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Background: Despite adequate treatment, a subgroup of patients with inflammatory bowel disease (IBD), including Crohn`s disease and ulcerative colitis, have persistent gastrointestinal symptoms that are not always related to mucosal damage. Recently, two autoantibodies, anti-CdtB and anti-vinculin, were validated as post-infectious IBS (PI-IBS) markers, however there is limited evidence of its diagnostic role in IBD population., Methods: Patients with more than 3 bowel movements/day and indication of colonoscopy were enrolled. Samples were collected at the time of colonoscopy for assessment of serum levels of anti-CdtB and anti-vinculin antibodies., Results: A total of 160 subjects were included in 4 groups: active IBD (n = 44); quiescent IBD and chronic diarrhea IBD-IBS (n = 25); predominant-diarrhea IBS (n = 45) and controls (n = 46). The mean value of the optical density for anti-CdtB was 1.2 ± 0.65 in group 1, 1.27 ± 0.64 in group 2, 1.49 ± 0.47 in the group 3 and 1.6 ± 0.68 in group 4, p = 0.012. For anti-vinculin, optical densities were: 1.34 ± 0.78 in group 1, 1.46 ± 0.92 in group 2, 1.31 ± 0.79 in group 3 and 1.41 ± 0.86 for controls (p = 0.875). Using a cut-off of 1.56 for anti-CdtB, the positivity between groups was n = 10 (22.7%) in group 1, n = 9 (34.6%) in group 2, 19 (43.2%) in group 3, 21 (45.7%) in group 4 (p = 0.106). The positivity of anti-vinculin using a cut-off of 1.6 was n = 18 (40.9%) in group 1, n = 11 (42.3%), n = 15 (34.1%), n = 22 (47.8%) (p = 0.622)., Conclusions: Our findings show that anti-CdtB and anti-vinculin could not identify IBD-IBS patients or discriminate IBS-D from healthy controls., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Ethics Review Board of Clinics Hospital, University of São Paulo School of Medicine. Written informed consent was obtained from patients before enrollment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicenter cohort of Brazilian patients with UC., Methods: We conducted a multicenter retrospective observational cohort study, including patients with moderate-to-severe UC (total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of 0) within 1 year from baseline. Secondary endpoints included clinical response between weeks 12 and 16, endoscopic response within 1 year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety., Results: A total of 50 patients were included (female, n  = 36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis ( n  = 38, 76.0%), and 43 (86.0%) were steroid dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n  = 31; vedolizumab [VDZ], n  = 27). The co-primary endpoints of clinical remission at 1 year and endoscopic remission within 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, and endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 46.5%, and 50.0%, respectively. The UST treatment persistence rate at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and 3 patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-seven adverse events (AEs) were reported, 16 of which were considered as serious AEs., Conclusions: In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST., Competing Interests: R.S.P. has received fees for serving as a speaker and/or an advisory board member for Takeda, Janssen, Abbvie, and Pfizer. J.M.F.C. has received fees for serving as a speaker and/or an advisory board member for Takeda, Janssen, AbbVie, Abbott, and Sandoz. M.F.C.A. has received fees for serving as a speaker and/or an advisory board member for Takeda, Abbvie, Pfizer, and Janssen. L.A.C. has received fees for serving as a speaker and/or an advisory board member for Takeda and Janssen. G.P.Z. has received fees for serving as a speaker and/or an advisory board member for Janssen, Abbvie, and Takeda. O.S.C. has received fees for serving as a speaker and/or an advisory board member for Nestle, Abbvie, Janssen, Takeda, and Buhlmann. R.S.B.F. is a speaker for Janssen, Abbvie, Takeda, Ferring, Pfizer, and CSL Vifor. G.O.S. is a speaker for Abbvie, Celtrion, Janssen, and Takeda; conducts clinical research for Janssen, Lilly, Takeda, Polpharma, and Roche; and serves as an advisory board member for Janssen and Pfizer. M.I. has received fees for serving as a speaker and/or an advisory board member for Abbvie, Janssen, Pfizer, and Takeda. A.C.S.M. has received fees for serving as a speaker and/or an advisory board member for Janssen, Abbvie, and Takeda. F.V.T. is a speaker and an advisory board member of Takeda. A.J.T.A.J. has received fees for serving as a speaker and/or an advisory board member for Janssen, Takeda, UCB, and Abbvie. N.L.T.G.J. is a speaker and an advisory board member of Janssen and Takeda. S.C.F. has received fees for serving as a speaker and/or an advisory board member for Janssen, Takeda, and Pfizer. S.F.Q.N. has received fees for serving as a speaker and/or an advisory board member for Takeda, Janssen, Abbvie, and Pfizer. P.G.K. has received fees for serving as a speaker and/or an advisory board member for Janssen, Abbvie, Pfizer, and Takeda. He also has received scientific grants from Pfizer and Takeda. M.L., D.O.M., and F.O. report no conflicts of interest. P.G.K. holds the position of Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript. N.S.F.Q. is a Deputy Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Biological therapies have revolutionized the treatment of patients with inflammatory bowel disease (IBD). Infliximab (IFX) has been shown to be effective in inducing and maintaining remission in patients with Crohn's disease and ulcerative colitis. However, about one-third of the patients are primary non-responders, and up to half can lose response over time. Hence, it is important to assess which factors are related to treatment failure., Objectives: We aimed to identify factors predicting clinical and endoscopic remission with IFX treatment during maintenance therapy in a Brazilian IBD referral center., Design: We conducted a cross-sectional study to describe demographic, clinical, and IBD therapy-related characteristics of IBD patients treated with IFX for at least 6 months in a Brazilian referral center. Subsequently, we evaluated factors associated with clinical and endoscopic remission (primary and secondary outcomes, respectively)., Methods: We used descriptive statistics to summarize the essential demographic and clinical characteristics of the population. The association of sociodemographic and clinical variables with outcomes was analyzed using multivariable logistic regression., Results: A total of 131 IBD patients (the mean age 41.7 years) were enrolled in this study. Clinical and endoscopic remission were observed in 79.4% and 58.2% of the patients, respectively. In the multivariable analysis, IFX therapy duration and higher albumin levels increased the likelihood of clinical remission, while previous surgery decreased its chance. Prior use of adalimumab and higher C-reactive protein levels reduced the likelihood of endoscopic remission., Conclusion: In summary, this study has enhanced our understanding of the predictive factors of treatment response to IFX in a well-characterized Brazilian IBD population., Trial Registration: 4.254.501 and 2.903.748., Competing Interests: Camilla de Almeida Martins and Sergio Carlos Nahas have no conflict of interest. Natália Sousa Freitas Queiroz has served as a speaker and advisory board member of Janssen, Takeda, and Abbvie. Carlos Walter Sobrado Junior has served as speaker for Janssen, Sandoz, and Abbvie. Alexandre Sousa Carlos has served as speaker for Janssen and Takeda. Matheus Freitas Cardoso de Azevedo and Aderson Omar Mourão Cintra Damião has served as a speaker for Abbvie, Janssen, and Takeda., (© The Author(s), 2023.)

Therapeutic drug monitoring (TDM) during induction therapy with anti-tumor necrosis factor drugs has emerged as a strategy to optimize response to these biologics and avoid undesired outcomes related to inadequate drug exposure. This study aimed to describe clinical, biological, and endoscopic remission rates at six months in Brazilian inflammatory bowel disease (IBD) patients following a proactive TDM algorithm guided by IFX trough levels (ITL) and antibodies to IFX (ATI) levels during induction, at week six. A total of 111 IBD patients were prospectively enrolled, excluding those previously exposed to the drug. ITL ≥ 10 μg/mL was considered optimal. Patients with suboptimal ITL (<10 µg/mL) were guided according to ATI levels. Those who presented ATI ≤ 200 ng/mL underwent dose intensification in the maintenance phase, and patients with ATI > 200 ng/mL discontinued IFX. In our study, proactive TDM was associated with persistence in the IFX rate at six months of 82.9%. At that time, rates of clinical, biological, and endoscopic remission in patients under IFX treatment were 80.2%, 73.9%, and 48.1%, respectively. Applying a simplified TDM-guided algorithm during induction seems feasible and can help improve patients' outcomes in clinical practice.

Background: The effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD., Methods: We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed., Results: Overall, 245 CD (mean age 39.9 [15-87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time., Conclusions: UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents., (© 2022. The Author(s).)

Background: As Crohn's disease (CD) is associated with a high risk of thromboembolic events (TE), including patients with subclinical inflammation, we aim to evaluate the correlation between the impact of endoscopic activity (EA) in the coagulation profiling of CD patients while in clinical remission., Methods: From 164 consecutive CD patients included in clinical remission [Crohn's disease activity index (CDAI) < 150], 75 were in the EA group [Simplified Endoscopic Score for CD (SES-CD) ⩾ 7], 89 were in the endoscopic remission (ER) group (SES-CD ⩽ 2), and 50 were included as healthy controls in the study. Blood samples were analyzed for tissue factor (TF), factor VIII (FVIII), thrombomodulin (TM), ADAMTS-13, von Willebrand factor (VWF), and endogenous thrombin potential (ETP), as well as collecting data regarding risk factors for TE and CD profile., Results: Mean plasma TF activity showed significantly higher levels in the EA group when compared with the ER and control groups (127 pM versus 103 pM versus 84 pM; p  = 0.001), although the VWF:Ag (160% versus 168% versus 110%; p  = 0.001), VWF/ADAMTS-13 (191 versus 219 versus 138; p  = 0.003), FVIII (150% versus 144% versus 90%; p  = 0.001) and TM (5.13 ng/ml versus 4.91 ng/mL versus 3.81 ng/ml; p  < 0.001) were only increased in CD regardless of EA status when compared with controls. Lastly, ETP with and without TM remained the same in all three groups., Conclusions: CD patients in clinical remission with EA present endothelial lesion inducing TF exposure and subsequent coagulation cascade activation. Recommended thromboprophylaxis for EA outpatient subgroups will require additional investigation in order to be validated., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Background: Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease (MS-IBD). This study hypothesized that as a standard of treatment and the primary alternative to biologics, conventional therapy should present robust effectiveness results in IBD outcomes., Aim: To investigate the effectiveness of conventional therapy for MS-IBD., Methods: A systematic review with no time limit was conducted in July 2017 through the Cochrane Collaboration, MEDLINE, and LILACS databases. The inclusion criteria encompassed meta-analyses, systematic reviews, randomized clinical trials, observational and case-control studies concerning conventional therapy in adult patients with MS-IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Corticosteroids (prednisone, hydrocortisone, budesonide, prednisolone, dexamethasone), 5-aminosalicylic acid (5-ASA) derivatives (mesalazine and sulfasalazine) and immunosuppressants [azathioprine (AZA), methotrexate (MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine (6-MP)] were considered conventional therapy. The exclusion criteria were sample size below 50; narrative reviews; specific subpopulations ( e.g ., pregnant women, comorbidities); studies on postoperative IBD; and languages other than English, Spanish, French or Portuguese. The primary outcome measures were clinical remission (induction or maintenance), clinical response and mucosal healing. As secondary outcomes, fecal calprotectin, hospitalization, death, and surgeries were analyzed. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria., Results: The search strategy identified 1995 citations, of which 27 were considered eligible (7 meta-analyses, 20 individual studies). For induction of clinical remission, four meta-analyses were selected (AZA and 6-MP showed no advantage over placebo, MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacrolimus was superior to placebo for UC in two meta-analyses). Only one meta-analysis evaluated clinical remission maintenance, showing no statistically significant difference between MTX and placebo, 5-ASA, or 6-MP in UC. AZA and 6-MP had no advantage over placebo in induction of clinical response in CD. Three meta-analyses showed the superiority of tacrolimus vs placebo for induction of clinical response in UC. The clinical response rates for cyclosporine were 41.7% in randomized controlled trials (RCTs) and 55.4% in non-RCTs for UC. For induction of mucosal healing, one meta-analysis showed a favorable rate with tacrolimus versus placebo for UC. For secondary outcomes, no meta-analyses specifically evaluated fecal calprotectin, hospitalization or death. Two meta-analyses were retrieved evaluating colectomy rates for tacrolimus and cyclosporine in UC. Most of the twenty individual studies retrieved contained a low or very low quality of evidence., Conclusion: High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin., Competing Interests: Conflict-of-interest statement: Adérson Omar Mourão Cintra Damião has been a speaker for Takeda, Abbvie, and Janssen; has been an advisory board member for Takeda; and has received conference grants from Janssen, Takeda and Abbvie. Matheus Freitas Cardoso de Azevedo and Alexandre de Sousa Carlos have received research grants from Takeda, Janssen, and Abbvie. Marcela Yumi Wada, Taciana Valéria Marcolino Silva and Flávio de Castro Feitosa work at Takeda Pharmaceuticals, Brazil.

Carbene transfer reactions are very important transformations in organic synthesis, allowing the generation of structurally challenging products by catalysed cyclopropanation, cyclopropenation, carbene C-H, N-H, O-H, S-H, and Si-H insertion, and olefination of carbonyl compounds. In particular, chiral and achiral metalloporphyrins have been successfully explored as biomimetic catalysts for these carbene transfer reactions under both homogeneous and heterogeneous conditions. In this work the use of synthetic metalloporphyrins (MPorph, M = Fe, Ru, Os, Co, Rh, Ir, Sn) as homogeneous or heterogeneous catalysts for carbene transfer reactions in the last years is reviewed, almost exclusively focused on the literature since the year 2010, except when reference to older publications was deemed to be crucial., Competing Interests: The authors declare no conflict of interest.

Antimicrobial Resistance (AMR) is a serious problem for the humans since it threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. One way around this problem is to act on the virulence factors, produced by bacteria, which increase their infection effectiveness. In view of these facts, new coumarin derivatives were synthesized and evaluated for their anti-virulence biological activity towards Pseudomonas aeruginosa. The results suggest that coumarin derivatives with a secondary carbon at C-3 position reduces P. aeruginosa growth whereas compounds with one additional substituent have a significant effect over pyocyanin production (10k EC50 7 ± 2 µM; 10l EC50 42 ± 13 µM). Moreover, 10k reduces P. aeruginosa motility and biofilm formation, what is compatible with a quorum sensing related mechanism of action., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Heterocyclic rings having nitrogen atoms are the molecular fragments most used in drug design by using the tools of medicinal chemistry. The 1,2,4-triazole rings are part of an extensive family of drugs that are in use in the pharmaceutical market. More recently, 1,2,3-triazole rings have begun to arouse the great interest of scientists and therefore, many researches have been developed seeking the synthesis of new substances and their possible biological activities. A number of articles have been published by us and others highlighting the synthetic and biological aspects of 1,2,3-triazoles. The growth of new substances of this class was largely due to the simple and selective synthetic method of 1,2,3- triazole ring developed by Sharpless et al. However, some 1,2,3-triazole cannot be synthesized by this method. This review focuses on other synthetic methods that give access to other variations around the 1,2,3-triazole core. The systematic arrangement in this review explores the possibility of providing practical guidance to alternatives of this heterocycle. It has been divided into sections according to the types of starting materials and reactions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Sporotrichosis is a serious public health problem in Brazil that affects human patients and domestic animals, mainly cats. Thus, the search for new antifungal agents is required also due to the emergence and to the lack of effective drugs available in the therapeutic arsenal. The aim of this study was to evaluate the in vitro antifungal profile of two synthetic series of coumarin derivatives against Sporothrix schenckii and Sporothrix brasiliensis. The three-components synthetic routes used for the preparation of coumarin derivatives have proved to be quite efficient and compounds 16 and 17 have been prepared in good yields. The inhibitory activity of nineteen synthetic coumarins derivatives 16a-i and 17a-j were evaluated against Sporothrix spp. yeasts and the most potent compounds were 16b and 17i. However, according to concentrations able to inhibit (minimum inhibitory concentrations) and kill (minimum fungicidal concentrations) the cells, 17i was more effective than 16b against Sporothrix spp. Thus, 17i exhibited good antifungal activity against S. brasiliensis and S. schenckii, suggesting that it is an important scaffold for the development of novel antifungal agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)