.- formation in peripheral blood mononuclear cells (PBMCs) from healthy donors. We also found that the O2- formation by CoCl2 within mitochondria is a generalized effect for all cell types used, while the formation of superoxide in cytosolic compartment is cell-type dependent. In summary, our data suggest that cobalt ions specifically induce the formation of O2.- , whereas the cobalt particles were better tolerated. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1246-1253, 2019.

The terminal complement pathway is activated in septic but not in aseptic shoulder revision arthroplasties.

BACKGROUND: The early diagnosis of suspected periprosthetic low-grade infections in shoulder arthroplasties is important for the outcome of the revision surgical procedures. The aim of this study was to investigate new biomarkers of infection in revision shoulder arthroplasties, taking into account the implant design, patient age, and comorbidities. METHODS: The study included 33 patients with shoulder arthroplasties undergoing revision surgical procedures. Microbiological diagnostic testing was performed in all cases. C-reactive protein serum levels and white blood cell counts were evaluated, and the periprosthetic tissue was stained immunohistologically for the terminal complement pathway components (C3, C5, and C9) and for CD68 and α-defensin. RESULTS: Microbiological diagnostic testing detected a periprosthetic infection in 10 reverse shoulder arthroplasties and in 4 anatomic shoulder arthroplasties, while the remaining 19 shoulder arthroplasties were classified as aseptic. We observed more Staphylococcus epidermidis infections in reverse shoulder arthroplasties and more Staphylococcus aureus infections in anatomic shoulder arthroplasties. The revision rate correlated with pre-existing comorbidities and number of previous surgical procedures. The C-reactive protein values and the incidence of specific periprosthetic radiolucent lines were significantly increased in septic revision cases. We found increased staining for all tested complement factors (C3, C5, and C9) but not for α-defensin and CD68 in septic tissue. The most interesting finding was that C9 separated septic from aseptic tissue with a predictive specificity of 100% and a sensitivity of 88.89%. CONCLUSION: We observed a strong correlation between C9 expressions in septic revision tissue. We propose that the terminal complement pathway, especially C9 deposition, may be a potential biomarker to identify septic complications using tissue biopsy specimens.

Accurate motor mapping in awake common marmosets using micro-electrocorticographical stimulation and stochastic threshold estimation.

OBJECTIVE: Motor map has been widely used as an indicator of motor skills and learning, cortical injury, plasticity, and functional recovery. Cortical stimulation mapping using epidural electrodes is recently adopted for animal studies. However, several technical limitations still remain. Test-retest reliability of epidural cortical stimulation (ECS) mapping has not been examined in detail. Many previous studies defined evoked movements and motor thresholds by visual inspection, and thus, lacked quantitative measurements. A reliable and quantitative motor map is important to elucidate the mechanisms of motor cortical reorganization. The objective of the current study was to perform reliable ECS mapping of motor representations based on the motor thresholds, which were stochastically estimated by motor evoked potentials and chronically implanted micro-electrocorticographical (µECoG) electrode arrays, in common marmosets. APPROACH: ECS was applied using the implanted µECoG electrode arrays in three adult common marmosets under awake conditions. Motor evoked potentials were recorded through electromyographical electrodes implanted in upper limb muscles. The motor threshold was calculated through a modified maximum likelihood threshold-hunting algorithm fitted with the recorded data from marmosets. Further, a computer simulation confirmed reliability of the algorithm. MAIN RESULTS: Computer simulation suggested that the modified maximum likelihood threshold-hunting algorithm enabled to estimate motor threshold with acceptable precision. In vivo ECS mapping showed high test-retest reliability with respect to the excitability and location of the cortical forelimb motor representations. SIGNIFICANCE: Using implanted µECoG electrode arrays and a modified motor threshold-hunting algorithm, we were able to achieve reliable motor mapping in common marmosets with the ECS system.

Ballooning osteolysis in 71 failed total ankle arthroplasties.

Background and purpose - Aseptic loosening is a major cause of failure in total ankle arthroplasty (TAA). In contrast to other total joint replacements, large periarticular cysts (ballooning osteolysis) have frequently been observed in this context. We investigated periprosthetic tissue responses in failed TAA, and performed an element analysis of retrieved tissues in failed TAA. Patients and methods - The study cohort consisted of 71 patients undergoing revision surgery for failed TAA, all with hydroxyapatite-coated implants. In addition, 5 patients undergoing primary TAA served as a control group. Radiologically, patients were classified into those with ballooning osteolysis and those without, according to defined criteria. Histomorphometric, immunohistochemical, and elemental analysis of tissues was performed. Von Kossa staining and digital microscopy was performed on all tissue samples. Results - Patients without ballooning osteolysis showed a generally higher expression of lymphocytes, and CD3+, CD11c+, CD20+, and CD68+ cells in a perivascular distribution, compared to diffuse expression. The odds of having ballooning osteolysis was 300 times higher in patients with calcium content >0.5 mg/g in periprosthetic tissue than in patients with calcium content ≤0.5 mg/g (p < 0.001). Interpretation - There have been very few studies investigating the pathomechanisms of failed TAA and the cause-effect nature of ballooning osteolysis in this context. Our data suggest that the hydroxyapatite coating of the implant may be a contributory factor.

Expression of CD11c in periprosthetic tissues from failed total hip arthroplasties.

In this work, we characterize integrin CD11c (αXß2) expression in periprosthetic tissues of 45 hip revisions. Tissues were retrieved from 23 ceramic-on-ultra-high molecular weight polyethylene (UHMWPE), 20 metal-on-UHMWPE, and 2 metal-on-metal total hip arthroplasties (THAs). Capsular tissue retrieved during primary THA from 19 patients served as controls. We identified a system to identify important immunohistochemical markers that are expressed in aseptic loosening. We focused on CD11c, CD68 and CD14. We observed that the CD11c molecule possesses four different cellular patterns in the periprosthetic tissues. Three of them are associated with the occurrence of UHMWPE abrasive material. Double staining with CD14 and CD68 was used for a more detailed analysis of the CD11c expressing cells. We observed that all forms of CD11c positive cells are CD68 positive however, only two forms of CD11c expressing cells are positive for CD14. Providing cellular diversity of CD11c expression in periprosthetic tissue, our results provide a contribution toward the further understanding of different cellular mechanisms to foreign body material.

SPECT/CT demonstrates the osseointegrative response of a stemless shoulder prosthesis.

BACKGROUND: This study evaluates bone remodeling processes in the proximal humerus induced by the implantation of a stemless shoulder prosthesis with regard to time of response and type and extent of bone turnover. METHODS: Twenty-eight patients with primary osteoarthritis of the shoulder undergoing a stemless shoulder arthroplasty were prospectively evaluated. The local metabolic bone activity in 5 regions of interest (ROIs 1-5) around the implant and in 1 reference region (ROI ref.) in the humeral diaphysis was analyzed after the application of technetium Tc 99m DPD using single-photon emission computed tomography integrated with multidetector computed tomography (SPECT/CT). The study cohort was divided into 4 groups according to the timing of the most recent follow-up appointment to evaluate the primary osseointegrative response after surgery. The bone uptake values were expressed in target (ROIs 1-5) to nontarget (ROI ref.) ratios. RESULTS: No difference within the 4 subgroups with respect to the time of local metabolic bone activity in the ROIs was found at 90 days after surgery. The highest initial metabolic activity and most temporal modifications were found in ROI 1, which was localized in the superior segment of the stem. CONCLUSIONS: SPECT/CT data suggest that the primary osseointegration of a stemless shoulder prosthesis is almost completed 3 months after implantation. Variations in metabolic activity pattern in the ROIs during follow-up may be caused by different loading conditions of the bone.

Metallic wear debris may regulate CXCR4 expression in vitro and in vivo.

CXCR4, the chemokine receptor for CXCL12, also known as SDF-1 (stromal cell derived factor-1), has been shown to play a pivotal role in bone metastasis, inflammatory, and autoimmune conditions but has not been investigated in periprosthetic osteolysis. We co-cultured osteoblast-like cells with increasing concentrations of metallic (Co-35Ni-20Cr-10Mo and Co-28Cr-6Mo) and Co-ions simulating wear debris. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to quantify gene and protein expression of CXCR4. The expression of tumor necrosis factor-alpha (TNF-α) and the effects of AMD3100 (bicyclam) on both CXCR4 and TNF-α expression among these cells was investigated. RT-PCR showed an increase in CXCR4 mRNA (7.5-fold for MG63 and 4.0-fold for SaOs-2 cells) among cells co-cultured with metal alloy particles. Western blotting showed a time-dependent increase in protein expression of CXCR4. The attempted blockade of CXCR4 by its known competitive receptor agonist AMD3100 led to a significant inhibition TNF-α mRNA expression. Immunohistochemistry showed CXCR4 positivity among patients with failed metal-on-metal hip replacements and radiographic evidence of osteolysis. Our data collectively suggest that the CXCR4 chemokine is upregulated in a dose- and time-dependent manner in the presence of metallic wear debris.

Mediolateral subchondral tibial bone mineral density difference does not predict osteoarthritis progression.

Data on the relationship between osteoporosis and osteoarthritis are conflicting. Most studies report "snapshot" prevalences, and there are few studies evaluating localized knee bone mineral density (BMD) measurements with respect to subsequent osteoarthritis progression. The authors hypothesize that increased mediolateral difference of the proximal tibial BMD may predict progression of knee osteoarthritis. In this study, 246 female volunteers were followed up prospectively over 2 years. Baseline BMD measurements of bilateral proximal (subchondral) tibiae were performed, and the mediolateral BMD ratio was calculated. Precision studies were performed on healthy volunteers to validate the technique. The patients were divided into osteoarthritis progressors and non-progressors based on Kellgren-Lawrence radiographic criteria at 2-year follow-up. Patients who were taking bisphosphonates or who had a history of inflammatory, infectious, or metabolic bone disease and previous hip and knee surgery were excluded. Demographic data, calcium supplementation, physical activity, baseline knee radiographs, and radiographs at 2-year follow-up were obtained. The study was adequately powered to detect an effect size of 0.4. There were 121 progressors and 125 non-progressors. Mean mediolateral BMD ratio was 1.02 among the progressors and 1.01 among the non-progressors (t=0.632, P=.528). Potential confounders were equally distributed among both groups. The data suggest that there is no link between proximal tibial BMD ratio and progression of knee osteoarthritis.

Low-frequency sonication may alter surface topography of endoprosthetic components and damage articular cartilage without eradicating biofilms completely.

Two-stage exchange arthroplasty is the current standard of care for arthroplasty-related infections. Reinfection rates up to 30% are reported, and there is significant morbidity for the patient. In cases of failure, arthrodesis or amputation may result. Ultrasonic treatment has the potential to eradicate biofilms and avoid two-stage exchange arthroplasty. Data in the specific context of arthroplasty infections is scant, and there is debate regarding optimal frequency and intensity of treatment. Surface topography alterations of the endoprosthetic components and damage to adjacent bone and cartilage have not been investigated. We found incomplete biofilm eradication and significant increase in surface roughness (maximum peak-to-valley height) of cobalt-chrome unicondylar knee components as well as reduction in articular cartilage thickness area from 10 retrieved femoral heads after low-frequency sonication treatment according to manufacturer-specified recommendations. Our data collectively suggest that sonication treatment for biofilm eradication in arthroplasty infections may not be effective and surface topography alterations may potentially reduce implant longevity.

On the estimation of silent period thresholds in transcranial magnetic stimulation.

OBJECTIVE: We evaluated the induction of corticospinal silent period (SP) using transcranial magnetic stimulation (TMS) at stimulation intensities normalized to resting motor threshold (rMT) or silent period thresholds (SPTs). The aim was to reduce the characteristic inter-individual variation in SP measurements in healthy population to improve the sensitivity of such measurements. METHODS: The cortical representation area of the right hand musculature of 12 healthy subjects was stimulated with navigated TMS with varying stimulating intensities. Subsequently, the individual SPTs for eliciting SPs of 20, 30, and 50ms in duration were determined from the input-output characteristics. RESULTS: While SPT for 20 and 50ms SPs differed from rMT, the SPT for 30ms was similar to rMT. Nevertheless, the inter-individual variation in SP duration was reduced significantly at 120% of SPT30 when compared with SP durations obtained at 120% of rMT. CONCLUSIONS: Inter-individual variation in the SP duration decreases when applying TMS at stimulation intensities normalized to the individual SPTs instead to the rMT. This makes the SP duration more specific to inhibition and less affected by changes in cortical excitability. SIGNIFICANCE: Use of individual SPTs may improve the sensitivity of the SP measures in studies with inter-individual design.