Cytokine-based models for efficient differentiation between infection and cytokine release syndrome in patients with hematological malignancies.

Although the efficacy of chimeric antigen receptor (CAR)-T cell therapy has been widely demonstrated, its clinical application is hampered by the complexity and fatality of its side effects. Cytokine release syndrome (CRS) is the most common toxicity following CAR-T cell infusion, and its symptoms substantially overlap with those of infection. Whereas, current diagnostic techniques for infections are time-consuming and not highly sensitive. Thus, we are aiming to develop feasible and efficient models to optimize the differential diagnosis in clinical practice. This study included 191 febrile patients from our center, including 85 with CRS-related fever and 106 with infectious fever. By leveraging the serum cytokine profile at the peak of fever, we generated differential models using a classification tree algorithm and a stepwise logistic regression analysis, respectively. The first model utilized three cytokines (IFN-ß, CXCL1, and CXCL10) and demonstrated high sensitivity (90% training, 100% validation) and specificity (98.44% training, 90.48% validation) levels. The five-cytokine model (CXCL10, CCL19, IL-4, VEGF, and CCL20) also showed high sensitivity (91.67% training, 95.65% validation) and specificity (98.44% training, 100% validation). These feasible and accurate differentiation models may prompt early diagnosis of infections during immune therapy, allowing for early and appropriate intervention.

Improved antioxidant activity and rumen fermentation in beef cattle under heat stress by dietary supplementation with creatine pyruvate.

Pyruvate and creatine, energetics and antioxidant substances, can promote rumen fermentation and metabolism. This study aimed to evaluate the stress resistance and rumen fermentation effects of the compound creatine pyruvate (CrPyr) in diets for beef cattle under heat stress. Four Jinjiang steers fitted with permanent rumen cannulas were used in a 4 × 4 Latin square design and fed a diet supplemented with CrPyr at 0, 20, 40, or 60 g/d. Heat stress was employed for 62 of 64 days. Supplementing with CrPyr elevated their levels of free triiodothyronine and triiodothyronine, superoxide dismutase activity, ruminal pH value, microbial crude protein concentration, crude fat digestibility, nitrogen intake, and levels of urine allantoin and total purine derivatives. It also reduced their levels of cortisol and corticosterone, malondialdehyde concentration, lactate dehydrogenase activity, and urine nitrogen excretion. In conclusion, CrPyr relieves the heat stress of beef cattle by improving antioxidant activity and rumen microbial protein synthesis.