Osteoarthritis patients exhibit an autonomic dysfunction with indirect sympathetic dominance.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease causing limited mobility and pain, with no curative treatment available. Recent in vivo studies suggested autonomic alterations during OA progression in patients, yet clinical evidence is scarce. Therefore, autonomic tone was analyzed in OA patients via heart rate variability (HRV) measurements. METHODS: Time-domain (SDRR, RMSSD, pRR50) and frequency-domain (LF, HF, LF/HF) HRV indices were determined to quantify sympathetic and parasympathetic activities. In addition, perceived stress, WOMAC pain as well as serum catecholamines, cortisol and dehydroepiandrosterone-sulphate (DHEA-S) were analyzed. The impact of the grade of disease (GoD) was evaluated by linear regression analysis and correlations with clinical data were performed. RESULTS: GoD significantly impacted the autonomic tone in OA patients. All time-domain parameters reflected slightly decreased HRV in early OA patients and significantly reduced HRV in late OA patients. Moreover, frequency-domain analysis revealed decreased HF and LF power in all OA patients, reflecting diminished parasympathetic and sympathetic activities. However, LF/HF ratio was significantly higher in early OA patients compared to late OA patients and implied a clear sympathetic dominance. Furthermore, OA patients perceived significantly higher chronic stress and WOMAC pain levels compared to healthy controls. Serum cortisol and cortisol/DHEA-S ratio significantly increased with GoD and positively correlated with WOMAC pain. In contrast, serum catecholamines only trended to increase with GoD and pain level. CONCLUSIONS: This prospective study provides compelling evidence of an autonomic dysfunction with indirect sympathetic dominance in early and late knee OA patients for the first time based on HRV analyses and further confirmed by serum stress hormone measurements. Increased sympathetic activity and chronic low-grade inflammation in OA as well as in its major comorbidities reinforce each other and might therefore create a vicious cycle. The observed autonomic alterations coupled with increased stress and pain levels highlight the potential of HRV as a prognostic marker. In addition, modulation of autonomic activity represents an attractive future therapeutic option.

Can we separately measure glenoid vs. humeral lateralization and distalization in reverse shoulder arthroplasty?

BACKGROUND: Lateralization and distalization in reverse shoulder arthroplasty (RSA) can be measured on anteroposterior (AP) radiographs using 2 previously described angles: lateralization shoulder angle (LSA) and distalization shoulder angle (DSA). However, these 2 angles measure global lateralization and distalization but do not allow to differentiate how much lateralization or distalization are attributable to the glenoid and the humerus. We hypothesized that new angles could allow us to separately measure glenoid vs. humeral lateralization and distalization. A more precise understanding of independent glenoid and humeral contributions to lateralization and distalization may be beneficial in subsequent clinical research. METHOD: Retrospective analysis of postoperative AP radiographs of 100 patients who underwent primary RSA for cuff-tear arthropathy, massive cuff tear, or glenohumeral osteoarthritis were analyzed. The new angles that we proposed use well-known bony landmarks (the acromion, glenoid, and humerus) and the most lateral point of the glenosphere, which we termed the "glenoid pivot point" (GPP). For lateralization, we used the GPP to split LSA into 2 new angles: glenoid lateralization angle (GLA) and humeral lateralization angle (HLA). For distalization, we introduced the modified distalization shoulder angle (mDSA) that can also be split into 2 new angles: glenoid distalization angle (GDA) and humeral distalization angle (HDA). Three orthopedic surgeons measured the new angles, using the online tool Tyche. Mean values with overall and individual standard deviations as well as intraclass correlation coefficients (ICCs) were calculated. RESULTS: Because the angles form a triangle, the following equations can be made: LSA = GLA + HLA, and mDSA = GDA + HDA. All angles showed excellent inter- and intraobserver reliability (ICC = 0.92-0.97) with low means of individual standard deviations that indicate a precision of 2° for each angle. CONCLUSION: Use of the most lateral part of the glenosphere (termed glenoid pivot point) allows us to separately measure glenoid vs. humeral lateralization and distalization. The 4 new angles (HLA, GLA, GDA, HDA) described in the present study can be used on true AP radiographs, routinely obtained after shoulder replacement, and the measured angles may be used with all types of reverse prostheses available.

Coxa valga and antetorta configuration leads to underestimation of the femoral component size: a matched case-control study of patients undergoing cementless total hip arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is the gold standard procedure for patients with end-stage osteoarthritis after failed conservative therapy. Digital templating is commonly employed in preoperative preparation for THA and contributes positively to its outcome. However, the impact of coxa valga and antetorta (CVA) configurations on stem size prediction accuracy remains not reported. Previous studies demonstrated that the size of the lesser trochanter (LT) can be used to determine femoral anteversion on pelvis radiographs. This study investigates the accuracy of preoperative digital templating in predicting stem size in patients with CVA undergoing cementless THA. METHODS: Preoperative radiographs of 620 patients undergoing cementless THA were retrospectively investigated. Radiographs were standardized with patients standing and the leg internally rotated by 15°. A CVA group was established including patients with a CCD angle greater than 140° and a lesser trochanter (LT) size of at least 10 mm for men and 8 mm for women. For the control group, radiographs with a CCD angle ranging from 125-135° and LT size 3-10 mm for men and 3-8 mm for women were selected. Preoperative templating was performed using mediCAD. To reduce confounding factors, case-control matching was carried out for BMI and body height. RESULTS: After case-control matching, a total of thirty-one matches were analyzed. Stem size was underestimated in 74% (23/31) in the CVA and 13% (4/31) in the control group (p < 0.001). Moreover, patients with CVA were more likely to be underestimated by two sizes compared to controls (p < 0.004). In contrast, the exact stem size was predicted more frequently in the control group (p < 0.001). CONCLUSION: Stem size in patients with a CVA configuration are at high risk of being underestimated when using digital templating. These findings can be valuable for guiding in intraoperative decisions and lowering the risk of complications associated with an undersized femoral component.

Morphology of the acromioclavicular-joint score (MAC).

INTRODUCTION: To date there is no generally accepted specific definition or classification of acromioclavicular (AC) joint osteoarthritis. The aim of this study is to analyze morphological parameters using magnetic resonance imaging (MRI) and to develop a scoring system as a basis for decision making to perform an AC-joint resection. MATERIALS AND METHODS: In a retrospective-monocentric matched pair study, healthy and affected subjects were investigated using T2 MRI scans in the transverse plane. There were two groups, group 1 (n = 151) included healthy asymptomatic adults with no history of trauma. In group 2, we included n = 99 patients with symptomatic AC joints, who underwent arthroscopic AC-joint resection. The central and posterior joint space width and the AC angle were measured. Morphological changes such as cartilage degeneration, cysts and bone edema were noted. Malalignment of the joint was defined as: posterior joint space width < 2 mm in conjunction with an AC angle > 12°. A scoring system consisting of the measured morphologic factors was developed. RESULTS: Symptomatic and asymptomatic patients showed significant differences in all measured items. We observed a significant difference in the MAC score for symptomatic and asymptomatic patients (mean 10.4 vs. 20.6, p = 0.0001). The ROC (receiver operator characteristic) analysis showed an excellent AUC of 0.899 (p = 0.001). The sensitivity of the MAC score was 0.81 and the specificity 0.86. The MAC score shows a significant moderate correlation with age (r = 0.358; p = 0.001). The correlation of age and the development of symptoms was only weak (r = 0.22, p = 0.001). Symptomatic patients showed significantly more frequent malalignment compared to asymptomatic patients (p = 0.001), but the positive predictive value that a patient with malalignment is also symptomatic is only 55%. CONCLUSION: Patients with symptomatic AC joints showed a typical pattern of morphological changes on axial MRI scans with early posterior contact of the joint surfaces, reduction of joint space and malalignment as the basis for the development of a scoring system. The MAC score shows excellent test characteristics, and therefore, proved to be both an appropriate guidance for clinical practice as well as an excellent tool for comparative studies and is superior to the assessment of malalignment alone. LEVEL OF EVIDENCE: Level IV, retrospective diagnostic study.

Correlation between Adrenoceptor Expression and Clinical Parameters in Degenerated Lumbar Intervertebral Discs.

Despite advanced knowledge of the cellular and biomechanical processes of intervertebral disc degeneration (IVDD), the trigger and underlying mechanisms remain unclear. Since the sympathetic nervous system (SNS) has been shown to exhibit catabolic effects in osteoarthritis pathogenesis, it is attractive to speculate that it also influences IVDD. Therefore, we explored the adrenoceptor (AR) expression profile in human IVDs and correlated it with clinical parameters of patients. IVD samples were collected from n = 43 patients undergoing lumbar spinal fusion surgery. AR gene expression was analyzed by semi-quantitative polymerase chain reaction. Clinical parameters as well as radiological Pfirrmann and Modic classification were collected and correlated with AR expression levels. In total human IVD homogenates α1A-, α1B-, α2A-, α2B-, α2C-, ß1- and ß2-AR genes were expressed. Expression of α1A- (r = 0.439), α2A- (r = 0.346) and ß2-AR (r = 0.409) showed a positive and significant correlation with Pfirrmann grade. α1A-AR expression was significantly decreased in IVD tissue of patients with adjacent segment disease (p = 0.041). The results of this study indicate that a relationship between IVDD and AR expression exists. Thus, the SNS and its neurotransmitters might play a role in IVDD pathogenesis. The knowledge of differential AR expression in different etiologies could contribute to the development of new therapeutic approaches for IVDD.

Anti-Inflammatory Effects of Endogenously Released Adenosine in Synovial Cells of Osteoarthritis and Rheumatoid Arthritis Patients.

Exogenous adenosine and its metabolite inosine exert anti-inflammatory effects in synoviocytes of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. We analyzed whether these cells are able to synthesize adenosine/inosine and which adenosine receptors (ARs) contribute to anti-inflammatory effects. The functionality of synthesizing enzymes and ARs was tested using agonists/antagonists. Both OA and RA cells expressed CD39 (converts ATP to AMP), CD73 (converts AMP to adenosine), ADA (converts adenosine to inosine), ENT1/2 (adenosine transporters), all AR subtypes (A1, A2A, A2B and A3) and synthesized predominantly adenosine. The CD73 inhibitor AMPCP significantly increased IL-6 and decreased IL-10 in both cell types, while TNF only increased in RA cells. The ADA inhibitor DAA significantly reduced IL-6 and induced IL-10 in both OA and RA cells. The A2AAR agonist CGS 21680 significantly inhibited IL-6 and induced TNF and IL-10 only in RA, while the A2BAR agonist BAY 60-6583 had the same effect in both OA and RA. Taken together, OA and RA synoviocytes express the complete enzymatic machinery to synthesize adenosine/inosine; however, mainly adenosine is responsible for the anti- (IL-6 and IL-10) or pro-inflammatory (TNF) effects mediated by A2A- and A2BAR. Stimulating CD39/CD73 with simultaneous ADA blockage in addition to TNF inhibition might represent a promising therapeutic strategy.

Arthroscopic subscapularis repair using the subscapularis interlocking (SICK)-stitch technique leads to restoration of clinical function with low complication and revision rates.

Background: The purpose of this study is to determine the mid-term outcome after arthroscopic subscapularis tendon (SCP) reconstruction using the subscapularis interlocking (SICK)-stitch technique. The hypotheses are that arthroscopically repaired SCP lesions using the SICK-stitch show a good restoration of shoulder function with low complication and failure rates. Methods: This is a retrospective monocentric study of n = 199 patients (n = 106 female) with arthroscopically treated SCP tears with the interlocking (SICK) stitch technique from July 2013 to October 2018. Inclusion criteria: minimum follow-up of 2 years. Exclusion criteria: irreparable and massive cuff tears, osteoarthritis, and fractures. The postoperative assessment consisted of the range of motion, constant score, simple shoulder test, simple shoulder value, disability of the shoulder and arm score, short form 12, and patient satisfaction. Results: Mean age was 61 years (25-83); n = 4 (2%) patients were lost to follow-up with mean follow-up time of 63.6 months (36-96). Additional supraspinatus tendon lesions (n = 147) were repaired in n = 101 cases. SCP grading (n = 69) (35% traumatic) (Fox/Romeo): n = 113 grade II, n = 71 grade III, n = 11 grade IV. A positive preoperative lift-off test (n = 132, 68%) was corrected in n = 124 (94%) of cases. Ninety seven percent of patients would undergo surgery again with a mean satisfaction score of 14.4/15. Results at final follow-up (data: mean pre; post; P value): lexion (130; 166; .001), abduction (123;159; .001), external rotation (35;82; .001), internal rotation (52; 68; .07), constant score (50; 82; .001), disability of the shoulder and arm score (40; 19; .001), simple shoulder test (5; 10; .001), and simple shoulder value (44; 83; .001) significantly improved. The mean physical health scale short form 12 was 46 (24-63) and 51 (15-66) for mental health. Age, body mass index, SCP-grading, and supraspinatus tendon repair did not significantly affect any outcome parameter. Three (1.5%) patients underwent revision surgery, of which 1 (0.5%) had an infection. Conclusion: Two years after arthroscopic SCP repair using the SICK-stitch technique, we observed excellent restoration of clinical function with low complication and revision rates. The SICK-stitch technique thus represents a good and reliable therapeutic option for the arthroscopic repair of SCP lesions.

A Lightweight Browser-Based Tool for Collaborative and Blinded Image Analysis.

Collaborative manual image analysis by multiple experts in different locations is an essential workflow in biomedical science. However, sharing the images and writing down results by hand or merging results from separate spreadsheets can be error-prone. Moreover, blinding and anonymization are essential to address subjectivity and bias. Here, we propose a new workflow for collaborative image analysis using a lightweight online tool named Tyche. The new workflow allows experts to access images via temporarily valid URLs and analyze them blind in a random order inside a web browser with the means to store the results in the same window. The results are then immediately computed and visible to the project master. The new workflow could be used for multi-center studies, inter- and intraobserver studies, and score validations.

Moderate mobility and high density in a small area: the population ecology of the marsh fritillary Euphydryas aurinia in Transylvania (Romania).

The Natura 2000 network is one of the most important tools for nature conservation in the EU. Therefore, knowledge of the ecology of the species listed on the Habitats Directive annexes is of particular relevance. One of these species is the butterfly Euphydryas aurinia. Much is already known about the ecology of this species at the European level, but information on Romania is scarce. Therefore, in a study area northwest of Cluj, the species was intensively studied in a mark-release-recapture study over its entire flight period. The investigated population harboured many individuals and had a high density. The dispersal behaviour of the individuals was somewhat more pronounced than in Mediterranean and partly also high alpine populations, but roughly comparable to other populations of the nominotypic subspecies. Overall, the ecological differences to Central and Western European populations were not very pronounced, and many of the conservation-relevant statements on this species in Central Europe should also be largely valid in Romania.

Patellar malalignment correlates with increased pain and increased synovial stress hormone levels-A cross-sectional study.

PURPOSE: Risk factors for the development of pain in the context of knee osteoarthritis (KOA) remain unclear. Radiological findings often do not correlate with clinical findings, so other pathomechanisms in the development and perception of pain must play a role. The purpose of this study is to investigate the correlation of increased sympathetic nervous system (SNS) activity (measured by subjective and objective chronic stress parameters) with KOA severity, patellofemoral malalignment, and pain. METHODS: 47 patients with KOA were assessed. Radiological measurements of tibiofemoral and patellofemoral parameters (Kellgren-Lawrence-score, patellar tilt (PT), Caton-Deschamps-Index and Hepp´s classification) were performed and correlated with knee-specific questionnaires (WOMAC®, KSS©) and chronic stress questionnaires (PSQ-20). Additionally, parameters associated with chronic stress were quantified in synovial fluid and serum samples from patients. RESULTS: PT correlated significantly with Caton-Deschamps-Index (r = 0.394,p = 0.006) and with medial patellofemoral joint space (r = 0.516,p<0.001). In addition, asymmetric trochlear groove (Hepp's classification > II) was associated with significantly higher PT values (p = 0.014). A negative correlation between PT and KSS©-symptoms subgroup was found (r = -0.340,p = 0.024). Patients with PT<5° had significantly higher scores in the Knee Society Score©-symptoms subgroup (p = 0.038). A positive and significant correlation between synovial aldosterone levels and PT was observed (r = 0.548,p = 0.042). CONCLUSION: The results of this study indicate that patellar malalignment might correlate with increased pain. The previous specification of standard PT values must be reconsidered as even low PT values seem to play a role in the occurrence of patellofemoral osteoarthritis symptoms. Lower PT values might lead to aggravated symptoms in patients with KOA due to a narrow medial patellofemoral joint space. In addition, PT might induce the release of synovial stress biomarkers and thus contribute to the progression of KOA.

Adrenergic signalling in osteoarthritis.

Adrenoceptors (ARs) mediate the effects of the sympathetic neurotransmitters norepinephrine (NE) and epinephrine (E) in the human body and play a central role in physiologic and pathologic processes. Therefore, ARs have long been recognized as targets for therapeutic agents, especially in the field of cardiovascular medicine. During the past decades, the contribution of the sympathetic nervous system (SNS) and particularly of its major peripheral catecholamine NE to the pathogenesis of osteoarthritis (OA) attracted growing interest. OA is the most common degenerative joint disorder worldwide and a disease of the whole joint. It is characterized by progressive degradation of articular cartilage, synovial inflammation, osteophyte formation, and subchondral bone sclerosis mostly resulting in chronic pain. The subchondral bone marrow, the periosteum, the synovium, the vascular meniscus and numerous tendons and ligaments are innervated by tyrosine hydroxylase-positive (TH+) sympathetic nerve fibers that release NE into the synovial fluid and cells of all abovementioned joint tissues express at least one out of nine AR subtypes. During the past decades, several in vitro studies explored the AR-mediated effects of NE on different cell types in the joint. So far, only a few studies used animal OA models to investigate the contribution of distinct AR subtypes to OA pathogenesis in vivo. This narrative review shortly summarizes the current background knowledge about ARs and their signalling pathways at first. In the second part, we focus on recent findings in the field of NE-induced AR-mediated signalling in different joint tissues during OA pathogenesis and at the end, we will delineate the potential of targeting the adrenergic signalling for OA prevention or treatment. We used the PubMed bibliographic database to search for keywords such as 'joint' or 'cartilage' or 'synovium' or 'bone' and 'osteoarthritis' and/or 'trauma' and 'sympathetic nerve fibers' and/or 'norepinephrine' and 'adrenergic receptors / adrenoceptors' as well as 'adrenergic therapy'.

Changing demography and dispersal behaviour: ecological adaptations in an alpine butterfly.

High mountain ecosystems are extreme habitats for all organisms and therefore demand specific adaptations. In this context, we studied the ecology of the butterfly Euphydryas aurinia debilis in the High Tauern (Austria) and compared the obtained data against the ecology of the species in lower elevation habitats. We performed mark-release-recapture studies over the entire flight periods (end of June to end of July) in 2007 and 2008 to analyse the fundamental ecological parameters of a population. The demography of males and females was similar in both years, and no indication of typical protandry was detected. We observed a generally low dispersal of the individuals in both years, but males dispersed significantly more than females in 2008; this finding of low vagility was supported by allozyme analyses. Furthermore, butterflies survived periods of several days of continuously closed snow cover without any indication of increased mortality rates. In these three traits, this alpine population of E. aurinia apparently has ecological and physiological adaptations to the extreme requirements of high-altitude habitats and strongly deviates from the lower elevation populations.

Reconstruction of a Central Full-Thickness Glenoid Defect Using Osteochondral Autograft Technique from the Ipsilateral Knee.

BACKGROUND: Osteochondral defects (OCDs) of the shoulder represent a typical clinical problem and are difficult to manage. OCDs of the upper extremity are less common than those of the lower extremity. The incidence is reported to be between 5-17% in which the humerus is affected more frequently than the glenoid. OCD is often accompanied with symptoms and may appear secondary to trauma, instability or prior operation. The problem of the lesions is the missing blood circulation which makes the healing impossible. The hazard of OCDs is the progression to osteoarthritis. In spite of the effectiveness of total shoulder arthroplasty it is not the first option for young and active patients. The therapy options of OCD depend on the size and localization of the defect. PURPOSE: The aim of this multimedia article is to reveal a therapy option for OCDs of the glenoid. METHODS: In this case we present the reconstruction of a central full-thickness osteochondral glenoid defect with an osteochondral autograft from the ipsilateral knee which was withdrawn using the OATS-Technique (Arthrex, Naples, Florida) to address the chondral as well as the osseous pathology. To the best of our knowledge there has been no such procedure performed and described so far. RESULTS: The procedure lead to proper restoration of the defect. CONCLUSION: The demonstrated technique can be used to perform the reconstruction of a full-thickness osteochondral glenoid defect.

Three in One--Multiple Faunal Elements within an Endangered European Butterfly Species.

Ice ages within Europe forced many species to retreat to refugia, of which three major biogeographic basic types can be distinguished: "Mediterranean", "Continental" and "Alpine / Arctic" species. However, this classification often fails to explain the complex phylogeography of European species with a wide range of latitudinal and altitudinal distribution. Hence, we tested for the possibility that all three mentioned faunal elements are represented within one species. Our data was obtained by scoring 1,307 Euphydryas aurinia individuals (46 European locations) for 17 allozyme loci, and sequencing a subset of 492 individuals (21 sites) for a 626 base pairs COI fragment. Genetic diversity indices, F statistics, hierarchical analyses of molecular variance, individual-based clustering, and networks were used to explore the phylogeographic patterns. The COI fragment represented 18 haplotypes showing a strong geographic structure. All but one allozyme loci analysed were polymorphic with a mean FST of 0.20, supporting a pronounced among population structure. Interpretation of both genetic marker systems, using several analytical tools, calls for the recognition of twelve genetic groups. These analyses consistently distinguished different groups in Iberia (2), Italy, Provence, Alps (3), Slovenia, Carpathian Basin, the lowlands of West and Central Europe as well as Estonia, often with considerable additional substructures. The genetic data strongly support the hypothesis that E. aurinia survived the last glaciation in Mediterranean, extra-Mediterranean and perialpine refugia. It is thus a rare example of a model organism that combines attributes of faunal elements from all three of these sources. The observed differences between allozymes and mtDNA most likely result from recent introgression of mtDNA into nuclear allozyme groups. Our results indicate discrepancies with the morphologically-based subspecies models, underlining the need to revise the current taxonomy.