Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity. � 2016 Michal Lotem et al

Serum hyaluronic acid levels in patients with ankylosing spondylitis

Our aim in this study was to investigate serum hyaluronic acid (HA) levels and the relationship between clinical parameters in ankylosing spondylitis (AS). Approximately 30 patients with AS and 30 healthy individuals were recruited in this study consecutively. Cross-sectional study was planned, and demographic, clinical, functional, radiological, and laboratory data of patients were evaluated. Disease activity, functional status, and quality of life were assessed, respectively, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Short-Form 36 (SF-36). Mander Enthesis Index (MEI) was used for evaluation of enthesis involvement. We examined serum concentrations of HA (ng/ml) in patients with AS and controls. The mean ages of patients and control group were 38.3 (SD=10.8) and 42.7 (SD=10.6) years, respectively. The mean of serum HA levels in AS patients was 40.4 (SD=34.8) ng/ml and in controls was 24.9 (SD=20.2). There was significant difference of HA levels between two groups (p=0.04). Furthermore, there was a significant correlation between HA level and distance of hand-floor (r=0.444, p=0.014), modified lumbar Schober's (r=-0.413, p=0.023), distance of chin to chest (r=0.436, p=0.016), right sacroiliit grade (r=0.601, p = 0.05). Serum HA level was significantly higher in AS patients than controls. However, there was no significant correlation between serum HA level and disease-specific measures as BASFI and BASDAI; it had significant relation with spinal mobility limitation, sacroiliitis, and laboratory parameters related with acute inflammation. The serum HA level may be a potential biomarker of axial inflammation and disease severity in AS

Serum hyaluronic acid levels in patients with ankylosing spondylitis

Our aim in this study was to investigate serum hyaluronic acid (HA) levels and the relationship between clinical parameters in ankylosing spondylitis (AS). Approximately 30 patients with AS and 30 healthy individuals were recruited in this study consecutively. Cross-sectional study was planned, and demographic, clinical, functional, radiological, and laboratory data of patients were evaluated. Disease activity, functional status, and quality of life were assessed, respectively, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Short-Form 36 (SF-36). Mander Enthesis Index (MEI) was used for evaluation of enthesis involvement. We examined serum concentrations of HA (ng/ml) in patients with AS and controls. The mean ages of patients and control group were 38.3 (SD = 10.8) and 42.7 (SD = 10.6) years, respectively. The mean of serum HA levels in AS patients was 40.4 (SD = 34.8) ng/ml and in controls was 24.9 (SD = 20.2). There was significant difference of HA levels between two groups (p = 0.04). Furthermore, there was a significant correlation between HA level and distance of hand-floor (r = 0.444, p = 0.014), modified lumbar Schober's (r = 0.413, p = 0.023), distance of chin to chest (r = 0.436, p = 0.016), right sacroiliit grade (r = 0.601, p <0.001), left sacroiliit grade (r = 0.610, p <0.001), C reactive protein level (r = 0.404, p = 0.027), albumin (r = 0.464, p = 0.010), C3 (p = 0.449, p = 0.013), and IgA levels (r = 0.369, p = 0.045). However, there was no significant correlation between HA levels with MEI, BASFI, BASDAI, and SF-36 (p ≥0.05). Serum HA level was significantly higher in AS patients than controls. However, there was no significant correlation between serum HA level and disease-specific measures as BASFI and BASDAI; it had significant relation with spinal mobility limitation, sacroiliitis, and laboratory parameters related with acute inflammation. The serum HA level may be a potential biomarker of axial inflammation and disease severity in AS. © Clinical Rheumatology 2007

Plains Zebras Prioritize Foraging Without Sacrificing Social Bonds During a Severe Drought

ABSTRACT Anthropogenically induced climate change has significantly increased the frequency of acute weather events, such as drought. As human activities amplify environmental stresses, animals may be forced to prioritize survival over behaviors less crucial to immediate fitness, such as socializing. Yet, social bonds may also enable individuals to weather the deleterious effects of environmental conditions. We investigated how the highly social plains zebra (Equus quagga) modify their activity budgets, social networks, and multimodal communication during a drought. Although animals prioritized feeding and the number of social interactions dramatically decreased in the late drought period, social associations remained robust. We observed age/sex class‐specific changes in social behavior, reflecting the nutritional needs and social niche of each individual. Stallions devoted more time to greeting behaviors, which could mitigate harassment by bachelor males and facilitate grazing time for the females of the harem. Juveniles significantly increased time spent active socializing, despite mothers showing the greatest decrease in the number of social interactions. Instead, unrelated, nonlactating females served as social partners, accommodating both juveniles' social needs and lactating mothers' nutritive requirements. Using a network‐based representation of multimodal communication, we observed a decrease in the number of signals used during the drought. Individuals used less diverse multimodal combinations, particularly in the costly context of aggression. These findings illustrate how social roles and differential responses to acute environmental stress within stable social groups may contribute to species resilience, and how communication flexibly responds to facilitate both survival and sociality under harsh environmental conditions