Ustekinumab safety and effectiveness in patients with ulcerative colitis: results from a large real-life study.

BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. RESEARCH DESIGN AND METHODS: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. RESULTS: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. CONCLUSION: This real-world study shows that UST effectively and safely treats patients with UC.

Use of tofacitinib as first or second-line therapy is associated with better outcomes in patients with ulcerative colitis: data from a real-world study.

BACKGROUND: Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients. RESEARCH DESIGN AND METHODS: A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF. RESULTS: We enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment (p = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded. CONCLUSIONS: Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Real-world efficacy and safety of vedolizumab in managing ulcerative colitis versus Crohn's disease: results from an Italian multicenter study.

BACKGROUND: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. RESEARCH DESIGN AND METHODS: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. RESULTS: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). CONCLUSION: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.

Evolution of mammalian longevity: age-related increase in autophagy in bats compared to other mammals.

Autophagy maintains cellular homeostasis and its dysfunction has been implicated in aging. Bats are the longest-lived mammals for their size, but the molecular mechanisms underlying their extended healthspan are not well understood. Here, drawing on >8 years of mark-recapture field studies, we report the first longitudinal analysis of autophagy regulation in bats. Mining of published population level aging blood transcriptomes (M. myotis, mouse and human) highlighted a unique increase of autophagy related transcripts with age in bats, but not in other mammals. This bat-specific increase in autophagy transcripts was recapitulated by the western blot determination of the autophagy marker, LC3II/I ratio, in skin primary fibroblasts (Myotis myotis,Pipistrellus kuhlii, mouse), that also showed an increase with age in both bat species. Further phylogenomic selection pressure analyses across eutherian mammals (n=70 taxa; 274 genes) uncovered 10 autophagy-associated genes under selective pressure in bat lineages. These molecular adaptations potentially mediate the exceptional age-related increase of autophagy signalling in bats, which may contribute to their longer healthspans.

Divergence by depth in an oceanic fish.

Despite the striking physical and environmental gradients associated with depth variation in the oceans, relatively little is known about their impact on population diversification, adaptation and speciation. Changes in light associated with increasing depth are likely to alter the visual environment of organisms, and adaptive changes in visual systems may be expected. The pelagic beaked redfish, Sebastes mentella, exhibits depth-associated patterns of substructure in the central North Atlantic, with a widely distributed shallow-pelagic population inhabiting waters between 250 and 550 m depth and a deep-pelagic population dwelling between 550 and 800 m. Here we performed a molecular genetic investigation of samples from fish collected from 'shallow' and 'deep' populations, using the mitochondrial control region and the gene coding for the visual-pigment rhodopsin. We identify patterns suggestive of potential adaptation to different depths, by detecting a specific amino acid replacement at the rhodopsin gene. Mitochondrial DNA results reflect a scenario of long-term demographic independence between the two S. mentella groups, and raise the possibility that these 'stocks' may in fact be two incipient species.