3T Magnetic resonance imaging and computed tomography of the bovine carpus.

BACKGROUND: Lameness in cattle is a major health problem and causes great economic losses. Carpal injury is a common cause of forelimb lameness in cattle. Radiography and/or ultrasonography of the carpus is a challenge due to complex anatomy of the joint. Additional imaging using computed tomography (CT) or magnetic resonance imaging (MRI) may be indispensable for reaching a decisive diagnosis. Precise evaluation of the clinical CT and MRI images necessitates an in-depth knowledge of the normal CT and MRI tissue variants. Therefore, our purpose was to provide a detailed description of the normal CT and MRI appearance of the osseous and soft tissue structures of twelve cadaveric bovine carpi using CT and 3 Tesla MRI. Carpi were frozen, transected in sagittal, dorsal and transverse planes then adjoined to their corresponding CT and MRI images. RESULTS: The clinically significant articular and peri-articular structures of the bovine carpus were identified and characterized on the CT and MRI images. CT images provided a remarkable delineation of the cortical, subchondral, and cancellous bone. The high-field 3 Tesla MRI offered high definition and distinction of the delicate soft tissues of the bovine carpus. CONCLUSIONS: 3 Tesla high-field MRI offers new opportunities in soft tissue tomography but cannot be compared with CT in terms of bone imaging. Clinicians have to determine whether CT, MRI or both imaging techniques are required in clinical situations.

Association of psychosocial and perceived environmental factors with park-based physical activity among elderly in two cities in China and Germany.

BACKGROUND: Urban parks play an important role in promoting physical activity (PA) among adults and especially among older city residents. According to the socioecological approach the association of physical environments and psychosocial factors in the context of park-based PA of elderly have not been systematically examined until now, let alone the relevance of the city (urban area) on a cross-cultural level. This study investigated selected aspects of (1) the association of psychosocial and park environmental factors with park-based physical activity (PBPA) of older people; and (2) the moderating effect of city on the association of these factors with PBPA. METHODS: A face-to-face survey was conducted of a mixed-culture sample from different urban surroundings in Hong Kong (HK) and Leipzig (L). In six parks of each city physically active elderly (> = 60 years; HK: n = 306; L: n = 311) were recruited. Multiple linear regressions were used to analyse the association between psychosocial factors and perceived environmental factors with PBPA and the moderating effect of city. RESULTS: Controlled for demographic variables, all other psychosocial factors were significantly related to PBPA, except social support. In terms of environmental factors, PBPA was positively associated with safety, attractiveness, features and negatively associated with park time distance. Controlled for demographic variables, psychosocial and environmental factors, the moderating effect of city on the associations of park features and park time distance with PBPA was not significant in HK. In contrast, there was a significant positive relationship for park features and a negative relationship for park time distance with PBPA in L. CONCLUSIONS: Psychosocial and perceived environmental factors significantly influence PBPA of older people. City moderates the associations of these factors and independently contributes to park-based PA of the elderly. The different interactions of environmental factors and urban area for PBPA of elderly can support policy makers on the municipal level in choosing adequate strategies for promoting PA of older people in parks.

Intravitreal injection of low-dose gentamicin for the treatment of recurrent or persistent uveitis in horses: Preliminary results.

BACKGROUND: Despite appropriate medical therapy, many horses with equine recurrent uveitis continue to suffer from recurrent bouts of inflammation. Surgical intervention via the pars plana vitrectomy or suprachoroidal cyclosporine implant placement may control and/or prevent recurrences, however, these procedures may be contraindicated, unavailable, or declined by an owner. Thus, an effective adjunctive treatment option may help to improve the clinical outcomes in those situations. There are several anecdotal reports on the use of intravitreal gentamicin injections, but to date, no data evaluating the complication rate and/or treatment effect following this treatment have been published. Thus, the aim of this prospective study was to describe the intravitreal gentamicin injection technique, describe the associated peri-injection (within 24 h) and post-injection (30 to 780 days) complications, and to report the effects of the injection on the clinical signs of uveitis. Additionally, evaluation of the systemic and ocular Leptospira-status, and its effect on the treatment outcome was performed. A total of 86 horses of various ages, breeds, and gender presenting with recurrent or persistent uveitis were treated via intravitreal injection of 4 mg of undiluted gentamicin (0.04 ml, Genta 100, 100 mg/ml in 35 horses) or preservative-free gentamicin (0.05 ml, 80 mg/ml in 52 horses) under sedation and local anesthesia. All 86 horses were observed for immediate peri-injection and post-injection complications. Response to therapy was evaluated in 59 of the 86 horses (follow-up: 30 to 780 days). RESULTS: Peri-injection complications consisted of subconjunctival (26/86; 30.2%) or intracameral hemorrhage (4/86; 4.7%); both of which completely resolved within 5 days. Post-injection complications consisted of cataract formation/maturation (5/59 horses, 8.5%) and diffuse retinal degeneration (3/59 eyes 5.1%). The majority of horses 52/59 (88.1%) with a minimum follow-up period of 30 days were controlled (absence of recurrent or persistent inflammation) at their last recheck examination. Recurrent inflammation was documented in 5/59 (8.5%) horses and persistent inflammation was diagnosed in 2/59 (3.4%) horses. CONCLUSIONS: Intravitreal injection of low-dose gentamicin shows promise at controlling different types and stages of uveitis. The ability of intravitreal injections of low-dose gentamicin (4 mg) to control persistent and recurrent inflammation warrants further investigation.

Transforming Growth Factor Beta 3-Loaded Decellularized Equine Tendon Matrix for Orthopedic Tissue Engineering.

Transforming growth factor beta 3 (TGFß3) promotes tenogenic differentiation and may enhance tendon regeneration in vivo. This study aimed to apply TGFß3 absorbed in decellularized equine superficial digital flexor tendon scaffolds, and to investigate the bioactivity of scaffold-associated TGFß3 in an in vitro model. TGFß3 could effectively be loaded onto tendon scaffolds so that at least 88% of the applied TGFß3 were not detected in the rinsing fluid of the TGFß3-loaded scaffolds. Equine adipose tissue-derived multipotent mesenchymal stromal cells (MSC) were then seeded on scaffolds loaded with 300 ng TGFß3 to assess its bioactivity. Both scaffold-associated TGFß3 and TGFß3 dissolved in the cell culture medium, the latter serving as control group, promoted elongation of cell shapes and scaffold contraction (p < 0.05). Furthermore, scaffold-associated and dissolved TGFß3 affected MSC musculoskeletal gene expression in a similar manner, with an upregulation of tenascin c and downregulation of other matrix molecules, most markedly decorin (p < 0.05). These results demonstrate that the bioactivity of scaffold-associated TGFß3 is preserved, thus TGFß3 application via absorption in decellularized tendon scaffolds is a feasible approach.

Palmar arthroscopic approach and intra-articular anatomy of the bovine carpal joints.

OBJECTIVE: To describe the palmar arthroscopic approaches to the bovine carpus and document the visible intra-articular structures in each approach. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Thirty fresh cadaveric bovine forelimbs. METHODS: Computed tomography (CT) and gross dissection were performed on 4 carpi. Latex models were produced from 6 carpi to define the gross anatomy and arthroscopic portals to the palmar carpal pouches. Ultrasonography and arthroscopy were performed on 20 carpi to document visualization of the local anatomy. RESULTS: A single palmar pouch was present on both sides of each joint on gross dissection and evaluation of latex models. The relationship between pouches and palmar structures was observed by CT. Small anechoic areas identified on ultrasonography increased after joint distension. Palmar arthroscopy of the antebrachiocarpal joint enabled visualization of the palmar surfaces of radial, intermediate, and ulnar carpal bones; distal radius; ulnar styloid process; palmar radiocarpal ligament; and articulation of accessory and ulnar carpal bones. Palmar arthroscopy of the middle carpal joint enabled inspection of the palmar aspects of ulnar, intermediate, radial, fused second and third and fourth carpal bones, palmar carpometacarpal ligament, and the short lateral collateral ligament. Palmar aspects of the fourth and fifth metacarpal bones were explored through the palmarolateral approach to the middle carpal joint. Instrument portals for each pouch were created under arthroscopic guidance. CONCLUSION: Palmar arthroscopy of the adult bovine carpus enabled visualization of the clinically relevant palmar intra-articular structures. CLINICAL SIGNIFICANCE: Palmar carpal arthroscopy should be considered as an adjunct to dorsal approach for the diagnosis and treatment of bovine carpal diseases.

Serum-free human MSC medium supports consistency in human but not in equine adipose-derived multipotent mesenchymal stromal cell culture.

For clinical applications of multipotent mesenchymal stromal cells (MSCs), serum-free culture is preferable to standardize cell products and prevent contamination with pathogens. In contrast to human MSCs, knowledge on serum-free culture of large animal MSCs is limited, despite its relevance for preclinical studies and development of veterinary cellular therapeutics. This study aimed to evaluate the suitability of a commercially available serum-free human MSC medium for culturing equine adipose-derived MSCs in comparison with human adipose MSCs. Enzyme-free isolation by explant technique and expansion of equine and human cells in the serum-free medium were feasible. However, serum-free culture altered the morphology and complicated handling of equine MSCs, with cell aggregation and spontaneous detachment of multilayers, compared to culture in standard medium supplemented with fetal bovine serum. Furthermore, proliferation and the surface immunophenotype of equine cells were more variable compared to the controls and appeared to depend on the lot of the serum-free medium. Particularly the expression of CD90 was different between experimental groups (P < 0.05), with lower percentages of CD90+ cells found in equine MSC samples cultured in serum-free medium (5.21-83.40%) compared to standard medium (86.20-99.50%). Additionally, small subpopulations expressing MSC exclusion markers such as CD14 (0.28-11.60%), CD34 (0.00-9.87%), CD45 (0.35-10.50%), or MHCII (0.00-3.67%) were found in equine samples after serum-free culture. In contrast, human samples displayed a more consistent morphology and a consistent CD29+ (98.60-99.90%), CD73+ (94.60-98.40%), CD90+ (99.60-99.90%), and CD105+ (97.40-99.80%) immunophenotype after culture in serum-free medium. The obtained data demonstrate that the serum-free medium was suitable for human MSC culture but did not lead to entirely satisfactory results in equine MSCs. This underlines that requirements regarding serum-free culture conditions are species-specific, indicating a need for serum-free media to be optimized for MSCs from relevant animal species. © 2017 International Society for Advancement of Cytometry.

Tenogenic Properties of Mesenchymal Progenitor Cells Are Compromised in an Inflammatory Environment.

Transplantation of multipotent mesenchymal progenitor cells is a valuable option for treating tendon disease. Tenogenic differentiation leading to cell replacement and subsequent matrix modulation may contribute to the regenerative effects of these cells, but it is unclear whether this occurs in the inflammatory environment of acute tendon disease. Equine adipose-derived stromal cells (ASC) were cultured as monolayers or on decellularized tendon scaffolds in static or dynamic conditions, the latter represented by cyclic stretching. The impact of different inflammatory conditions, as represented by supplementation with interleukin-1ß and/or tumor necrosis factor-α or by co-culture with allogeneic peripheral blood leukocytes, on ASC functional properties was investigated. High cytokine concentrations increased ASC proliferation and osteogenic differentiation, but decreased chondrogenic differentiation and ASC viability in scaffold culture, as well as tendon scaffold repopulation, and strongly influenced musculoskeletal gene expression. Effects regarding the latter differed between the monolayer and scaffold cultures. Leukocytes rather decreased ASC proliferation, but had similar effects on viability and musculoskeletal gene expression. This included decreased expression of the tenogenic transcription factor scleraxis by an inflammatory environment throughout culture conditions. The data demonstrate that ASC tenogenic properties are compromised in an inflammatory environment, with relevance to their possible mechanisms of action in acute tendon disease.

Testing the validity of a stage assessment on health enhancing physical activity in a chinese university student sample.

BACKGROUND: The study examined the measurement quality of a stage algorithm measuring the Four steps from Inactivity to activity Theory (FIT Model). METHODS: In a cross-sectional study, stages were assessed in 1012 Chinese university students in terms of physical activity, social-cognitive variables and health outcomes. Main outcome measures were stages of change, self-reported physical activity, perceived barriers, intrinsic motivation, plans, fitness and health satisfaction. Misclassification, sensitivity, specificity, receiver operating characteristic (ROC) curves, nonlinear trends, and planned comparison were computed. RESULTS: Compared to previous studies, sensitivity was at the average level (64 %-71 %), and specificity was comparably higher (76%-89%). When using higher PA intensity criteria (moderate and strenuous intensities), sensitivity was higher, whereas specificity was lower in comparison to the lower PA intensity criteria (also including mild activity). After running contrast and trend analyses, nonlinear trends for all indicative variables across the stages and a match of 77 % of predictions of stage differences were confirmed. CONCLUSION: The measurement quality of the stage algorithm was supported in a young adult sample.

Retrospective Evaluation of Hemithyroidectomy in 14 Horses.

OBJECTIVE: To describe the presentation, presurgical diagnostic findings, treatment, and outcome of horses with histologically confirmed, unilateral thyroid neoplasia. The complications, particularly laryngeal hemiplegia, were investigated. STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned horses (n=14). METHODS: Medical records of horses presenting with a unilateral thyroid mass due to neoplasia from 2003-2015 were reviewed. Horses must have undergone preoperative clinical evaluations that included ultrasound examination of the mass and upper airway endoscopy. Short-term follow-up at 2 weeks after surgery and owner questionnaire for long-term follow-up at >6 months were completed. RESULTS: Fourteen horses aged 6-21 years were included. The majority of tumors were adenocarcinomas (11/14), mainly diagnosed in mares (9/14). Intraoperative complications included hemorrhage (1/14) and postoperative complications included seroma formation (4/14). No horse developed postoperative laryngeal hemiplegia. No horses developed clinical signs of metastases or a thyroid disorder long term (mean follow-up 4.9 years). All owners reported a successful long-term outcome. CONCLUSION: The clinical findings of thyroid neoplasia in horses are not associated with the diagnosis of malignancy. Complete surgical resection of the abnormal lobe prevents local recurrence of neoplastic thyroid tissue. The modified hemithyroidectomy technique preserves the function of the recurrent laryngeal nerve.

Comparative immunophenotyping of equine multipotent mesenchymal stromal cells: an approach toward a standardized definition.

Horses are an approved large animal model for therapies of the musculoskeletal system. Especially for tendon disease where cell-based therapy is commonly used in equine patients, the translation of achieved results to human medicine would be a great accomplishment. Immunophenotyping of equine mesenchymal stromal cells (MSCs) remains the last obstacle to meet the criteria of the International Society for Cellular Therapy (ISCT) definition of human MSCs. Therefore, the surface antigen expression of CD 29, CD 44, CD 73, CD 90, CD 105, CD 14, CD 34, CD 45, CD 79α, and MHC II in equine MSCs from adipose tissue, bone marrow, umbilical cord blood, umbilical cord tissue, and tendon tissue was analyzed using flow cytometry. Isolated cells from the different sources and donors varied in their expression pattern of MSC-defining antigens. In particular, CD 90 and 105 showed most heterogeneity. However, cells from all samples were robustly positive for CD 29 and CD 44, while being mostly negative for CD 73 and the exclusion markers CD 14, CD 34, CD 45, CD 79α and MHC II. Furthermore, it was evident that enzymes used for cell detachment after in vitro-culture affected the detection of antigen expression. These results emphasize the need of standardization of MSC isolation, culturing, and harvesting techniques. As the equine MSCs did not meet all criteria the ISCT defined for human MSCs, further investigations for a better characterization of the cell type should be conducted.

Bovine thoracoscopy: surgical technique and normal anatomy.

OBJECTIVE: To describe a surgical technique for thoracoscopy and report visible anatomy within the thoracic cavity of standing cattle. STUDY DESIGN: Prospective study. ANIMALS: Adult clinically healthy Holstein-Friesian cows (n = 15). METHODS: Each cow had four thoracoscopic examinations. Initially, the left hemithorax was examined after passive lung collapse, then again 24 hours later after CO2 insufflation. The right hemithorax was examined 24 hours later after passive lung collapse and again 24 hours later after CO2 insufflation. RESULTS: CO2 insufflation did not significantly improve visibility within the pleural space. Collapsed lung, aorta, esophagus, diaphragm, and azygos vein were readily viewed; however, the pericardial region was not consistently visible. Minor laceration of the lung occurred in 1 cow with adhesions, otherwise there were no intra- or postoperative complications. All cows recovered without signs of discomfort. No local swelling or emphysema occurred at the portals. CONCLUSIONS: Thoracoscopy can be safely performed on healthy standing cattle.

Equine Models of Temporomandibular Joint Osteoarthritis: A Review of Feasibility, Biomarkers, and Molecular Signaling.

Osteoarthritis (OA) of the temporomandibular joint (TMJ) occurs spontaneously in humans and various animal species, including horses. In humans, obtaining tissue samples is challenging and clinical symptoms appear late in the disease progression. Therefore, genetically modified, induced, and naturally occurring animal models play a crucial role in understanding the pathogenesis and evaluating potential therapeutic interventions for TMJ OA. Among the naturally occurring models, the equine TMJ OA model is characterized by slow, age-related progression, a wide range of clinical examinations, and imaging modalities that can be performed on horses, as well as easy tissue and synovial fluid collection. The morphological and functional similarities of TMJ structures in both species make the equine model of TMJ OA an excellent opportunity to track disease progression and response to treatment. However, much work remains to be carried out to determine the utility of human TMJ OA biomarkers in horses. Among the main TMJ OA biomarkers, IL-1, IL-6, TGF-ß, TNF-α, and PGE2 have been recently investigated in the equine model. However, the majority of biomarkers for cartilage degradation, chondrocyte hypertrophy, angiogenesis, and TMJ overload-as well as any of the main signaling pathways-have not been studied so far. Therefore, it would be advisable to focus further research on equine specimens, considering both mediators and signaling.

High positive end-expiratory pressure ventilation mitigates the progression from unilateral pulmonary contusion to ARDS: An animal study.

BACKGROUND: Pulmonary contusion (PC) is common in severely traumatized patients and can lead to respiratory failure requiring mechanical ventilation (MV). Ventilator-induced lung injury (VILI) might aggravate lung damage. Despite underrepresentation of trauma patients in trials on lung-protective MV, results are extrapolated to these patients, potentially disregarding important pathophysiological differences. METHODS: Three MV protocols with different positive end-expiratory pressure (PEEP) levels: ARDSnetwork lower PEEP (ARDSnet-low), ARDSnetwork higher PEEP (ARDSnet-high), and open lung concept (OLC) were applied in swine for 24 hours following PC. Gas exchange, lung mechanics, quantitative computed tomography, and diffuse alveolar damage (DAD) score were analyzed. Results are given as median (interquartile range) at 24 hours. Statistical testing was performed using general linear models (group effect) over all measurement points and pairwise Mann-Whitney U tests for DAD. RESULTS: There were significant differences between groups: PEEP ( p < 0.0001) ARDSnet-low (8 [8-10] cmH 2 O), ARDSnet-high (12 [12-12] cmH 2 O), OLC (21 [20-22] cmH 2 O). The fraction of arterial partial pressure of oxygen and inspired oxygen fraction ( p = 0.0016) was lowest in ARDSnet-low (78 (73-111) mm Hg) compared with ARDSnet-high (375 (365-423) mm Hg) and OLC (499 (430-523) mm Hg). The end-expiratory lung volume (EELV) differed significantly ( p < 0.0001), with highest values in OLC (64% [60-70%]) and lowest in ARDSnet-low (34% [24-37%]). Costa's surrogate for mechanical power differed significantly ( p < 0.0001), with lowest values for ARDSnet-high (73 [58-76]) compared with OLC (105 [108-116]). Diffuse alveolar damage was lower in ARDSnet-high compared with ARDSnet-low (0.0007). CONCLUSION: Progression to ARDS, 24 hours after PC, was mitigated by OLC and ARDSnet-high. Both concepts restored EELV. ARDSnet-high had the lowest mechanical power surrogate and DAD. Our data suggest, that ARDSnet-high restored oxygenation and functional lung volume and reduced physiological and histological surrogates for VILI. ARDSnet-low generated unfavorable outcomes, such as loss of EELV, increased mechanical power and DAD after PC in swine. The high respiratory rate in the OLC may blunt favorable effects of lung recruitment.

Equine cellular therapy--from stall to bench to bedside?

Pioneering clinical stem cell research is being performed in the horse, a recipient of cutting edge veterinary medicine as well as a unique animal model, paving the way for human medical applications. Although demonstrable progress has been made on the clinical front, in vitro characterization of equine stem cells is still in comparatively early stages. To translate the promising results of clinical stem cell therapy in the horse, advances must be made in the characterization of equine stem cells. Aiming to improve communication between veterinarians and other natural scientists, this review gives an overview of veterinary "bedside" achievements, focusing on stem cell therapies in equine orthopedics as well as the current state of in vitro characterization of equine multipotent mesenchymal stromal cells (MSCs) and equine embryonic stem cells (ESCs).

Isolation of equine multipotent mesenchymal stromal cells by enzymatic tissue digestion or explant technique: comparison of cellular properties.

BACKGROUND: The treatment of tendon lesions with multipotent mesenchymal stromal cells (MSCs) is widely used in equine medicine. Cell sources of MSCs include bone marrow, as well as solid tissues such as adipose tissue. MSCs can be isolated from these solid tissues either by enzymatic digestion or by explant technique. However, the different preparation techniques may potentially influence the properties of the isolated MSCs. Therefore, the aim of this study was to investigate and compare the effects of these two different methods used to isolate MSCs from solid tissues.Equine adipose tissue, tendon and umbilical cord matrix served as solid tissue sources of MSCs with different stiffness and density. Subsequent to tissue harvest, MSCs were isolated either by enzymatic digestion with collagenase or by explant technique. Cell yield, growth, differentiation potential and tendon marker expression were analysed. RESULTS: At first passage, the MSC yield was significantly higher in enzymatically digested tissue samples than in explanted tissue samples, despite a shorter period of time in primary culture. Further analysis of cell proliferation, migration and differentiation revealed no significant differences between MSCs isolated by enzymatic digestion and MSCs isolated by explant technique. Interestingly, analysis of gene expression of tendon markers revealed a significantly higher expression level of scleraxis in MSCs isolated by enzymatic digestion. CONCLUSIONS: Both isolation techniques are feasible methods for successful isolation of MSCs from solid tissues, with no major effects on cellular proliferation, migration or differentiation characteristics. However, higher MSC yields were achieved in a shorter period of time by collagenase digestion, which is advantageous for the therapeutic use of MSCs. Moreover, based on the higher level of expression of scleraxis in MSCs isolated by enzymatic digestion, these cells might be a better choice when attempting tendon regeneration.

Evaluation of a training model to teach veterinary students a technique for injecting the jugular vein in horses.

In this study, a newly-developed model for training veterinary students to inject the jugular vein in horses was evaluated as an additional tool to supplement the current method of teaching. The model was first validated by 19 experienced equine veterinarians, who judged the model to be a realistic and valuable tool for learning the technique. Subsequently, it was assessed using 24 students who were divided randomly into two groups. The injection technique was taught conventionally in a classroom lecture and a live demonstration to both groups, but only group 1 received additional training on the new model. All participants filled out self-assessment questionnaires before and after group 1 received training on the model. Finally, the proficiency of both groups was assessed using an objective structured clinical evaluation (OSCE) on live horses. Students from group 1 showed significantly improved confidence after their additional training on the model and also showed greater confidence when compared to group 2 students. In the OSCE, group 1 had a significantly better score compared to group 2: the median (with inter-quartile range) was 15 (0.7) vs. 11.5 (2.8) points out of 15, respectively. The training model proved to be a useful tool to teach veterinary students how to perform jugular vein injections in horses in a controlled environment, without time limitations or animal welfare concerns. The newly developed training model offers an inexpensive, efficient, animal-sparing way to teach this clinical skill to veterinary students.

Pyelonephritic end-stage kidney and ureterocutaneous fistula in a Shetland pony.

A 12-y-old Shetland Pony was presented with a mucus-secreting fistula in the right paralumbar fossa. Surgery was performed to unravel the origin of the fistula. The horse died under anesthesia and was forwarded to autopsy. The right kidney was markedly atrophic and fibrotic, consistent with unilateral end-stage kidney. The right ureter was markedly thickened, but with luminal continuity leading into the urinary bladder where a partial obstruction caused by nodular para-ureteral fat necrosis was evident. The lumen of the cutaneous fistula was continuous with the right ureter; therefore, we diagnosed the lesion as a ureterocutaneous fistula. Anomalies of the ureter are uncommon, and ureterocutaneous fistula formation in equids has not been reported previously to our knowledge.

Systematic review and meta-analysis of positive long-term effects after intra-articular administration of orthobiologic therapeutics in horses with naturally occurring osteoarthritis.

Equine veterinarians face challenges in treating horses with osteoarthritic joint pain in routine veterinary practice. All common treatment options aim to reduce the clinical consequences of osteoarthritis (OA) characterized by persistent synovitis and progressive degradation of articular cartilage. A range of joint-associated cell types and extracellular matrices are involved in the not yet entirely understood chronic inflammatory process. Regeneration of articular tissues to re-establish joint hemostasis is the future perspective when fundamental healing of OA is the long-term goal. The use of intra-articular applied biologic therapeutics derived from blood or mesenchymal stroma cell (MSC) sources is nowadays a well-accepted treatment option. Although this group of therapeutics is not totally consistent due to the lack of clear definitions and compositions, they all share a potential regenerative effect on articular tissues as described in in vivo and in vitro studies. However, the current stage of science in regenerative medicine needs to be supported by clinical reports as in fact, in vitro studies as well as studies using induced OA models still represent a fragment of the complex pathomechanism of naturally occurring OA. This systemic review aims to determine the long-term effect of orthobiologic therapeutics in horses suffering naturally occurring OA. Thereby, a meta-analysis of randomized controlled trials (RCTs) is conducted to describe the efficiency and safety of intra-articular applied orthobiologics in terms of lameness reduction in the long-term. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, thirteen studies met the inclusion criteria for the systemic review. Four of those studies have further been evaluated by the meta-analysis comparing the long-term effect in lameness reduction. Each study was examined for risk of bias. For data evaluation, a random-effects model was used, describing the overall outcome in a forest plot. The I2 statistic was used to assess heterogeneity. Results indicate, that orthobiologic therapies represent an effective long-term and safe OA treatment option. Due to the inhomogeneity of included studies, no statements are provided addressing specific orthobiologic therapies, affected joints, OA stage and horse's intended use. Future clinical trials should follow standardized study designs to provide comparable data.

Use of Autologous Conditioned Serum (ACS) for Osteoarthritis Treatment in Horses: A Systematic Review of Clinical Data.

The utilization of Autologous Conditioned Serum (ACS) for treating osteoarthritis (OA) in horses has seen a notable increase in recent years. In vitro studies have consistently identified ACS as a promising therapy for OA joints, contributing to its growing popularity in OA treatment. Despite this, there is a noticeable absence of systematic reviews focused solely on the clinical data of OA patients treated with ACS, excluding the in vitro perspective. This study aims to address this gap by systematically reviewing the latest literature, concentrating solely on clinical data in in vivo studies to evaluate the efficacy of ACS in OA lesions. All clinical studies involving ACS treatments for horses with OA were included in the assessment. Surprisingly, only six trials met the inclusion criteria for this systematic review. The results indicate that the majority of the considered articles support the use of ACS as a treatment for horses, albeit with a control group provided in only one study. However, the absence of a control group and the exclusion of histological evaluation diminish the validity of the majority of clinical research. While several studies suggest a beneficial effect of ACS on OA horses without significant adverse effects, this systematic review affirms that there is no definitive evidence for its effectiveness. Therefore, further investigation of the efficacy of ACS products as a treatment for OA is warranted, emphasizing the need for more controlled trials. Poorly designed and biased studies, lacking blinding or control and adopting inadequate outcome measures, may favor positive results and, thus, necessitate a more rigorous approach to validate the efficacy of ACS in OA treatment.