E. M. Gaughan

The purpose of the study is to document the prevalence of articular surface osteochondrosis lesions in feral horses. Eighty yearling feral horses were used. Radiographic images of the left stifle, both tarsocrural, metatarsophalangeal, metacarpophalangeal joints were taken. Radiographs were examined for the presence of osteochondral fragmentation and abnormal outline of subchondral bone suggestive of osteochondrosis. The prevalence of each lesion was calculated for each joint as well as for overall prevalence within the group, the latter being 6.25%. Typical osteochondrosis lesions were found within the tarsocrural and metatarsophalangeal joints. Based on the difference in prevalence of osteochondrosis between feral and certain domestic horses, management practices and perhaps genetic base may have a greater influence on the development of the disease in horses than trauma alone.

Summary The ability of polysulfated glycosaminoglycans ( psgag ) to inhibit the complement cascade was evaluated. The role of complement in inflammation and infection has been well documented. Inhibition of the complement cascade by psgag could explain why intra-articularly administered psgag diminish diarthrodial joint inflammation and potentiate septic arthritis in horses. Hemolytic complement testing was performed to evaluate the effect of psgag on the equine classical and alternate pathways of complement, using rabbit erythrocytes as the target cells. Concentration of psgag between 0.2 mg/ml and 0.6 mg/ml significantly ( P < 0.05) inhibited equine complement in dose-related fashion. Further increase in complement inhibition was not observed at psgag concentration >0.6 mg/ml. Difference was not apparent in the extent of inhibition of complement from each of the 4 horses tested. Polysulfated glycosaminoglycans appeared to inhibit the classical and alternate complement pathways equally, indicating possible effect on complement components common to both pathways. Heat inactivation of complement function completely inhibited ( P <0.01) the hemolytic activity of the serum from all horses.

BACKGROUND: Host physiological factors may influence immune response, treatment tolerance, and survival during immune checkpoint inhibitor (ICI) therapy. Allostatic load (AL) summarizes cumulative physiological dysregulation across multiple biological systems. We evaluated whether pre-treatment AL is associated with immune-related toxicity and clinical outcomes among patients with advanced melanoma receiving ICIs. METHODS: We analyzed 399 patients with melanoma treated with ICIs at the University of Virginia Cancer Center (2013-2025). AL was derived from routinely collected clinical laboratory biomarkers measured prior to treatment initiation. Multinominal logistic and Cox regression models assessed associations between AL and immune-related adverse events (irAEs), treatment response, disease progression, and overall survival (OS), adjusting for demographic, clinical, and treatment factors. RESULTS: The mean AL score was 4.43. Each 1-unit increase in AL was associated with higher odds of grade ≥ 2 toxicity (adjusted odds ratio [OR] = 1.30; 95% confidence interval [CI]: 1.08-1.57). Among patients who developed irAEs, higher AL was associated with poorer treatment response (adjusted OR = 1.24; 95% CI: 1.01-1.54) and increased risk of disease progression (adjusted hazard ratio [HR] = 1.14; 95% CI: 0.98-1.33). Higher AL was also associated with shorter OS, with a 26% higher mortality risk per 1-unit increase in AL (adjusted HR = 1.26; 95% CI: 1.14-1.39). CONCLUSIONS: Higher pre-treatment AL was associated with increased immune-related toxicity and poorer survival in melanoma patients treated with ICIs. AL represents a feasible pre-treatment marker of host physiological vulnerability that may complement existing clinical predictors. Prospective studies are needed to validate these findings and assess clinical utility.