The effect of intra-articular botulinum toxin A on substance P, prostaglandin E-2, and tumor necrosis factor alpha in the canine osteoarthritic joint

Background: Recently, intra-articular botulinum toxin A (IA BoNT A) has been shown to reduce joint pain in osteoarthritic dogs. Similar results have been reported in human patients with arthritis. However, the mechanism of the antinociceptive action of IA BoNT A is currently not known. The aim of this study was to explore this mechanism of action by investigating the effect of IA BoNT A on synovial fluid (SF) and serum substance P (SP), prostaglandin E-2 (PGE(2)), and tumor necrosis factor alpha (TNF-alpha) in osteoarthritic dogs. Additionally, the aim was to compare SF SP and PGE(2) between osteoarthritic and non-osteoarthritic joints, and investigate associations between SP, PGE(2), osteoarthritic pain, and the signalment of dogs. Thirty-five dogs with chronic naturally occurring osteoarthritis and 13 non-osteoarthritic control dogs were included in the study. Osteoarthritic dogs received either IA BoNT A (n = 19) or IA placebo (n = 16). Serum and SF samples were collected and osteoarthritic pain was evaluated before (baseline) and 2 and 8 weeks after treatment. Osteoarthritic pain was assessed with force platform, Helsinki Chronic Pain Index, and joint palpation. Synovial fluid samples were obtained from control dogs after euthanasia. The change from baseline in SP and PGE(2) concentration was compared between the IA BoNT A and placebo groups. The synovial fluid SP and PGE(2) concentration was compared between osteoarthritic and control joints. Associations between SP, PGE(2), osteoarthritic pain, and the signalment of dogs were evaluated. Results: There was no significant change from baseline in SP or PGE(2) after IA BoNT A. Synovial fluid PGE(2) was significantly higher in osteoarthritic compared to control joints. Synovial fluid PGE(2) correlated with osteoarthritic pain. No associations were found between SP or PGE2 and the signalment of dogs. The concentration of TNF-alpha remained under the detection limit of the assay in all samples. Conclusions: The results suggest that the antinociceptive effect of IA BoNT A in the joint might not be related to the inhibition of SP nor PGE(2). Synovial fluid PGE(2,) but not SP, could be a marker for chronic osteoarthritis and pain in dogs.Peer reviewe

Correction effects of the ScoliOlogiC(® )„Chêneau light" brace in patients with scoliosis

BACKGROUND: Different bracing concepts are used today for the treatment of scoliosis. The plaster cast method worldwide seems to be the most practiced technique at the moment. CAD (Computer Aided Design) systems are on the market which allow brace adjustments without plaster. The latest development however, is the use of the ScoliOlogiC™ off the shelf system enabling the orthopaedic technician to construct a light brace for scoliosis correction from a variety of pattern specific shells to be connected to an anterior and a posterior upright. This „Chêneau light" brace, developed according to the Chêneau principle, promises a reduced impediment of quality of life in the brace. However, material reduction should not result in reduced effectiveness. Therefore the primary correction effect in the „Chêneau light" brace has been evaluated and compared with that of other braces used today. METHODS: The correction effects of the first 81 patients (main diagnosis Adolescent Idiopathic Scoliosis (AIS) [n = 64] or Early Onset Scoliosis (EOS) [n = 15]), treated according to the principle of the „Chêneau light" brace were evaluated after an average treatment time of 6 weeks by a full-body X-ray made in the standing position whilst wearing the brace and compared with the last X-ray before bracing. The average curvature angle of the whole group was 35,6°, the average age was 12,9 years (SD 1,9), average Risser sign was 1,3 (SD 1,5), average Tanner rating 2,75 (SD 0,7). RESULTS: The Cobb angle in the whole group was reduced by an average of 16,4°, which corresponds to a correction effect of 51%. The differences were highly significant in the T-test (T = 17,4; p < 0,001). The best correction effects reported in literature so far are about 40% in two different studies. The correction effect was highest in lumbar and thoracolumbar curve pattern (62 %; n = 18). In thoracic scoliosis the correction effect was 36 % (n = 41) and in double major curve pattern 50 % (n = 22). The correction effect correlated slightly negative with age (r = -0,24; p = 0,014), negatively with the Risser stage (-0,29; p = 0,0096) and correlated negatively with the Cobb angle measured before treatment (r = -0,43; p < 0,0001). CONCLUSION: The use of the „Chêneau light" brace leads to correction effects above average when compared to the correction effects of other braces described in literature. The reduction of material seems to affect the desired correction in a positive way

Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy : Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical)

"Brace technology" thematic series - the Gensingen brace™ in the treatment of scoliosis

<p>Abstract</p> <p>Background</p> <p>Bracing concepts in use today for the treatment of scoliosis include symmetric and asymmetric hard braces usually made of polyethylene (PE) and soft braces. A new asymmetric Chêneau style CAD/CAM derivate has been designed to overcome problems the author experienced with other Chêneau CAD/CAM systems over the recent years.</p> <p>Brace description</p> <p>This CAD/CAM Chêneau derivate has been called Gensingen brace™, a brace available to address all possible curve patterns. Once the patients' trunk is scanned with the help of a whole trunk optical 3D-scan and the patients' data from the clinical measurements are recorded, a model of the brace can be created by (1) modifying the trunk model of the patient 'on screen' to achieve a very individual brace model using the CAD/CAM tools provided or by (2) choosing a brace model from our library and re-size it to the patients' properties 'on screen'.</p> <p>Results</p> <p>End-result studies have been published on the Chêneau brace as early as 1985. Cohort studies on the Chêneau brace are available as is a prospective controlled study respecting the SRS criteria for bracing studies, demonstrating beneficial outcomes, when compared to the controls using a soft brace. Sufficient in-brace correction effects have been demonstrated to be achievable when the Chêneau principles of correction are used appropriately. As there is a positive correlation between in-brace correction and the final outcome, the Chêneau concept of bracing with sufficient in-brace corrections as published can be regarded as being efficient when applied well. Case reports with high in-brace corrections, as shown within this paper using the Gensingen brace™ promise beneficial outcomes when a good compliance can be achieved.</p> <p>Conclusions</p> <p>The use of the Gensingen brace™ leads to sufficient in-brace corrections, when compared to the correction effects achieved with other braces, as described in literature.</p> <p>According to the patients' reports, the Gensingen brace™ is comfortable to wear, when adjusted properly.</p> <p>Further studies are necessary (1) in order to evaluate brace comfort and (2) effectiveness using the SRS inclusion criteria.</p

Persistence of single species of symbionts across multiple closelyrelated host species

Some symbiont species are highly host-specific, inhabiting only one or a very few host species, and typically have limited dispersal abilities. When they do occur on multiple host species, populations of such symbionts are expected to become genetically structured across these different host species, and this may eventually lead to new symbiont species over evolutionary timescales. However, a low number of dispersal events of symbionts between host species across time might be enough to prevent population structure and species divergence. Overall, processes of evolutionary divergence and the species status of most putative multi-host symbiont systems are yet to be investigated. Here, we used DNA metabarcoding data of 6,023 feather mites (a total of 2,225 OTU representative sequences) from 147 infracommunities (i.e., the assemblage consisting of all mites of different species collected from the same bird host individual) to investigate patterns of population genetic structure and species status of three different putative multi-host feather mite species Proctophyllodes macedo Vitzthum, 1922, Proctophyllodes motacillae Gaud, 1953, and Trouessartia jedliczkai (Zimmerman, 1894), each of which inhabits a variable number of different closely related wagtail host species (genus Motacilla). We show that mite populations from different host species represent a single species. This pattern was found in all the mite species, suggesting that each of these species is a multi-host species in which dispersal of mites among host species prevents species divergence. Also, we found evidence of limited evolutionary divergence manifested by a low but significant level of population genetic structure among symbiont populations inhabiting different host species. Our study agrees with previous studies showing a higher than expected colonization opportunities in host-specific symbionts. Indeed, our results support that these dispersal events would allow the persistence of multi-host species even in symbionts with limited dispersal capabilities, though additional factors such as the geographical structure of some bird populations may also play a role.This work was supported by the MINECO CGL2011-24466 to RJ and CGL2015-69650-P to RJ and DS

Neuropeptides in the arthritic TMJ and symptoms and signs from the stomatognathic system with special consideration to rheumatoid arthritis

The contribution of the nervous system to the pathophysiology of rheumatoid arthritis has been proposed to be mediated by certain neuropeptides. Neuropeptide Y, calcitonin gene-related peptide, substance P, and neurokinin A are considered modulators of inflammatory joint disease. Parameters of pain, as well as occlusal signs of tissue destruction from the arthritic TMJ and the corresponding neuropeptide concentrations in TMJ synovial fluid, were investigated in patients with various inflammatory joint diseases. The patients with rheumatoid arthritis were also examined in a separate diagnostic group. Visual analog scale, palpatory tenderness, maximal voluntary mouth opening, and anterior open bite were correlated to neuropeptide-like immunoreactivities of the above four neuropeptides. It was found that high concentrations of calcitonin gene-related peptide and neuropeptide Y in TMJ fluid are associated with pain, impairment of mandibular mobility, and occlusal signs of TMJ destruction in patients with rheumatoid arthritis. The results indicated neuropeptide involvement in rheumatoid arthritis, proposing a potentiation of the symptoms and signs by the inflammatory action of calcitonin gene-related peptide and neuropeptide Y

Relation between intra-articular temperature of the arthritic temporomandibular joint and presence of calcitonin gene-related peptide in the joint fluid. A clinical study

Arthritic temporomandibular joints were investigated for intra-articular temperature and joint fluid content of calcitonin gene-related peptide. Eleven patients (16 joints) with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or chronic unspecific polyarthritis or monarthritis participated in the study. The intra-articular temperature varied between 35.5 and 37.5 degrees C, with a mean of 36.5 degrees C. The concentration of calcitonin gene-related peptide varied between 7.5 and 749.0 pmol/l, with a mean of 108.6 pmol/l. There was a positive correlation between the intra-articular temperature and the joint fluid concentration of calcitonin gene-related peptide. The plasma level of the peptide was on an average 5% of the joint fluid level