To determine the normal optical nerve sheath (ONS) diameter ultrasonography (ONSUS) and evaluate the possible effects of drugs on ONS diameter during anesthetic induction in healthy pigs. Methods: Healthy piglets were divided into three groups: a control group, that received xylazine and ketamine (X/K); other that received xylazine, ketamine and propofol (X/K/P); and a third group that received xylazine, ketamine, and thiopental (X/K/T). The sheath diameter was assessed by ultrasonography calculating the average of three measurements of each eye from the left and right sides. Results: 118 animals were anesthetized (49 X/K 33 X/K/P and 39 X/K/T). Mean ONS sizes on both sides in each group were 0.394 ± 0.048 (X/K), 0.407 ± 0.029 (X/K/P) and 0.378 ± 0.042 cm (X/K/T) (medians of 0.400, 0.405 and 0.389, respectively). The ONS diameter varied from 0.287-0.512 cm (mean of 0.302 ± 0.039 cm). For group X/K, the mean diameter was 0.394 ± 0.048 cm. Significant differences in ONS sizes between the groups P and T (X/K/P > X/K/T, p = 0.003) were found. No statistically significant differences were detected when other groups were compared (X/K = X/K/P, p = 0.302; X/K = X/K/T, p = 0.294). Conclusion: Sedation with thiopental lead to significative ONS diameter reduction in comparison with propofol. ONSUS may be useful to evaluate responses to thiopental administration.

Background This preliminary study describes the Brazilian experience on dual biologic therapy or small molecule combined with a biologic therapy in patients with inflammatory bowel disease (IBD) refractory to multiple biologics. Methods We identified patients from 6 IBD centers in Brazil between April 2020 and November 2022 who received treatment with a combination of two biologics or a biologic and a small molecule drug due to refractory disease or concomitant immunomediated condition. The primary endpoint was clinical remission at week 16, defined as a total Mayo score of ≤2 for UC and Harvey-Bradshaw Index (HBI) <4 for CD. Secondary endpoints were improvement in disease activity scores and biomarkers. Adverse events were monitored and summarized descriptively. Results Twenty-nine patients were identified (69% CD, n=20), 51.8% female, mean age 38.8 years old [SD= ± 14.8 years]). Seventy per cent (n=14) had penetrating behavior among CD patients. Twenty-seven had failed to, at least, one anti-TNF; 79.9% had failed to ustekinumab (UST), and 34.5% to vedolizumab (VEDO). Twenty-six patients were treated with combination advanced therapy due to loss of response to biologics and three patients had concomitant ankylosing spondylitis. The most common combination used was UST+ADA (n=12, 41.4%), followed by UST+VEDO (n=6, 21.7%). Mean treatment time was 53.8 weeks (SD= 40.4 weeks, CI 95% [37.5 – 70]). At week 16, clinical remission rates were 80% and 66% for CD and UC, respectively. All patients under VEDO + UST combination achieved clinical remission at 16w, in both diseases. Baseline HBI mean was 10.8 (SD= ± 3.6 points; CI 95% [9.1- 12.5]), decreasing to a mean of 5.5 at week 16 (SD= ± 3.5 points; CI 95% [3.8 - 7.2]) and plateauing at 7 by week 24 (SD= ±5.4 CI 95% [3.4- 10.6]). There was a notable decrease in HBI at week 16 (p< 0.001) and a significant decrease at week 24 (p= 0.02) compared to baseline. Mean CRP at week 16 was significantly lower than baseline in CD (17.4mg/dL vs 5.5 mg/dL, p=0.001) and numerically lower in UC (from 14.3mg/dL to 9.9mg/dL, p= 0.5). Fecal calprotectin decreased from 2509mcg/g to 1472mcg/g in both groups (p=0,2). In addition, all patients with ankylosing spondylitis showed symptomatic remission. No new safety signals were identified during follow-up Conclusion Despite combination of advanced therapies in IBD is not yet recommended by treatment guidelines, this strategy seems to be a promising option for patients with refractory IBD or concomitant autoimmune disease. Our data indicate that further investigation in this direction is worthwhile.

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